Molecular Epidemiology of Rotavirus in Cats in the United Kingdom

PubMed Central

Iturriza-Gómara, M.; Dove, W.; Sandrasegaram, M.; Nakagomi, T.; Nakagomi, O.; Cunliffe, N.; Radford, A. D.; Morgan, K. L.

2014-01-01

Rotaviruses are leading causes of gastroenteritis in the young of many species. Molecular epidemiological studies in children suggest that interspecies transmission contributes to rotavirus strain diversity in people. However, population-based studies of rotaviruses in animals are few. We investigated the prevalence, risk factors for infection, and genetic diversity of rotavirus A in a cross-sectional survey of cats housed within 25 rescue catteries across the United Kingdom. Morning litter tray fecal samples were collected during the winter and summer in 2012 from all pens containing kittens and a random sample of those housing adult cats. Group A rotavirus RNA was detected by real-time reverse transcription-PCR, and positive samples were G and P genotyped using nested VP4 and VP7 PCR assays. A total of 1,727 fecal samples were collected from 1,105 pens. Overall, the prevalence of rotavirus was 3.0% (95% confidence interval [CI], 1.2 to 4.9%). Thirteen out of 25 (52%; 95% CI, 31.3 to 72.2%) centers housed at least one rotavirus-positive cat. The prevalence of rotavirus was associated with season (odds ratio, 14.8 [95% CI, 1.1 to 200.4]; P = 0.04) but not age or diarrhea. It was higher during the summer (4.7%; 95% CI, 1.2 to 8.3%) than in winter (0.8%; 95% CI, 0.2 to 1.5%). Asymptomatic epidemics of infection were detected in two centers. G genotypes were characterized for 19 (33.3%) of the 57 rotavirus-positive samples and P genotypes for 36 (59.7%). Two rotavirus genotypes were identified, G3P[9] and G6P[9]. This is the first population-based study of rotavirus in cats and the first report of feline G6P[9], which questions the previous belief that G6P[9] in people is of bovine origin. PMID:25411173

Effectiveness of rotavirus vaccines against rotavirus infection and hospitalization in Latin America: systematic review and meta-analysis.

PubMed

Santos, Victor S; Marques, Daniella P; Martins-Filho, Paulo R S; Cuevas, Luis E; Gurgel, Ricardo Q

2016-08-12

Rotavirus was the leading cause of childhood diarrhoea-related hospitalisations and death before the introduction of rotavirus vaccines. We describe the effectiveness of rotavirus vaccines to prevent rotavirus infections and hospitalizations and the main rotavirus strains circulating before and after vaccine introduction through a systematic review and meta-analysis of studies published between 1990 and 2014. 203 studies were included to estimate the proportion of infections due to rotavirus and 10 to assess the impact of the vaccines. 41 of 46 studies in the post-vaccination period were used for meta-analysis of genotypes, 20 to calculate VE against infection, eight for VE against hospitalisation and seven for VE against severe rotavirus-diarrhoea. 24.3 % (95 % CI 22.1-26.5) and 16.1 % (95 % CI 13.2-19.3) of cases of diarrhoea were due to rotavirus before and after vaccine introduction, respectively. The most prevalent G types after vaccine introduction were G2 (51.6 %, 95 % CI 38-65), G9 (14.5 %, 95 % CI 7-23) and G1 (14.2 %, 95 % CI 7-23); while the most prevalent P types were P[4] (54.1 %, 95 % CI 41-67) and P[8] (33 %, 95 % CI 22-46). G2P[4] was the most frequent genotype combination after vaccine introduction. Effectiveness was 53 % (95 % CI 46-60) against infection, 73 % (95 % CI, 66-78) against hospitalisation and 74 % (95 % CI, 68.0-78.0) against severe diarrhoea. Reductions in hospitalisations and mortality due to diarrhoea were observed in countries that adopted universal rotavirus vaccination. Rotavirus vaccines are effective in preventing rotavirus-diarrhoea in children in Latin America. The vaccines were associated with changes in genotype distribution.

Rotavirus genotypes associated with acute diarrhea in Egyptian infants.

PubMed

Ahmed, Salwa F; Mansour, Adel M; Klena, John D; Husain, Tupur S; Hassan, Khaled A; Mohamed, Farag; Steele, Duncan

2014-01-01

Before the introduction of rotavirus vaccine in Egypt, information on the burden of disease and the circulating rotavirus genotypes is critical to monitor vaccine effectiveness. A cohort of 348 Egyptian children was followed from birth to 2 years of age with twice-weekly home visits to detect diarrheal illness. VP7 and VP4 genes were genotyped by reverse-transcription polymerase chain reaction and DNA sequencing. Forty percentage of children had rotavirus-associated diarrhea at least once by their second birthday. One hundred and twelve children experienced a single rotavirus diarrheal episodes (RDE) at a median age of 9 months; while 27 infants had their second RDE at a median age of 15 months and 1 infant had 3 RDE at the age of 2, 16 and 22 months. Of the 169 RDE, 82% could be assigned a G-type, while 58% had been identified a P-type. The most prevalent genotype was G2 (32%), followed by G1 (24%) and G9 (19%). G2P[4] rotavirus episodes were significantly associated with fever (P = 0.03) and vomiting (P = 0.06) when compared with other genotypes. G2 strains were the predominant genotype causing 50% of the second RDE while G9 represented 25% of the second RDE. Genotypes identified are similar to those detected globally except for absence of G4. Our finding that 75% of the second RDE were due to G2 and G9 indicates a possible reduction in natural protection afforded by these types compared with G1, where 90% of G1 cases did not experience a second xposure, indicating greater protection against recurrent symptomatic infection.

In Vitro Neutralisation of Rotavirus Infection by Two Broadly Specific Recombinant Monovalent Llama-Derived Antibody Fragments

PubMed Central

Aladin, Farah; Einerhand, Alexandra W. C.; Bouma, Janneke; Bezemer, Sandra; Hermans, Pim; Wolvers, Danielle; Bellamy, Kate; Frenken, Leon G. J.; Gray, Jim; Iturriza-Gómara, Miren

2012-01-01

Rotavirus is the main cause of viral gastroenteritis in young children. Therefore, the development of inexpensive antiviral products for the prevention and/or treatment of rotavirus disease remains a priority. Previously we have shown that a recombinant monovalent antibody fragment (referred to as Anti-Rotavirus Proteins or ARP1) derived from a heavy chain antibody of a llama immunised with rotavirus was able to neutralise rotavirus infection in a mouse model system. In the present work we investigated the specificity and neutralising activity of two llama antibody fragments, ARP1 and ARP3, against 13 cell culture adapted rotavirus strains of diverse genotypes. In addition, immunocapture electron microscopy (IEM) was performed to determine binding of ARP1 to clinical isolates and cell culture adapted strains. ARP1 and ARP3 were able to neutralise a broad variety of rotavirus serotypes/genotypes in vitro, and in addition, IEM showed specific binding to a variety of cell adapted strains as well as strains from clinical specimens. These results indicated that these molecules could potentially be used as immunoprophylactic and/or immunotherapeutic products for the prevention and/or treatment of infection of a broad range of clinically relevant rotavirus strains. PMID:22403728

Characterization of rotavirus causing acute diarrhoea in children in Kathmandu, Nepal, showing the dominance of serotype G12.

PubMed

Ansari, Shamshul; Sherchand, Jeevan Bahadur; Rijal, Basista Prasad; Parajuli, Keshab; Mishra, Shyam Kumar; Dahal, Rajan Kumar; Shrestha, Shovita; Tandukar, Sarmila; Chaudhary, Raina; Kattel, Hari Prasad; Basnet, Amul; Pokhrel, Bharat Mani

2013-01-01

Diarrhoeal diseases are a major problem in developing countries. Though precise data on childhood mortality associated with diarrhoeal diseases in Nepal are not available, it has been estimated that approximately 25 % of child deaths are associated with diarrhoeal disease, particularly acute diarrhoea. The purpose of this study was to assess the incidence of rotavirus causing acute diarrhoea in children less than 5 years of age. A total of 525 children with acute diarrhoea in a children's hospital of Kathmandu, Nepal, were enrolled between April and September 2011. The incidence of acute diarrhoea due to rotavirus was 25.9 % (136/525) as determined by ELISA. The percentage of rotavirus-infected males was higher (64.5 %) than females (35.5 %). The frequency of rotavirus cases was higher in children less than 2 years of age, among which the majority of cases (80.2 %) were in children between 6 and 24 months old (P<0.01). Genotypic characterization by RT-PCR revealed that the serotype G12 represented 55.9 % of cases in this study associated with P-types of either P[6], P[4] or P[8]. Further to this, a total of eight G/P combinations were identified, G12P[6] being the most common strain type of rotavirus in Nepal, with a prevalence rate of 46.4 %. The aim of this study was to find out the major genotypes of rotavirus causing acute diarrhoea in children.

Hospital-based Surveillance for Rotavirus Gastroenteritis Among Young Children in Bangladesh: Defining the Potential Impact of a Rotavirus Vaccine Program.

PubMed

Satter, Syed M; Gastanaduy, Paul A; Islam, Khaleda; Rahman, Mahmudur; Rahman, Mustafizur; Luby, Stephen P; Heffelfinger, James D; Parashar, Umesh D; Gurley, Emily S

2017-02-01

In anticipation of introduction of a rotavirus vaccine into the national immunization program of Bangladesh, active hospital-based surveillance was initiated to provide prevaccine baseline data on rotavirus disease. Children 5 years of age and younger admitted with acute gastroenteritis (AGE) (≥3 watery or looser-than-normal stools or ≥1 episode of forceful vomiting) at 7 hospitals throughout Bangladesh were identified. Clinical information and stool specimens were collected from every 4th patient. Specimens were tested for rotavirus antigen by enzyme immunoassays; 25% of detected rotaviruses were genotyped. From July 2012 to June 2015, rotavirus was detected in 2432 (64%) of 3783 children hospitalized for AGE. Eight enrolled children died, including 4 (50%) who were rotavirus positive. Rotavirus was detected year-round in Bangladesh with peak detection rates of >80% during November-February. Most (86%) rotavirus AGE cases were 6-23 months of age. Sixty-nine percent of children with rotavirus had severe disease (Vesikari score, ≥11). Among 543 strains genotyped, G1P[8] (31%) and G12P[8] (29%) were the most common. Rotavirus is a major cause of morbidity in Bangladeshi children, accounting for nearly two-thirds of AGE hospitalizations. These data highlight the potential value of rotavirus vaccination in Bangladesh, and will be the key for future measurement of vaccine impact.

Group A rotavirus gastroenteritis: post-vaccine era, genotypes and zoonotic transmission

PubMed Central

Luchs, Adriana; Timenetsky, Maria do Carmo Sampaio Tavares

2016-01-01

ABSTRACT This article provides a review of immunity, diagnosis, and clinical aspects of rotavirus disease. It also informs about the changes in epidemiology of diarrheal disease and genetic diversity of circulating group A rotavirus strains following the introduction of vaccines. Group A rotavirus is the major pathogen causing gastroenteritis in animals. Its segmented RNA genome can lead to the emergence of new or unusual strains in human populations via interspecies transmission and/or reassortment events. PMID:27462899

Human rotavirus group a serotypes causing gastroenteritis in children less than 5 years and HIV-infected adults in Viwandani slum, Nairobi.

PubMed

Raini, S K; Nyangao, J; Kombich, J; Sang, C; Gikonyo, J; Ongus, J R; Odari, E O

2015-01-01

Rotavirus remains a leading cause of acute gastroenteritis in children worldwide with an estimated 2000 deaths each day in developing countries. Due to HIV/AIDS scourge in Kenya, it is possible that rotavirus-related gastroenteritis has been aggravated in adults. The Global Alliance for Immunizations has ranked rotavirus infection a priority for vaccine, and, to ensure its success, there is a need to document the local strain(s) circulating in different regions. A cross-sectional study was conducted to document human rotavirus group A serotypes in children below 5 years and HIV-infected adults in Viwandani slum in Nairobi, Kenya. A total of 260 (128 from children and 132 from HIV infected adults) fecal specimen samples were analyzed from August 2012 to July 2013. Screening for rotavirus was done by antigen based enzyme immune-sorbent assay (ELISA), Polyacrylamide gel electrophoresis (PAGE) was used to detect rotavirus electropherotypes and finally genotyping was done by RT-PCR using genotype-specific primer sets targeting VP4 and VP7 genes. Rotavirus was detected in 23% and 8% of children and adult, respectively. Prevalence was high in children of < 2 years and adults of > 48 years. Long electropherotypes accounted for 80% and 60% while short electropherotypes accounted for 20% and 40% in children and adult, respectively. The common globally distributed strains, G1 and G3, accounted for 60% detections while the unusual G9 strain accounted for 80% infection in adults. G1P[8] was the common genotypic combination in children, accounting for 40% infection, whereas G9 [P8] accounted for 60% of the infections in adults. This study shows the existence of strain diversity between rotavirus circulating in children and adults within this study group. It further shows that as currently constituted, the 2 vaccines recommended for rotavirus would cover the circulating strain in Viwandani slum. Finally, there is a need for continuous rotavirus strain surveillance in children and a further focus on HIV infected adults.

One-step multiplex real-time RT-PCR assay for detecting and genotyping wild-type group A rotavirus strains and vaccine strains (Rotarix® and RotaTeq®) in stool samples.

PubMed

Gautam, Rashi; Mijatovic-Rustempasic, Slavica; Esona, Mathew D; Tam, Ka Ian; Quaye, Osbourne; Bowen, Michael D

2016-01-01

Background. Group A rotavirus (RVA) infection is the major cause of acute gastroenteritis (AGE) in young children worldwide. Introduction of two live-attenuated rotavirus vaccines, RotaTeq® and Rotarix®, has dramatically reduced RVA associated AGE and mortality in developed as well as in many developing countries. High-throughput methods are needed to genotype rotavirus wild-type strains and to identify vaccine strains in stool samples. Quantitative RT-PCR assays (qRT-PCR) offer several advantages including increased sensitivity, higher throughput, and faster turnaround time. Methods. In this study, a one-step multiplex qRT-PCR assay was developed to detect and genotype wild-type strains and vaccine (Rotarix® and RotaTeq®) rotavirus strains along with an internal processing control (Xeno or MS2 RNA). Real-time RT-PCR assays were designed for VP7 (G1, G2, G3, G4, G9, G12) and VP4 (P[4], P[6] and P[8]) genotypes. The multiplex qRT-PCR assay also included previously published NSP3 qRT-PCR for rotavirus detection and Rotarix® NSP2 and RotaTeq® VP6 qRT-PCRs for detection of Rotarix® and RotaTeq® vaccine strains respectively. The multiplex qRT-PCR assay was validated using 853 sequence confirmed stool samples and 24 lab cultured strains of different rotavirus genotypes. By using thermostable rTth polymerase enzyme, dsRNA denaturation, reverse transcription (RT) and amplification (PCR) steps were performed in single tube by uninterrupted thermocycling profile to reduce chances of sample cross contamination and for rapid generation of results. For quantification, standard curves were generated using dsRNA transcripts derived from RVA gene segments. Results. The VP7 qRT-PCRs exhibited 98.8-100% sensitivity, 99.7-100% specificity, 85-95% efficiency and a limit of detection of 4-60 copies per singleplex reaction. The VP7 qRT-PCRs exhibited 81-92% efficiency and limit of detection of 150-600 copies in multiplex reactions. The VP4 qRT-PCRs exhibited 98.8-100% sensitivity, 100% specificity, 86-89% efficiency and a limit of detection of 12-400 copies per singleplex reactions. The VP4 qRT-PCRs exhibited 82-90% efficiency and limit of detection of 120-4000 copies in multiplex reaction. Discussion. The one-step multiplex qRT-PCR assay will facilitate high-throughput rotavirus genotype characterization for monitoring circulating rotavirus wild-type strains causing rotavirus infections, determining the frequency of Rotarix® and RotaTeq® vaccine strains and vaccine-derived reassortants associated with AGE, and help to identify novel rotavirus strains derived by reassortment between vaccine and wild-type strains.

One-step multiplex real-time RT-PCR assay for detecting and genotyping wild-type group A rotavirus strains and vaccine strains (Rotarix® and RotaTeq®) in stool samples

PubMed Central

Mijatovic-Rustempasic, Slavica; Esona, Mathew D.; Tam, Ka Ian; Quaye, Osbourne; Bowen, Michael D.

2016-01-01

Background. Group A rotavirus (RVA) infection is the major cause of acute gastroenteritis (AGE) in young children worldwide. Introduction of two live-attenuated rotavirus vaccines, RotaTeq® and Rotarix®, has dramatically reduced RVA associated AGE and mortality in developed as well as in many developing countries. High-throughput methods are needed to genotype rotavirus wild-type strains and to identify vaccine strains in stool samples. Quantitative RT-PCR assays (qRT-PCR) offer several advantages including increased sensitivity, higher throughput, and faster turnaround time. Methods. In this study, a one-step multiplex qRT-PCR assay was developed to detect and genotype wild-type strains and vaccine (Rotarix® and RotaTeq®) rotavirus strains along with an internal processing control (Xeno or MS2 RNA). Real-time RT-PCR assays were designed for VP7 (G1, G2, G3, G4, G9, G12) and VP4 (P[4], P[6] and P[8]) genotypes. The multiplex qRT-PCR assay also included previously published NSP3 qRT-PCR for rotavirus detection and Rotarix® NSP2 and RotaTeq® VP6 qRT-PCRs for detection of Rotarix® and RotaTeq® vaccine strains respectively. The multiplex qRT-PCR assay was validated using 853 sequence confirmed stool samples and 24 lab cultured strains of different rotavirus genotypes. By using thermostable rTth polymerase enzyme, dsRNA denaturation, reverse transcription (RT) and amplification (PCR) steps were performed in single tube by uninterrupted thermocycling profile to reduce chances of sample cross contamination and for rapid generation of results. For quantification, standard curves were generated using dsRNA transcripts derived from RVA gene segments. Results. The VP7 qRT-PCRs exhibited 98.8–100% sensitivity, 99.7–100% specificity, 85–95% efficiency and a limit of detection of 4–60 copies per singleplex reaction. The VP7 qRT-PCRs exhibited 81–92% efficiency and limit of detection of 150–600 copies in multiplex reactions. The VP4 qRT-PCRs exhibited 98.8–100% sensitivity, 100% specificity, 86–89% efficiency and a limit of detection of 12–400 copies per singleplex reactions. The VP4 qRT-PCRs exhibited 82–90% efficiency and limit of detection of 120–4000 copies in multiplex reaction. Discussion. The one-step multiplex qRT-PCR assay will facilitate high-throughput rotavirus genotype characterization for monitoring circulating rotavirus wild-type strains causing rotavirus infections, determining the frequency of Rotarix® and RotaTeq® vaccine strains and vaccine-derived reassortants associated with AGE, and help to identify novel rotavirus strains derived by reassortment between vaccine and wild-type strains. PMID:26839745

Human rotavirus vaccine Rotarix™ provides protection against diverse circulating rotavirus strains in African infants: a randomized controlled trial.

PubMed

Steele, Andrew Duncan; Neuzil, Kathleen M; Cunliffe, Nigel A; Madhi, Shabir A; Bos, Pieter; Ngwira, Bagrey; Witte, Desiree; Todd, Stacy; Louw, Cheryl; Kirsten, Mari; Aspinall, Sanet; Van Doorn, Leen Jan; Bouckenooghe, Alain; Suryakiran, Pemmaraju V; Han, Htay Htay

2012-09-13

Rotaviruses are the most important cause of severe acute gastroenteritis worldwide in children <5 years of age. The human, G1P[8] rotavirus vaccine Rotarix™ significantly reduced severe rotavirus gastroenteritis episodes in a Phase III clinical trial conducted in infants in South Africa and Malawi. This paper examines rotavirus vaccine efficacy in preventing severe rotavirus gastroenteritis, during infancy, caused by the various G and P rotavirus types encountered during the first rotavirus-season. Healthy infants aged 5-10 weeks were enrolled and randomized into three groups to receive either two (10 and 14 weeks) or three doses of Rotarix™ (together forming the pooled Rotarix™ group) or three doses of placebo at a 6,10,14-week schedule. Weekly home visits were conducted to identify gastroenteritis episodes. Rotaviruses were detected by ELISA and genotyped by RT-PCR and nucleotide sequencing. The percentage of infants with severe rotavirus gastroenteritis caused by the circulating G and P types from 2 weeks post-last dose until one year of age and the corresponding vaccine efficacy was calculated with 95% CI. Overall, 4939 infants were vaccinated and 4417 (pooled Rotarix™ = 2974; placebo = 1443) were included in the per protocol efficacy cohort. G1 wild-type was detected in 23 (1.6%) severe rotavirus gastroenteritis episodes from the placebo group. This was followed in order of detection by G12 (15 [1%] in placebo) and G8 types (15 [1%] in placebo). Vaccine efficacy against G1 wild-type, G12 and G8 types were 64.1% (95% CI: 29.9%; 82%), 51.5% (95% CI:-6.5%; 77.9%) and 64.4% (95% CI: 17.1%; 85.2%), respectively. Genotype P[8] was the predominant circulating P type and was detected in 38 (2.6%) severe rotavirus gastroenteritis cases in placebo group. The remaining circulating P types comprised of P[4] (20 [1.4%] in placebo) and P[6] (13 [0.9%] in placebo). Vaccine efficacy against P[8] was 59.1% (95% CI: 32.8%; 75.3%), P[4] was 70.9% (95% CI: 37.5%; 87.0%) and P[6] was 55.2% (95% CI: -6.5%; 81.3%) Rotarix™ vaccine demonstrated efficacy against severe gastroenteritis caused by diverse circulating rotavirus types. These data add to a growing body of evidence supporting heterotypic protection provided by Rotarix™. NCT00241644.

Genotypic and Phenotypic Characterization of Enterotoxigenic Escherichia coli Strains Isolated from Peruvian Children

DTIC Science & Technology

2010-09-01

Organization (WHO), ETEC is the second most common cause of diarrhea after rotavirus in children less than 5 years of age and is therefore an...pathogens (Shigella, Salmonella. Vibrio, Campylo/Jacter, Gi- ardia Iamblia, Cryptosporidium, and rotavirus ) by conventional methods. Five lactose...DAEC (2% and 3%, respec- tively), Campylobacter (20% and 6%, respectively), and Shi- gella (2% and 0%, respectively). Rotavirus was found in 10% ( 4

Circulating rotavirus genotypes in the Irish paediatric population prior to the introduction of the vaccination programme.

PubMed

Yandle, Z; Coughlan, S; Drew, R J; O'Flaherty, N; O'Gorman, J; De Gascun, C

2017-11-01

Rotavirus is the leading cause of viral gastroenteritis in children, and it is anticipated that the introduction of the Rotarix™ vaccine (GlaxoSmithKline Biologicals S.A., Rixensart, Belgium) into the Irish immunisation schedule will result in a significant reduction of rotavirus-associated disease. In the pre- and post-vaccination eras, it is important to determine circulating strains of rotavirus to assess vaccine effectiveness, to monitor vaccine failures, and to detect potential emerging strains. This study was a collaboration between the Temple Street Children's University Hospital (TSCUH), Dublin, and the National Virus Reference Laboratory (NVRL), Dublin, to determine the then circulating rotavirus strains in a paediatric hospital. In the 2015/2016 period (July 2015-June 2016) 89 faecal samples from paediatric patients (53 from TSCUH, 36 from other hospitals) were characterised. The results showed G1P[8] to be the predominant genotype (57%), followed by G9P[8] (34%), G4P[8] (6%), G2P[4] (2%), and G12P[8] (1%). This distribution of genotypes is comparable to those found in other European countries prior to vaccination suggesting that the vaccine should be highly efficacious in the Irish population.

Rotavirus A strains obtained from children with acute gastroenteritis in Mozambique, 2012-2013: G and P genotypes and phylogenetic analysis of VP7 and partial VP4 genes.

PubMed

João, Eva Dora; Strydom, Amy; O'Neill, Hester G; Cuamba, Assa; Cassocera, Marta; Acácio, Sozinho; Mandomando, Inácio; Motanyane, Lithabiso; Page, Nicola; de Deus, Nilsa

2018-01-01

In Mozambique rotavirus (RV) was shown to be the greatest cause of acute diarrhoea in infants from 0 to 11 months, and in 2015, national rotavirus vaccination was introduced. As with other developing countries, there is very limited active strain characterisation. Rotavirus positive clinical specimens, collected between 2012 and 2013, have now provided information on the genotypes circulating in southern Mozambique prior to vaccine introduction. Genotypes G2 (32.4%), G12 (28.0%), P[4] (41.4%) and P[6] (22.9%) (n = 157) strains were commonly detected with G2P[4] (42.3%) RVs being predominant, specifically during 2013. Phylogenetic evaluation of the VP7 and VP8* encoding genes showed, for the majority of the Mozambican strains, that they clustered with other African strains based on genotype. RVA/Human-wt/MOZ/0153/2013/G2P[4], RVA/Human-wt/MOZ/0308/2012/G2P[4] and RVA/Human-wt/MOZ/0288/2012/G12P[8] formed separate clusters from the other Mozambican strains with similar genotypes, suggesting possible reassortment. Amino acid substitutions in selected epitope regions also supported phylogenetic clustering. As expected, the VP7 and VP8* genes from the Mozambican strains differed from both the RotaTeq ® (SC2-9) G2P[5] and Rotarix ® (A41CB052A) G1P[8] genes. This study provides information on the genetic diversity of rotavirus strains prior to vaccine introduction and generates baseline data for future monitoring of any changes in rotavirus strains in response to vaccine pressure.

Symptomatic and Subclinical Infection with Rotavirus P[8]G9, Rural Ecuador

PubMed Central

Endara, Pablo; Trueba, Gabriel; Solberg, Owen D.; Bates, Sarah J.; Ponce, Karina; Cevallos, William; Matthijnssens, Jelle

2007-01-01

During the past decade, rotavirus genotype G9 has spread throughout the world, adding to and sometimes supplanting the common genotypes G1–G4. We report evidence of this spread in a population sample within rural Ecuador. A total of 1,656 stool samples were collected from both patients with diarrhea and asymptomatic residents in 22 remote communities in northwestern Ecuador from August 2003 through February 2006. Rotavirus was detected in 23.4% of case-patients and 3.2% of controls. From these 136 rotavirus-positive samples, a subset of 47 were genotyped; 72% were of genotype G9, and 62% were genotype P[8]G9. As a comparison, 29 rotavirus-positive stool samples were collected from a hospital in Quito during March 2006 and genotyped; 86% were of genotype P[8]G9. Few countries have reported P[8]G9 rotavirus detection rates as high as those of the current study. This growing prevalence may require changes to current vaccination programs to include coverage for this genotype. PMID:17553272

Human rotavirus vaccine Rotarix™ provides protection against diverse circulating rotavirus strains in African infants: a randomized controlled trial

PubMed Central

2012-01-01

Background Rotaviruses are the most important cause of severe acute gastroenteritis worldwide in children <5 years of age. The human, G1P[8] rotavirus vaccine Rotarix™ significantly reduced severe rotavirus gastroenteritis episodes in a Phase III clinical trial conducted in infants in South Africa and Malawi. This paper examines rotavirus vaccine efficacy in preventing severe rotavirus gastroenteritis, during infancy, caused by the various G and P rotavirus types encountered during the first rotavirus-season. Methods Healthy infants aged 5–10 weeks were enrolled and randomized into three groups to receive either two (10 and 14 weeks) or three doses of Rotarix™ (together forming the pooled Rotarix™ group) or three doses of placebo at a 6,10,14-week schedule. Weekly home visits were conducted to identify gastroenteritis episodes. Rotaviruses were detected by ELISA and genotyped by RT-PCR and nucleotide sequencing. The percentage of infants with severe rotavirus gastroenteritis caused by the circulating G and P types from 2 weeks post-last dose until one year of age and the corresponding vaccine efficacy was calculated with 95% CI. Results Overall, 4939 infants were vaccinated and 4417 (pooled Rotarix™ = 2974; placebo = 1443) were included in the per protocol efficacy cohort. G1 wild-type was detected in 23 (1.6%) severe rotavirus gastroenteritis episodes from the placebo group. This was followed in order of detection by G12 (15 [1%] in placebo) and G8 types (15 [1%] in placebo). Vaccine efficacy against G1 wild-type, G12 and G8 types were 64.1% (95% CI: 29.9%; 82%), 51.5% (95% CI:-6.5%; 77.9%) and 64.4% (95% CI: 17.1%; 85.2%), respectively. Genotype P[8] was the predominant circulating P type and was detected in 38 (2.6%) severe rotavirus gastroenteritis cases in placebo group. The remaining circulating P types comprised of P[4] (20 [1.4%] in placebo) and P[6] (13 [0.9%] in placebo). Vaccine efficacy against P[8] was 59.1% (95% CI: 32.8%; 75.3%), P[4] was 70.9% (95% CI: 37.5%; 87.0%) and P[6] was 55.2% (95% CI: -6.5%; 81.3%) Conclusions Rotarix™ vaccine demonstrated efficacy against severe gastroenteritis caused by diverse circulating rotavirus types. These data add to a growing body of evidence supporting heterotypic protection provided by Rotarix™. Trial registration number NCT00241644 PMID:22974466

A multicenter prospective hospital-based surveillance to estimate the burden of rotavirus gastroenteritis in children less than five years of age in India.

PubMed

Saluja, T; Sharma, S D; Gupta, M; Kundu, R; Kar, S; Dutta, A; Silveira, M; Singh, J V; Kamath, V G; Chaudhary, A; Rao, J V; Ravi, M D; Murthy, S R K; Babji, S; Prasad, R; Gujjula, R; Rao, R; Dhingra, M S

2014-08-11

Rotavirus is the leading cause of severe, dehydrating diarrhea in children aged <5 years globally, with an estimated 25 million outpatient visits and 2 million hospitalizations attributable to rotavirus infections each year. The aim of this hospital-based surveillance was to summarize the local epidemiological and virological features of rotavirus and to estimate the disease burden in the population under surveillance in India. During the 16 months surveillance period from April 2011 through July 2012, a total of 4711 children under the age of 5 years were admitted with acute diarrhea at 12 medical centers attached to medical schools throughout India. Stool samples were randomly collected from 2051 (43.5%) subjects and were analyzed for rotavirus positivity using commercial enzyme immunoassay kit (Premier Rotaclone Qualitative Elisa) at the respective study centers. Rotavirus positive samples were genotyped for VP7 and VP4 by reverse-transcription polymerase chain reaction (RT-PCR) at a central laboratory. During the study period, maximum number of rotavirus related hospitalizations were reported from December 2011 through February 2012. Out of the 2051 stool samples tested for rotavirus, overall 541 (26.4%) samples were positive for rotavirus VP6 antigen in stool. The highest positivity was observed in the month of December, 2011 (52.5%) and lowest in the month of May, 2011 (10.3%). We found that majority of the rotavirus positive cases (69.7%) were in children <24 months of age. The most common genotypes reported were G1 (38%), G2 (18%), G9 (18%), G12 (9%) and mixed strains (17%). The results of this study confirm the significant burden of acute rotavirus gastroenteritis as a cause of hospitalizations in under five children in India. Copyright © 2014. Published by Elsevier Ltd.

Prevalence of rotavirus genotypes in children younger than 5 years of age before the introduction of a universal rotavirus vaccination program: report of rotavirus surveillance in Turkey.

PubMed

Durmaz, Riza; Kalaycioglu, Atila Taner; Acar, Sumeyra; Bakkaloglu, Zekiye; Karagoz, Alper; Korukluoglu, Gulay; Ertek, Mustafa; Torunoglu, Mehmet Ali

2014-01-01

Group A rotaviruses are the most common causative agent of acute gastroenteritis among children less than 5 years of age throughout the world. This sentinel surveillance study was aimed to obtain baseline data on the rotavirus G and P genotypes across Turkey before the introduction of a universal rotavirus vaccination program. Rotavirus antigen-positive samples were collected from 2102 children less than 5 years of age who attended hospitals participating in the Turkish Rotavirus Surveillance Network. Rotavirus antigen was detected in the laboratories of participating hospitals by commercial serological tests such as latex agglutination, immunochromatographic test or enzyme immunoassay. Rotavirus G and P genotypes were determined by reverse transcription polymerase chain reaction (RT-PCR) using consensus primers detecting the VP7 and VP4 genes, followed by semi-nested type-specific multiplex PCR. RT-PCR found rotavirus RNA in 1644 (78.2%) of the samples tested. The highest rate of rotavirus positivity (38.7%) was observed among children in the 13 to 24 month age group, followed by children in the age group of 25 to 36 months (28.3%). A total of eight different G types, six different P types, and 42 different G-P combinations were obtained. Four common G types (G1, G2, G3, and G9) and two common P types (P[8] and P[4]) accounted for 95.1% and 98.8% of the strains, respectively. G9P[8] was the most common G/P combination found in 40.5% of the strains followed by G1P[8] (21.6%), G2P[8] (9.3%), G2P[4] (6.5%), G3P[8] (3.5%), and finally, G4P[8] (3.4%). These six common genotypes included 83.7% of the strains tested in this study. The rate of uncommon genotypes was 14%. The majority of the strains analyzed belonged to the G1-G4 and G9 genotypes, suggesting high coverage of current rotavirus vaccines. This study also demonstrates a dramatic increase in G9 genotype across the country.

Viral gastroenteritis in rotavirus negative hospitalized children <5 years of age from the independent states of the former Soviet Union.

PubMed

Chhabra, Preeti; Samoilovich, Elena; Yermalovich, Marina; Chernyshova, Liudmyla; Gheorghita, Stela; Cojocaru, Radu; Shugayev, Nazim; Sahakyan, Gayane; Lashkarashvili, Marina; Chubinidze, Marina; Zakhashvili, Khatuna; Videbaek, Dovile; Wasley, Annemarie; Vinjé, Jan

2014-12-01

Rotavirus causes nearly 40% of all hospitalizations for AGE among children <5 years of age in the NIS of the former Soviet Union. The etiologic role of other established gastroenteritis viruses in this age group is unknown. Laboratory-confirmed rotavirus negative fecal specimens (N=495) collected between January and December 2009 from children in 6 NIS (Armenia, Azerbaijan, Belarus, Georgia, Republic of Moldova and Ukraine) were tested for norovirus, sapovirus, enteric adenovirus and astrovirus by real-time RT-PCR. Genotyping was carried out by sequencing and phylogenetic analysis. Norovirus, enteric adenovirus, sapovirus and astrovirus were detected in 21.8%, 4.0%, 3.2%, and 1.4% of the rotavirus negative specimens, respectively. Mixed infections were identified in 4.1% of the specimens. Phylogenetic analysis showed co-circulation of several different genotypes with GII.4 Den Haag (2006b) norovirus, GI.2 sapovirus, adenovirus type 41, and astrovirus type 1 causing majority of the infections. Norovirus, enteric adenovirus, sapovirus and astrovirus account for a significant proportion (30.5%) of AGE in hospitalized children <5 years of age in 6 NIS. Copyright © 2014 Elsevier B.V. All rights reserved.

Continuous detection and genetic diversity of human rotavirus A in sewage in eastern China, 2013-2014.

PubMed

Zhou, Nan; Lv, Dong; Wang, Suting; Lin, Xiaojuan; Bi, Zhenwang; Wang, Haiyan; Wang, Pei; Zhang, Huaning; Tao, Zexin; Hou, Peibin; Song, Yanyan; Xu, Aiqiang

2016-09-13

Rotavirus is the leading viral agent for pediatric gastroenteritis. However, the case-based surveillance for rotavirus is limited in China, and its circulation in the environment is not well investigated. From 2013 to 2014, rotavirus was detected in raw sewage samples of Jinan and Linyi by quantitative PCR (qPCR) and conventional reverse transcription PCR (RT-PCR). After sequenced and genotyped, sequences analysis was conducted. A total of 46 sewage samples were collected monthly for the detection of rotavirus, and rotavirus was positive in 43 samples (93.5 %, 43/46). By quantitative assessment, the concentrations of rotavirus in raw sewage ranged from 4.1 × 10(3) to 1.3 × 10(6) genome copies (GC)/L in Jinan, and from 1.5 × 10(3) to 3.0 × 10(5) GC/L in Linyi. A total of 318 sequences of 5 G-genotypes and 318 sequences of 5 P-genotypes were obtained. G9 (91.8 %, 292/318) and P[8] (56.0 %, 178/318) were the most common G- and P-genotype, respectively. Multiple transmission lineages were recognized in these genotypes. Interestingly, an intragenic recombination event between two G9 lineages was observed. This study provided the first report of comprehensive environmental surveillance for rotavirus in China. The results suggest that the concentration of rotavirus in raw sewage was high, and multiple rotavirus transmission lineages continuously co-circulated in Shandong.

Distribution of rotavirus genotypes after introduction of rotavirus vaccines, Rotarix® and RotaTeq®, into the National Immunization Program of Australia.

PubMed

Kirkwood, Carl D; Boniface, Karen; Barnes, Graeme L; Bishop, Ruth F

2011-01-01

Rotavirus vaccines, RotaTeq and Rotarix, were introduced into the Australian National Immunization Program on July 1, 2007. The simultaneous introduction in different Australian states and territories provides a unique opportunity to compare the affect of each vaccine on the types of circulating rotavirus strains. This report describes the rotavirus genotypes responsible for the hospitalization of children during the first 2-year period after vaccine introduction. A total of 764 rotavirus-associated diarrheal cases were collected from children presenting to hospital in 10 Australian centers. Rotavirus genotype was determined using reverse transcription polymerase chain reaction assays. G1P[8] was the dominant genotype nationally (52%), followed by G2P[4] (19.8%), G9P[8] (12.2%), and G3P[8] (11%). Differences in the prevalence rates of G2P[4] and G3P[8] were seen in the various states. G2P[4] strains were more prevalent in states using Rotarix, whereas G3P[8] strains were more prevalent in states using RotaTeq. Differences in rotavirus genotypes were observed across Australia, which suggest that different immune pressures are exerted by the different vaccines, but do not necessarily imply lack of protection by either vaccine. These differences may simply be related to the variation that can occur because of natural annual fluctuation in rotavirus strain prevalence.

Clinical and molecular epidemiologic trends reveal the important role of rotavirus in adult infectious gastroenteritis, in Shanghai, China.

PubMed

Wang, Yan; Zhang, Jinan; Liu, Pengbo

2017-01-01

As a leading cause of severe diarrhea in children, the pathogenic role of rotavirus in adults has been underestimated for a long time. A hospital-based prospective clinical and molecular epidemiologic study of rotavirus infections in adults was performed between April 2014 and March 2015 in Shanghai, China. Overall, rotavirus was detected in 48 of 441 (10.9%) specimens with prevalence peaking in December (33.3%) and January (27.9%), whereas bacteria were identified in 45 of 846 (5.3%) samples (p<0.01). The rotavirus winter-spring seasonality (November - March) contrasts with the marked summer-fall seasonality (April - October) of bacterial pathogens (p<0.01). Compared with bacterial pathogens, rotavirus infection from child-to-adult transmission (29.8%, p<0.01) was the most important epidemiologic setting generating a major impact on public health, i.e. increased adult burden of infectious gastroenteritis and genetic diversity of circulating rotaviruses; adults infected with rotavirus developed more severe gastroenteritis symptoms (p<0.01) accompanied with mild intestinal and blood inflammations. Thirty-three G9 (lineages VIe and IIId), seven G2 (lineages IVa-1, IVa-3, and V) and two G1 (lineage Va) strains, together with thirty-eight P[8]-III and eight P[4]-V strains, were identified in this study with multiple amino acid differences observed between sample strains and homotypic vaccines. G9P[8] was the predominant genotype (66.7%), followed by G2P[4] (14.6%) and G1P[8] (4.2%). Eight conserved amino acid substitutions in prototype strain K-1, especially A212T in antigenic region C, formed a novel G9-lineage VIe variant that has emerged worldwide since 2010. Our results indicated that emerging rotavirus G9-VIeP[8]-III predominated over all the genotypes with a short time window in adults in Shanghai, China, and caused a local epidemic during the 2014-2015 rotavirus season. These findings reinforce the importance for inclusion of rotavirus in routine clinical diagnosis, and further surveillance of rotavirus variants is recommended to improve current vaccination program. Copyright © 2016 Elsevier B.V. All rights reserved.

Epidemiology of acute diarrhea caused by rotavirus in sentinel surveillance sites of Vietnam, 2012-2015.

PubMed

Huyen, Dang Thi Thanh; Hong, Duong Thi; Trung, Nguyen Thanh; Hoa, Tran Thi Nguyen; Oanh, Nguyen Kieu; Thang, Ho Vinh; Thao, Nguyen Thi Thanh; Hung, Do Manh; Iijima, Makiko; Fox, Kimberley; Grabovac, Varja; Heffelfinger, James; Batmunkh, Nyambat; Anh, Dang Duc

2018-05-18

A prospective, multicentre study was conducted in four sentinel surveillance hospitals to assess the trend and epidemiology of acute diarrhea caused by Rotavirus in Vietnam. During the period 2012-2015, a total 8,889 children under 5 years of age were enrolled in the surveillance, and 8689 stool samples were collected. Of these cases, Rotavirus was most common pathogen 46.7% (4054 cases); in which 26.6% (1117) rotavirus-positive stool samples were evaluated to identify genotypes. The proportion of rotavirus positive specimens decreased annually from 54.7% in 2012 to 36.6% in 2015. Rotavirus was detected year-round, but most rotavirus gastroenteritis cases (77.1%) occurred between December and May, corresponding to the rotavirus seasonality. It is found that the peaks varied by regions. Rotavirus positivities varied between the youngest and oldest age, but children 6-11 months old (38.8%) and 12-23 months old (38.4%) counted for most cases. A significant higher number of diarrhea within 24 hours (8.3 times, 95%CI: 8.1-8.4 times) and higher proportion of severe dehydration (12.9%) in Rotavirus positive group than that in Rotavirus negative group (7.7 times, 95%CI: 7.6-7.9 times; and 9.7%, respectively). A downtrend of prevalence of G1P[8] was observed from 82% in 2013 to 15% in 2015. However, G2P[4] was found in 5% of samples in 2012, 9% in 2013, 36% in 2014, and 28% in 2015. Rotavirus infection is the most important cause of acute diarrhea among hospitalized children in Vietnam, and a rotavirus vaccination program for children may significantly reduce this disease. Copyright © 2018. Published by Elsevier Ltd.

Prevalence of Rotavirus Genotypes in Children Younger than 5 Years of Age before the Introduction of a Universal Rotavirus Vaccination Program: Report of Rotavirus Surveillance in Turkey

PubMed Central

Durmaz, Riza; Kalaycioglu, Atila Taner; Acar, Sumeyra; Bakkaloglu, Zekiye; Karagoz, Alper; Korukluoglu, Gulay; Ertek, Mustafa; Torunoglu, Mehmet Ali

2014-01-01

Background Group A rotaviruses are the most common causative agent of acute gastroenteritis among children less than 5 years of age throughout the world. This sentinel surveillance study was aimed to obtain baseline data on the rotavirus G and P genotypes across Turkey before the introduction of a universal rotavirus vaccination program. Methods Rotavirus antigen-positive samples were collected from 2102 children less than 5 years of age who attended hospitals participating in the Turkish Rotavirus Surveillance Network. Rotavirus antigen was detected in the laboratories of participating hospitals by commercial serological tests such as latex agglutination, immunochromatographic test or enzyme immunoassay. Rotavirus G and P genotypes were determined by reverse transcription polymerase chain reaction (RT-PCR) using consensus primers detecting the VP7 and VP4 genes, followed by semi-nested type-specific multiplex PCR. Results RT-PCR found rotavirus RNA in 1644 (78.2%) of the samples tested. The highest rate of rotavirus positivity (38.7%) was observed among children in the 13 to 24 month age group, followed by children in the age group of 25 to 36 months (28.3%). A total of eight different G types, six different P types, and 42 different G–P combinations were obtained. Four common G types (G1, G2, G3, and G9) and two common P types (P[8] and P[4]) accounted for 95.1% and 98.8% of the strains, respectively. G9P[8] was the most common G/P combination found in 40.5% of the strains followed by G1P[8] (21.6%), G2P[8] (9.3%), G2P[4] (6.5%), G3P[8] (3.5%), and finally, G4P[8] (3.4%). These six common genotypes included 83.7% of the strains tested in this study. The rate of uncommon genotypes was 14%. Conclusion The majority of the strains analyzed belonged to the G1–G4 and G9 genotypes, suggesting high coverage of current rotavirus vaccines. This study also demonstrates a dramatic increase in G9 genotype across the country. PMID:25437502

Evidence for presumable feline origin of sporadic G6P[9] rotaviruses in humans.

PubMed

Pietsch, Corinna; Liebert, Uwe G

2018-05-31

Species A rotaviruses are highly diverse and impose a substantial burden to human and animal health. Interspecies transmission between livestock, domestic animals and humans is commonly observed, but spread of animal-like rotaviruses within the human population is limited. During the continued monitoring of rotavirus strains in Germany, an unusual G6P[9] rotavirus strain was detected in feces of a child. The complete rotavirus coding sequences revealed a unique G6-P[9]-I2-R2-C2-M2-A3-N2-T3-E2-H3 genotype constellation. The virus was phylogenetically related to feline G3P[9] strains and other human G6P[9] rotaviruses of presumable zoonotic origin. Analysis of primer binding sites of G6 specific genotyping revealed further evidence of a G6P[9] feline reservoir. Moreover, substantial deficits of conventional semi-nested PCR genotyping approaches in detecting contemporary G6P[9] were revealed. Rotavirus strain GER29-14 most likely resulted from a direct or recent interspecies transmission from a cat to human. Further studies could assess nucleic acid sequences and genotype constellations of feline rotavirus to confirm the likely feline origin of sporadic human G6P[9] strains. Copyright © 2018 Elsevier B.V. All rights reserved.

Distribution of rotavirus genotypes associated with acute diarrhoea in Zimbabwean children less than five years old before and after rotavirus vaccine introduction.

PubMed

Mukaratirwa, Arnold; Berejena, Chipo; Nziramasanga, Pasipanodya; Ticklay, Ismail; Gonah, Archebald; Nathoo, Kusum; Manangazira, Portia; Mangwanya, Douglas; Marembo, Joan; Mwenda, Jason M; Weldegebriel, Goitom; Seheri, Mapaseka; Tate, Jacqueline E; Yen, Catherine; Parashar, Umesh; Mujuru, Hilda

2018-04-05

Sentinel surveillance for diarrhoea is important to monitor changes in rotavirus epidemiological trends and circulating genotypes among children under 5 years before and after vaccine introduction. The Zimbabwe Ministry of Health and Child Care introduced rotavirus vaccine in national immunization program in May 2014. Active hospital-based surveillance for diarrhoea was conducted at 3 sentinel sites from 2008 to 2016. Children aged less than 5 years, who presented with acute gastroenteritis as a primary illness and who were admitted to a hospital ward or treated at the emergency unit, were enrolled and had a stool specimen collected and tested for rotavirus by enzyme immunoassay (EIA). Genotyping of positive stools was performed using reverse-transcription polymerase chain reaction and genotyping assays. Pre-vaccine introduction, 10% of all positive stool specimens were genotyped and all adequate positive stools were genotyped post-vaccine introduction. During the pre-vaccine period, a total of 6491 acute gastroenteritis stools were collected, of which 3016 (46%) tested positive for rotavirus and 312 (10%) of the rotavirus positive stools were genotyped. During the post-vaccine period, a total of 3750 acute gastroenteritis stools were collected, of which 937 (25%) tested positive for rotavirus and 784 (84%) were genotyped. During the pre-vaccine introduction the most frequent genotype was G9P[8] (21%) followed by G2P[4] (12%), G1P[8] (6%), G2P[6] (5%), G12P[6] (4%), G9P[6] (3%) and G8P[4] (3%). G1P[8] (30%) was most dominant two years after vaccine introduction followed by G9P[6] (20%), G2P[4] (15%), G9P[8] (11%) and G1P[6] (4%). The decline in positivity rate is an indication of early vaccine impact. Diversity of circulating strains underscores the importance of continued monitoring and strain surveillance after vaccine introduction. Copyright © 2018. Published by Elsevier Ltd.

Group A rotavirus genotypes in hospital-acquired gastroenteritis in Italy, 2012-14.

PubMed

Ianiro, G; Delogu, R; Fiore, L; Monini, M; Ruggeri, F M

2017-07-01

Group A rotaviruses (RVA) are the leading cause of acute gastroenteritis (AGE) in young (aged <5 years) children, causing ∼250,000 deaths worldwide, mostly in developing countries. Differences on nucleotide sequences of VP7 (G-type) and VP4 (P-type) genes are the basis for the binary RVA nomenclature. Although at least 32 G-types and 47 P-types of rotavirus are presently known, most RVA infections in humans worldwide are related to five major G/P combinations: G1P[8], G2P[4], G3P[8], G4P[8], and G9P[8]. To provide the hospitals of the Italian surveillance network with update information on RVA AGE. During RVA gastroenteritis surveillance in Italy in 2012-14, a total of 2341 RVA-positive faecal samples were collected from children hospitalized with AGE, and RVA strains were genotyped following standard EuroRotaNet protocols. Most strains analysed belonged to the five major human genotypes and 118 out of 2341 (5.0%) were reported to be hospital-acquired. Comparison of the distributions of the RVA genotypes circulating in the community or associated with nosocomial infections showed a different distribution of genotypes circulating inside the hospital wards, with respect to those observed in the community. G1P[8] and G9P[8] RVA strains were detected frequently, whereas G12P[8] caused a single large nosocomial outbreak. The information from this study will be useful to implement guidelines for preventing RVA AGE and optimizing the management of patients in hospital wards. Copyright © 2017 The Healthcare Infection Society. Published by Elsevier Ltd. All rights reserved.

Recommendations for the classification of group A rotaviruses using all 11 genomic RNA segments.

PubMed

Matthijnssens, Jelle; Ciarlet, Max; Rahman, Mustafizur; Attoui, Houssam; Bányai, Krisztián; Estes, Mary K; Gentsch, Jon R; Iturriza-Gómara, Miren; Kirkwood, Carl D; Martella, Vito; Mertens, Peter P C; Nakagomi, Osamu; Patton, John T; Ruggeri, Franco M; Saif, Linda J; Santos, Norma; Steyer, Andrej; Taniguchi, Koki; Desselberger, Ulrich; Van Ranst, Marc

2008-01-01

Recently, a classification system was proposed for rotaviruses in which all the 11 genomic RNA segments are used (Matthijnssens et al. in J Virol 82:3204-3219, 2008). Based on nucleotide identity cut-off percentages, different genotypes were defined for each genome segment. A nomenclature for the comparison of complete rotavirus genomes was considered in which the notations Gx-P[x]-Ix-Rx-Cx-Mx-Ax-Nx-Tx-Ex-Hx are used for the VP7-VP4-VP6-VP1-VP2-VP3-NSP1-NSP2-NSP3-NSP4-NSP5/6 encoding genes, respectively. This classification system is an extension of the previously applied genotype-based system which made use of the rotavirus gene segments encoding VP4, VP7, VP6, and NSP4. In order to assign rotavirus strains to one of the established genotypes or a new genotype, a standard procedure is proposed in this report. As more human and animal rotavirus genomes will be completely sequenced, new genotypes for each of the 11 gene segments may be identified. A Rotavirus Classification Working Group (RCWG) including specialists in molecular virology, infectious diseases, epidemiology, and public health was formed, which can assist in the appropriate delineation of new genotypes, thus avoiding duplications and helping minimize errors. Scientists discovering a potentially new rotavirus genotype for any of the 11 gene segments are invited to send the novel sequence to the RCWG, where the sequence will be analyzed, and a new nomenclature will be advised as appropriate. The RCWG will update the list of classified strains regularly and make this accessible on a website. Close collaboration with the Study Group Reoviridae of the International Committee on the Taxonomy of Viruses will be maintained.

Prevalence and genotypes of Rotavirus among children under 5 years presenting with diarrhoea in Moshi, Tanzania: a hospital based cross sectional study.

PubMed

Mchaile, Deborah N; Philemon, Rune N; Kabika, Sonia; Albogast, Evelyn; Morijo, Kikoti J; Kifaro, Emmanuel; Mmbaga, Blandina T

2017-10-30

Diarrhoea is a main cause of morbidity and mortality in children under 5 responsible for approximately four billion cases and 1.1 million deaths annually. In developing countries, it causes two million deaths each year. The major causative organism responsible is Rotavirus which is responsible for one-third of hospitalizations with approximately 40% mortality. The prevalence of Rotavirus infection was 26.4% (73/277). The predominant strain of Rotavirus found was G1 21/73 (53.8%), followed by G8 9/73 (23.1%), G12 5/73 (12.8%), G9 3/73(7.7%) and G4 1/73 (2.6%). All serotypes identified were in children who had completed Rotavirus vaccination except for one who had G8 in whom the vaccine was introduced after they had completed immunizations. The overall prevalence of rotavirus has reduced from 33.2% in 2009 to 26.4% in 2016. We have found G1 to be the predominant serotype as well as other circulating serotypes namely G4, G8, G9 and G12. Despite a reduction in prevalence, there is a need for further rotavirus surveillance in the region.

Burden of Norovirus and Rotavirus in Children after Rotavirus Vaccine Introduction, Cochabamba, Bolivia

PubMed Central

McAtee, Casey L.; Webman, Rachel; Gilman, Robert H.; Mejia, Carolina; Bern, Caryn; Apaza, Sonia; Espetia, Susan; Pajuelo, Mónica; Saito, Mayuko; Challappa, Roxanna; Soria, Richard; Ribera, Jose P.; Lozano, Daniel; Torrico, Faustino

2016-01-01

The effectiveness of rotavirus vaccine in the field may set the stage for a changing landscape of diarrheal illness affecting children worldwide. Norovirus and rotavirus are the two major viral enteropathogens of childhood. This study describes the prevalence of norovirus and rotavirus 2 years after widespread rotavirus vaccination in Cochabamba, Bolivia. Stool samples from hospitalized children with acute gastroenteritis (AGE) and outpatients aged 5–24 months without AGE were recruited from an urban hospital serving Bolivia's third largest city. Both viruses were genotyped, and norovirus GII.4 was further sequenced. Norovirus was found much more frequently than rotavirus. Norovirus was detected in 69/201 (34.3%) of specimens from children with AGE and 13/71 (18.3%) of those without diarrhea. Rotavirus was detected in 38/201 (18.9%) of diarrheal specimens and 3/71 (4.2%) of non-diarrheal specimens. Norovirus GII was identified in 97.8% of norovirus-positive samples; GII.4 was the most common genotype (71.4% of typed specimens). Rotavirus G3P[8] was the most prevalent rotavirus genotype (44.0% of typed specimens) and G2P[4] was second most prevalent (16.0% of typed specimens). This community is likely part of a trend toward norovirus predominance over rotavirus in children after widespread vaccination against rotavirus. PMID:26598569

Efficacy of human rotavirus vaccine against severe gastroenteritis in Malawian children in the first two years of life: a randomised, double-blind, placebo controlled trial

PubMed Central

Cunliffe, Nigel A; Witte, Desiree; Ngwira, Bagrey M; Todd, Stacy; Bostock, Nancy J; Turner, Ann M; Chimpeni, Philips; Victor, John C; Steele, A Duncan; Bouckenooghe, Alain; Neuzil, Kathleen M

2014-01-01

Rotavirus gastroenteritis is a major cause of morbidity and mortality among African infants and young children. A phase III, placebo-controlled, multi-centre clinical trial of a live, oral G1P[8] human rotavirus vaccine (RIX4414) undertaken in Malawi and South Africa significantly reduced the incidence of severe rotavirus gastroenteritis in the first year of life. We now report on vaccine efficacy in the Malawi cohort of children who were followed into the second year of life. A total of 1,773 healthy infants were enrolled in Blantyre, Malawi into three groups. Two groups received three doses of RIX4414 or placebo at age 6, 10, and 14 weeks and the third group received placebo at 6 weeks and RIX4414 at age 10 and 14 weeks. Subjects were followed by weekly home visits for episodes of gastroenteritis until 1 year of age, and were then re-consented for further follow-up to 18-24 months of age. Severity of gastroenteritis episodes was graded according to the Vesikari scoring system. Seroconversion for anti-rotavirus IgA was determined on a subset of children by using ELISA on pre- and post-vaccine blood samples. Rotavirus VP7 (G) and VP4 (P) genotypes were determined by RT-PCR. A total of 70/1030 (6.8%, 95% CI 5.3 - 8.5) subjects in the pooled (2 dose plus 3 dose) RIX4414 group compared with 53/483 (11.0%, 8.3 – 14.1) subjects in the placebo group developed severe rotavirus gastroenteritis in the entire follow-up period (Vaccine Efficacy 38.1% (9.8 – 57.3). The point estimate of efficacy in the second year of life (17.6%; −59.2 – 56.0) was lower than in the first year of life (49.4%; 19.2 – 68.3). There were non-significant trends towards a higher efficacy in the second year of life among children who received the three-dose schedule compared with the two-dose schedule, and a higher anti-rotavirus IgA seroresponse rate in the three-dose RIX4414 group. Rotavirus strains detected included genotype G12 (31%); G9 (23%); and G8 (18%); only 18% of strains belonged to the G1P[8] genotype. While the optimal dosing schedule of RIX4414 in African infants requires further investigation, vaccination with RIX4414 significantly reduced the incidence of severe gastroenteritis caused by diverse rotavirus strains in an impoverished African population with high rotavirus disease burden in the first two years of life. PMID:22520135

Efficacy of human rotavirus vaccine against severe gastroenteritis in Malawian children in the first two years of life: a randomized, double-blind, placebo controlled trial.

PubMed

Cunliffe, Nigel A; Witte, Desiree; Ngwira, Bagrey M; Todd, Stacy; Bostock, Nancy J; Turner, Ann M; Chimpeni, Philips; Victor, John C; Steele, A Duncan; Bouckenooghe, Alain; Neuzil, Kathleen M

2012-04-27

Rotavirus gastroenteritis is a major cause of morbidity and mortality among African infants and young children. A phase III, placebo-controlled, multi-centre clinical trial of a live, oral G1P[8] human rotavirus vaccine (RIX4414) undertaken in Malawi and South Africa significantly reduced the incidence of severe rotavirus gastroenteritis in the first year of life. We now report on vaccine efficacy in the Malawi cohort of children who were followed into the second year of life. A total of 1773 healthy infants were enrolled in Blantyre, Malawi into three groups. Two groups received three doses of RIX4414 or placebo at age 6, 10, and 14 weeks and the third group received placebo at 6 weeks and RIX4414 at age 10 and 14 weeks. Subjects were followed by weekly home visits for episodes of gastroenteritis until 1 year of age, and were then re-consented for further follow-up to 18-24 months of age. Severity of gastroenteritis episodes was graded according to the Vesikari scoring system. Seroconversion for anti-rotavirus IgA was determined on a subset of children by using ELISA on pre- and post-vaccine blood samples. Rotavirus VP7 (G) and VP4 (P) genotypes were determined by RT-PCR. A total of 70/1030 (6.8%, 95% CI 5.3-8.5) subjects in the pooled (2 dose plus 3 dose) RIX4414 group compared with 53/483 (11.0%, 8.3-14.1) subjects in the placebo group developed severe rotavirus gastroenteritis in the entire follow-up period (vaccine efficacy 38.1% (9.8-57.3)). The point estimate of efficacy in the second year of life (17.6%; -59.2 to 56.0) was lower than in the first year of life (49.4%; 19.2-68.3). There were non-significant trends towards a higher efficacy in the second year of life among children who received the three-dose schedule compared with the two-dose schedule, and a higher anti-rotavirus IgA seroresponse rate in the three-dose RIX4414 group. Rotavirus strains detected included genotype G12 (31%); G9 (23%); and G8 (18%); only 18% of strains belonged to the G1P[8] genotype. While the optimal dosing schedule of RIX4414 in African infants requires further investigation, vaccination with RIX4414 significantly reduced the incidence of severe gastroenteritis caused by diverse rotavirus strains in an impoverished African population with high rotavirus disease burden in the first two years of life. Copyright © 2011 Elsevier Ltd. All rights reserved.

Structural basis of glycan specificity in neonate-specific bovine-human reassortant rotavirus

DOE PAGES

Hu, Liya; Ramani, Sasirekha; Czako, Rita; ...

2015-09-30

We report that strain-dependent variation of glycan recognition during initial cell attachment of viruses is a critical determinant of host specificity, tissue-tropism and zoonosis. Rotaviruses (RVs), which cause life-threatening gastroenteritis in infants and children, display significant genotype-dependent variations in glycan recognition resulting from sequence alterations in the VP8* domain of the spike protein VP4. The structural basis of this genotype-dependent glycan specificity, particularly in human RVs, remains poorly understood. Here, from crystallographic studies, we show how genotypic variations configure a novel binding site in the VP8* of a neonate-specific bovine-human reassortant to uniquely recognize either type I or type IImore » precursor glycans, and to restrict type II glycan binding in the bovine counterpart. In conclusion, such a distinct glycan-binding site that allows differential recognition of the precursor glycans, which are developmentally regulated in the neonate gut and abundant in bovine and human milk provides a basis for age-restricted tropism and zoonotic transmission of G10P[11] rotaviruses.« less

Structural basis of glycan specificity in neonate-specific bovine-human reassortant rotavirus

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hu, Liya; Ramani, Sasirekha; Czako, Rita

We report that strain-dependent variation of glycan recognition during initial cell attachment of viruses is a critical determinant of host specificity, tissue-tropism and zoonosis. Rotaviruses (RVs), which cause life-threatening gastroenteritis in infants and children, display significant genotype-dependent variations in glycan recognition resulting from sequence alterations in the VP8* domain of the spike protein VP4. The structural basis of this genotype-dependent glycan specificity, particularly in human RVs, remains poorly understood. Here, from crystallographic studies, we show how genotypic variations configure a novel binding site in the VP8* of a neonate-specific bovine-human reassortant to uniquely recognize either type I or type IImore » precursor glycans, and to restrict type II glycan binding in the bovine counterpart. In conclusion, such a distinct glycan-binding site that allows differential recognition of the precursor glycans, which are developmentally regulated in the neonate gut and abundant in bovine and human milk provides a basis for age-restricted tropism and zoonotic transmission of G10P[11] rotaviruses.« less

Burden of Norovirus and Rotavirus in Children After Rotavirus Vaccine Introduction, Cochabamba, Bolivia.

PubMed

McAtee, Casey L; Webman, Rachel; Gilman, Robert H; Mejia, Carolina; Bern, Caryn; Apaza, Sonia; Espetia, Susan; Pajuelo, Mónica; Saito, Mayuko; Challappa, Roxanna; Soria, Richard; Ribera, Jose P; Lozano, Daniel; Torrico, Faustino

2016-01-01

The effectiveness of rotavirus vaccine in the field may set the stage for a changing landscape of diarrheal illness affecting children worldwide. Norovirus and rotavirus are the two major viral enteropathogens of childhood. This study describes the prevalence of norovirus and rotavirus 2 years after widespread rotavirus vaccination in Cochabamba, Bolivia. Stool samples from hospitalized children with acute gastroenteritis (AGE) and outpatients aged 5-24 months without AGE were recruited from an urban hospital serving Bolivia's third largest city. Both viruses were genotyped, and norovirus GII.4 was further sequenced. Norovirus was found much more frequently than rotavirus. Norovirus was detected in 69/201 (34.3%) of specimens from children with AGE and 13/71 (18.3%) of those without diarrhea. Rotavirus was detected in 38/201 (18.9%) of diarrheal specimens and 3/71 (4.2%) of non-diarrheal specimens. Norovirus GII was identified in 97.8% of norovirus-positive samples; GII.4 was the most common genotype (71.4% of typed specimens). Rotavirus G3P[8] was the most prevalent rotavirus genotype (44.0% of typed specimens) and G2P[4] was second most prevalent (16.0% of typed specimens). This community is likely part of a trend toward norovirus predominance over rotavirus in children after widespread vaccination against rotavirus. © The American Society of Tropical Medicine and Hygiene.

Evaluation of BBL™ Sensi-Discs™ and FTA® cards as sampling devices for detection of rotavirus in stool samples

PubMed Central

Tam, Ka Ian; Esona, Mathew D.; Williams, Alice; Ndze, Valentine N.; Boula, Angeline; Bowen, Michael D.

2015-01-01

Rotavirus is the most important cause of severe childhood gastroenteritis worldwide. Rotavirus vaccines are available and rotavirus surveillance is carried out to assess vaccination impact. In surveillance studies, stool samples are stored typically at 4°C or frozen to maintain sample quality. Uninterrupted cold storage is a problem in developing countries because of power interruptions. Cold-chain transportation of samples from collection sites to testing laboratories is costly. In this study, we evaluated the use of BBL™ Sensi-Discs™ and FTA® cards for storage and transportation of samples for virus isolation, EIA, and RT-PCR testing. Infectious rotavirus was recovered after 30 days of storage on Sensi-Discs™ at room temperature. We were able to genotype 98–99% of samples stored on Sensi-Discs™ and FTA® cards at temperatures ranging from −80°C to 37°C up to 180 days. A field sampling test using samples prepared and shipped from Cameroon, showed that both matrices yielded 100% genotyping success compared with whole stool and Sensi-Discs™ demonstrated 95% concordance with whole stool in EIA testing. The utilization of BBL™ Sensi-Discs™ and FTA® cards for stool sample storage and shipment has the potential to have great impact on global public health by facilitating surveillance and epidemiological investigations of rotavirus strains worldwide at a reduced cost. PMID:26022083

Evaluation of BBL™ Sensi-Discs™ and FTA® cards as sampling devices for detection of rotavirus in stool samples.

PubMed

Tam, Ka Ian; Esona, Mathew D; Williams, Alice; Ndze, Valantine N; Boula, Angeline; Bowen, Michael D

2015-09-15

Rotavirus is the most important cause of severe childhood gastroenteritis worldwide. Rotavirus vaccines are available and rotavirus surveillance is carried out to assess vaccination impact. In surveillance studies, stool samples are stored typically at 4°C or frozen to maintain sample quality. Uninterrupted cold storage is a problem in developing countries because of power interruptions. Cold-chain transportation of samples from collection sites to testing laboratories is costly. In this study, we evaluated the use of BBL™ Sensi-Discs™ and FTA(®) cards for storage and transportation of samples for virus isolation, EIA, and RT-PCR testing. Infectious rotavirus was recovered after 30 days of storage on Sensi-Discs™ at room temperature. We were able to genotype 98-99% of samples stored on Sensi-Discs™ and FTA(®) cards at temperatures ranging from -80°C to 37°C up to 180 days. A field sampling test using samples prepared and shipped from Cameroon, showed that both matrices yielded 100% genotyping success compared with whole stool and Sensi-Discs™ demonstrated 95% concordance with whole stool in EIA testing. The utilization of BBL™ Sensi-Discs™ and FTA(®) cards for stool sample storage and shipment has the potential to have great impact on global public health by facilitating surveillance and epidemiological investigations of rotavirus strains worldwide at a reduced cost. Published by Elsevier B.V.

Effectiveness of Pentavalent and Monovalent Rotavirus Vaccines in Concurrent Use Among US Children <5 Years of Age, 2009–2011

PubMed Central

Payne, Daniel C.; Boom, Julie A.; Staat, Mary Allen; Edwards, Kathryn M.; Szilagyi, Peter G.; Klein, Eileen J.; Selvarangan, Rangaraj; Azimi, Parvin H.; Harrison, Christopher; Moffatt, Mary; Johnston, Samantha H.; Sahni, Leila C.; Baker, Carol J.; Rench, Marcia A.; Donauer, Stephanie; McNeal, Monica; Chappell, James; Weinberg, Geoffrey A.; Tasslimi, Azadeh; Tate, Jacqueline E.; Wikswo, Mary; Curns, Aaron T.; Sulemana, Iddrisu; Mijatovic-Rustempasic, Slavica; Esona, Mathew D.; Bowen, Michael D.; Gentsch, Jon R.; Parashar, Umesh D.

2015-01-01

Background We assessed vaccine effectiveness (VE) for RotaTeq (RV5; 3 doses) and Rotarix (RV1; 2 doses) at reducing rotavirus acute gastroenteritis (AGE) inpatient and emergency department (ED) visits in US children. Methods We enrolled children <5 years of age hospitalized or visiting the ED with AGE symptoms from November 2009–June 2010 and from November 2010–June 2011 at 7 medical institutions. Fecal specimens were tested for rotavirus by enzyme immunoassay and genotyped. Vaccination among laboratory-confirmed rotavirus cases was compared with rotavirus-negative AGE controls. Regression models calculated VE estimates for each vaccine, age, ethnicity, genotype, and clinical setting. Results RV5-specific analyses included 359 rotavirus cases and 1811 rotavirus-negative AGE controls. RV1-specific analyses included 60 rotavirus cases and 155 rotavirus-negative AGE controls. RV5 and RV1 were 84% (95% confidence interval [CI], 78%–88%) and 70% (95% CI, 39%–86%) effective, respectively, against rotavirus-associated ED visits and hospitalizations combined. By clinical setting, RV5 VE against ED and inpatient rotavirus-associated visits was 81% (95% CI, 70%–84%) and 86% (95% CI, 74%–91%), respectively. RV1 was 78% (95% CI, 46%–91%) effective against ED rotavirus disease; study power was insufficient to evaluate inpatient RV1 VE. No waning of immunity was evident during the first 4 years of life for RV5, nor during the first 2 years of life for RV1. RV5 provided genotype-specific protection against each of the predominant strains (G1P[8], G2P[4], G3P[8], G12P[8]), while RV1 VE was statistically significant for the most common genotype, G3P[8]. Conclusions Both RV5 and RV1 significantly protected against medically attended rotavirus gastroenteritis in this real-world assessment. PMID:23487388

Incidence of rotavirus gastroenteritis hospitalizations and genotypes, before and five years after introducing universal immunization in Israel.

PubMed

Muhsen, Khitam; Kassem, Eias; Rubenstein, Uri; Goren, Sophy; Ephros, Moshe; Cohen, Dani; Shulman, Lester M

2016-11-21

Uncertainty exists about the sustainability of the reduction in rotavirus gastroenteritis (RVGE) following the introduction of rotavirus vaccines into national immunization programs, and on its potential impact on circulating genotypes. RotaTeq was introduced into the Israeli national immunization program in December 2010, and vaccination coverage is around 80%. To examine the change in incidence of RVGE hospitalization and rotavirus genotypes, during the five years after introduction of RotaTeq into the Israeli national immunization program. Data were obtained prospectively on hospitalization of children aged 0-59months due to acute gastroenteritis (N=7346) from three hospitals in northern Israel. Stool samples were tested for rotavirus by immunochromatography. Rotavirus was genotyped (N=506) by RT-PCR and/or sequencing. The average incidence of RVGE hospitalization declined by 61.0% (95% CI 49.0-73.4%), from 5.6 per 1000 (95% CI 5.0-6.2) in the pre-universal immunization period (2008-2010) to 2.2 per 1000 (95% CI 1.8-2.5) during the universal immunization period (2012-2015), but yearly fluctuations were still observed. The most common genotypes in the pre-universal immunization period were G1P[8] (35.3%) followed by G2P[4] (15.5%), G3P[8] (8.8%), G4P[8] (4.3%) and G9P[8] (4.3%), and 19.5% were mixed infections. The dominance of G1P[8] continued into the universal immunization period (48.6%), followed by G3P[8] (21.5%), G9P[8] (15.9%) and G12P[8] (4.7%), while mixed rotavirus infections were no longer detected. Universal immunization with RotaTeq in Israel was associated a sustained reduction in RVGE hospitalization. It is unclear whether changes in the circulating rotavirus genotypes are due to vaccine-induced selective pressure. Assessment of the long-term impact of rotavirus vaccination on the incidence of rotavirus gastroenteritis and continued strain surveillance is warranted. Copyright © 2016. Published by Elsevier Ltd.

Prevalence and clinical profile of rotavirus A infection among diarrheal children and phylogenetic analysis with vaccine strains in Chengdu, West China, 2009-2014.

PubMed

Chen, Yu-Hang; Chen, Fan; Zhou, Tao; Chen, Jia-Yi; Zheng, Tian-Li; Xu, Xin; Pei, Xiao-Fang

2018-05-19

Rotaviruses are the most common cause of severe diarrheal disease in young children. However, little is known about the epidemiological and clinical profile of rotavirus A (RVA) in diarrheal children or the efficacy of Lanzhou lamb rotavirus vaccine (LLR) in Chengdu, China. This study aimed to determine the prevalence and clinical profile of RVA in diarrheal children and provide gene analysis information for RVA vaccination programs. 1121 fecal samples were collected from outpatient children with diarrhea between 2009 and 2014. RT-PCR was performed to detect RVA infection and other gastroenteritis viruses. VP4 and VP7 genes of 13 RVA strains were sequenced to compare their similarity with vaccine strains. The overall RVA infection rate was 17.48%. G1 (54.72%) and G3 (18.87%) were the predominant G genotypes; P[8] (72.36%) and P[4] (11.38%) were the main P genotypes. 16 genotypes were identified; G1P[8] (57.33%), G9P[8] (12.00%) were the most prevalent. The proportion of coinfection with RVA and other gastroenteritis viruses was 18.88%. RVA was mostly detected in winter and in diarrheal children 1 to 2 years of age. The genotypes of Rotarix and RotaTeq vaccines were consistent with RVA strains prevalent in Sichuan and shared high identity. RVA was one of the major etiological agents of diarrheal children in Chengdu. Genotype distribution differed within each year and the gene analysis implied low efficacy of LLR. Continuous epidemiological monitoring of RVA is essential for the national vaccination program. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

Molecular characterization of a human G20P[28] rotavirus a strain with multiple genes related to bat rotaviruses.

PubMed

Esona, Mathew D; Roy, Sunando; Rungsrisuriyachai, Kunchala; Gautam, Rashi; Hermelijn, Sandra; Rey-Benito, Gloria; Bowen, Michael D

2018-01-01

Group A rotaviruses are the major cause of severe gastroenteritis in the young of mammals and birds. This report describes characterization of an unusual G20P[28] rotavirus strain detected in a 24month old child from Suriname. Genomic sequence analyses revealed that the genotype constellation of the Suriname strain RVA/Human-wt/SUR/2014735512/2013/G20P[28] was G20-P[28]-I13-R13-C13-M12-A23-N13-T15-E20-H15. Genes VP1, VP2, VP3, NSP1, NSP2, NSP3, NSP4 and NSP5 were recently assigned novel genotypes by the Rotavirus Classification Working Group (RCWG). Three of the 11 gene segments (VP7, VP4, VP6) were similar to cognate gene sequences of bat-like human rotavirus strain Ecu534 from Ecuador and the VP7, NSP3 and NSP5 gene segments of strain RVA/Human-wt/SUR/2014735512/2013/G20P[28] were found to be closely related to gene sequences of bat rotavirus strain 3081/BRA detected in Brazil. Although distantly related, the VP1 gene of the study strain and bat strain BatLi09 detected in Cameroon in 2014 are monophyletic. The NSP1 gene was found to be most closely related to human strain QUI-35-F5 from Brazil. These findings suggest that strain RVA/Human-wt/SUR/2014735512/2013/G20P[28] represents a zoonotic infection from a bat host. Published by Elsevier B.V.

Whole genome sequencing of a rare rotavirus from archived stool sample demonstrates independent zoonotic origin of human G8P[14] strains in Hungary.

PubMed

Marton, Szilvia; Dóró, Renáta; Fehér, Enikő; Forró, Barbara; Ihász, Katalin; Varga-Kugler, Renáta; Farkas, Szilvia L; Bányai, Krisztián

2017-01-02

Genotype P[14] rotaviruses in humans are thought to be zoonotic strains originating from bovine or ovine host species. Over the past 30 years only few genotype P[14] strains were identified in Hungary totaling<0.1% of all human rotaviruses whose genotype had been determined. In this study we report the genome sequence and phylogenetic analysis of a human genotype G8P[14] strain, RVA/Human-wt/HUN/182-02/2001/G8P[14]. The whole genome constellation (G8-P[14]-I2-R2-C2-M2-A11-N2-T6-E2-H3) of this strain was shared with another Hungarian zoonotic G8P[14] strain, RVA/Human-wt/HUN/BP1062/2004/G8P[14], although phylogenetic analyses revealed the two rotaviruses likely had different progenitors. Overall, our findings indicate that human G8P[14] rotavirus detected in Hungary in the past originated from independent zoonotic events. Further studies are needed to assess the public health risk associated with infections by various animal rotavirus strains. Copyright © 2016. Published by Elsevier B.V.

Rotavirus surveillance in urban and rural areas of Niger, April 2010-March 2012.

PubMed

Page, Anne-Laure; Jusot, Viviane; Mamaty, Abdoul-Aziz; Adamou, Lagare; Kaplon, Jérôme; Pothier, Pierre; Djibo, Ali; Manzo, Mahamane L; Toure, Brahima; Langendorf, Céline; Collard, Jean-Marc; Grais, Rebecca F

2014-04-01

Knowledge of rotavirus epidemiology is necessary to make informed decisions about vaccine introduction and to evaluate vaccine impact. During April 2010-March 2012, rotavirus surveillance was conducted among 9,745 children <5 years of age in 14 hospitals/health centers in Niger, where rotavirus vaccine has not been introduced. Study participants had acute watery diarrhea and moderate to severe dehydration, and 20% of the children were enrolled in a nutrition program. Of the 9,745 children, 30.6% were rotavirus positive. Genotyping of a subset of positive samples showed a variety of genotypes during the first year, although G2P[4] predominated. G12 genotypes, including G12P[8], which has emerged as a predominant strain in western Africa, represented >80% of isolates during the second year. Hospitalization and death rates and severe dehydration among rotavirus case-patients did not differ during the 2 years. The emergence of G12P[8] warrants close attention to the characteristics of associated epidemics and possible prevention measures.

Detection and sequencing of rotavirus among sudanese children.

PubMed

Magzoub, Magzoub Abbas; Bilal, Naser Eldin; Bilal, Jalal Ali; Alzohairy, Mohammad Abdulrahman; Elamin, Bahaeldin Khalid; Gasim, Gasim Ibrahim

2017-01-01

Diarrheal diseases are a big public health problem worldwide, particularly among developing countries. The current study was conducted to detect and characterize group A rotavirus among admitted children with gastroenteritis to the pediatric hospitals, Sudan. A total of 755 stool samples were collected from Sudanese children with less than 5 years of age presenting with acute gastroenteritis during the period from April to September 2010. Enzyme-linked immunosorbent assay (ELISA) was used to Detection of Rotavirus antigens. Ribonucleic acid (RNAs) were extracted from rotavirus-positive stool samples using (QIAamp ® Viral RNA Mini Kit). (Omniscript ® Reverse Transcription kit) was used to convert RNA to complementary Deoxyribonucleic acid (cDNA). The cDNAs were used as template for detection of VP4-P (P for Protease-sensitive) and VP7-G (G for Glycoprotein) genotyping of Rotavirus using nested PCR and sequencing. Out of the 755 stool samples from children with acute gastroenteritis, 121 were positive for rotavirus A. Among 24 samples that were sequenced; the VP7 predominant G type was G1 (83.3%), followed by G9 (16.7%). Out of these samples, only one VP4 P[8] genotype was detected. As a conclusion the VP7 predominant G type was G1, followed by G9 whereas only one VP4 genotype was detected and showed similarity to P[8] GenBank strain. It appears that the recently approved rotavirus vaccines in Sudan are well matched to the rotavirus genotypes identified in this study, though more studies are needed.

Long-term Consistency in Rotavirus Vaccine Protection: RV5 and RV1 Vaccine Effectiveness in US Children, 2012-2013.

PubMed

Payne, Daniel C; Selvarangan, Rangaraj; Azimi, Parvin H; Boom, Julie A; Englund, Janet A; Staat, Mary Allen; Halasa, Natasha B; Weinberg, Geoffrey A; Szilagyi, Peter G; Chappell, James; McNeal, Monica; Klein, Eileen J; Sahni, Leila C; Johnston, Samantha H; Harrison, Christopher J; Baker, Carol J; Bernstein, David I; Moffatt, Mary E; Tate, Jacqueline E; Mijatovic-Rustempasic, Slavica; Esona, Mathew D; Wikswo, Mary E; Curns, Aaron T; Sulemana, Iddrisu; Bowen, Michael D; Gentsch, Jon R; Parashar, Umesh D

2015-12-15

Using a multicenter, active surveillance network from 2 rotavirus seasons (2012 and 2013), we assessed the vaccine effectiveness of RV5 (RotaTeq) and RV1 (Rotarix) rotavirus vaccines in preventing rotavirus gastroenteritis hospitalizations and emergency department (ED) visits for numerous demographic and secular strata. We enrolled children hospitalized or visiting the ED with acute gastroenteritis (AGE) for the 2012 and 2013 seasons at 7 medical institutions. Stool specimens were tested for rotavirus by enzyme immunoassay and genotyped, and rotavirus vaccination histories were compared for rotavirus-positive cases and rotavirus-negative AGE controls. We calculated the vaccine effectiveness (VE) for preventing rotavirus associated hospitalizations and ED visits for each vaccine, stratified by vaccine dose, season, clinical setting, age, predominant genotype, and ethnicity. RV5-specific VE analyses included 2961 subjects, 402 rotavirus cases (14%) and 2559 rotavirus-negative AGE controls. RV1-specific VE analyses included 904 subjects, 100 rotavirus cases (11%), and 804 rotavirus-negative AGE controls. Over the 2 rotavirus seasons, the VE for a complete 3-dose vaccination with RV5 was 80% (confidence interval [CI], 74%-84%), and VE for a complete 2-dose vaccination with RV1 was 80% (CI, 68%-88%).Statistically significant VE was observed for each year of life for which sufficient data allowed analysis (7 years for RV5 and 3 years for RV1). Both vaccines provided statistically significant genotype-specific protection against predominant circulating rotavirus strains. In this large, geographically and demographically diverse sample of US children, we observed that RV5 and RV1 rotavirus vaccines each provided a lasting and broadly heterologous protection against rotavirus gastroenteritis. Published by Oxford University Press on behalf of the Infectious Diseases Society of America 2015. This work is written by (a) US Government employee(s) and is in the public domain in the US.

Molecular characterization of rotavirus strains detected during a clinical trial of a human rotavirus vaccine in Blantyre, Malawi

PubMed Central

Nakagomi, Toyoko; Nakagomi, Osamu; Dove, Winifred; Doan, Yen Hai; Witte, Desiree; Ngwira, Bagrey; Todd, Stacy; Steele, A Duncan; Neuzil, Kathleen M; Cunliffe, Nigel A

2014-01-01

The human, G1P[8] rotavirus vaccine (Rotarix) significantly reduced severe rotavirus gastroenteritis episodes in a clinical trial in South Africa and Malawi, but vaccine efficacy was lower in Malawi (49.5%) than reported in South Africa (76.9%) and elsewhere. The aim of this study was to examine the molecular relationships of circulating wild-type rotaviruses detected during the clinical trial in Malawi to RIX4414 (the strain contained in Rotarix) and to common human rotavirus strains. Of 88 rotavirus-positive, diarrhoeal stool specimens, 43 rotaviruses exhibited identifiable RNA migration patterns when examined by polyacrylamide gel electrophoresis. The genes encoding VP7, VP4, VP6 and NSP4 of 5 representative strains possessing genotypes G12P[6], G1P[8], G9P[8], and G8P[4] were sequenced. While their VP7 (G) and VP4 (P) genotype designations were confirmed, the VP6 (I) and NSP4 (E) genotypes were either I1E1 or I2E2, indicating that they were of human rotavirus origin. RNA-RNA hybridization using 21 culture-adapted strains showed that Malawian rotaviruses had a genomic RNA constellation common to either the Wa-like or DS-1 like human rotaviruses. Overall, the Malawi strains appear similar in their genetic make-up to rotaviruses described in countries where vaccine efficacy is greater, suggesting that the lower efficacy in Malawi is unlikely to be explained by the diversity of circulating strains. PMID:22520123

Molecular characterization of rotavirus strains detected during a clinical trial of a human rotavirus vaccine in Blantyre, Malawi.

PubMed

Nakagomi, Toyoko; Nakagomi, Osamu; Dove, Winifred; Doan, Yen Hai; Witte, Desiree; Ngwira, Bagrey; Todd, Stacy; Duncan Steele, A; Neuzil, Kathleen M; Cunliffe, Nigel A

2012-04-27

The human, G1P[8] rotavirus vaccine (Rotarix™) significantly reduced severe rotavirus gastroenteritis episodes in a clinical trial in South Africa and Malawi, but vaccine efficacy was lower in Malawi (49.5%) than reported in South Africa (76.9%) and elsewhere. The aim of this study was to examine the molecular relationships of circulating wild-type rotaviruses detected during the clinical trial in Malawi to RIX4414 (the strain contained in Rotarix™) and to common human rotavirus strains. Of 88 rotavirus-positive, diarrhoeal stool specimens, 43 rotaviruses exhibited identifiable RNA migration patterns when examined by polyacrylamide gel electrophoresis. The genes encoding VP7, VP4, VP6 and NSP4 of 5 representative strains possessing genotypes G12P[6], G1P[8], G9P[8], and G8P[4] were sequenced. While their VP7 (G) and VP4 (P) genotype designations were confirmed, the VP6 (I) and NSP4 (E) genotypes were either I1E1 or I2E2, indicating that they were of human rotavirus origin. RNA-RNA hybridization using 21 culture-adapted strains showed that Malawian rotaviruses had a genomic RNA constellation common to either the Wa-like or the DS-1 like human rotaviruses. Overall, the Malawi strains appear similar in their genetic make-up to rotaviruses described in countries where vaccine efficacy is greater, suggesting that the lower efficacy in Malawi is unlikely to be explained by the diversity of circulating strains. Copyright © 2011 Elsevier Ltd. All rights reserved.

Distribution of Rotavirus Genotypes from the 2008/2009 to the 2015/2016 Season in Nara Prefecture, Japan.

PubMed

Sugimoto, Daichi; Nakano, Mamoru; Inada, Machi; Fujitani, Misako; Chiba, Shoko; Sakai, Takeshi

2017-09-25

This study was conducted to investigate the distribution of rotavirus genotypes in Nara Prefecture, Japan before and after the introduction of rotavirus vaccination in 2011. Since the 2011/2012 season, DS-1-like G1P[8] strains have been detected in Nara Prefecture, accounting for about half of all strains in the 2014/2015 season. During the 2015/2016 season, no DS-1-like G1P[8] strains were detected; G2P[4] was the predominant genotype.

Population Impact and Effectiveness of Monovalent Rotavirus Vaccination in Urban Malawian Children 3 Years After Vaccine Introduction: Ecological and Case-Control Analyses

PubMed Central

Bar-Zeev, Naor; Jere, Khuzwayo C.; Bennett, Aisleen; Pollock, Louisa; Tate, Jacqueline E.; Nakagomi, Osamu; Iturriza-Gomara, Miren; Costello, Anthony; Mwansambo, Charles; Parashar, Umesh D.; Heyderman, Robert S.; French, Neil; Cunliffe, Nigel A.

2016-01-01

Background. Rotavirus vaccines have been introduced in many low-income African countries including Malawi in 2012. Despite early evidence of vaccine impact, determining persistence of protection beyond infancy, the utility of the vaccine against specific rotavirus genotypes, and effectiveness in vulnerable subgroups is important. Methods. We compared rotavirus prevalence in diarrheal stool and hospitalization incidence before and following rotavirus vaccine introduction in Malawi. Using case-control analysis, we derived vaccine effectiveness (VE) in the second year of life and for human immunodeficiency virus (HIV)–exposed and stunted children. Results. Rotavirus prevalence declined concurrent with increasing vaccine coverage, and in 2015 was 24% compared with prevaccine mean baseline in 1997–2011 of 32%. Since vaccine introduction, population rotavirus hospitalization incidence declined in infants by 54.2% (95% confidence interval [CI], 32.8–68.8), but did not fall in older children. Comparing 241 rotavirus cases with 692 test-negative controls, VE was 70.6% (95% CI, 33.6%–87.0%) and 31.7% (95% CI, −140.6% to 80.6%) in the first and second year of life, respectively, whereas mean age of rotavirus cases increased from 9.3 to 11.8 months. Despite higher VE against G1P[8] than against other genotypes, no resurgence of nonvaccine genotypes has occurred. VE did not differ significantly by nutritional status (78.1% [95% CI, 5.6%–94.9%] in 257 well-nourished and 27.8% [95% CI, −99.5% to 73.9%] in 205 stunted children; P = .12), or by HIV exposure (60.5% [95% CI, 13.3%–82.0%] in 745 HIV-unexposed and 42.2% [95% CI, −106.9% to 83.8%] in 174 exposed children; P = .91). Conclusions. Rotavirus vaccination in Malawi has resulted in reductions in disease burden in infants <12 months, but not in older children. Despite differences in genotype-specific VE, no genotype has emerged to suggest vaccine escape. VE was not demonstrably affected by HIV exposure or stunting. PMID:27059359

Population Impact and Effectiveness of Monovalent Rotavirus Vaccination in Urban Malawian Children 3 Years After Vaccine Introduction: Ecological and Case-Control Analyses.

PubMed

Bar-Zeev, Naor; Jere, Khuzwayo C; Bennett, Aisleen; Pollock, Louisa; Tate, Jacqueline E; Nakagomi, Osamu; Iturriza-Gomara, Miren; Costello, Anthony; Mwansambo, Charles; Parashar, Umesh D; Heyderman, Robert S; French, Neil; Cunliffe, Nigel A

2016-05-01

Rotavirus vaccines have been introduced in many low-income African countries including Malawi in 2012. Despite early evidence of vaccine impact, determining persistence of protection beyond infancy, the utility of the vaccine against specific rotavirus genotypes, and effectiveness in vulnerable subgroups is important. We compared rotavirus prevalence in diarrheal stool and hospitalization incidence before and following rotavirus vaccine introduction in Malawi. Using case-control analysis, we derived vaccine effectiveness (VE) in the second year of life and for human immunodeficiency virus (HIV)-exposed and stunted children. Rotavirus prevalence declined concurrent with increasing vaccine coverage, and in 2015 was 24% compared with prevaccine mean baseline in 1997-2011 of 32%. Since vaccine introduction, population rotavirus hospitalization incidence declined in infants by 54.2% (95% confidence interval [CI], 32.8-68.8), but did not fall in older children. Comparing 241 rotavirus cases with 692 test-negative controls, VE was 70.6% (95% CI, 33.6%-87.0%) and 31.7% (95% CI, -140.6% to 80.6%) in the first and second year of life, respectively, whereas mean age of rotavirus cases increased from 9.3 to 11.8 months. Despite higher VE against G1P[8] than against other genotypes, no resurgence of nonvaccine genotypes has occurred. VE did not differ significantly by nutritional status (78.1% [95% CI, 5.6%-94.9%] in 257 well-nourished and 27.8% [95% CI, -99.5% to 73.9%] in 205 stunted children;P= .12), or by HIV exposure (60.5% [95% CI, 13.3%-82.0%] in 745 HIV-unexposed and 42.2% [95% CI, -106.9% to 83.8%] in 174 exposed children;P= .91). Rotavirus vaccination in Malawi has resulted in reductions in disease burden in infants <12 months, but not in older children. Despite differences in genotype-specific VE, no genotype has emerged to suggest vaccine escape. VE was not demonstrably affected by HIV exposure or stunting. © The Author 2016. Published by Oxford University Press for the Infectious Diseases Society of America.

Re-emergence of genotype G9 during a five-and-a-half-year period in Turkish children with rotavirus diarrhea.

PubMed

Bozdayi, Gulendam; Altay, Aylin; Yahiro, Takaaki; Ahmed, Sharnali; Meral, Melda; Dogan, Bora; Dinc, Bedia; Yeniaras, Ayça; Bilge, Yildiz Dallar; Ahmed, Kamruddin

2016-10-01

This study was done to understand the dynamics of rotavirus genotype distribution in Turkish children. Samples were collected from January 2006 through August 2011 from children at a hospital in Ankara. Rotavirus was detected in 28 % (241/889) of the samples. Genotype G9P[8] was predominant (28 %), followed by G1P[8] (16.3 %) and G2P[8] (15.9 %). G9 was absent in the samples from 2006 and 2007 and then re-emerged in 2008 and increased gradually. Phylogenetic analysis showed that Turkish G9 rotaviruses of the present study formed a sublineage with strains from Italy and Ethiopia, possibly indicating spread of a clone in these countries.

Investigation of Rotavirus with Various Methods in Children with Acute Gastroenteritis and Determination of Its Molecular Epidemiology in Kayseri Province, Turkey.

PubMed

Artiran, Sukran; Atalay, Altay; Gökahmetoglu, Selma; Ozturk, Mehmet Adnan; Balci, Nurgul; Cakir, Nuri; Kilic, Huseyin; Durmaz, Riza

2017-03-01

In this study, the fresh stool samples from 254 children under 5 years of age with acute gastroenteritis which were delivered between October 2012 and December 2013 were collected. In the stool samples, rotavirus antigens were investigated using two different immunochromatographic methods which are routinely used at different times, namely the RIDA ® QUICK Rotavirus/Adenovirus Combi Test (R-Biopharm AG, Germany) and the Genx ® Rotavirus Test (Diamed-Lab, Turkey), in addition to the Rotavirus Ag (Stool) ELISA (DRG, Germany) kit. The results were compared with reverse transcriptase PCR (RT-PCR). When the Genx ® Rotavirus Test and RIDA ® QUICK Rotavirus/Adenovirus Combi Test immunochromatographic methods were compared with RT-PCR, their sensitivity and specificity were found as 97.1%, 100%, and 80.4%, 72%, respectively. As to the Rotavirus Ag (Stool) ELISA method, on the other hand, its sensitivity was found to be 95.1% and its specificity was 86.5%. The most common genotype was G9P[8] (40%), which was followed by the G1P[8] (18.7%) and G3P[8] (9.6%) genotypes. Consequently, it was revealed that the sensitivity of ELISA and immunochromatographic methods, which provide results in a short time and are used in the investigation of rotavirus antigen, was high and their specificity was low; further studies to determine the distribution of G and P genotypes will contribute to establishing strategies for vaccine development for rotavirus in the world. © 2016 Wiley Periodicals, Inc.

Rotavirus epidemiology and surveillance before vaccine introduction in Argentina, 2012-2014.

PubMed

Degiuseppe, Juan Ignacio; Reale, Ezequiel Agustín; Stupka, Juan Andrés

2017-03-01

Group A Rotavirus has been widely described as one of the most important infantile diarrheal pathogens worldwide. In Argentina, it is responsible for over 200,000 acute diarrhea cases and from 30 to 50 deaths annually in children under 5 years. The aim of this study is to analyze frequency, seasonality, age group distribution, and circulating genotypes based on data notified in the 2012-2014 period and in turn to assess the pre-vaccine scenario, considering that rotavirus vaccine was introduced in 2015. Data were taken from the Viral Diarrhea Notification module of the Argentine SNVS-SIVILA surveillance tool. Analyses of circulating genotypes were performed on rotavirus-positive stool specimens by conventional binary characterization of the outermost capsid genes. Overall data showed rotavirus detection in about 25% of samples tested, and higher rates in children under 2 years old were observed. Rotavirus positive cases were distributed according to a typical winter seasonal pattern. A heterogeneous regional pattern of prevalence was also observed, with higher rates detected in the North region. Genotype co-circulation and annual fluctuation were observed. In general, G1P[8], G2P[4], G3P[8], and G12P[8] were the most frequently detected genotypes. This study represents the last survey taken of a population considered to be naïve. J. Med. Virol. 89:423-428, 2017. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

First study conducted in Northern India that identifies group C rotavirus as the etiological agent of severe diarrhea in children in Delhi.

PubMed

Tiku, Vasundhara Razdan; Jiang, Baoming; Kumar, Praveen; Aneja, Satender; Bagga, Arvind; Bhan, Maharaj Kishen; Ray, Pratima

2017-05-30

Group C Rotavirus (RVC) is an enteric pathogen responsible for acute gastroenteritis in children and adults globally. At present there are no surveillance studies on group C Rotaviruses in India and therefore their prevalence in India remains unknown. The present study aimed to evaluate group C rotavirus infection among <5 years old children hospitalized with acute gastroenteritis in New Delhi. A total of 350 fecal specimens were collected during September 2013 to November 2014 from <5 years old diarrheal patients admitted at KSCH hospital, Delhi. The samples found negative for group A rotavirus (N = 180) by Enzyme immunoassay were screened for group C rotavirus by RT-PCR with VP6, VP7 and VP4 gene specific primers. The PCR products were further sequenced (VP6, VP7, VP4) and analyzed to ascertain their origin and G and P genotypes. Six out of 180 (group A rotavirus negative) samples were found positive for group C rotavirus by VP6 gene specific RT-PCR, of which 3 were also found positive for VP7 and VP4 genes. Phylogenetic analysis of VP7 and VP4 genes of these showed them to be G4 and P[2] genotypes. Overall, the nucleotide sequence data (VP6, VP7 and VP4) revealed a close relationship with the human group C rotavirus with no evidence of animal ancestry. Interestingly, the nucleotide sequence analysis of various genes also indicated differences in their origin. While the identity matrix of VP4 gene (n = 3) showed high amino acid sequence identity (97.60 to 98.20%) with Korean strain, the VP6 gene (n = 6) showed maximum identity with Nigerian strain (96.40 to 97.60%) and VP7 gene (n = 3) with Bangladeshi and USA strains. This is true for all analyzed samples. Our study demonstrated the group C rotavirus as the cause of severe diarrhea in young children in Delhi and provides insights on the origin of group C rotavirus genes among the local strains indicating their source of transmission. Our study also highlights the need for a simple and reliable diagnostic test that can be utilized to determine the disease burden due to group C rotavirus in India.

Unbiased whole-genome deep sequencing of human and porcine stool samples reveals circulation of multiple groups of rotaviruses and a putative zoonotic infection

PubMed Central

Phan, My V. T.; Anh, Pham Hong; Cuong, Nguyen Van; Munnink, Bas B. Oude; van der Hoek, Lia; My, Phuc Tran; Tri, Tue Ngo; Bryant, Juliet E.; Baker, Stephen; Thwaites, Guy; Woolhouse, Mark; Kellam, Paul; Rabaa, Maia A.

2016-01-01

Abstract Coordinated and synchronous surveillance for zoonotic viruses in both human clinical cases and animal reservoirs provides an opportunity to identify interspecies virus movement. Rotavirus (RV) is an important cause of viral gastroenteritis in humans and animals. In this study, we document the RV diversity within co-located humans and animals sampled from the Mekong delta region of Vietnam using a primer-independent, agnostic, deep sequencing approach. A total of 296 stool samples (146 from diarrhoeal human patients and 150 from pigs living in the same geographical region) were directly sequenced, generating the genomic sequences of sixty human rotaviruses (all group A) and thirty-one porcine rotaviruses (thirteen group A, seven group B, six group C, and five group H). Phylogenetic analyses showed the co-circulation of multiple distinct RV group A (RVA) genotypes/strains, many of which were divergent from the strain components of licensed RVA vaccines, as well as considerable virus diversity in pigs including full genomes of rotaviruses in groups B, C, and H, none of which have been previously reported in Vietnam. Furthermore, the detection of an atypical RVA genotype constellation (G4-P[6]-I1-R1-C1-M1-A8-N1-T7-E1-H1) in a human patient and a pig from the same region provides some evidence for a zoonotic event. PMID:28748110

Did Large-Scale Vaccination Drive Changes in the Circulating Rotavirus Population in Belgium?

PubMed Central

Pitzer, Virginia E.; Bilcke, Joke; Heylen, Elisabeth; Crawford, Forrest W.; Callens, Michael; De Smet, Frank; Van Ranst, Marc; Zeller, Mark; Matthijnssens, Jelle

2015-01-01

Vaccination can place selective pressures on viral populations, leading to changes in the distribution of strains as viruses evolve to escape immunity from the vaccine. Vaccine-driven strain replacement is a major concern after nationwide rotavirus vaccine introductions. However, the distribution of the predominant rotavirus genotypes varies from year to year in the absence of vaccination, making it difficult to determine what changes can be attributed to the vaccines. To gain insight in the underlying dynamics driving changes in the rotavirus population, we fitted a hierarchy of mathematical models to national and local genotype-specific hospitalization data from Belgium, where large-scale vaccination was introduced in 2006. We estimated that natural- and vaccine-derived immunity was strongest against completely homotypic strains and weakest against fully heterotypic strains, with an intermediate immunity amongst partially heterotypic strains. The predominance of G2P[4] infections in Belgium after vaccine introduction can be explained by a combination of natural genotype fluctuations and weaker natural and vaccine-induced immunity against infection with strains heterotypic to the vaccine, in the absence of significant variation in strain-specific vaccine effectiveness against disease. However, the incidence of rotavirus gastroenteritis is predicted to remain low despite vaccine-driven changes in the distribution of genotypes. PMID:26687288

Molecular Epidemiology of Rotavirus in Children under Five in Africa (2006-2016): A Systematic Review.

PubMed

Ouermi, D; Soubeiga, D; Nadembega, W M C; Sawadogo, P M; Zohoncon, T M; Obiri-Yeboah, D; Djigma, F W; Nordgren, J; Simpore, J

2017-01-01

Group A human rotaviruses (RVA) are the most common causes of severe viral gastroenteritis in infants and young children worldwide. The available vaccines, while effective in Europe and North America have shown a reduced efficacy in Africa. One issue raised is the genetic variability of RVA. The objective of this study was to perform a literature review of molecular epidemiology to determine the prevalence of RVA genotypes circulating in Africa so as to establish a mapping of reliable data on these various genotypes. The search for articles was done from the National Institutes of Health (PUBMED) using three set of keywords. Articles were selected with inclusion criteria such as the date of publication, the age of the children, the sample size and the diagnostic techniques (standardized laboratory techniques). The data were imported into STATA SE version 11 software. Specific prevalence was estimated with Confidence Intervals (CI) of 95%. A total of 326 published studies were initially retrieved, out of which 27 studies were finally selected for the systematic review. The selected studies cover 20 African countries. The most encountered genotypes in Africa during this period were G1 (32.72%), followed by G2 (17.17%), G3 (9.88%), G9 (8.61%) and G12 (7.56%) among the G-types. The most common P-types were P[8] (48.71%) followed by P[6] (22.60%) and P[4] (11.58%) and the G1P[8] combination (22.64%) was the most encountered followed by G2P[4] (8.29%), G9P[8] (6.95%) and G2P[6] (5.00%). North Africa presented the highest prevalence of the P[8] genotype (65.70%). This review provides a comprehensive view of the current circulating rotavirus strains in Africa, which can be important in light of the new rotavirus vaccinations. Indeed, in Africa, the pursuit of national and continental studies for epidemiological surveillance of circulating rotavirus strains is vital for the promotion of future successful vaccines.

Evaluation of Immunochromatographic Test for Dual Detection of Noroviruses and Group A Rotaviruses in Stool Samples.

PubMed

Khamrin, Pattara; Kumthip, Kattareeya; Thongprachum, Aksara; Takanashi, Sayaka; Okitsu, Shoko; Maneekarn, Niwat; Hayakawa, Satoshi; Ushijima, Hiroshi

2018-05-01

Viral enteric infections, such as noroviruses and rotaviruses are considered as the major causes of acute gastroenteritis in young children and elderly people all over the world. These viruses are responsible for numerous outbreaks of nonbacterial gastroenteritis in several settings such as hospitals, day care centers, nursing homes, and restaurants. Therefore, a rapid and sensitive diagnostic tool for virus detections could be helpful for disease control. A new immunochromatographic test for the dual detection of noroviruses and group A rotaviruses was evaluated by using specimens that were known to be positive for noroviruses and rotaviruses, as well as other diarrheal viruses. The sensitivity of detections for noroviruses and group A rotaviruses were 89.5% and 100%, respectively, while the specificity was 100% for both viruses. This immunochromatographic test was reactive to several norovirus and group A rotavirus genotypes (NoV GII.2, GII.3, GII.4, GII.6, GII.7, GII.17 and RVA G1P[8], G2P[4], G3P[8], G8P[8], G9P[8]). The speed and ease of use of the immunochromatographic test makes this kit particularly attractive as an alternative method for the detections of noroviruses and group A rotaviruses in the primary care unit.

Zooanthroponotic transmission of rotavirus in Haryana State of Northern India.

PubMed

Choudhary, P; Minakshi, P; Ranjan, K; Basanti, B

Rotaviruses are the major cause of severe gastroenteritis and mortality in young children and animals. Due to segmented nature of dsRNA genome and wide host range, vast genetic and antigenic diversity exists amongst different isolates of rotaviruses. A total of 230 fecal ovine and caprine samples collected from organized farms and villages in Haryana were screened for rotavirus detection. Samples were screened by latex agglutination test and RNA-PAGE followed by RT-PCR and nucleic acid sequencing. The latex agglutination test showed 25 newborn lamb and 4 kid fecal samples positive for rotavirus. However, RNA-PAGE showed only 9 lamb fecal samples positive for rotavirus. All the samples were subjected to RT-PCR employing vp4 and vp7 gene specific primers of group A rotavirus of ovine, bovine and human origin. Only two samples from lamb (Sheep18/Hisar/2013 and Sheep22/Hisar/2013) showed vp4 and vp7 gene specific amplification with human group A rotavirus (GAR) specific primer. However, they did not show any amplification with ovine and bovine rotavirus specific primers. The nucleotide as well as deduced amino acid sequence analysis of vp4 gene of these isolates showed >98/97% and vp7 gene >95/94% nt/aa identity with human GAR from different regions of the world. Based on nucleotide similarity search, Sheep18/Hisar/2013 and Sheep22/Hisar/2013 isolates were genotyped as G1P[8] and G1P[4]. Phylogenetic analysis also confirmed that these isolates were clustered closely with human rotaviruses from different regions of the world. Earlier, higher prevalence of human rotaviruses was reported from the sample collecting area. The amplification of ovine samples with human rotavirus gene specific primers, sequence identity and phylogenetic analysis strongly suggests the zoonotic transmission of human GAR to sheep.

Whole genome analysis of selected human and animal rotaviruses identified in Uganda from 2012 to 2014 reveals complex genome reassortment events between human, bovine, caprine and porcine strains.

PubMed

Bwogi, Josephine; Jere, Khuzwayo C; Karamagi, Charles; Byarugaba, Denis K; Namuwulya, Prossy; Baliraine, Frederick N; Desselberger, Ulrich; Iturriza-Gomara, Miren

2017-01-01

Rotaviruses of species A (RVA) are a common cause of diarrhoea in children and the young of various other mammals and birds worldwide. To investigate possible interspecies transmission of RVAs, whole genomes of 18 human and 6 domestic animal RVA strains identified in Uganda between 2012 and 2014 were sequenced using the Illumina HiSeq platform. The backbone of the human RVA strains had either a Wa- or a DS-1-like genetic constellation. One human strain was a Wa-like mono-reassortant containing a DS-1-like VP2 gene of possible animal origin. All eleven genes of one bovine RVA strain were closely related to those of human RVAs. One caprine strain had a mixed genotype backbone, suggesting that it emerged from multiple reassortment events involving different host species. The porcine RVA strains had mixed genotype backbones with possible multiple reassortant events with strains of human and bovine origin.Overall, whole genome characterisation of rotaviruses found in domestic animals in Uganda strongly suggested the presence of human-to animal RVA transmission, with concomitant circulation of multi-reassortant strains potentially derived from complex interspecies transmission events. However, whole genome data from the human RVA strains causing moderate and severe diarrhoea in under-fives in Uganda indicated that they were primarily transmitted from person-to-person.

Distinguishing the genotype 1 genes and proteins of human Wa-like rotaviruses vs. porcine rotaviruses

PubMed Central

Silva, Fernanda D.F.; Gregori, F.; McDonald, Sarah M.

2016-01-01

Group A rotaviruses (RVAs) are 11-segmented, double-stranded RNA viruses and important causes of gastroenteritis in the young of many animal species. Previous studies have suggested that human Wa-like RVAs share a close evolutionary relationship with porcine RVAs. Specifically, the VP1-VP3 and NSP2-5/6 genes of these viruses are usually classified as genotype 1 with >81% nucleotide sequence identity. Yet, it remains unknown whether the genotype 1 genes and proteins of human Wa-like strains are distinguishable from those of porcine strains. To investigate this, we performed comprehensive bioinformatic analyses using all known genotype 1 gene sequences. The RVAs analyzed represent wildtype strains isolated from humans or pigs at various geographical locations during the years of 2004–2013, including 11 newly-sequenced porcine RVAs from Brazil. We also analyzed archival strains that were isolated during the years of 1977–1992 as well as atypical strains involved in inter-species transmission between humans and pigs. We found that, in general, the genotype 1 genes of typical modern human Wa-like RVAs clustered together in phylogenetic trees and were separate from those of typical modern porcine RVAs. The only exception was for the NSP5/6 gene, which showed no host-specific phylogenetic clustering. Using amino acid sequence alignments, we identified 34 positions that differentiated the VP1-VP3, NSP2, and NSP3 genotype 1 proteins of typical modern human Wa-like RVAs versus typical modern porcine RVAs and documented how these positions vary in the archival/unusual isolates. No host-specific amino acid positions were identified for NSP4, NSP5, or NSP6. Altogether, the results of this study support the notion that human Wa-like RVAs and porcine RVAs are evolutionarily related, but indicate that some of their genotype 1 genes and proteins have diverged over time possibly as a reflection of sequestered replication and protein co-adaptation in their respective hosts. PMID:27180895

Further characterization of field strains of rotavirus from Nigeria VP4 genotype P6 most frequently identified among symptomatically infected children.

PubMed

Adah, M I; Rohwedder, A; Olaleye, O D; Durojaiye, O A; Werchau, H

1997-10-01

Polymerase chain reaction was utilized to characterize the VP4 types of 39 Rotavirus field isolates from symptomatically infected children in Nigeria. Genotype P6 was identified most frequently, occurring in 41.03 per cent of the typed specimens. Genotype P8 was identified as the next most prevalent (33.3% per cent). Genotype p6 was widespread (68.75 per cent) among infected neonates in Southern Nigeria, but mix infection was more prevalent (70 per cent) among Northern Nigerian children. Four distinct strains were identified with four different P genotypes. Overall strain G1P8 predominated (22.22 per cent) followed by G3P6 (17.8 per cent). Strain G1P8 was most prevalent (70 per cent) among infants aged 3.1-9 months, but strain G3P6 was most frequently identified among neonates < or = 3 months (50 per cent). While strain G1P8 was circulating across the country at this time, strain G3P6 was regionally most identified (77.8 per cent) in Southern Nigeria. The presence of untypeable VP4 gene in Nigeria was demonstrated. The occurance of mix infection genotype demonstrates the potential for reassortment events among different rotavirus genogroups in Nigeria. The epidemiological implications of these findings for rotavirus vaccine development and application in the country were discussed.

Molecular epidemiology of rotavirus in four provinces of Angola before vaccine introduction.

PubMed

Esteves, Aida; Nordgren, Johan; Pereira, Joana; Fortes, Filomeno; Dimbu, Rafael; Saraiva, Nilton; Mendes, Cristina; Istrate, Claudia

2016-09-01

Angola is a sub-Saharan country in southern Africa highly affected by diarrhoeal disease with limited epidemiological data regarding etiologic agents. This study was performed during 2012-2013, prior to rotavirus vaccine introduction, with the objective to detect and characterize the rotavirus strains circulating in four provinces of the country: Huambo, Luanda, Zaire, and Cabinda. A high rotavirus detection rate (35%, 117/334) was observed. G1 was the most common G-genotype (83.6%), whereas P[8] (50.9%) followed by P[6] (38.8%) were the most common P-types. G1P[8] was identified as the predominant combination (50%), followed by the unusual G1P[6] (29.3%). Strains such G2P[4], G8P[6], G9P[6], and G12P[6] were also found in lower frequencies (5.2-1.7%). The P[6] strains did not cluster in the phylogenetic trees according to their geographic origin or even the corresponding G-genotype, suggesting a limited number of recent introductions and extensive reassortment events. Our results represent the first report on rotavirus genotype profiles in Angola, showing a wide circulation of the unusual genotype G1P[6], and underline the importance of RV surveillance after the vaccine introduction. J. Med. Virol. 88:1511-1520, 2016. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Rotavirus genotypes in Malaysia and Universal rotavirus vaccination

PubMed Central

Lee, Way Seah; Lim, Benjamin Tze Ying; Chai, Pei Fan; Kirkwood, Carl D.; Lee, Jimmy Kok Foo

2012-01-01

Group A rotavirus (RV-A) genotypes isolated in Malaysia was studied to estimate the effectiveness of a universal RV-A vaccination in Malaysia. A simple mathematical model was used, with input from a two-year, two-center, prospective study on hospitalization of RV-A gastroenteritis (RVGE) in young children, published data on RV-A hospitalizations and genotypes, mortality on childhood GE and published genotype-specific efficacy data on two RV-A vaccines. Assuming a 95% vaccine coverage, the overall projected effectiveness was 75.7 to 88.1% for Rotateq® and 78.7 to 90.6% for Rotarix® against RVGE-related hospitalizations. The projected annual reduction in RVGE-related deaths was 27 to 32 deaths (from 34 deaths) for Rotateq® and 28 to 32 deaths annually forRotarix®. A universal RV-A vaccine is efficacious in reducing RVGE-related hospitalizations and mortality in Malaysia. PMID:23022710

Emergence of Human G2P[4] Rotaviruses in the Post-vaccination Era in South Korea: Footprints of Multiple Interspecies Re-assortment Events.

PubMed

Thanh, Hien Dang; Tran, Van Trung; Lim, Inseok; Kim, Wonyong

2018-04-16

After the introduction of two global rotavirus vaccines, RotaTeq in 2007 and Rotarix in 2008 in South Korea, G1[P8] rotavirus was the major rotavirus genotype in the country until 2012. However, in this study, an emergence of G2P[4] as the dominant genotype during the 2013 to 2015 season has been reported. Genetic analysis revealed that these viruses had typical DS-1-like genotype constellation and showed evidence of re-assortment in one or more genome segments, including the incorporation of NSP4 genes from strains B-47/2008 from a cow and R4/Haryana/2007 from a buffalo in India, and the VP1 and VP3 genes from strain GO34/1999 from a goat in Bangladesh. Compared to the G2 RotaTeq vaccine strain, 17-24 amino acid changes, specifically A87T, D96N, S213D, and S242N substitutions in G2 epitopes, were observed. These results suggest that multiple interspecies re-assortment events might have contributed to the emergence of G2P[4] rotaviruses in the post-vaccination era in South Korea.

Rotavirus vaccine and health-care utilization for rotavirus gastroenteritis in Tsu City, Japan

PubMed Central

Kamiya, Hajime; Suga, Shigeru; Nagao, Mizuho; Ichimi, Ryoji; Fujisawa, Takao; Umemoto, Masakazu; Tanaka, Takaaki; Ito, Hiroaki; Tanaka, Shigeki; Ido, Masaru; Taniguchi, Koki; Ihara, Toshiaki; Nakano, Takashi

2016-01-01

Background Rotavirus vaccines were introduced in Japan in November 2011. We evaluated the subsequent reduction of the health-care burden of rotavirus gastroenteritis. Methods We conducted active surveillance for rotavirus gastroenteritis among children under 5 years old before and after the vaccine introduction. We surveyed hospitalization rates for rotavirus gastroenteritis in children in Tsu City, Mie Prefecture, Japan, from 2007 to 2015 and surveyed the number of outpatient visits at a Tsu City clinic from 2010 to 2015. Stool samples were obtained for rotavirus testing and genotype investigation. We assessed rotavirus vaccine coverage for infants living in Tsu City. Results In the pre-vaccine years (2007–2011), hospitalization rates for rotavirus gastroenteritis in children under 5 years old were 5.5, 4.3, 3.1 and 3.9 cases per 1000 person-years, respectively. In the post-vaccine years (2011–2015), the rates were 3.0, 3.5, 0.8 and 0.6 cases per 1000 person-years, respectively. The hospitalization rate decreased significantly in the 2013–2014 and 2014–2015 seasons compared to the average of the seasons before vaccine introduction (P < 0.0001). In one pre-vaccine year (2010–2011), the number of outpatient visits due to the rotavirus infection was 66. In the post-vaccine years (2011–2015), the numbers for each season was 23, 23, 7 and 5, respectively. The most dominant rotavirus genotype shifted from G3P[8] to G1P[8] and to G2P[4]. The coverage of one dose of rotavirus vaccine in Tsu City was 56.5% in 2014. Conclusion After the vaccine introduction, the hospitalization rates and outpatient visits for rotavirus gastroenteritis greatly decreased. PMID:28246579

Rotavirus seasonality in urban sewage from Argentina: effect of meteorological variables on the viral load and the genetic diversity.

PubMed

Barril, P A; Fumian, T M; Prez, V E; Gil, P I; Martínez, L C; Giordano, M O; Masachessi, G; Isa, M B; Ferreyra, L J; Ré, V E; Miagostovich, M; Pavan, J V; Nates, S V

2015-04-01

In Argentina, the rotavirus disease exhibits seasonal variations, being most prevalent in the fall and winter months. To deepen the understanding of rotavirus seasonality in our community, the influence of meteorological factors on the rotavirus load and the genetic diversity in urban raw sewage from Córdoba city, Argentina were evaluated. Wastewater samples were collected monthly during a three-year study period and viral particles were concentrated by polyethylene glycol precipitation. RT-nested PCR was applied for rotavirus detection, and VP7/VP4 characterization and real-time PCR for rotavirus quantification. Both molecular techniques showed relatively similar sensitivity rates and revealed rotavirus presence in urban wastewater in cold and warm seasons, indicating its circulation in the local community all year round. However, a slight trend for rotavirus circulation was noted by real-time PCR in the fall and winter seasons, showing a significantly higher peak of rotavirus concentration at mean temperatures lower than 18°C and also higher, although not statistically different during drier weather. VP7 and VP4 gene characterization showed that G1 and P[8] genotypes were dominant, and temporal variations in genotype distribution were not observed. Rotavirus spread is complex and our results point out that weather factors alone cannot explain the seasonal quantitative pattern of the rotavirus disease. Therefore, alternative transmission routes, changes in human behavior and susceptibility, and the stability and survivability of the virus might all together contribute to the seasonality of rotavirus. The results obtained here provide evidence regarding the dynamics of rotavirus circulation and maintenance in Argentina. Copyright © 2015 Elsevier Inc. All rights reserved.

The molecular epidemiology of bovine rotaviruses circulating in Iran: a two-year study.

PubMed

Pourasgari, Farzaneh; Kaplon, Jérôme; Karimi-Naghlani, Shahla; Fremy, Céline; Otarod, Vahid; Ambert-Balay, Katia; Mirjalili, Ali; Pothier, Pierre

2016-12-01

Bovine group A rotavirus (bovine RVA) is recognized as a major cause of severe gastroenteritis in newborn calves. The purpose of this study was to estimate the prevalence and identify the genotypes of circulating bovine RVA in newborn diarrheic calves. Two hundred fifty-three stool samples of diarrheic calves up to 1 month old were collected from 42 industrial dairy farms in two Iranian provinces during March 2010 to February 2012. All collected samples were screened for the presence of bovine RVA by RT-PCR, and the G and P genotypes were determined by semi-nested multiplex RT-PCR assay. The results of RT-PCR indicated that 49.4 % (125 out of 253) of the samples were positive for bovine RVA. The G and P genotyping of a subset of positive samples (n = 85) by semi-nested multiplex RT-PCR revealed that G6 (55.3 %) and G10 (43.5 %) and P[5] (51.8 %) and P[11] (27 %) were the most prevalent G and P genotypes, respectively. G6P[5] was the dominant genotype (35.3 %), followed by G10P[5], G10P[11] and G6P[11], with prevalence rates of 16.5 %, 15.3 % and 10.6 %, respectively. Sequence analysis of 20 VP7 and four VP4 genes showed highest nucleotide sequence identity with the corresponding genes of strains RVA/Cow-tc/GBR/UK/1973/G6P7[5] and RVA/Cow-tc/USA/B223/XXXX/G10P[11]. The results of this study reveal the diversity of G and P genotypes in bovine RVA samples from diarrheic Iranian calves and expands our knowledge of bovine RVA infections in the Middle East. These results also highlight the importance of producing of an effective rotavirus vaccine and its inclusion in the national cattle immunization program.

Diversity of rotavirus strains circulating in children under 5 years of age admitted to hospital for acute gastroenteritis in Morocco, June 2006 to May 2009.

PubMed

Benhafid, Mohammed; Elomari, Nezha; Elqazoui, Maria; Meryem, Azzouzi Idrissi; Rguig, Ahmed; Filali-Maltouf, Abdelkarim; Elaouad, Rajae

2013-02-01

Rotavirus vaccine was introduced in Morocco during 2010. In anticipation of introducing rotavirus vaccines, the Ministry of Health in Morocco established a rotavirus surveillance network in June 2006 at four hospitals in Morocco to obtain baseline data on rotavirus disease burden and prevalent strains. From June 2006 to May 2009, stool samples were collected from children under 5 years of age admitted for diarrhea to four sentinel hospitals serving different regions of Morocco. Rotaviruses were detected in stools using enzyme immunoassay, then genotyped by reverse-transcriptase polymerase chain reaction. Samples with adequate stool in which the P or G types could not be determined by RT-PCR were subjected to nucleotide sequence analysis. Overall, 42% (579 of 1,388) of the stools samples tested were positive for rotavirus. Genotyping of 548 (95%) samples demonstrated that G1P[8] (55%) was the most prevalent strain, followed by G9P[8] (11.3%), G2P[4] (9.1%), G4P[8] (0.9%), and G3P[8] (0.4%). Several other strains were identified including G1P[4] (0.2%), G1P[6] (0.9%), G2P[6] (4.3%), G2P[8] (0.2%), G3P[6] (0.4%), G3P[4] (0.2%), and G9P[6] (0.2%). A high prevalence of mixed infections was found (15% of all samples) of which G1G2P[8] (4%) and G1G3P[8] (3.6%) accounted for the majority. Considerable diversity of rotavirus genotypes was present among strains circulating in Morocco prior to the introduction of the vaccine. This study highlighted the need for maintaining active surveillance to monitor changes in rotavirus disease burden and strain dynamics and to detect changes over time that could impact the effectiveness of the vaccination program. Copyright © 2012 Wiley Periodicals, Inc.

Rotavirus Strain Trends During the Postlicensure Vaccine Era: United States, 2008–2013

PubMed Central

Bowen, Michael D.; Mijatovic-Rustempasic, Slavica; Esona, Mathew D.; Teel, Elizabeth N.; Gautam, Rashi; Sturgeon, Michele; Azimi, Parvin H.; Baker, Carol J.; Bernstein, David I.; Boom, Julie A.; Chappell, James; Donauer, Stephanie; Edwards, Kathryn M.; Englund, Janet A.; Halasa, Natasha B.; Harrison, Christopher J.; Johnston, Samantha H.; Klein, Eileen J.; McNeal, Monica M.; Moffatt, Mary E.; Rench, Marcia A.; Sahni, Leila C.; Selvarangan, Rangaraj; Staat, Mary A.; Szilagyi, Peter G.; Weinberg, Geoffrey A.; Wikswo, Mary E.; Parashar, Umesh D.; Payne, Daniel C.

2016-01-01

Background Group A rotaviruses (RVA) are a significant cause of pediatric gastroenteritis worldwide. The New Vaccine Surveillance Network (NVSN) has conducted active surveillance for RVA at pediatric hospitals and emergency departments at 3–7 geographically diverse sites in the United States since 2006. Methods Over 6 consecutive years, from 2008 to 2013, 1523 samples from NVSN sites that were tested positive by a Rotaclone enzyme immunoassay were submitted to the Centers for Disease Control and Prevention for genotyping. Results In the 2009, 2010, and 2011 seasons, genotype G3P[8] was the predominant genotype throughout the network, with a 46%–84% prevalence. In the 2012 season, G12P[8] replaced G3P[8] as the most common genotype, with a 70% prevalence, and this trend persisted in 2013 (68.0% prevalence). Vaccine (RotaTeq; Rotarix) strains were detected in 0.6%–3.4% of genotyped samples each season. Uncommon and unusual strains (eg, G8P[4], G3P[24], G2P[8], G3P[4], G3P[6], G24P[14], G4P[6], and G9P[4]) were detected sporadically over the study period. Year, study site, and race were found to be significant predictors of genotype. Conclusions Continued active surveillance is needed to monitor RVA genotypes in the United States and to detect potential changes since vaccine licensure. PMID:27302190

Isolation and characterization of a novel type of rotavirus species A in sugar gliders (Petaurus breviceps).

PubMed

Okadera, Kota; Abe, Masako; Ito, Naoto; Mitake, Hiromichi; Okada, Kazuma; Nakagawa, Kento; Une, Yumi; Tsunemitsu, Hiroshi; Sugiyama, Makoto

2016-05-01

To estimate the risk of interspecies transmission of rotavirus species A (RVA) from exotic pets to other mammalian species, the prevalence of RVA in sugar gliders (Petaurus breviceps) was investigated. RVAs were detected in 10 of 44 sugar gliders by reverse transcription (RT)-semi-nested PCR. These viruses were classified as G27P[3] and G27P[36] genotypes, with G27 and P[36] being new genotypes as assigned by the Rotavirus Classification Working Group. To characterize sugar glider RVA in detail, one strain, RVA/SugarGlider-tc/JPN/SG385/2012/G27P[36] (SG385-tc), was isolated. All of the genes of the strain were classified as new genotypes (G27-P[36]-I19-R10-C10-M9-A20-N11-T13-E17-H12). The enterotoxin domain in NSP4, which is important for the induction of diarrhoea, was conserved between SG385-tc and previously reported mammalian strains, suggesting the potential of sugar glider RVA to cause diarrhoea in mammalian species. In fact, seven out of nine suckling mice inoculated orally with 3.9 × 104 f.f.u. of strain SG385-tc had diarrhoea and the 50 % diarrhoea-inducing dose (DD50) of strain SG385-tc in suckling mice was 1.2 × 104 f.f.u. Our findings suggest that sugar glider RVA is infective to and possibly pathogenic in other mammalian species.

Molecular epidemiology of Rotavirus A, causing acute gastroenteritis hospitalizations among children in Nha Trang, Vietnam, 2007-2008: Identification of rare G9P[19] and G10P[14] strains.

PubMed

Do, Loan Phuong; Kaneko, Miho; Nakagomi, Toyoko; Gauchan, Punita; Agbemabiese, Chantal Ama; Dang, Anh Duc; Nakagomi, Osamu

2017-04-01

Rotavirus A (RVA) causes acute diarrhea in children as well as animals. As part of a cross-sectional study of children less than 5 years of age hospitalized for acute diarrhea in Vietnam during a 15-month period (2007-2008), 322 (43.5%) of 741 fecal specimens contained RVA with 92% either G1P[8] or G3P[8]. This study was undertaken to further characterize strains that remained untypeable to complete the G and P genotypes of the 322 rotavirus-positive specimens. While 307 (95.3%) strains possessed the common human RVA genotypes: G1P[8] (45.0%), G2P[4] (2.8%), G3P[8] (46.9%), and G9P[8] (0.6%), sequencing of initially untypeable specimens revealed the presence of two unusual strains designated NT0073 and NT0082 possessing G9P[19] and G10P[14], respectively. The genotype constellation of NT0073 (G9-P[19]-I5-R1-C1-M1-A8-N1-T7-E1-H1) and the phylogenetic trees suggested its origin as a porcine RVA strain causing diarrhea in a 24-month-old girl whereas the genotype constellation of NT0082 (G10-P[14]-I2-R2-C2-M2-A3-N2-T6-E2-H3) and the phylogenetic trees suggested its origin as an RVA strain of artiodactyl origin (such as cattle, sheep and goats) causing diarrhea in a 13-month-old boy. This study showed that RVA strains of animal host origin were not necessarily attenuated in humans. A hypothesis may be postulated that P[19] and P[14] VP4 spike proteins helped the virus to replicate in the human intestine but that efficient onward human-to-human spread after crossing the host species barrier may require the virus to obtain some additional features as there was no evidence of widespread transmission with the limited sampling performed over the study period. J. Med. Virol. 89:621-631, 2017. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Genotypic and epitope characteristics of group A porcine rotavirus strains circulating in Canada.

PubMed

Naseer, Omer; Jarvis, Matthew C; Ciarlet, Max; Marthaler, Douglas G

2017-07-01

Surveillance of Rotavirus A (RVA) infections in North America swine populations are limited and not performed over a significant time period to properly assess the diversity of RVA strains in swine. The VP7 (G) and VP4 (P) genes of 32 Canadian RVA strains, circulating between 2009 and 2015 were sequenced, identifying the G3P[13], G5P[7], G9P[7], G9[13], and G9[19] genotype combinations. The Canadian RVA strains were compared to the RVA strains present in the swine ProSystems RCE rotavirus vaccine. The comparison revealed multiple amino acid differences in the G and P antigenic epitopes, regardless of the G and P genotypes but specifically in the Canadian G3, P[13] and P[19] genotypes. Our study further contributes to the characterization of RVA's evolution and disease mitigation among swine, which may optimize target vaccine design, thereby minimizing RVA disease in this economically important animal population. Copyright © 2017 Elsevier Inc. All rights reserved.

Association of rotavirus strains and severity of gastroenteritis in Indian children.

PubMed

Saluja, Tarun; Dhingra, Mandeep S; Sharma, Shiv D; Gupta, Madhu; Kundu, Ritabrata; Kar, Sonali; Dutta, Ashok K; Silveira, Maria D P; Singh, Jai V; Kamath, Veena G; Chaudhary, Anurag; Rao, Venkateswara; Ravi, Mandyam D; Murthy, Kesava; Arumugam, Rajesh; Moureau, Annick; Prasad, Rajendra; Patnaik, Badri N

2017-03-04

Rotavirus is the leading cause of severe and dehydrating diarrhea in children aged under 5 years. We undertook this hospital-based surveillance study to examine the possible relationship between the severity of diarrhea and the various G-group rotaviruses circulating in India. Stool samples (n = 2,051) were systematically collected from 4,711 children aged <5 years admitted with severe acute gastroenteritis to 12 medical school centers from April 2011 to July 2012. Rotavirus testing was undertaken using a commercially available enzyme immunoassay kit for the rotavirus VP6 antigen (Premier Rotaclone Qualitative ELISA). Rotavirus positive samples were genotyped for VP7 and VP4 antigens by reverse-transcription polymerase chain reaction at a central laboratory. Of the stool samples tested for rotavirus antigen, 541 (26.4%) were positive for VP6 antigen. Single serotype infections from 377 stool samples were compared in terms of gastroenteritis severity. Among those with G1 rotavirus infection, very severe diarrhea (Vesikari score ≥ 16) was reported in 59 (33.9%) children, severe diarrhea (Vesikari score 11-15) in 104 (59.8%), moderate (Vesikari score 6-10) and mild diarrhea (Vesikari score 0-5) in 11 (6.3%). Among those with G2 infection, very severe diarrhea was reported in 26 (27.4%) children, severe diarrhea in 46 (48.4%), and moderate and mild diarrhea in 23 (24.2 %). Among those with G9 infection, very severe diarrhea was reported in 47 (54.5%) children, severe diarrhea in 29 (33.6%), and moderate and mild diarrhea in 10 (11.9%). Among those with G12 infection, very severe diarrhea was reported in 9 (40.9%) children and severe diarrhea in 13 (59.1%). The results of this study indicate some association between rotavirus serotypes and severity of gastroenteritis.

Real-World Effectiveness of Pentavalent Rotavirus Vaccine Among Bedouin and Jewish Children in Southern Israel.

PubMed

Leshem, Eyal; Givon-Lavi, Noga; Tate, Jacqueline E; Greenberg, David; Parashar, Umesh D; Dagan, Ron

2016-05-01

Pentavalent rotavirus vaccine (RV5) was introduced into the Israeli National Immunization Program in January 2011. We determined RV5 vaccine effectiveness (VE) in southern Israel, a region characterized by 2 distinct populations: Bedouins living in a low- to middle-income, semirural setting, and Jews living in a high-income, urban setting. We enrolled vaccine-eligible children who visited the emergency department (ED) or were hospitalized due to acute gastroenteritis (AGE) during the first 3 rotavirus seasons after RV5 vaccine introduction (2011-2013). Fecal specimens were tested for rotavirus by enzyme immunoassay and genotyped. Vaccination among laboratory-confirmed rotavirus cases was compared with rotavirus-negative AGE controls. Regression models were used to calculate VE estimates by age, clinical setting, and ethnicity. Of 515 enrolled patients, 359 (70%) were Bedouin. Overall, 185 (36%) patients were rotavirus positive; 79 of 119 (66%) were G1P[8] genotype. The adjusted VE for a full 3-dose course of RV5 against ED visit or hospitalization was 63% (95% confidence interval [CI], 38%-78%). RV5 provided G1P[8] genotype-specific effectiveness of 78% (95% CI, 58%-88%). By age, RV5 VE was 64% (95% CI, 21%-84%) and 71% (95% CI, 39%-86%) among children aged 6-11 months and 12-23 months, respectively. By clinical setting, RV5 VE was 59% (95% CI, 23%-78%) against hospitalization, and 67% (95% CI, 11%-88%) against ED visit. The adjusted VE of a full RV5 course among Bedouin children was 62% (95% CI, 29%-79%). RV5 significantly protected against rotavirus-associated ED visits and hospitalizations in a diverse population of vaccine-eligible children living in southern Israel. Published by Oxford University Press for the Infectious Diseases Society of America 2016. This work is written by (a) US Government employee(s) and is in the public domain in the US.

Sequence analysis of VP7 and VP4 genes of G1P[8] rotaviruses circulating among diarrhoeic children in Pune, India: a comparison with Rotarix and RotaTeq vaccine strains.

PubMed

Kulkarni, Ruta; Arora, Ritu; Arora, Rashmi; Chitambar, Shobha D

2014-08-11

The G1P[8] rotaviruses are a common cause of rotavirus diarrhoea among children in India. Two rotavirus vaccines licensed in India, Rotarix and RotaTeq, contain strains with G1 and P[8] genotypes. A comparative analysis of these genotypes in the live rotavirus vaccines with circulating rotavirus strains is essential for assessment of rotavirus diversity. G1P[8] strains detected during rotavirus surveillance among diarrhoeic children hospitalized in Pune in 1992-1993 and 2006-2008, were included in the study. Amplification, sequencing and phylogenetic analysis of the VP7 and VP4 genes were carried out for identification of the G1 and P[8] lineages, respectively. Antigenic epitopes of VP7 and VP4 encoded proteins were compared to determine the differences between the G1P[8] strains from Pune and the vaccine strains. G1-Lineage 1, P[8]-Lineage 3 strains were predominant in Pune during 1992-1993 and 2006-2008. Strains of G1-Lineage 2, P[8]-Lineage 3 and G1-Lineage 1, P[8]-Lineage 4 were detected at low levels during 2006-2008. The G1-Lineage 1, P[8]-Lineage 3 strains showed up to eight amino acid changes, each in the VP7 and VP4 epitopes, with respect to the Rotarix vaccine strain (G1-Lineage 2, P[8]-Lineage 1) and the G1 (Lineage-3) and P[8] (Lineage 2) components of the RotaTeq vaccine. The G1-Lineage 2 strains were closer to both vaccine strains with no or only two amino acid substitutions in the VP7 epitopes. The divergent P[8]-Lineage 4 (OP354-like) strains showed fourteen and fifteen amino acid differences, with Rotarix and RotaTeq vaccine strains, respectively, in the VP4 epitopes. The differences between the G1P[8] strains in Pune and the G1 and P[8] components of the vaccine strains need to be described for appropriate evaluation of vaccine shedding. Continuous monitoring of the G1P[8] subgenotypic lineages would be necessary to study any long term impact of vaccine use on G1P[8] strain evolution. Copyright © 2014. Published by Elsevier Ltd.

Molecular analysis of group A rotaviruses detected in hospitalized children from Rawalpindi, Pakistan during 2014.

PubMed

Umair, Massab; Abbasi, Bilal Haider; Nisar, Nadia; Alam, Muhammad Masroor; Sharif, Salmaan; Shaukat, Shahzad; Rana, Muhammad Suleman; Khurshid, Adnan; Mujtaba, Ghulam; Aamir, Uzma Bashir; Zaidi, Syed Sohail Zahoor

2017-09-01

As a part of strategy to control diarrheal diseases, World Health Organization (WHO) recommends to include rotavirus vaccines in national immunization programs. Sentinel surveillance networks have been established to monitor rotavirus disease burden and genotype distribution in both pre and post vaccine era in many countries. Unfortunately, due to lack of proper surveillance programs, data on rotavirus disease burden and genotype distribution from Pakistan is scarce. We investigated 502 stool samples from children (<5years) hospitalized due to gastroenteritis in Rawalpindi, Pakistan during 2014 for the presence of group A rotavirus (RVA) and its genotypic diversity. Among 147 ELISA positive samples, 131 were successfully genotyped for RVA. Common G types detected were G1 (23.6%), followed by G3 (22.9%), G12 (19.8%), G2 (19.08%) and G9 (9.9%). The most common P-type was P[8] (41.2%), followed by P[6] (29%) and P[4] (28.24%). G3P[8] (17.55%) was the most prevalent genotype combination followed by G12P[6] (16.7%), G2P[4] (15.2%) and G1P[8] (14.5%). Mixed infection of rotavirus G-P types was also observed in 6% of samples. Phylogenetic analysis of VP7 and VP4 genes of Pakistani strains showed that G1, G2, G9 and P[4], P[6], P[8] were closely related to strains circulating worldwide as well as previously reported strains from Pakistan. Pakistani G12P[8] strains NIH-BBH-3981 and NIH-BBH-4003 belonged to lineage 3 cluster 3a along with strains from USA and Italy whereas G12P[6] strains NIH-BBH-3978, NIH-BBH-4052 and NIH-BBH-4444 were closely related to strains from Italy, Thailand, United Kingdom and with previously reported G12 strains from Pakistan within lineage 3 cluster 3b. This pre-vaccination data supports the need for RVA vaccine inclusion at our national level and will be helpful in assessing the effect of vaccination on RVA genotype diversity due to vaccine selection pressure once post-vaccination data becomes available. Copyright © 2017 Elsevier B.V. All rights reserved.

Observations on the epidemiology of rotavirus infection among hospitalized children younger than 5 years in 2 Ukrainian hospitals, 2007-2015.

PubMed

Chernyshova, Liudmyla I; Radionova, Nataliya M; Demchyshyna, Iryna V; Kotlik, Liudmyla S; Sadkova, Oleksandra B; Samoilovich, Elena O; Semeiko, Galina V; Daniels, Danni S; Cohen, Adam L; Aliabadi, Negar

2017-11-29

Acute gastroenteritis remains a burden among children under 5 years of age. Ukraine joined the World Health Organization's Global Rotavirus Surveillance Network in 2006, with a goal of providing accurate rotavirus burden data to aid policy makers in planning for rotavirus vaccine introduction. This analysis describes rotavirus epidemiology among Ukrainian children enrolled in Kyiv and Odesa, two large Ukrainian cities. Children 0-59 months of age hospitalized for acute gastroenteritis at 2 sentinel sites in Kyiv and Odesa were enrolled into the active, prospective surveillance program. In Odesa, the surveillance period was during 2007-2015 and in Kyiv, it was during 2011-2015. Acute gastroenteritis was defined as 3 or more episodes of diarrhea per day during a 24 h period, with symptom duration before hospitalization not exceeding 7 days. Guardians of enrolled children completed a questionnaire including demographic, clinical and treatment information. Each child provided a stool specimen within 2 days of hospitalization. Stools were tested for rotavirus using ProSpecT™ Rotavirus Kit (Oxoid Ltd., Great Britain), and positive specimens were genotyped. Descriptive data are reported, as well as comparison of demographic, clinical and treatment data among rotavirus positive and negative children. During July 2007-June 2015, 12,350 children were enrolled in the surveillance programs and had stool specimens collected and tested for rotavirus. Overall, rotavirus infection was diagnosed in 5412/12350 (44%) of children, 929/1734 (54%) of those in Kyiv and 4483/10616 (42%) in Odesa. Rotavirus infections peaked during the winter months. Children with rotavirus acute gastroenteritis displayed more severe clinical symptoms than those without rotavirus. Predominant genotypes identified included G1P[8], G2P[4], G3 P[8], G4 P[8] and G9 P[8]. Active surveillance of acute gastroenteritis in hospitalized children younger 5 years in two large Ukrainian cities reveals a significant burden of rotavirus infection. These data provide scientific justification for incorporating rotavirus vaccines into the Ukrainian national immunization schedule. Published by Elsevier Ltd.

Rotavirus Strain Trends During the Postlicensure Vaccine Era: United States, 2008-2013.

PubMed

Bowen, Michael D; Mijatovic-Rustempasic, Slavica; Esona, Mathew D; Teel, Elizabeth N; Gautam, Rashi; Sturgeon, Michele; Azimi, Parvin H; Baker, Carol J; Bernstein, David I; Boom, Julie A; Chappell, James; Donauer, Stephanie; Edwards, Kathryn M; Englund, Janet A; Halasa, Natasha B; Harrison, Christopher J; Johnston, Samantha H; Klein, Eileen J; McNeal, Monica M; Moffatt, Mary E; Rench, Marcia A; Sahni, Leila C; Selvarangan, Rangaraj; Staat, Mary A; Szilagyi, Peter G; Weinberg, Geoffrey A; Wikswo, Mary E; Parashar, Umesh D; Payne, Daniel C

2016-09-01

Group A rotaviruses (RVA) are a significant cause of pediatric gastroenteritis worldwide. The New Vaccine Surveillance Network (NVSN) has conducted active surveillance for RVA at pediatric hospitals and emergency departments at 3-7 geographically diverse sites in the United States since 2006. Over 6 consecutive years, from 2008 to 2013, 1523 samples from NVSN sites that were tested positive by a Rotaclone enzyme immunoassay were submitted to the Centers for Disease Control and Prevention for genotyping. In the 2009, 2010, and 2011 seasons, genotype G3P[8] was the predominant genotype throughout the network, with a 46%-84% prevalence. In the 2012 season, G12P[8] replaced G3P[8] as the most common genotype, with a 70% prevalence, and this trend persisted in 2013 (68.0% prevalence). Vaccine (RotaTeq; Rotarix) strains were detected in 0.6%-3.4% of genotyped samples each season. Uncommon and unusual strains (eg, G8P[4], G3P[24], G2P[8], G3P[4], G3P[6], G24P[14], G4P[6], and G9P[4]) were detected sporadically over the study period. Year, study site, and race were found to be significant predictors of genotype. Continued active surveillance is needed to monitor RVA genotypes in the United States and to detect potential changes since vaccine licensure. Published by Oxford University Press for the Infectious Diseases Society of America 2016. This work is written by (a) US Government employee(s) and is in the public domain in the US.

Epidemiology of rotavirus A diarrhea in Chókwè, Southern Mozambique, from February to September, 2011.

PubMed

Langa, Jerónimo S; Thompson, Ricardo; Arnaldo, Paulo; Resque, Hugo Reis; Rose, Tatiana; Enosse, Sonia M; Fialho, Alexandre; de Assis, Rosane Maria Santos; da Silva, Marcelle Figueira Marques; Leite, José Paulo Gagliardi

2016-10-01

Acute diarrhea disease caused by Rotaviruses A (RVA) is still the leading cause of morbidity and mortality in children ≤5 years old in developing countries. An exploratory cross-sectional study was conducted between February and September, 2011 to determine the proportion of acute diarrhea caused by RVA. A total of 254 stool specimens were collected from children ≤5 years old with acute diarrhea, including outpatients (222 children) and inpatients (32 children), in three local health centers in Chókwè District, Gaza Province, South of Mozambique. RVA antigens were detected using enzyme immunoassay (EIA); the RVA G (VP7) and P (VP4) genotypes were determined by RT-PCR or analysis sequencing. Sixty (24%) out of 254 fecal specimens were positive for RVA by EIA; being 58 (97%) from children ≤2 years of age. RVA prevalence peaks in June and July (coldest and drier months) and the G[P] binary combination observed were G12P[8] (57%); G1P[8] (9%); G12P[6] (6%); and 2% for each of the following genotypes: G1P[6], G2P[6] G4P[6], and G9P[8]. Non-Typeable (NT) G and/or P genotypes were observed as follows: G12P [NT] (6%); G1P [NT], G3P[NT] and GNTP[NT] (4%). Considering the different GP combinations, G12 represented 67% of the genotypes. This is the first data showing the diversity of RVA genotypes in Mozambique highlighting the epidemiological importance of these viruses in acute diarrhea cases in children ≤2 years old. In addition, these findings will provide a baseline data before the introduction of the RVA monovalent (Rotarix(®) ) vaccine in the National Immunization Program in September 2015. J. Med. Virol. 88:1751-1758, 2016. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Detection of rotavirus and other enteropathogens in children hospitalized with acute gastroenteritis in Havana, Cuba.

PubMed

Ribas, María de Los Angeles; Tejero, Yahisel; Cordero, Yanislet; de Los Angeles León, María; Rodriguez, Misladys; Perez-Lastre, Jorge; Triana, Thelma; Guerra, Mabel; Ayllón, Lucía; Escalante, Gladys; Hadad, Jorge

2015-08-01

The aim of the study was to diagnose infections with rotavirus and other enteric pathogens in children under five years old with acute gastroenteritis and to identify the most common epidemiological and clinical characteristics of these pathogens. The study was conducted using 110 stool samples from the same number of children under five years old who were inpatients at three paediatric hospitals in Havana, Cuba, between October and December 2011. The samples were tested for rotavirus and other enteric pathogens using traditional and molecular microbiological methods. Pathogens were detected in 85 (77.3 %) of the children. Rotavirus was the most commonly found, appearing in 54.5 % of the children, followed by bacteria (29 %) and parasites (10.9 %). Other viral pathogens detected included adenovirus (6.4 %) and astrovirus (3.6 %). In rotavirus-positives cases, at least one other pathogen was detected, usually a bacterium (26.6 %). More than three episodes of watery diarrhea in 24 hours were observed in 78.3 % of the cases. Dehydration was found in 30 (50 %) rotavirus-positive children, of whom seven (11.6 %) were transferred to an intensive care unit due to complications of metabolic acidosis. Rotavirus was most commonly observed among children under 12 months old (65 %). The highest incidence of infection occurred in children who were under the care of a relative at home (78.3 %), had not been breastfed (65 %), or had been breastfed for less than six months (28.3 %). The genotype combinations most frequently found were G9P8 (28.3 %) and G1P8 (10 %). This study demonstrates the presence of rotavirus and other enteric pathogens as causes of gastroenteritis in hospitalized infants and young children in Cuba.

Detection of Rotavirus Genotypes in Korea 5 Years after the Introduction of Rotavirus Vaccines.

PubMed

Chung, Ju-Young; Kim, Min-Sung; Jung, Tae Woong; Kim, Seong Joon; Kang, Jin-Han; Han, Seung Beom; Kim, Sang Yong; Rhim, Jung Woo; Kim, Hwang-Min; Park, Jae Hong; Jo, Dae Sun; Ma, Sang Hyuk; Jeong, Hye-Sook; Cheon, Doo-Sung; Kim, Jong-Hyun

2015-10-01

Rotavirus (RV) is one of the most important viral etiologic agents of acute gastroenteritis (AGE) in children. Although effective RV vaccines (RVVs) are now used worldwide, novel genotypes and outbreaks resulting from rare genotype combinations have emerged. This study documented RV genotypes in a Korean population of children with AGE 5 yr after the introduction of RVV and assessed potential genotype differences based on vaccination status or vaccine type. Children less than 5-yr-old diagnosed with AGE between October 2012 and September 2013 admitted to 9 medical institutions from 8 provinces in Korea were prospectively enrolled. Stool samples were tested for RV by enzyme immunoassay and genotyped by multiplex reverse-transcription polymerase chain reaction. In 346 patients, 114 (32.9%) were RV-positive. Among them, 87 (76.3%) patients were infected with RV alone. Eighty-six of 114 RV-positive stool samples were successfully genotyped, and their combinations of genotypes were G1P[8] (36, 41.9%), G2P[4] (12, 14.0%), and G3P[8] (6, 7.0%). RV was detected in 27.8% of patients in the vaccinated group and 39.8% in the unvaccinated group (P=0.035). Vaccination history was available for 67 of 86 cases with successfully genotyped RV-positive stool samples; RotaTeq (20, 29.9%), Rotarix (7, 10.4%), unvaccinated (40, 59.7%). The incidence of RV AGE is lower in the RV-vaccinated group compared to the unvaccinated group with no evidence of substitution with unusual genotype combinations.

Group A rotavirus gastroenteritis: post-vaccine era, genotypes and zoonotic transmission.

PubMed

Luchs, Adriana; Timenetsky, Maria do Carmo Sampaio Tavares

2016-01-01

ABSTRACTThis article provides a review of immunity, diagnosis, and clinical aspects of rotavirus disease. It also informs about the changes in epidemiology of diarrheal disease and genetic diversity of circulating group A rotavirus strains following the introduction of vaccines. Group A rotavirus is the major pathogen causing gastroenteritis in animals. Its segmented RNA genome can lead to the emergence of new or unusual strains in human populations via interspecies transmission and/or reassortment events.RESUMOEste artigo fornece uma revisão sobre imunidade, diagnóstico e aspectos clínicos da doença causada por rotavírus. Também aponta as principais mudanças no perfil epidemiológico da doença diarreica e na diversidade genética das cepas circulantes de rotavírus do grupo A, após a introdução vacinal. O rotavírus do grupo A é o principal patógeno associado à gastroenterite em animais. Seu genoma RNA segmentado pode levar ao surgimento de cepas novas ou incomuns na população humana, por meio de transmissão entre espécies e eventos de rearranjo.

Detection of rotavirus species A, B and C in domestic mammalian animals with diarrhoea and genotyping of bovine species A rotavirus strains.

PubMed

Otto, Peter H; Rosenhain, Stefanie; Elschner, Mandy C; Hotzel, Helmut; Machnowska, Patrycja; Trojnar, Eva; Hoffmann, Kathrin; Johne, Reimar

2015-09-30

Rotaviruses (RVs) are a major cause of neonatal diarrhoea in humans and animals worldwide. In this study, 425 faecal samples were collected between 1999 and 2013 from diarrhoeic livestock and companion animals at different locations in Germany and tested for RVs. A previously published real-time RT-PCR assay was optimized for detection of a larger variety of RV species A (RVA) strains, and real-time RT-PCR assays for detection of RV species B (RVB) and C (RVC) were newly developed. The detection limits of the assays were 1.54×10(2), 3.95×10(2) and 3.60×10(3) genome copies for RVA, RVB and RVC, respectively. RVA was identified in 85.2% of bovine samples, 51.2% of porcine samples, 50.0% of feline samples, 43.2% of equine samples and 39.7% of canine samples. RVB was found in 3.0% of bovine samples, 2.7% of equine samples and 1.6% of porcine samples. RVC was detected in 31.0% of porcine samples, 21.7% of feline samples, 9.0% of canine samples and 6.0% of bovine samples. For genotyping, 101 RVA-positive bovine samples were further analysed by semi-nested RT-PCR. Genotype combination G6P[5] was most frequently detected (67.3% of samples), followed by G6P[11] (13.9%), G10P[5] (4.0%), G8P[11] (3.0%), G6P[1] (1.0%), and G10P[11] (1.0%). Mixed RVA infections were detected in 5.9% of samples; no or incomplete typing was possible in 4.0% of the samples. This first overview on RV species and RVA genotypes in diarrhoeic livestock and companion animals from Germany indicates a broad circulation of a large variety of RVs. Copyright © 2015 Elsevier B.V. All rights reserved.

Active, population-based surveillance for rotavirus gastroenteritis in Chinese children: Beijing Municipality and Gansu Province, China.

PubMed

Zhang, Jing; Liu, Haixia; Jia, Lei; Payne, Daniel C; Hall, Aron J; Xu, Ziqian; Gao, Zhiyong; Chang, Zhaorui; Jiang, Baoming; Parashar, Umesh D; Meng, Lei; Yu, Hongjie; Duan, Zhaojun

2015-01-01

Estimates of population-based incidence for rotavirus inpatient and outpatient visits, as well as their associated medical costs, can provide valuable information to assess the potential benefits of rotavirus vaccination. We conducted active surveillance for rotavirus gastroenteritis at 6 medical institutions for children younger than 5 years from July 2012 to June 2013 in Beijing Municipality and Gansu Province. We collected stool samples of diarrhea patients for testing rotavirus, and epidemiological, clinical and cost data. The proportion of rotavirus-positive for inpatient and outpatient visits from Beijing was 28.7% (138/481) and 19.4% (133/687); a statistically lower proportion than observed in Gansu among inpatient visits (45.2%, 245/542, P < 0.001) and among outpatient visits (28.8%, 66/229, P = 0.003), respectively. The G9P[8] genotype was most prevalent in Beijing (60.6%) and in Gansu (77.6%). The median Vesikari scale value was 16 for rotavirus inpatients and 15 for nonrotavirus inpatients. Population-based estimated rates of rotavirus-related hospitalizations were 14.4 (95% CI, 13-16) per 10,000 children, and the rate of rotavirus gastroenteritis in the outpatient setting was 149 (95% CI, 145-153) per 10,000 children younger than 5 years. The estimated total number of rotavirus-related inpatient visits were 3790 (95% CI, 2488-3827) cases and 29,101 (95% CI: 27,748-29,279) outpatient visits. The total cost of rotavirus infection was $1.4 million (95% CI, $0.9-1.4 million) for hospitalizations and $4.2 million (95% CI, $4.0-4.2 million) for outpatient visits per year in Beijing and Gansu. Rotavirus is the most common cause of severe acute gastroenteritis (AGE) in children younger than 5 years worldwide,accounting for an estimated 25 million clinic visits, 2 million hospitalizations and 453,000 deaths each year. In China, the world's most populous nation, surveillance at sentinel hospitals showed that approximately 48% of AGE hospitalizations among children younger than 5 years were attributed to rotavirus from 2003 to 2007, and 13,387 rotavirus deaths were estimated in China in 2002 alone.The Lanzhou lamb rotavirus vaccine, consisting of serotype G10P[12], was licensed in 2000 but is not included in the National Expanded Program of Immunization vaccine recommendations for Chinese children. License applications for new rotavirus vaccines (Rotarix, produced by GlaxoSmithKline Biologicals, and RotaTeq, produced by Merck and Company) have been submitted for administering these vaccines to Chinese infants [corrected].

The prevalence and genetic diversity of group A rotaviruses on pig farms in the Mekong Delta region of Vietnam

PubMed Central

Hong Anh, Pham; Carrique-Mas, Juan J.; Van Cuong, Nguyen; Hoa, Ngo Thi; Lam Anh, Nguyet; Duy, Do Tien; Hien, Vo Be; Vu Tra My, Phan; Rabaa, Maia A.; Farrar, Jeremy; Baker, Stephen; Bryant, Juliet E.

2014-01-01

Group A rotaviruses (ARoVs) are a common cause of severe diarrhea among children worldwide and the cause of approximately 45% of pediatric hospitalizations for acute diarrhea in Vietnam. ARoVs are known to cause significant economic losses to livestock producers by reducing growth performance and production efficiencies, however little is known about the implications of asymptomatic endemic circulation of ARoV. We aimed to determine the prevalence and predominant circulating genotypes of ARoVs on pig farms in a southern province of Vietnam. We found overall animal-level and farm-level prevalence of 32.7% (239/730) and 74% (77/104), respectively, and identified six different G types and 4 P types in various combinations (G2, G3, G4, G5, G9, G11 and P[6], P[13], P[23], and P[34]). There was no significant association between ARoV infection and clinical disease in pigs, suggesting that endemic asymptomatic circulation of ARoV may complicate rotavirus disease attribution during outbreaks of diarrhea in swine. Sequence analysis of the detected ARoVs suggested homology to recent human clinical cases and extensive genetic diversity. The epidemiological relevance of these findings for veterinary practitioners and to ongoing pediatric ARoV vaccine initiatives in Vietnam merits further study. PMID:24679960

Surveillance and molecular characterization of group A rotaviruses in Goroka, Papua New Guinea.

PubMed

Horwood, Paul Francis; Luang-Suarkia, Dagwin; Bebes, Sauli; Boniface, Karen; Datta, Siddhartha Sankar; Siba, Peter Max; Kirkwood, Carl Dunn

2012-12-01

In this study, we investigated the molecular epidemiology of group A rotaviruses in cases of acute gastroenteritis in Goroka, Papua New Guinea. From April 2008 through November 2010, 813 diarrheal stool samples were collected from children < 5 years of age hospitalized with acute gastroenteritis. Rotavirus antigen was detected in 31.2% of samples using a commercial enzyme-linked immunosorbent assay. Genotyping revealed the presence of the globally circulating strains G1P[8] (50.0%), G3P[8] (23.0%), and G2P[4] (8.2%). The globally emerging strains G9 and G12 were detected in 1.2% and 6.1% of samples, respectively. Mixed infections were detected in a high proportion of samples (11.9%), with 9.0% and 3.7% of samples displaying multiple G and P genotypes, respectively.

Neonatal Infection with G10P[11] Rotavirus Did Not Confer Protection against Subsequent Rotavirus Infection in a Community Cohort in Vellore, South India

PubMed Central

Banerjee, Indrani; Gladstone, Beryl Primrose; Le Fevre, Andrea M.; Ramani, Sasirekha; Iturriza-Gomara, Miren; Gray, James J.; Brown, David W.; Estes, Mary K.; Muliyil, Jaya Prakash; Jaffar, Shabbar; Kang, Gagandeep

2008-01-01

Background Various observational studies have suggested that neonatal rotavirus infection confers protection against diarrhea due to subsequent rotavirus infection. We examined the incidence of rotavirus infection and diarrhea during the first 2 years of life among children infected with the G10P[11] rotavirus strain during the neonatal period and those not infected with rotavirus. Methods Children were recruited at birth and were followed up at least twice weekly. Stool samples, collected every 2 weeks for surveillance and at each episode of diarrhea, were screened by enzyme-linked immunosorbent assay and were genotyped by polymerase chain reaction. Results Among 33 children infected neonatally with G10P[11] and 300 children not infected with rotavirus, there was no significant difference in the rates of rotavirus-positive diarrhea (rate ratio [RR], 1.05 [95% confidence interval {CI}, 0.61–1.79]), moderate or severe rotavirus-positive diarrhea (RR, 1.42 [95% CI, 0.73–2.78]), or asymptomatic rotavirus shedding (RR, 1.25 [95% CI, 0.85–1.83]). Conclusion Neonatal G10P[11] infection with a strain resembling a vaccine candidate did not confer protection against subsequent rotavirus infection or diarrhea of any severity in this setting. PMID:17262703

Analysis of the full genome of human group C rotaviruses reveals lineage diversification and reassortment.

PubMed

Medici, Maria Cristina; Tummolo, Fabio; Martella, Vito; Arcangeletti, Maria Cristina; De Conto, Flora; Chezzi, Carlo; Fehér, Enikő; Marton, Szilvia; Calderaro, Adriana; Bányai, Krisztián

2016-08-01

Group C rotaviruses (RVC) are enteric pathogens of humans and animals. Whole-genome sequences are available only for few RVCs, leaving gaps in our knowledge about their genetic diversity. We determined the full-length genome sequence of two human RVCs (PR2593/2004 and PR713/2012), detected in Italy from hospital-based surveillance for rotavirus infection in 2004 and 2012. In the 11 RNA genomic segments, the two Italian RVCs segregated within separate intra-genotypic lineages showed variation ranging from 1.9 % (VP6) to 15.9 % (VP3) at the nucleotide level. Comprehensive analysis of human RVC sequences available in the databases allowed us to reveal the existence of at least two major genome configurations, defined as type I and type II. Human RVCs of type I were all associated with the M3 VP3 genotype, including the Italian strain PR2593/2004. Conversely, human RVCs of type II were all associated with the M2 VP3 genotype, including the Italian strain PR713/2012. Reassortant RVC strains between these major genome configurations were identified. Although only a few full-genome sequences of human RVCs, mostly of Asian origin, are available, the analysis of human RVC sequences retrieved from the databases indicates that at least two intra-genotypic RVC lineages circulate in European countries. Gathering more sequence data is necessary to develop a standardized genotype and intra-genotypic lineage classification system useful for epidemiological investigations and avoiding confusion in the literature.

Group A Human Rotavirus Genomics: Evidence that Gene Constellations Are Influenced by Viral Protein Interactions▿ †

PubMed Central

Heiman, Erica M.; McDonald, Sarah M.; Barro, Mario; Taraporewala, Zenobia F.; Bar-Magen, Tamara; Patton, John T.

2008-01-01

Group A human rotaviruses (HRVs) are the major cause of severe viral gastroenteritis in infants and young children. To gain insight into the level of genetic variation among HRVs, we determined the genome sequences for 10 strains belonging to different VP7 serotypes (G types). The HRVs chosen for this study, D, DS-1, P, ST3, IAL28, Se584, 69M, WI61, A64, and L26, were isolated from infected persons and adapted to cell culture to use as serotype references. Our sequencing results revealed that most of the individual proteins from each HRV belong to one of three genotypes (1, 2, or 3) based on their similarities to proteins of genogroup strains (Wa, DS-1, or AU-1, respectively). Strains D, P, ST3, IAL28, and WI61 encode genotype 1 (Wa-like) proteins, whereas strains DS-1 and 69M encode genotype 2 (DS-1-like) proteins. Of the 10 HRVs sequenced, 3 of them (Se584, A64, and L26) encode proteins belonging to more than one genotype, indicating that they are intergenogroup reassortants. We used amino acid sequence alignments to identify residues that distinguish proteins belonging to HRV genotype 1, 2, or 3. These genotype-specific changes cluster in definitive regions within each viral protein, many of which are sites of known protein-protein interactions. For the intermediate viral capsid protein (VP6), the changes map onto the atomic structure at the VP2-VP6, VP4-VP6, and VP7-VP6 interfaces. The results of this study provide evidence that group A HRV gene constellations exist and may be influenced by interactions among viral proteins during replication. PMID:18786998

Analysis of complete genome sequences of G9P[19] rotavirus strains from human and piglet with diarrhea provides evidence for whole-genome interspecies transmission of nonreassorted porcine rotavirus.

PubMed

Yodmeeklin, Arpaporn; Khamrin, Pattara; Chuchaona, Watchaporn; Kumthip, Kattareeya; Kongkaew, Aphisek; Vachirachewin, Ratchaya; Okitsu, Shoko; Ushijima, Hiroshi; Maneekarn, Niwat

2017-01-01

Whole genomes of G9P[19] human (RVA/Human-wt/THA/CMH-S070-13/2013/G9P[19]) and porcine (RVA/Pig-wt/THA/CMP-015-12/2012/G9P[19]) rotaviruses concurrently detected in the same geographical area in northern Thailand were sequenced and analyzed for their genetic relationships using bioinformatic tools. The complete genome sequence of human rotavirus RVA/Human-wt/THA/CMH-S070-13/2013/G9P[19] was most closely related to those of porcine rotavirus RVA/Pig-wt/THA/CMP-015-12/2012/G9P[19] and to those of porcine-like human and porcine rotaviruses reference strains than to those of human rotavirus reference strains. The genotype constellation of G9P[19] detected in human and piglet were identical and displayed as the G9-P[19]-I5-R1-C1-M1-A8-N1-T1-E1-H1 genotypes with the nucleotide sequence identities of VP7, VP4, VP6, VP1, VP2, VP3, NSP1, NSP2, NSP3, NSP4, and NSP5 at 99.0%, 99.5%, 93.2%, 97.7%, 97.7%, 85.6%, 89.5%, 93.2%, 92.9%, 94.0%, and 98.1%, respectively. The findings indicate that human rotavirus strain RVA/Human-wt/THA/CMH-S070-13/2013/G9P[19] containing the genome segments of porcine genetic backbone is most likely a human rotavirus of porcine origin. Our data provide an evidence of interspecies transmission and whole-genome transmission of nonreassorted G9P[19] porcine RVA to human occurring in nature in northern Thailand. Copyright © 2016. Published by Elsevier B.V.

Impact of routine rotavirus vaccination on all-cause and rotavirus hospitalizations during the first four years following vaccine introduction in Rwanda.

PubMed

Sibomana, Hassan; Rugambwa, Celse; Mwenda, Jason M; Sayinzoga, Felix; Iraguha, Gisele; Uwimana, Jeanine; Parashar, Umesh D; Tate, Jacqueline E

2018-05-10

Rwanda introduced pentavalent rotavirus vaccine into its national immunization program in 2012. To determine the long-term impact of rotavirus vaccine on disease burden in a high burden setting, we examined trends in rotavirus and all-cause diarrhea hospitalizations in the first four years following rotavirus vaccine introduction. We used data from an active surveillance system, from a review of pediatric ward registries, and from the Health Management Information System to describe trends in rotavirus and all-cause diarrhea hospitalizations from January 2009 through December 2016. Percent reductions were calculated to compare the number of all-cause and rotavirus diarrhea hospitalizations pre- and post-rotavirus vaccine introduction. The proportion of diarrhea hospitalizations due to rotavirus declined by 25-44% among all children <5 years of age during 2013-2015 with a shift in rotavirus hospitalizations to older age groups. The proportion of total hospitalizations due to diarrhea among children <5 years of age decreased from 19% pre-vaccine introduction to 12-13% post-vaccine introduction. In the national hospital discharge data, substantial decreases were observed in all-cause diarrhea hospitalizations among children <5 years of age in 2013 and 2014 but these gains lessened in 2015-2016. Continued monitoring of long-term trends in all-cause diarrhea and rotavirus hospitalizations is important to ensure that the impact of the vaccination program is sustained over time and to better understand the changing age dynamics of diarrhea and rotavirus hospitalizations in the post-vaccine introduction era. Published by Elsevier Ltd.

Rotavirus infection as a frequent cause of neonatal fever.

PubMed

Kang, Ha-Na; Park, Hyun Kyung; Lee, Hyun-Ju; Moon, Jin-Hwa; Oh, Jae Won; Kim, Chang-Ryul

2018-04-01

Fever rather than diarrhea or vomiting was the most common symptom of neonatal rotavirus (RV) infection in our previous study. We investigated whether RV infection is a major cause of neonatal fever and compared the clinical characteristics of bacterial infection, viral infection and unknown causes of neonatal fever. We reviewed the electronic medical records of 48 newborns aged ≤28 days who were admitted to the Special Care Nursery of Hanyang University Guri Hospital for fever (≥38°C) from 2005 to 2009. All the newborns underwent complete blood count, urinalysis, C-reactive protein, cultures of blood, urine, and cerebrospinal fluid as well as stool RV enzyme-linked immunosorbent assay. Respiratory virus polymerase chain reaction for cough or rhinorrhea, and stool culture for diarrhea were also done. All the babies were term, with mean age 13 ± 8 days and peak body temperature 38.5 ± 0.5°C. The causes of neonatal fever were viral (44%), bacterial (10%) and unknown (46%). The viral infections included RV (n = 12), enterovirus (n = 6), respiratory syncytial virus (n = 2), and rhinovirus (n = 1). All the rotavirus genotypes were G4P[6]. Only three of 12 RV-infected febrile newborns had diarrhea. The bacterial infections included three cases of urinary tract infection (Escherichia coli, n = 2; Klebsiella pneumoniae, n = 1), and two cases of sepsis complicated with meningitis (all Streptococcus agalactiae). RV infection is the most common single cause of neonatal fever. It may be necessary to include stool RV tests for febrile newborns. © 2017 Japan Pediatric Society.

Burden of rotavirus gastroenteritis in the Middle Eastern and North African pediatric population.

PubMed

Khoury, Hanane; Ogilvie, Isla; El Khoury, Antoine C; Duan, Yinghui; Goetghebeur, Mireille M

2011-01-07

Rotavirus gastroenteritis (RVGE) is the most common cause of severe childhood diarrhea worldwide. Objectives were to estimate the burden of RVGE among children less than five years old in the Middle East (Bahrain, Iran, Iraq, Israel, Jordan, Kuwait, Oman, Qatar, Saudi Arabia, Syria, UAE, Yemen), North Africa (Algeria, Egypt, Libya, Morocco, Tunisia) and Turkey. A comprehensive literature search was conducted in major databases on the epidemiology and burden of rotavirus among children less than five years old between 1999 and 2009. Data from each country was extracted and compared. The search identified 43 studies. RVGE was identified in 16-61% of all cases of acute gastroenteritis, with a peak in the winter. RVGE-related hospitalization rates ranged from 14% to 45%, compared to 14%-28% for non-RVGE. Annually, RVGE caused up to 112 fatalities per 100,000 in certain countries in the region. Hospitalization costs ranged from $1.8 to $4.6 million annually, depending on the country. The most recent literature available showed that G1P[8] was the most prevalent genotype combination in 8 countries (range 23%-56%). G2P[4] was most prevalent in 4 countries (26%-48%). G9P[8] and G4P[8] were also frequently detected. RVGE is a common disease associated with significant morbidity, mortality, and economic burden. Given the variety and diverse rotavirus types in the region, use of a vaccine with broad and consistent serotype coverage would be important to help decrease the burden of RVGE in the Middle East and North Africa.

Detection of the first G6P[14] human rotavirus strain in an infant with diarrhoea in Ghana.

PubMed

Damanka, Susan; Lartey, Belinda; Agbemabiese, Chantal; Dennis, Francis E; Adiku, Theophilus; Nyarko, Kofi; Ofori, Michael; Armah, George E

2016-11-10

Rotaviruses with G6P[14] specificity are mostly isolated in cattle and have been established as a rare cause of gastroenteritis in humans. This study reports the first detection of G6P[14] rotavirus strain in Ghana from the stool of an infant during a hospital-based rotavirus surveillance study in 2010. Viral RNA was extracted and rotavirus VP7 and VP4 genes amplified by one step RT-PCR using gene-specific primers. The DNA was purified, sequenced and genotypes determined using BLAST and RotaC v2.0. Phylogenetic tree was constructed using maximum likelihood method in MEGA v6.06 software and statistically supported by bootstrapping with 1000 replicates. Phylogenetic distances were calculated using the Kimura-2 parameter model. The study strain, GHA-M0084/2010 was characterised as G6P[14]. The VP7 gene of the Ghanaian strain clustered in G6 lineage-III together with artiodactyl and human rotavirus (HRV) strains. It exhibited the highest nucleotide (88.1 %) and amino acid (86.9 %) sequence identity with Belgian HRV strain, B10925. The VP8* fragment of the VP4 gene was closely related to HRV strains detected in France, Italy, Spain and Belgium. It exhibited the strongest nucleotide sequence identity (87.9 %) with HRV strains, PA169 and PR/1300 (Italy) and the strongest amino acid sequence identity (89.3 %) with HRV strain R2775/FRA/07 (France). The study reports the first detection of G6P[14] HRV strain in an infant in Ghana. The detection of G6P[14], an unusual strain pre-vaccine introduction in Ghana, suggests a potential compromise of vaccine effectiveness and indicates the necessity for continuous surveillance in the post vaccine era.

Epidemiology and economic burden of rotavirus gastroenteritis in hospitals and paediatric clinics in Taiwan, 2005-2006.

PubMed

Mast, T Christopher; Chen, Po-Yen; Lu, Kun-Chia; Hsu, Chun-Ming; Lin, Hsiao Chuan; Liao, Wen-Chen; Lin, Da-Pi; Chen, Hung-Chih; Lac, Christina

2010-04-09

Baseline estimates of rotavirus disease burden and epidemiology are useful for the evaluation of newly introduced rotavirus vaccination programs. Prospective, cross-sectional surveillance for acute gastroenteritis (AGE) was conducted in hospitals and outpatient paediatric clinics in Taiwan to assess the prevalence of rotavirus gastroenteritis and associated medical costs prior to rotavirus vaccine introduction. Faecal specimens were collected from 1130 children <5 years of age from December 2004 to June 2006. The year-round rate of rotavirus detection in faecal specimens was 46% for children seen in hospitals and 14% for children seen in paediatric clinics. In the winter season, the burden was higher, reaching a peak of 60% and 21% in hospitals and paediatric clinics, respectively. The rotavirus genotype distributions were 39% (G1), 34% (G9), 12% (G2), 15% (G3), and 0.3% (G5). Total medical and nonmedical costs were US $754 for a rotavirus hospitalisation and US $60 for an outpatient clinic visit. Parental work loss averaged 4.0 days per hospital visit and 1.3 days per paediatric clinic visit. These data show that rotavirus was associated with a substantial proportion of AGE medical visits and had considerable medical costs prior to rotavirus vaccine introduction. Copyright 2010 Elsevier Ltd. All rights reserved.

Norovirus genotypes causing gastroenteritis outbreaks in Finland 1998-2002.

PubMed

Maunula, L; Von Bonsdorff, C-H

2005-11-01

Outbreak investigation methods for enteric viruses were improved in 1990s when gene amplification techniques were established in viral laboratories. The objective of the study was to determine the causative agents for Finnish viral gastroenteritis outbreaks. Our aim was also to further characterise the norovirus strains, reveal the temporal occurrence of norovirus (NV) genotypes and to study some epidemiological aspects concerning the outbreaks. A total of 416 Finnish viral gastroenteritis outbreaks that occurred during 5 years (1998-2002), excluding those among hospitalised children, were investigated for enteric viruses. Stool samples were screened by electron microscopy as well as analyzed by specific noro- and astrovirus RT-PCR tests. Amplicon sequence analysis was used to find out norovirus genotypes. Noroviruses caused 252 (60.6%) of the outbreaks; other viruses, astro- or rotavirus, caused four epidemics. Norovirus epidemics occurred in all kinds of settings, most often in hospitals (30.6%) and in restaurants and canteens (14.3%). Both NV genogroups were found every year, but NV GGII outbreaks always outnumbered those of GGI. All but one outbreak at hospitals and nursing homes were of genotype GII. Polymerase sequence analysis revealed a variety of NV genotypes; six GI and at least eight GII genotypes. The GI.3 Birmingham-like and GII.4 Bristol-like genotype appeared every year, whereas the other types were circulating for shorter periods or sporadically. During the study period the genotypes GII.4 (Bristol), GII.1 (Hawaii), an emerging genotype GIIb, and a new variant of GII.4 predominated in that order. Indication for rapid genetic changes in the genotype GII.4 was also noticed. Noroviruses were the most prevalent causative agents in the outbreaks. Many NV genotypes were circulating, and a shift in the predominant genotypes was evident between epidemic seasons.

Simultaneous detection of group a rotavirus in Swine and rat on a pig farm in Brazil.

PubMed

Tonietti, Paloma de Oliveira; da Hora, Aline Santana; Silva, Fernanda Dornellas F; Ferrari, Karen Linares; Brandão, Paulo Eduardo; Richtzenhain, Leonardo José; Gregori, Fabio

2013-01-01

This study investigated the occurrence of rotavirus in porcine and Rattus norvegicus, at the same time, on a pig farm in the city of Jaguariúna, São Paulo, Brazil. Swine (n = 21) and rat (n = 6) fecal samples were analyzed by nested RT-PCR assay. Rotavirus occurred in seven porcine and two rat samples. A total of three pig and one rat samples were further submitted to genetic sequencing. The partial NSP5 gene phylogeny showed that all strains were segregated in the genotype H1. These results point toward a cross-species transmission between rats and pigs on the surveyed farm and represent the first detection of rotavirus in Rattus norvegicus in Brazil.

Upsurge and spread of G3 rotaviruses in Eastern India (2014-2016): Full genome analyses reveals heterogeneity within Wa-like genomic constellation.

PubMed

Banerjee, Anindita; Lo, Mahadeb; Indwar, Pallavi; Deb, Alok K; Das, Santasabuj; Manna, Byomkesh; Dutta, Shanta; Bhadra, Uchhal K; Bhattacharya, Mala; Okamoto, Keinosuke; Chawla-Sarkar, Mamta

2018-05-26

Advent of new strains and shift in predominantly circulating genotypes are characteristics of group- A rotavirus (RVA), one of the major causes of childhood gastroenteritis. During diarrheal disease surveillance at Kolkata, India (2014-2016), a shift in circulating RVA strains from G1P[8] to G3P[8] was seen. Stool samples from children (n = 3048) with acute gastroenteritis were tested of which 38.7% were RVA positive. G1 was the predominant strain (65.3%) in 2014-2015 whereas in late 2015 and 2016, G3 became the preponderant strain (44.6%). In the past decade G3 strains were not observed in this region, we conducted whole genome sequencing of representative strains to gain insight into the phenomenon of emergence and genetic constellation of these circulating human G3 strains. The analyses revealed intergenogroup reassortment in G3P[4] strains (among Wa and DS-1-like genogroup) whereas G3P[8] strains were authentic Wa-like. Phylogenetic analysis revealed Kolkata G3 strains as polymorphic and thus they formed two sub-clusters due to antigenic differences in their VP7 protein. One of the sub-clusters had the wild-type threonine at 87 amino acid position while another sub-cluster had an isoleucine mutation. Presence of additional N-linked glycosylation site at amino acid 283 of VP7 glycoprotein suggests that the major neutralizing epitope on the VP7 (G3) of RotaTeq vaccine differs from the currently circulating G3 strains. The study is important as efficiency of rotavirus vaccine depends on the circulating heterogeneous genotype constellations. Continuous monitoring of circulating RVA strains in endemic settings like India is therefore important in pre- and post-vaccination period to monitor the emergence of new reassortant genotypes in addition to assessing vaccine efficacy. Copyright © 2018. Published by Elsevier B.V.

Molecular characterization of different equine-like G3 rotavirus strains from Germany.

PubMed

Pietsch, Corinna; Liebert, Uwe G

2018-01-01

The genetic heterogeneity of rotaviruses constitutes a substantial burden to human and animal health. Occasional interspecies transmissions can generate novel virus strains in the human population. We detected equine-like G3P[8] strains in feces sampled from three children in Germany in 2015 and 2016, respectively. Thereof two showed a DS-1-like backbone. In one strain the NSP2 gene segment was of distinct genotype (G3-P[8]-I2-R2-C2-M2-A2-N1-T2-E2-H2). Phylogenetic analyses of the German strains showed a relation to other equine-like G3 rotaviruses circulating in different countries. The reconstruction of reassortment events in the evolution of novel equine-like G3 rotaviruses suggests an independent introduction of the three strains into the local human rotavirus population. Copyright © 2017 Elsevier B.V. All rights reserved.

Complete molecular genome analyses of equine rotavirus A strains from different continents reveal several novel genotypes and a largely conserved genotype constellation.

PubMed

Matthijnssens, Jelle; Miño, Samuel; Papp, Hajnalka; Potgieter, Christiaan; Novo, Luis; Heylen, Elisabeth; Zeller, Mark; Garaicoechea, Lorena; Badaracco, Alejandra; Lengyel, György; Kisfali, Péter; Cullinane, Ann; Collins, P J; Ciarlet, Max; O'Shea, Helen; Parreño, Viviana; Bányai, Krisztián; Barrandeguy, María; Van Ranst, Marc

2012-04-01

In this study, the complete genome sequences of seven equine group A rotavirus (RVA) strains (RVA/Horse-tc/GBR/L338/1991/G13P[18], RVA/Horse-wt/IRL/03V04954/2003/G3P[12] and RVA/Horse-wt/IRL/04V2024/2004/G14P[12] from Europe; RVA/Horse-wt/ARG/E30/1993/G3P[12], RVA/Horse-wt/ARG/E403/2006/G14P[12] and RVA/Horse-wt/ARG/E4040/2008/G14P[12] from Argentina; and RVA/Horse-wt/ZAF/EqRV-SA1/2006/G14P[12] from South Africa) were determined. Multiple novel genotypes were identified and genotype numbers were assigned by the Rotavirus Classification Working Group: R9 (VP1), C9 (VP2), N9 (NSP2), T12 (NSP3), E14 (NSP4), and H7 and H11 (NSP5). The genotype constellation of L338 was unique: G13-P[18]-I6-R9-C9-M6-A6-N9-T12-E14-H11. The six remaining equine RVA strains showed a largely conserved genotype constellation: G3/G14-P[12]-I2/I6-R2-C2-M3-A10-N2-T3-E2/E12-H7, which is highly divergent from other known non-equine RVA genotype constellations. Phylogenetic analyses revealed that the sequences of these equine RVA strains are related distantly to non-equine RVA strains, and that at least three lineages exist within equine RVA strains. A small number of reassortment events were observed. Interestingly, the three RVA strains from Argentina possessed the E12 genotype, whereas the three RVA strains from Ireland and South Africa possessed the E2 genotype. The unusual E12 genotype has until now only been described in Argentina among RVA strains collected from guanaco, cattle and horses, suggesting geographical isolation of this NSP4 genotype. This conserved genetic configuration of equine RVA strains could be useful for future vaccine development or improvement of currently used equine RVA vaccines.

Molecular Characterization of Rotavirus Gastroenteritis Strains, Iraqi Kurdistan

PubMed Central

Ahmed, Herish M.; Coulter, J. Brian S.; Nakagomi, Osamu; Zaki, Jamal M.; Al-Rabaty, Abas A.; Dove, Winifred; Cunliffe, Nigel A.

2006-01-01

Of 260 children with acute diarrhea in Erbil, Iraqi Kurdistan, 96 (37%) were infected with rotavirus. Reverse transcription–polymerase chain reaction identified G1, G4, G2, G9, P[8], P[6], and P[4] as the most common genotypes. Eight G/P combinations were found, but P[8]G1 and P[4]G2 accounted for >50% of the strains. PMID:16704845

Whole-genome sequencing and analyses identify high genetic heterogeneity, diversity and endemicity of rotavirus genotype P[6] strains circulating in Africa.

PubMed

Nyaga, Martin M; Tan, Yi; Seheri, Mapaseka L; Halpin, Rebecca A; Akopov, Asmik; Stucker, Karla M; Fedorova, Nadia B; Shrivastava, Susmita; Duncan Steele, A; Mwenda, Jason M; Pickett, Brett E; Das, Suman R; Jeffrey Mphahlele, M

2018-05-18

Rotavirus A (RVA) exhibits a wide genotype diversity globally. Little is known about the genetic composition of genotype P[6] from Africa. This study investigated possible evolutionary mechanisms leading to genetic diversity of genotype P[6] VP4 sequences. Phylogenetic analyses on 167 P[6] VP4 full-length sequences were conducted, which included six porcine-origin sequences. Of the 167 sequences, 57 were newly acquired through whole genome sequencing as part of this study. The other 110 sequences were all publicly-available global P[6] VP4 full-length sequences downloaded from GenBank. The strength of association between the phenotypic features and the phylogeny was also determined. A number of reassortment and mixed infections of RVA genotype P[6] strains were observed in this study. Phylogenetic analyses demostrated the extensive genetic diversity that exists among human P[6] strains, porcine-like strains, their concomitant clades/subclades and estimated that P[6] VP4 gene has a higher substitution rate with the mean of 1.05E-3 substitutions/site/year. Further, the phylogenetic analyses indicated that genotype P[6] strains were endemic in Africa, characterised by an extensive genetic diversity and long-time local evolution of the viruses. This was also supported by phylogeographic clustering and G-genotype clustering of the P[6] strains when Bayesian Tip-association Significance testing (BaTS) was applied, clearly supporting that the viruses evolved locally in Africa instead of spatial mixing among different regions. Overall, the results demonstrated that multiple mechanisms such as reassortment events, various mutations and possibly interspecies transmission account for the enormous diversity of genotype P[6] strains in Africa. These findings highlight the need for continued global surveillance of rotavirus diversity. Copyright © 2018 Elsevier B.V. All rights reserved.

Rotavirus Vaccine

MedlinePlus

Why get vaccinated?Rotavirus is a virus that causes diarrhea, mostly in babies and young children. The diarrhea can be severe, and lead ... and fever are also common in babies with rotavirus.Before rotavirus vaccine, rotavirus disease was a common ...

Current status of rotavirus vaccines.

PubMed

Wang, Ching-Min; Chen, Shou-Chien; Chen, Kow-Tong

2015-11-01

Rotaviruses remain the major cause of childhood diarrheal disease worldwide and of diarrheal deaths of infants and children in developing countries. The huge burden of childhood rotavirus-related diarrhea in the world continues to drive the remarkable pace of vaccine development. Research articles were searched using terms "rotavirus" and "rotavirus vaccine" in MEDLINE and PubMed. Articles not published in the English language, articles without abstracts, and opinion articles were excluded from the review. After preliminary screening, all articles were reviewed and synthesized to provide an overview of current vaccines and vaccination programs. In this review of the global rotavirus vaccines and vaccination programs, the principles of rotavirus vaccine development and the efficacy of the currently licensed vaccines from both developed and developing countries were summarized. Rotavirus is a common cause of diarrhea in children in both developed and developing countries. Rotavirus vaccination is a cost-effective measure to prevent rotavirus diarrhea.

Rotavirus burden among children in the newly independent states of the former union of soviet socialist republics: literature review and first-year results from the rotavirus surveillance network.

PubMed

Mirzayeva, Radmila; Cortese, Margaret M; Mosina, Liudmila; Biellik, Robin; Lobanov, Andrei; Chernyshova, Lyudmila; Lashkarashvili, Marina; Turkov, Soibnazar; Iturriza-Gomara, Miren; Gray, Jim; Parashar, Umesh D; Steele, Duncan; Emiroglu, Nedret

2009-11-01

Data on rotavirus burden among children in the 15 newly independent states of the former Union of Soviet Socialist Republics, particularly contemporary data from poorer countries, are not widely available. These data are desired by policy makers to assess the value of rotavirus vaccination, especially since the GAVI Alliance approved financial support for the region's eligible countries. The Rotavirus Surveillance Network was established to provide these data. We reviewed the region's literature on rotavirus burden. We established an active surveillance network for rotavirus and analyzed data from 2007 from 4 sentinel hospitals in 3 countries (Georgia, Tajikistan, and Ukraine) that were collected using standardized enrollment and stool sample testing methods. Specimens for rotavirus testing were collected before 1997 in most studies, and the majority of studies were from 1 country, the Russian Federation. Overall, the studies indicated that approximately 33% of hospitalizations for gastroenteritis among children were attributable to rotavirus. The Rotavirus Surveillance Network documented that 1425 (42%) of 3374 hospitalizations for acute gastroenteritis among children aged <5 years were attributable to rotavirus (site median, 40%). Seasonal peaks (autumn through spring) were observed. Genotype data on 323 samples showed that G1P[8] was the most common type (32%), followed by G9P[8] (20%), G2P[4] (18%), and G4P[8] (18%). Infections due to G10 and G12 and mixed infections were also detected. The burden of rotavirus disease in the newly independent states is substantial. Vaccines should be considered for disease prevention.

Impact of high coverage of monovalent human rotavirus vaccine on Emergency Department presentations for rotavirus gastroenteritis.

PubMed

Davey, Heather M; Muscatello, David J; Wood, James G; Snelling, Thomas L; Ferson, Mark J; Macartney, Kristine K

2015-03-30

Australia was one of the first countries to introduce nationally funded rotavirus vaccination. The program has had a substantial impact on both rotavirus and all-cause acute gastroenteritis (AGE) hospitalisations and rotavirus laboratory tests. Evidence for an impact on Emergency Department (ED) presentations is limited. This study assessed changes in ED presentations for rotavirus in children aged <5 years in New South Wales, Australia, following introduction of monovalent human rotavirus vaccine (RV1, Rotarix(®), GlaxoSmithKline Australia Pty Ltd., Victoria, Australia). A time series analysis to examine trends in total non-admitted ED presentations for all-cause AGE and in the rotavirus-attributable fraction using data on rotavirus positive laboratory tests. A decline in the rate of non-admitted ED presentations for all-cause AGE was observed for all ages, being most notable in 1 year old children. Compared with the pre-vaccination period, we estimated the average weekly rate was lower across the first 4.5 years of the program for both all-cause AGE (18.3%; 70.5 versus 57.5 per 100,000 population) and rotavirus attributable (55.4%; 17.3 versus 7.7 per 100,000 population) presentations. In the fourth year of the program, estimated annual rotavirus attributable presentations were 77% lower than the pre-vaccination annual mean (996 versus 4300 per year). The program was associated with a substantial decline in rotavirus attributable non-admitted AGE presentations to ED among children aged <5 years. Crown Copyright © 2015. Published by Elsevier Ltd. All rights reserved.

Impact of rotavirus vaccination on rotavirus and all-cause gastroenteritis in peri-urban Kenyan children.

PubMed

Wandera, Ernest Apondi; Mohammad, Shah; Bundi, Martin; Komoto, Satoshi; Nyangao, James; Kathiiko, Cyrus; Odoyo, Erick; Miring'u, Gabriel; Taniguchi, Koki; Ichinose, Yoshio

2017-09-12

A monovalent rotavirus vaccine (RV1) was introduced into the National Immunization Program in Kenya in July 2014. We examined the impact of the vaccine on hospitalization for all-cause acute gastroenteritis (AGE) and rotavirus-specific AGE and strain distribution at a large referral hospital which serves a predominantly peri-urban population in Central Kenya. Data on rotavirus AGE and strain distribution were derived from ongoing hospital-based AGE surveillance. Hospital administrative data were used to compare trends in all-cause AGE. Pre-vaccine (July 2009-June 2014) and post-vaccine (July 2014-June 2016) periods were compared for changes in hospitalization for all-cause AGE and rotavirus AGE and strain distribution. Following the vaccine introduction, the proportion of children aged <5years hospitalized for rotavirus declined by 30% (95% CI: 19-45%) in the first year and 64% (95% CI: 49-77%) in the second year. Reductions in rotavirus positivity were most pronounced among the vaccine-eligible group (<12months) in the first year post-vaccination at 42% (95% CI: 28-56%). Greater reductions of 67% (95% CI: 51-79%) were seen in the second year in the 12-23months age group. Similarly, hospitalizations for all-cause AGE among children <5years of age decreased by 31% (95% CI: 24-40%) in the first year and 58% (95% CI: 49-67%) in the second year of vaccine introduction. Seasonal peaks of rotavirus and all-cause AGE were reduced substantially. There was an increased detection of G2P[4], G3P[6] and G3P[8], which coincided temporally with the timing of the vaccine introduction. Thus, introducing the rotavirus vaccine into the routine immunization program in Kenya has resulted in a notable decline in rotavirus and all-cause AGE hospitalizations in Central Kenya. This provides early evidence for public health policy makers in Kenya to support the sustained use of the rotavirus vaccine in routine immunizations. Copyright © 2017 Elsevier Ltd. All rights reserved.

Antigenic and genetic characterization of serotype G2 human rotavirus strains from the African continent.

PubMed

Page, N A; Steele, A D

2004-02-01

Serotype G2 rotavirus strains were isolated in seven countries on the African continent during 1999 and 2000. To investigate the associated DS-1 genogroup characteristics, subgroup (VP6) enzyme-linked immunosorbent assay, polyacrylamide gel electrophoresis, and P genotyping were performed on 10 G2 strains. The antigenic and genetic variation of the gene encoding the major neutralization glycoprotein (VP7) was also investigated by using G2-specific monoclonal antibodies and sequence analysis. Alterations in the characteristic DS-1 genogroup gene constellations were more likely to occur in the VP4 gene, and three genotypes were observed: P[4], P[6], and a dual P[4]-P[6] type. The failure of G2-specific monoclonal antibodies to type African G2 strains was more likely due to improper storage of the original stool, although G2 monotypes were detected. Phylogenetic analyses revealed clusters of serotype G2 strains that were more commonly associated with seasons during which G2 was predominant. No rotavirus vaccine trials have been conducted in an area where G2 strains were the predominant circulating serotype, and the continued surveillance of rotavirus epidemics in Africa will be preparation for future vaccine implementation in an area that clearly needs these preventative medicines.

Full genome analysis of rotavirus G9P[8] strains identified in acute gastroenteritis cases reveals genetic diversity: Pune, western India.

PubMed

Tatte, Vaishali S; Chaphekar, Deepa; Gopalkrishna, Varanasi

2017-08-01

Group A rotaviruses (RVA) are the major enteric etiological agents of severe acute gastroenteritis among children globally. As G9 RVA now represents as one of the major human RVA genotypes, studies on full genome of this particular genotype are being carried out worldwide. So far, no such studies on G9P[8] RVAs have been reported from Pune, western part of India. Keeping in view of this, the study was undertaken to understand the degree of genetic diversity of the commonly circulating G9P[8] RVA strains. Rotavirus surveillance studies carried out earlier during the years 2009-2011 showed increase in the prevalence of G9P[8] RVAs. Representative G9P[8] RVA strains from the years 2009, 2010, and 2011 were selected for the study. In general, all the G9 RVA strains showed clustering in the globally circulating sublineage of the VP7 gene and showed nucleotide/amino acid identities of 96.8-99.7%/96.9-99.8% with global G9 RV strains. Full genome analysis, of all three RVAs in this study indicated Wa-like genotype constellation G9-P[8]-I1-R1-C1-M1-A1-N1-T1-E1-H1. Within the strains nucleotide/amino acid divergence of 0.1-3.4%/0.0-4.1% was noted in all the RVA structural and non-structural genes. In conclusion, the present study highlights intra-genotypic variations throughout the RVA genome. The study further emphasizes the need for surveillance and analysis of the whole genomic constellation of the commonly circulating RVA strains of other regions in the country for understanding to a greater degree of the impact of rotavirus vaccination recently introduced in India. © 2017 Wiley Periodicals, Inc.

Rotavirus vaccine RIX4414 (Rotarix).

PubMed

Keating, Gillian M

2006-01-01

RIX4414 is a human, live attenuated rotavirus vaccine containing a rotavirus strain of G1P[8] specificity; it is administered orally using a two-dose schedule. RIX4414 showed good immunogenicity in healthy infants in several well designed trials in terms of both seroconversion rates and vaccine take. Moreover, RIX4414 did not impair the immune response of infants to other vaccines. RIX4414 provided significant protection against severe rotavirus gastroenteritis. In a subgroup analysis (n = 20 169) of a large (n = 63 225), well designed, placebo-controlled, phase III trial (conducted in Latin America and Finland), the efficacy of RIX4414 against severe rotavirus gastroenteritis was 85% in healthy infants, with an efficacy against hospitalization for severe rotavirus gastroenteritis of 85%. RIX4414 provided cross-protection against non-G1 serotypes containing the P[8] antigen. Moreover, in this trial, RIX4414 had a protective efficacy against severe gastroenteritis of any cause of 40%, with an efficacy against hospitalization because of severe gastroenteritis of any cause of 42%. In another well designed, placebo-controlled, phase III trial (conducted in Europe; n = 3874), RIX4414 had an efficacy against rotavirus gastroenteritis of any severity of 87%, an efficacy against severe rotavirus gastroenteritis of 96%, and an efficacy against hospitalization because of rotavirus gastroenteritis of 100%. RIX4414 protected against rotavirus gastroenteritis from the first dose onwards. A meta-analysis revealed that RIX4414 had a protective efficacy against rotavirus gastroenteritis of any severity caused by the G2P[4] serotype of 81% and against severe rotavirus gastroenteritis caused by the G2P[4] serotype of 71%. RIX4414 was generally well tolerated in healthy infants. The vaccine did not appear to be associated with an increased risk of intussusception.

One year environmental surveillance of rotavirus specie A (RVA) genotypes in circulation after the introduction of the Rotarix® vaccine in Rio de Janeiro, Brazil.

PubMed

Fumian, Tulio Machado; Leite, José Paulo Gagliardi; Rose, Tatiana Lundgreen; Prado, Tatiana; Miagostovich, Marize Pereira

2011-11-01

Rotavirus specie A (RVA) infection is the leading cause of severe acute diarrhea among young children worldwide. To reduce this major RVA health impact, the Rotarix® vaccine (GlaxoSmithKline, Rixensart, Belgium) was introduced in the Brazilian Expanded Immunization Program in March 2006 and became available to the entire birth cohort. The aim of this study was to evaluate the spread of RVA in the environment after the introduction of Rotarix® in Brazil. For this purpose, a Wastewater Treatment Plant (WTP) in Rio de Janeiro was monitored for one year to detect, characterize and discriminate RVA genotypes and identify possible circulation of vaccine strains. Using TaqMan® quantitative PCR (qPCR), RVA was detected in 100% (mean viral loads from 2.40×10(5) to 1.16×10(7) genome copies (GC)/L) of sewage influent samples and 71% (mean viral loads from 1.35×10(3) to 1.64×10(5)GC/L) of sewage effluent samples. The most prevalent RVA genotypes were P[4], P[6] and G2, based on VP4 and VP7 classification. Direct nucleotide sequencing (NSP4 fragment) and restriction enzyme digestion (NSP3) analysis did not detect RVA vaccine-like strains from the sewage samples. These data on RVA detection, quantification and molecular characterization highlight the importance of environmental monitoring as a tool to study RVA epidemiology in the surrounding human population and may be useful on ongoing vaccine monitoring programs, since sewage may be a good screening option for a rapid and economical overview of the circulating genotypes. Copyright © 2011 Elsevier Ltd. All rights reserved.

Detection of uncommon G3P[3] rotavirus A (RVA) strain in rat possessing a human RVA-like VP6 and a novel NSP2 genotype.

PubMed

Ianiro, Giovanni; Di Bartolo, Ilaria; De Sabato, Luca; Pampiglione, Guglielmo; Ruggeri, Franco M; Ostanello, Fabio

2017-09-01

Rotavirus is one of the leading causes of acute gastroenteritis in infants and young children. RVAs infect not only humans but also a wide range of mammals including rats, which represent a reservoir of several other zoonotic pathogens. Due to the segmented nature of the RVA genome, animal RVA strains can easily adapt to the human host by reassortment with co-infecting human viruses. This study aims to detect and characterize RVA in the intestinal content of Italian sinantropic rats (Rattus rattus). Out of 40 samples examined following molecular approach, one resulted positive for RVA. The molecular characterization of VP1-4, 6 and 7, and NSP1-5 genes by sequencing revealed the genomic constellation G3-P[3]-I1-R11-C11-M10-A22-N18-T14-E18-H13. This uncommon genomic combination includes: the VP1-4,VP7, the NSP1, 3, 4 and 5 gene segments, closely related to those of RVA from rodents, the N18 novel genotype established for the NSP2 gene segment and the human Wa-like VP6 gene, suggesting interspecies reassortment. Copyright © 2017 Elsevier B.V. All rights reserved.

Mucosal Immunity and acute viral gastroenteritis

PubMed Central

Rose, Markus A

2014-01-01

Acute gastroenteritis is a major killer of the very young worldwide. Rotavirus is the most common intestinal virus, causing acute gastroenteritis and extra-intestinal complications especially in young and chronically ill subjects. As early as 1991, the WHO recommended as high priority the development of a vaccine against rotavirus, the major pathogen causing enteric infections. Since the introduction of rotavirus vaccines for infant immunization programmes in different parts of the world in 2006, vaccination against rotavirus has resulted in substantial declines in severe gastroenteritis. The oral rotavirus vaccines RotaTeq® and Rotarix® are excellent examples for their unique features and principles of mucosal immunization. We elaborate on rotavirus immunity and the success of rotavirus vaccination and aspects also beyond infants’ acute gastroenteritis. PMID:25424826

Human rotavirus strains circulating in Venezuela after vaccine introduction: predominance of G2P[4] and reemergence of G1P[8].

PubMed

Vizzi, Esmeralda; Piñeros, Oscar A; Oropeza, M Daniela; Naranjo, Laura; Suárez, José A; Fernández, Rixio; Zambrano, José L; Celis, Argelia; Liprandi, Ferdinando

2017-03-21

Rotavirus (RV) is the most common cause of severe childhood diarrhea worldwide. Despite Venezuela was among the first developing countries to introduce RV vaccines into their national immunization schedules, RV is still contributing to the burden of diarrhea. Concerns exist about the selective pressure that RV vaccines could exert on the predominant types and/or emergence of new strains. To assess the impact of RV vaccines on the genotype distribution 1 year after the vaccination was implemented, a total of 912 fecal specimens, collected from children with acute gastroenteritis in Caracas from February 2007 to April 2008, were screened, of which 169 (18.5%) were confirmed to be RV positive by PAGE. Rotavirus-associated diarrhea occurred all year-round, although prevailed during the coolest and driest months among unvaccinated children under 24 months old. Of 165 RV strains genotyped for G (VP7) and P (VP4) by seminested multiplex RT-PCR, 77 (46.7%) were G2P[4] and 63 (38.2%) G1P[8]. G9P[8], G3P[8] and G2P[6] were found in a lower proportion (7.3%). Remarkable was also the detection of <5% of uncommon combinations (G8P[14], G8P[4], G1P[4] and G4P[4]) and 3.6% of mixed infections. A changing pattern of G/P-type distribution was observed during the season studied, with complete predominance of G2P[4] from February to June 2007 followed by its gradual decline and the reemergence of G1P[8], predominant since January 2008. Phylogenetic analysis of VP7 and VP4 genes revealed a high similarity among G2P[4] and global strains belonging to G2-II and P[4]-V lineages. The amino acid substitution 96D → N, related with reemergence of the G2 genotype elsewhere, was observed. The G1P[8] strains from Caracas were grouped into the lineages G1-I and P[8]-III, along with geographically remote G1P[8] rotaviruses, but they were rather distant from Rotarix ® vaccine and pre-vaccine strains. Unique amino acid substitutions observed on neutralization domains of the VP7 sequence from Venezuelan post-vaccine G1P[8] could have conditioned their re-emergence and a more efficient dissemination into susceptible population. The results suggest that natural fluctuations of genotypes in combination with forces driving the genetic evolution could determine the spread of novel strains, whose long-term effect on the efficacy of available vaccines should be determined.

Genetic Diversity of G3 Rotavirus Strains Circulating in Argentina during 1998–2012 Assessed by Full Genome Analyses

PubMed Central

Degiuseppe, Juan Ignacio; Parra, Gabriel Ignacio; Stupka, Juan Andrés

2014-01-01

Seasonal shifts in the predominant strains and the periodic emergence of new strains are epidemiological features of human rotaviruses. After the sporadic detection in two samples in 1998, G3P[8] strains reemerged as the predominant rotavirus during 2008–2009 in Argentina. Notably, in 2011 6.3% (37/587) of samples presented the G3P[6] genotypes, which coincided with the recent detection of G3P[6] and G2P[6] strains in South America and Europe. Analyses of the 11 gene segments of four G3P[8] and two G3P[6] strains revealed that G3P[8] strains detected a decade apart (1998 and 2009) presented minor differences, while the G3P[6] strains presented a complete different genomic constellation albeit showing a similar VP7 gene. This study provides insights in the dynamics and evolution of one of the genotypes with the wider range of hosts and inter-species transmission potential. PMID:25337915

Epidemiological features and genetic characterization of virus strains in rotavirus associated gastroenteritis in children of Odisha in Eastern India.

PubMed

Mohanty, Eileena; Dwibedi, Bhagirathi; Kar, S K; Acharya, A S

2017-09-01

We have studied the clinical characteristics, severity and seasonality of rotavirus infection and prevalent genotypes in 652 non-rota vaccinated children in Odisha in eastern India. P genotypes were analysed for their association with host blood group antigens. P type of the virus is determined by the VP8* gene, and specific recognition of A - type of Histo - blood group antigen by P[14]VP8* has been reported. VP4, VP7 and VP6 genes of commonly identified G1P[8] strain were compared with genes of the same strain isolated from other parts of India, elsewhere and strains used for Rotarix and Rotateq vaccines. In 54.75% of children with gastroenteritis, rota virus was found. 9.65% of children had moderate, 78.07% severe, and 12.28% very severe disease as assessed using the Vesikari scoring system. The incidence of infection was highest during winter months. There was no association between any blood group and specific P genotypes. G1P[8] was the commonest cause of gastroenteritis, followed by G1P[11], G3P[8], G9P[8], G2P[4], G2P[6], G9P[4], G9P[11] and G1P[6]. Predominant G genotypes identified were G1 (72.9%), G9 (10.81%), G2 (8.10%) and G3 (8.10%). Sequence analysis of the VP7 gene, placed the G1P[8] strain in lineage 1 and of VP6 gene placed nine G1P[8] strains in subgroup II and one in subgroup I. The VP7 gene segment of two Odisha G1P[8] strains were found to cluster relatively close to the VP7 sequences of Rotarix vaccine. Antigenic differences were found with vaccine strains. Ten G1P[8] strains sequenced for the VP4 gene had 91-93% nucleotide and 92-96% amino acid identity with Rotateq vaccine P[8]). Rotarix vaccine VP4 had 89-91% nucleotide and 90-92% amino acid identity. Our findings indicate genetic variability of rotavirus strains circulating in the region and are significant, given the introduction of rota vaccination in the State. Copyright © 2017 Elsevier B.V. All rights reserved.

Detection of nineteen enteric viruses in raw sewage in Japan.

PubMed

Thongprachum, Aksara; Fujimoto, Tsuguto; Takanashi, Sayaka; Saito, Hiroyuki; Okitsu, Shoko; Shimizu, Hiroyuki; Khamrin, Pattara; Maneekarn, Niwat; Hayakawa, Satoshi; Ushijima, Hiroshi

2018-05-10

One-year surveillance for enteric viruses in raw sewage was conducted in Kansai area, central part of Japan from July 2015 to June 2016. The raw sewage was collected monthly from an inlet polluted pool and was concentrated by polyethylene glycol (PEG) precipitation. Twelve sewage samples were screened for nineteen kinds of enteric viruses by using RT-PCR method and further analyzed by nucleotide sequencing. Twelve enteric viruses were found in the investigative sewage samples. Rotavirus A and norovirus GI and GII with several genotypes were detected all year round. Interestingly, norovirus GII.17 (Kawasaki-like strain) and rotavirus G2 that caused the outbreaks in Japan last epidemic season were also found in sewage. Moreover, adenovirus, astrovirus, sapovirus, bocavirus, human parechovirus, enterovirus, Aichi virus, Saffold virus and salivirus were also detected. Enterovirus D68 was detected only in the same month as those of enterovirus D68 outbreak in Japan. The rotavirus B and C, hepatitis A and E viruses, human cosavirus, bufavirus and rosavirus were not detected in this surveillance. The study provides the information on the enteric viruses contaminated in raw sewage, which is valuable for risk assessment. Our results imply that the viruses detected in sewage may be associated with infections in the Japanese population. Copyright © 2017. Published by Elsevier B.V.

Detection of unusual strains of RV in patients with acute diarrhoea in Mexico.

PubMed

del R González-Losa, Maria; Rodríguez-Angulo, Elsa; Manzano-Cabrera, Luis; Mejía-Cámara, Javier; Puerto-Solís, Marylin

2005-04-01

Group A rotaviruses are a major cause of acute gastroenteritis in infants. Human strains with a short RNA pattern generally exhibit subgroup I, G2, P1B[4] specificity, those with a long RNA pattern show subgroup II, G1, G3 or G4, P1A[8] specificity. The presence of strains with unusual specificities has been reported worldwide over the last decade. To determine antigenic diversity among rotaviruses isolated from patients with diarrhoea. A laboratory-based survey study was carried out with faecal samples from patients with acute gastroenteritis form January to April 2000. To classify the samples PAGE and ELISA with specific antibodies to serotype G and P and RT-PCR were carried out. Twenty one specimens from patients with dehydrating diarrhoea had unusual specifies. Nine specimens had unusual combination of long pattern and subgroup I. Twelve specimens with short pattern belong to G1 serotype. As far as the serotypes and genotypes concern 11 samples were P1A, P[4] and one specimen was P1A, P[9]. These results demonstrated the unexpected presence of unusual strains of rotavirus in Mexico. Detection of strains with both human and animal characteristics may indicate interspecies transmission of RV between humans and animals.

Rotavirus Antigenemia in Children Is Associated with Viremia

PubMed Central

Blutt, Sarah E; Matson, David O; Crawford, Sue E; Staat, Mary Allen; Azimi, Parvin; Bennett, Berkeley L; Piedra, Pedro A; Conner, Margaret E

2007-01-01

Background Antigenemia is commonly detected in rotavirus-infected children. Although rotavirus RNA has been detected in serum, definitive proof of rotavirus viremia has not been shown. We aimed to analyze a defined patient population to determine if infectious virus could be detected in sera from children with rotavirus antigenemia. Methods and Findings Serum samples obtained upon hospitalization from children with gastroenteritis (57 stool rotavirus-positive and 41 rotavirus-negative), children with diagnosed bronchiolitis of known (n = 58) or unknown (n = 17) viral etiology, children with noninfectious, nonchronic conditions (n = 17), and healthy adults (n = 28) were tested for rotavirus antigen by enzyme immunoassay (EIA). Results of serum antigen testing were assessed for association with clinical and immunological attributes of the children. Rotavirus antigenemia was detected in 90% (51/57) of children with rotavirus-positive stools, in 89% (8/9) of children without diarrhea but with rotavirus-positive stools, in 12% (2/17) of children with bronchiolitis of unknown etiology without gastroenteritis, and in 12% (5/41) of children with gastroenteritis but with rotavirus-negative stools. Antigenemia was not detected in sera from children with noninfectious nonchronic conditions, children with bronchiolitis of known etiology and no gastroenteritis, or healthy adults. Neither age nor timing of serum collection within eight days after onset of gastroenteritis significantly affected levels of antigenemia, and there was no correlation between antigenemia and viral genotype. However, there was a negative correlation between serum rotavirus antigen and acute rotavirus-specific serum IgA (r = −0.44, p = 0.025) and IgG (r = −0.40, p = 0.01) titers. We examined 11 antigen-positive and nine antigen-negative sera for infectious virus after three blind serial passages in HT-29 cells using immunofluorescence staining for rotavirus structural and nonstructural proteins. Infectious virus was detected in 11/11 (100%) sera from serum antigen-positive children and in two out of nine (22%) sera samples from antigen-negative children (p = 0.002). Conclusions Most children infected with rotavirus are viremic. The presence of viremia is directly related to the detection of antigenemia and is independent of the presence of diarrhea. Antigenemia load is inversely related to the titer of antirotavirus antibody in the serum. The finding of infectious rotavirus in the blood suggests extraintestinal involvement in rotavirus pathogenesis; however, the impact of rotavirus viremia on clinical manifestations of infection is unknown. PMID:17439294

Sustained Effectiveness of Rotavirus Vaccine Against Very Severe Rotavirus Disease Through the Second Year of Life, Bolivia 2013-2014.

PubMed

Pringle, Kimberly D; Patzi, Maritza; Tate, Jacqueline E; Iniguez Rojas, Volga; Patel, Manish; Inchauste Jordan, Lucia; Montesano, Raul; Zarate, Adolfo; De Oliveira, Lucia; Parashar, Umesh

2016-05-01

In Bolivia, monovalent rotavirus vaccine was introduced in 2008 and a previous evaluation reported a vaccine effectiveness (VE) of 77% with 2 doses of vaccine in children aged <3 years. This evaluation sought to determine if rotavirus vaccine provided protection through the second year of life against circulating genotypes. A case-control study was performed in 5 hospitals from April 2013 to March 2014. Among enrolled participants who met study criteria and had rotavirus stool testing performed and vaccine status confirmed, we calculated VE using a logistic regression model. Subgroup analyses were performed among children aged <1 year and those aged ≥1 year, among children with severe diarrhea (Vesikari score ≥11) and very severe diarrhea (Vesikari score ≥15), and among G and P strains with at least 40 specimens. A total of 776 children were enrolled. For children <1 year and ≥1 year of age with severe diarrhea, VE for 2 doses was 75% (95% confidence interval [CI], 46%-88%) and 53% (95% CI, 9%-76%), respectively. For children <1 year and ≥1 year of age with very severe diarrhea, VE for 2 doses was 80% (95% CI, 44%-93%) and 74% (95% CI, 35%-90%), respectively. Genotype-specific analysis demonstrated similar VE for the 4 most common G and P types (G3, G9, P[6] and P[8]). A monovalent rotavirus vaccine remains effective against a broad range of circulating strains as part of a routine immunization program >5 years after its introduction in Bolivia. Although VE appears to wane in children aged ≥1 year, it still provides significant protection, and does not wane against severe disease. Published by Oxford University Press for the Infectious Diseases Society of America 2016. This work is written by (a) US Government employee(s) and is in the public domain in the US.

Implementation of Rotavirus Surveillance and Vaccine Introduction - World Health Organization African Region, 2007-2016.

PubMed

Mwenda, Jason M; Burke, Rachel M; Shaba, Keith; Mihigo, Richard; Tevi-Benissan, Mable Carole; Mumba, Mutale; Biey, Joseph Nsiari-Muzeyi; Cheikh, Dah; Poy MSc, Alain; Zawaira, Felicitas R; Aliabadi, Negar; Tate, Jacqueline E; Hyde, Terri; Cohen, Adam L; Parashar, Umesh D

2017-11-03

Rotavirus is a leading cause of severe pediatric diarrhea globally, estimated to have caused 120,000 deaths among children aged <5 years in sub-Saharan Africa in 2013 (1). In 2009, the World Health Organization (WHO) recommended rotavirus vaccination for all infants worldwide (2). Two rotavirus vaccines are currently licensed globally: the monovalent Rotarix vaccine (RV1, GlaxoSmithKline; 2-dose series) and the pentavalent RotaTeq vaccine (RV5, Merck; 3-dose series). This report describes progress of rotavirus vaccine introduction (3), coverage (using estimates from WHO and the United Nations Children's Fund [UNICEF]) (4), and impact on pediatric diarrhea hospitalizations in the WHO African Region. By December 2016, 31 (66%) of 47 countries in the WHO African Region had introduced rotavirus vaccine, including 26 that introduced RV1 and five that introduced RV5. Among these countries, rotavirus vaccination coverage (completed series) was 77%, according to WHO/UNICEF population-weighted estimates. In 12 countries with surveillance data available before and after vaccine introduction, the proportion of pediatric diarrhea hospitalizations that were rotavirus-positive declined 33%, from 39% preintroduction to 26% following rotavirus vaccine introduction. These results support introduction of rotavirus vaccine in the remaining countries in the region and continuation of rotavirus surveillance to monitor impact.

Comparative analysis of pentavalent rotavirus vaccine strains and G8 rotaviruses identified during vaccine trial in Africa.

PubMed

Heylen, Elisabeth; Zeller, Mark; Ciarlet, Max; Lawrence, Jody; Steele, Duncan; Van Ranst, Marc; Matthijnssens, Jelle

2015-10-06

RotaTeqTM is a pentavalent rotavirus vaccine based on a bovine rotavirus genetic backbone in vitro reassorted with human outer capsid genes. During clinical trials of RotaTeqTM in Sub-Saharan Africa, the vaccine efficacy over a 2-year follow-up was lower against the genotypes contained in the vaccine than against the heterotypic G8P[6] and G8P[1] rotavirus strains of which the former is highly prevalent in Africa. Complete genome analyses of 43 complete rotavirus genomes collected during phase III clinical trials of RotaTeqTM in Sub-Saharan Africa, were conducted to gain insight into the high level of cross-protection afforded by RotaTeqTM against these G8 strains. Phylogenetic analysis revealed the presence of a high number of bovine rotavirus gene segments in these human G8 strains. In addition, we performed an in depth analysis on the individual amino acid level which showed that G8 rotaviruses were more similar to the RotaTeqTM vaccine than non-G8 strains. Because RotaTeqTM possesses a bovine genetic backbone, the high vaccine efficacy against G8 strains might be partially explained by the fact that all these strains contain a complete or partial bovine-like backbone. Altogether, this study supports the hypothesis that gene segments other than VP7 and VP4 play a role in vaccine-induced immunity.

Rotavirus and the Vaccine (Drops) to Prevent It

MedlinePlus

... intussusception case in every 20,000 infants to 1 intussusception case in every 100,000 infants after vaccination. There are 2 brands of rotavirus vaccine: RotaTeq and Rotarix. They are both given by mouth, not by a shot. What is rotavirus? Rotavirus causes severe diarrhea and ...

Rotavirus and the Vaccine (Drops) to Prevent It

MedlinePlus

... intussusception case in every 20,000 infants to 1 intussusception case in every 100,000 infants after vaccination. There are two brands of rotavirus vaccine: RotaTeq and Rotarix. They are both given by mouth, not by a shot. What is rotavirus? Rotavirus causes severe diarrhea and ...

Lack of nonspecific protection against all-cause nonrotavirus gastroenteritis by vaccination with orally administered rotavirus vaccine.

PubMed

Grant, Lindsay; Watt, James; Moulton, Lawrence; Weatherholtz, Robert; Reid, Raymond; Santosham, Mathuram; O'Brien, Katherine

2013-06-01

Acute gastroenteritis (AGE) is recognized as a global, common threat to child survival, especially in developing countries. Rotavirus, in particular, has been implicated as a leading cause of severe AGE; however, there are numerous other pathogens that also cause AGE. Several studies have demonstrated that oral vaccination against rotavirus has generated the unanticipated benefit of protecting against AGE caused by nonrotavirus pathogens. Safety and efficacy of the pentavalent bovine-human reassortant rotavirus vaccine were studied in multiple populations, including children of the Navajo and White Mountain Apache tribes in the southwestern United States. Stool specimens were collected from children with AGE and tested for rotavirus using an enzyme immunoassay. Analyses were conducted to detect the presence or absence of a vaccine effect on incidence, severity, and duration of AGE in which rotavirus was not detected. The majority of AGE (N = 558: 472 nonrotavirus vs 86 rotavirus) occurred between August 2002 and March 2004 among children ranging from ages 4 to 23 months. The incidence of nonrotavirus AGE was similar by vaccine groups with an incidence rate ratio of 1.07 (incidence rate ratio = vaccinated/unvaccinated, 95% confidence interval 0.89-1.29). The hazards of first, second, third, or any AGE in which rotavirus was not detected differed little by vaccination status (P > 0.05). Duration of symptoms and severity of nonrotavirus AGE were similar by vaccine group. There was no vaccine effect on frequency or severity of nonrotavirus AGE.

Rotavirus Infections

MedlinePlus

Rotavirus is a virus that causes gastroenteritis. Symptoms include severe diarrhea, vomiting, fever, and dehydration. Almost all ... the U.S. are likely to be infected with rotavirus before their 5th birthday. Infections happen most often ...

Rotavirus Viremia and Extraintestinal Viral Infection in the Neonatal Rat Model

PubMed Central

Crawford, Sue E.; Patel, Dinesh G.; Cheng, Elly; Berkova, Zuzana; Hyser, Joseph M.; Ciarlet, Max; Finegold, Milton J.; Conner, Margaret E.; Estes, Mary K.

2006-01-01

Rotaviruses infect mature, differentiated enterocytes of the small intestine and, by an unknown mechanism, escape the gastrointestinal tract and cause viremia. The neonatal rat model of rotavirus infection was used to determine the kinetics of viremia, spread, and pathology of rotavirus in extraintestinal organs. Five-day-old rat pups were inoculated intragastrically with an animal (RRV) or human (HAL1166) rotavirus or phosphate-buffered saline. Blood was collected from a subset of rat pups, and following perfusion to remove residual blood, organs were removed and homogenized to analyze rotavirus-specific antigen by enzyme-linked immunosorbent assay and infectious rotavirus by fluorescent focus assay or fixed in formalin for histology and immunohistochemistry. Viremia was detected following rotavirus infection with RRV and HAL1166. The RRV 50% antigenemia dose was 1.8 × 103 PFU, and the 50% diarrhea dose was 7.7 × 105 PFU, indicating that infection and viremia occurred in the absence of diarrhea and that detecting rotavirus antigen in the blood was a more sensitive measure of infection than diarrhea. Rotavirus antigens and infectious virus were detected in multiple organs (stomach, intestines, liver, lungs, spleen, kidneys, pancreas, thymus, and bladder). Histopathological changes due to rotavirus infection included acute inflammation of the portal tract and bile duct, microsteatosis, necrosis, and inflammatory cell infiltrates in the parenchymas of the liver and lungs. Colocalization of structural and nonstructural proteins with histopathology in the liver and lungs indicated that the histological changes observed were due to rotavirus infection and replication. Replicating rotavirus was also detected in macrophages in the lungs and blood vessels, indicating a possible mechanism of rotavirus dissemination. Extraintestinal infectious rotavirus, but not diarrhea, was observed in the presence of passively or actively acquired rotavirus-specific antibody. These findings alter the previously accepted concept of rotavirus pathogenesis to include not only gastroenteritis but also viremia, and they indicate that rotavirus could cause a broad array of systemic diseases in a number of different organs. PMID:16641274

Rotavirus A genotype G1P[8]: a novel method to distinguish wild-type strains from the Rotarix vaccine strain.

PubMed

Rose, Tatiana L; Miagostovich, Marize P; Leite, José Paulo G

2010-12-01

Rotaviruses are important enteric pathogens for humans and animals. Group A rotaviruses (RV-A) are the most common agents of severe gastroenteritis in infants and young children and vaccination is the most effective method to reduce RV-A-associated diseases. G1P[8], the most prevalent RV-A genotype worldwide, is included in the RV-A vaccine Rotarix®. The discrimination between wild-type G1P[8] and vaccine G1P[8] strains is an important topic in the study of RV-A epidemiology to manage outbreaks and to define control measures for vaccinated children. In this study, we developed a novel method to segregate the wild-type and vaccine strains using restriction endonucleases. The dsRNA from the Rotarix® vaccine was sequenced and the NSP3 gene was selected as the target gene. The vaccine strain has a restriction pattern that is different than that of wild-type RV-A G1P[8] isolates after digestion with the restriction endonuclease BspHI. This pattern could be used as a marker for the differentiation of wild-type G1P[8] strains from the vaccine strain.

Analyses of health outcomes from the 5 sites participating in the Africa and Asia clinical efficacy trials of the oral pentavalent rotavirus vaccine.

PubMed

Breiman, Robert F; Zaman, K; Armah, George; Sow, Samba O; Anh, Dang Duc; Victor, John C; Hille, Darcy; Ciarlet, Max; Neuzil, Kathleen M

2012-04-27

Efficacy of the pentavalent rotavirus vaccine (PRV), RotaTeq(®), against severe rotavirus gastroenteritis (RVGE) was evaluated in two double-blind, placebo-controlled, multicenter Phase III clinical trials conducted in GAVI-eligible countries in Africa (Ghana, Kenya, and Mali) and in Asia (Bangladesh and Vietnam) from March 2007 through March 2009. The findings from each continent have been analyzed and presented separately, according to a single identical protocol. Ad hoc analyses combining data from the five sites were performed to further assess the impact of PRV. 6674 infants (4705 infants from Africa and 1969 infants from Asia), randomized 1:1 to receive 3 doses of PRV/placebo at approximately 6-, 10-, and 14-weeks of age according to each country's EPI schedule, were included in the per protocol efficacy analysis. Breastfeeding and concomitant administration of EPI vaccines, including OPV, were allowed. Episodes of gastroenteritis (GE) in infants who presented to study facilities were captured and scored using the 20-point Vesikari scale. Stool samples were analyzed by rotavirus-specific EIA to detect presence of rotavirus antigen and RT-PCR to determine the G/P genotypes. We assessed efficacy to prevent all-cause GE and RVGE at a variety of cut-off points (score≥11, severe; score≥15, very severe). Vaccine efficacy (VE) against RVGE, regardless of serotype, through the entire follow-up period for any severity, severe (score≥11), and very severe (score≥15) was 33.9%, 95% CI (22.7, 43.5), 42.5%, 95% CI (27.4, 54.6), and 51.2%, 95% CI (26.3, 68.2), respectively. Through the first year of life, VE against severe RVGE was 58.9%, 95% CI (40.0, 72.3) and against all-cause severe GE was 23.0%, 95% CI (5.4, 37.3). VE against severe RVGE caused by non-vaccine G serotypes, G8 and G9, through the entire follow-up period was 87.5%, 95% CI (6.8, 99.7) and 48.0%, 95% CI (-5.5, 75.6), respectively. All G8 strains were associated with P2A[6] (a P-type not contained in PRV), while the majority of the G9 strains were associated with P1A[8] (a P-type contained in PRV). Combining data from the 5 sites strengthens the precision of VE estimates and reveals rising VE with increased RVGE severity. Extrapolating data from VE against severe GE and RVGE suggest that 39% of severe GE episodes during the first year of life were due to rotavirus, highlighting substantial, potentially preventable, public health burden of RVGE. PRV provides protection against non-vaccine serotypes (G8P2A[6]). Published by Elsevier Ltd.

Impact of vaccination uptake on hospitalizations due to rotavirus acute gastroenteritis in 2 different socioeconomic areas of Spain

PubMed Central

Giménez Sánchez, Francisco; Nogueira, Esperanza Jiménez; Sánchez Forte, Miguel; Ibáñez Alcalde, Mercedes; Cobo, Elvira; Angulo, Raquel; Garrido Fernández, Pablo

2016-01-01

ABSTRACT Rotavirus is the leading cause of hospitalization due to acute gastroenteritis (AGE) in infants and toddlers. However, rotavirus vaccination has been associated with a decline in hospitalization rates due to rotavirus AGE. A descriptive retrospective study was conducted to analyze the impact of rotavirus vaccination on the rate of hospitalizations due to AGE among children ≤2 years old in 2 areas of the province of Almería, Spain. After eight years of rotavirus vaccination, rates of hospitalizations due to rotavirus AGE are diminished. This decline is closely related to vaccine coverage in the studied areas. PMID:26810147

Rotavirus infection

PubMed Central

Crawford, Sue E.; Ramani, Sasirekha; Tate, Jacqueline E.; Parashar, Umesh D.; Svensson, Lennart; Hagbom, Marie; Franco, Manuel A.; Greenberg, Harry B.; O’Ryan, Miguel; Kang, Gagandeep; Desselberger, Ulrich; Estes, Mary K.

2017-01-01

Rotavirus infections are a leading cause of severe, dehydrating gastroenteritis in children <5 years of age. Despite the global introduction of vaccinations for rotavirus over a decade ago, rotavirus infections still result in >200,000 deaths annually, mostly in low-income countries. Rotavirus primarily infects enterocytes and induces diarrhoea through the destruction of absorptive enterocytes (leading to malabsorption), intestinal secretion stimulated by rotavirus non-structural protein 4 and activation of the enteric nervous system. In addition, rotavirus infections can lead to antigenaemia (which is associated with more severe manifestations of acute gastroenteritis) and viraemia, and rotavirus can replicate in systemic sites, although this is limited. Reinfections with rotavirus are common throughout life, although the disease severity is reduced with repeat infections. The immune correlates of protection against rotavirus reinfection and recovery from infection are poorly understood, although rotavirus-specific immunoglobulin A has a role in both aspects. The management of rotavirus infection focuses on the prevention and treatment of dehydration, although the use of antiviral and anti-emetic drugs can be indicated in some cases. PMID:29119972

The epidemiology of all-cause and rotavirus acute gastroenteritis and the characteristics of rotavirus circulating strains before and after rotavirus vaccine introduction in Yemen: analysis of hospital-based surveillance data.

PubMed

Banajeh, Salem M; Abu-Asba, Basheer A

2015-10-13

Rotavirus (RV) vaccine was added to Yemen's childhood vaccination schedule in late 2012. We evaluated the effect of vaccination on the epidemiology of acute gastroenteritis (AGE) and the characteristics of circulating RV strains. Surveillance data was obtained at two sentinel hospitals from 5,691 children with acute gastroenteritis (AGE) who were under 5 years of age. Data collected before (2007-2011) and after (2013-2014) RV vaccine introduction were retrospectively analyzed. Treatment outcome, presence of severe dehydration, and the proportion of all-cause AGE due to RV-antigen positive AGE were calculated for each period and compared. Binominal generalized linear models were used to calculate adjusted odds ratios (ORs) and 95 % confidence intervals (CIs). We also compared severe RVAGE and severe dehydration proportions in hospitalized children with severe AGE and characterized RV circulating strains in available specimens from the two periods. Before RV vaccination, mean RVAGE prevalence peaked in October (58.8 %), November (69.5 %), and December (56.4 %). In 2013-2014, the variation became less defined, with only a few RVAGE cases. The average annual prevalence of severe RVAGE needing hospitalization was 42.9 % in 2007-2011, decreased to 21.1 % in 2013, and to 18.5 % in 2014, representing declines of 50.8 % (95 % CI: 36.4-65.0) and 56.9 % (95 % CI: 42.1-70.5). The proportion of children <12 months of age with all-cause AGE decreased significantly after introduction of RV vaccination (58.7 % vs. 62.3 %; p = 0.042), severe dehydration decreased by 50 % (14.7 % vs. 21.7 %; OR = 0.501, p < 0.0001), and RVAGE proportion decreased by 48 % (19.9 % vs. 41.6 %; OR = 0.52, p < 0.0001). The proportion of severe RVAGE in hospitalized patients decreased by 67 % (20.1 % vs. 43.5 %; OR = 0.33, p < 0.0001), and severe dehydration decreased by 58 % (17.2 % vs. 33.1 %; OR = 0.42, p < 0.0001). Non-RV AGE prevalence significantly increased, with ORs of 2.8-3.1 in favor of non-RV AGE in 2013-2014. Analysis of 128 available stool specimens revealed that circulation of the G1 genotype did not change following vaccination (33.3 % vs. 41.3 %; p = 0.366). G2 significantly decreased in 2013-2014 (4.2 % vs. 42.5 % p = 0.0001), and G9 increased (29.2 % vs. 6.3 %; p = 0.001). G1P[8] and G2P[4] remained prevalent, and G9P[8] and G9P[4], which were not detected in the pre-vaccine period appeared in 2013-2014. G and [P] mixed genotypes became more prevalent in 2013-2014. It is not known if this predominance is related to the vaccine introduction or attributable to normal genotype fluctuations. Rotarix substantially reduced the prevalence of RVAGE, with a 67 % reduction of severe RVAGE hospitalizations, and over 50 % reduction of diarrhea with severe dehydration. Circulation of RV G and [P] mix strains was significantly increased in 2013-2014 and needs continuous monitoring.

Burden of Rotavirus Disease in Norway: Using National Registries for Public Health Research.

PubMed

Bruun, Tone; Salamanca, Beatriz Valcarcel; Bekkevold, Terese; Vainio, Kirsti; Gibory, Moustafa; Haugstad, Kirsti Egge; Rojahn, Astrid; Jakobsen, Kirsti; Størvold, Gunnar; Lunde, Anette; Størdal, Ketil; Kanestrøm, Anita; Eidem, Magnhild Owesen; Døllner, Henrik; Skanke, Lars Høsøien; Nordbø, Svein Arne; Sivertsen, Heidi Christin; Gilje, Ann Marit; Haarr, Elisebet; Flem, Elmira

2016-04-01

Norway introduced routine rotavirus immunization for all children born on or after September 1, 2014. We estimated the healthcare burden of all-cause gastroenteritis and rotavirus disease in children <5 years old to establish the prevaccine baseline and support the ongoing immunization program. We examined national registry data on gastroenteritis-associated primary care consultations and hospitalizations for 2009-2013 and data on all deaths in children <5 years old reported during 2000-2013. We also established rotavirus hospital surveillance from February 2014 through January 2015. Before vaccine introduction, 114.5 cases per 1000 children <5 years old were treated in primary care and 11.8 children per 1000 were hospitalized with gastroenteritis annually. During hospital surveillance, rotavirus was detected in 65% (95% confidence interval: 60-70) of inpatient gastroenteritis cases. We estimated that 4.0 inpatient and 2.3 outpatient cases per 1000 children were seen in hospital with rotavirus disease annually, suggesting that 1 in 32 children was hospitalized by age 5. Additional 30.6 rotavirus cases per 1000 children consulted primary care annually or 1 in every 7 children by the age of 5 years. Rotavirus-associated mortality was estimated at 0.17 deaths per 100,000 children <5 years old, corresponding to 1 death every second year. Rotavirus remains the primary cause of severe gastroenteritis in children in Norway. The unique population-based registers, in combination with an established rotavirus surveillance platform, provide a well-suited setting to evaluate the impact of rotavirus vaccination.

Estimating the herd immunity effect of rotavirus vaccine.

PubMed

Pollard, Suzanne L; Malpica-Llanos, Tanya; Friberg, Ingrid K; Fischer-Walker, Christa; Ashraf, Sania; Walker, Neff

2015-07-31

Diarrhea is one of the leading causes of death in children under 5, and an estimated 39% of these deaths are attributable to rotavirus. Currently two live, oral rotavirus vaccines have been introduced on the market; however, the herd immunity effect associated with rotavirus vaccine has not yet been quantified. The purpose of this meta-analysis was to estimate the herd immunity effects associated with rotavirus vaccines. We performed a systematic literature review of articles published between 2008 and 2014 that measured the impact of rotavirus vaccine on severe gastroenteritis (GE) morbidity or mortality. We assessed the quality of published studies using a standard protocol and conducted meta-analyses to estimate the herd immunity effect in children less than one year of age across all years presented in the studies. We conducted these analyses separately for studies reporting a rotavirus-specific GE outcome and those reporting an all-cause GE outcome. In studies reporting a rotavirus-specific GE outcome, four of five of which were conducted in the United States, the median herd effect across all study years was 22% [19-25%]. In studies reporting an all-cause GE outcome, all of which were conducted in Latin America, the median herd effect was 24.9% [11-30%]. There is evidence that rotavirus vaccination confers a herd immunity effect in children under one year of age in the United States and Latin American countries. Given the high variability in vaccine efficacy across regions, more studies are needed to better examine herd immunity effects in high mortality regions. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

Visualizing geographic and temporal trends in rotavirus activity in the United States, 1991 to 1996. National Respiratory and Enteric Virus Surveillance System Collaborating Laboratories.

PubMed

Török, T J; Kilgore, P E; Clarke, M J; Holman, R C; Bresee, J S; Glass, R I

1997-10-01

Rotavirus is the leading cause of severe pediatric gastroenteritis worldwide. A vaccine may soon be licensed for use in the United States to prevent this disease. To characterize US geographic and temporal trends in rotavirus activity, we made contour maps showing the timing of peak rotavirus activity. From July, 1991, through June, 1996, 79 laboratories participating in the National Respiratory and Enteric Virus Surveillance System reported on a weekly basis the number of stool specimens that tested positive for rotavirus. The peak weeks in rotavirus detections from each laboratory were mapped using kriging, a modeling technique originally developed for geostatistics. During the 5-year period 118,716 fecal specimens were examined, of which 27,616 (23%) were positive for rotavirus. Timing of rotavirus activity varied by geographic location in a characteristic pattern in which peak activity occurred first in the Southwest from October through December and last in the Northeast in April or May. The Northwest exhibited considerable year-to-year variability (range, December to May) in the timing of peak activity, whereas the temporal pattern in the remainder of the contiguous 48 states was relatively constant. Kriging is a useful method for visualizing geographic and temporal trends in rotavirus activity in the United States. This analysis confirmed trends reported in previous years, and it also identified unexpected variability in the timing of peak rotavirus activity in the Northwest. The causes of the seasonal differences in rotavirus activity by region are unknown. Tracking of laboratory detections of rotavirus may provide an effective surveillance tool to assess the impact of a rotavirus vaccination campaign in the United States.

Efficacy of a pentavalent human-bovine reassortant rotavirus vaccine against rotavirus gastroenteritis among American Indian children.

PubMed

Grant, Lindsay R; Watt, James P; Weatherholtz, Robert C; Moulton, Lawrence H; Reid, Raymond; Santosham, Mathuram; O'Brien, Katherine L

2012-02-01

Before the widespread use of rotavirus vaccines, rotavirus was a leading cause of gastroenteritis among children. Navajo and White Mountain Apache children suffer a disproportionate burden of severe rotavirus disease compared with the general U.S. population. We enrolled Navajo and White Mountain Apache infants in a multicenter, double-blind, placebo-controlled trial of pentavalent human-bovine reassortant rotavirus vaccine (PRV). Subjects received 3 doses of vaccine or placebo at 4 to 10 week intervals, with the first dose given between 6 and 12 weeks of age. Gastroenteritis episodes were identified by active surveillance. Disease severity was determined by a standardized scoring system. There were 509 and 494 randomized children who received vaccine and placebo, respectively. Among placebo recipients, the incidence of rotavirus gastroenteritis was 34.2 episodes/100 child-years (95% confidence interval [95% CI]: 25.8-38.9) versus 8.1 episodes/100 child-years (95% CI: 5.4-12.5) in the vaccine group. The percentage of rotavirus episodes caused by serotypes G1, G2, and G3 was 72.3%, 23.4%, and 2.1%, respectively. There were no severe rotavirus episodes among vaccinees and 4 among placebo recipients. PRV was 77.1% (95% CI: 59.7-87.6), 89.5% (95% CI: 65.9-97.9), and 82.9% (95% CI: 61.1-93.6) effective against G1-G4 rotavirus disease, severe and moderate rotavirus disease combined, and outpatient visits for rotavirus disease, respectively. The risk of adverse events was similar for the vaccine and placebo groups. PRV was highly effective in preventing rotavirus disease and related health care utilization in these American Indian infants. Vaccine efficacy and immunogenicity were similar to the overall study population enrolled in the multicenter trial.

Estimated hospitalizations attributed to norovirus and rotavirus infection in Canada, 2006-2010.

PubMed

Morton, V K; Thomas, M K; McEwen, S A

2015-12-01

Enteric viruses including norovirus and rotavirus are leading causes of gastroenteritis in Canada. However, only a small number of clinical cases are actually tested for these pathogens leading to systematic underestimation of attributed hospitalizations in administrative databases. The objective of this analysis was to estimate the number of hospitalizations due to norovirus and rotavirus in Canada. Hospitalization records for acute gastroenteritis-associated discharges at all acute-care hospitals in Canada between 2006 and 2011 were analysed. Cause-unspecified gastroenteritis hospitalizations were modelled using age-specific negative binomial models with cause-specified gastroenteritis admissions as predictors. The coefficients from the models were used to estimate the number of norovirus and rotavirus admissions. The total annual hospitalizations for rotavirus were estimated to be between 4500 and 10 000. Total annual hospitalizations for norovirus were estimated to be between 4000 and 11 000. The mean total annual cost associated with these hospitalizations was estimated to be at least $16 million for rotavirus and $21 million for norovirus (all figures in Canadian dollars). This study is the first comprehensive analysis of norovirus and rotavirus hospitalizations in Canada. These estimates provide a more complete assessment of the burden and economic costs of these pathogens to the Canadian healthcare system.

Stomach Flu: How Long Am I Contagious?

MedlinePlus

... the last time they vomit or have diarrhea. Rotavirus. Symptoms of rotavirus — the leading cause of viral gastroenteritis in infants ... or linens that might be contaminated. Two oral rotavirus vaccines are available for young infants — RotaTeq and ...

Global Impact of Rotavirus Vaccination on Childhood Hospitalizations and Mortality From Diarrhea.

PubMed

Burnett, Eleanor; Jonesteller, Christine L; Tate, Jacqueline E; Yen, Catherine; Parashar, Umesh D

2017-06-01

In 2006, 2 rotavirus vaccines were licensed. We summarize the impact of rotavirus vaccination on hospitalizations and deaths from rotavirus and all-cause acute gastroenteritis (AGE) during the first 10 years since vaccine licensure, including recent evidence from countries with high child mortality. We used standardized guidelines (PRISMA) to identify observational evaluations of rotavirus vaccine impact among children <5 years of age that presented at least 12 months of pre- and post-vaccine introduction surveillance data. We identified 57 articles from 27 countries. Among children <5 years of age, the median percentage reduction in AGE hospitalizations was 38% overall and 41%, 30%, and 46% in countries with low, medium, and high child mortality, respectively. Hospitalizations and emergency department visits due to rotavirus AGE were reduced by a median of 67% overall and 71%, 59%, and 60% in countries with low, medium, and high child mortality, respectively. Implementation of rotavirus vaccines has substantially decreased hospitalizations from rotavirus and all-cause AGE. Published by Oxford University Press for the Infectious Diseases Society of America 2017. This work is written by (a) US Government employee(s) and is in the public domain in the US.

Clinical and Molecular Characteristics of Human Rotavirus G8P[8] Outbreak Strain, Japan, 2014.

PubMed

Kondo, Kenji; Tsugawa, Takeshi; Ono, Mayumi; Ohara, Toshio; Fujibayashi, Shinsuke; Tahara, Yasuo; Kubo, Noriaki; Nakata, Shuji; Higashidate, Yoshihito; Fujii, Yoshiki; Katayama, Kazuhiko; Yoto, Yuko; Tsutsumi, Hiroyuki

2017-06-01

During March-July 2014, rotavirus G8P[8] emerged as the predominant cause of rotavirus gastroenteritis among children in Hokkaido Prefecture, Japan. Clinical characteristics were similar for infections caused by G8 and non-G8 strains. Sequence and phylogenetic analyses suggest the strains were generated by multiple reassortment events between DS-1-like P[8] strains and bovine strains from Asia.

Changes in Rotavirus Genotypes before and after Vaccine Introduction: a Multicenter, Prospective Observational Study in Three Areas of Japan.

PubMed

Tanaka, Takaaki; Kamiya, Hajime; Asada, Kazutoyo; Suga, Shigeru; Ido, Masaru; Umemoto, Masakazu; Ouchi, Kazunobu; Ito, Hiroaki; Kuroki, Haruo; Nakano, Takashi; Taniguchi, Koki

2017-07-24

In Japan, monovalent and pentavalent rotavirus (RV) vaccines were approved in 2011 and 2012, respectively. To monitor changes in the RV genotypes before and after vaccine introduction, we performed a prospective observational study among children (＜ 5 years) with gastroenteritis who tested RV-positive on antigen rapid tests. Stool samples were collected from 3 different sites in Japan: Tsu City, Mie Prefecture; Kurashiki City, Okayama Prefecture; and Isumi City, Chiba Prefecture. RV genotypes were determined using reverse transcription-polymerase chain reaction. In Tsu City, G3P[8] was dominant (61.0-77.1%) before vaccine introduction, but decreased after introduction. Meanwhile, in an inverse proportion to the decrease in G3P[8], G1P[8] increased until the 2013/14 season, when a sudden predominance of G2P[4] (100%) occurred. A similar trend was observed in Kurashiki City in terms of the extent of reduction in G3P[8] and the emergence of G2P[4]. In Isumi City, G1P[8] was dominant (70.3%) before vaccine introduction, and G9P[8] became predominant (83.3%) in the 2013/14 season. To determine whether the genotype changes are attributable to vaccines or natural epidemiological changes, ongoing continuous monitoring of the RV genotypes is required.

Characterization of rotavirus infection in children with acute gastroenteritis in Bengo province, Northwestern Angola, prior to vaccine introduction

PubMed Central

Mirante, Maria Clara; Mendes, Cristina; Mayer, Carlos; Vaz Nery, Susana; Brito, Miguel

2017-01-01

Background Rotavirus group A (RVA) is considered the leading cause of pediatric diarrhea, responsible for the high burden of diarrheal diseases in sub-Saharan Africa. Despite recent studies, the existent data are scarce for some African countries like Angola, a country with one of the highest RVA-related death estimates. The aim of this study was to determine the RVA detection rate and circulating genotypes in children less than five years of age with acute gastroenteritis attended at the Bengo General Hospital in Caxito, Bengo province, Angola, before vaccine introduction. Methods Between September 2012 and December 2013, 342 fecal specimens were collected from children enrolled. Positive samples for RVA by immunochromatographic rapid test were G and P-typed by hemi-nested type-specific multiplex PCR, and subgrouped for the VP6 gene. VP4 and VP7 genes from a subset of samples were sequenced for phylogenetic analysis. Results During the study period, a high RVA detection rate was registered (25.1%, 86/342). The age group most affected by RVA infection includes children under 6 months of age (p<0.01). Vomiting was highly associated with RVA infection (72.1%; p<0.001). From the 86 RVA-positive samples, 72 (83.7%) were genotyped. The most prevalent genotype was G1P[8] (34/72; 47.2%), followed by the uncommon G1P[6] (21/72; 29.2%), and G2P[4] (9/72; 12.5%). Only two G-types were found: G1 (60/72; 83.3%) and G2 (11/72; 15.3%). Among the P-genotypes, P[8] was the most prevalent (34/72; 47.2%), followed by P[6] (22/72; 30.6%) and P[4] (9/72; 12.5%). In the phylogenetic trees, the identified G and P-types clustered tightly together and with reference sequences in specific monophyletic groups, with highly significant bootstrap values (≥92%). Conclusion This pre-vaccination study revealed, for the first time for Bengo province (Angola), the RVA genotype profile, including phylogenetic relationships, and a high RVA detection rate, supporting the immediate introduction of a RVA vaccine in the national immunization programme. PMID:28422995

Characterization of rotavirus infection in children with acute gastroenteritis in Bengo province, Northwestern Angola, prior to vaccine introduction.

PubMed

Gasparinho, Carolina; Piedade, João; Mirante, Maria Clara; Mendes, Cristina; Mayer, Carlos; Vaz Nery, Susana; Brito, Miguel; Istrate, Claudia

2017-01-01

Rotavirus group A (RVA) is considered the leading cause of pediatric diarrhea, responsible for the high burden of diarrheal diseases in sub-Saharan Africa. Despite recent studies, the existent data are scarce for some African countries like Angola, a country with one of the highest RVA-related death estimates. The aim of this study was to determine the RVA detection rate and circulating genotypes in children less than five years of age with acute gastroenteritis attended at the Bengo General Hospital in Caxito, Bengo province, Angola, before vaccine introduction. Between September 2012 and December 2013, 342 fecal specimens were collected from children enrolled. Positive samples for RVA by immunochromatographic rapid test were G and P-typed by hemi-nested type-specific multiplex PCR, and subgrouped for the VP6 gene. VP4 and VP7 genes from a subset of samples were sequenced for phylogenetic analysis. During the study period, a high RVA detection rate was registered (25.1%, 86/342). The age group most affected by RVA infection includes children under 6 months of age (p<0.01). Vomiting was highly associated with RVA infection (72.1%; p<0.001). From the 86 RVA-positive samples, 72 (83.7%) were genotyped. The most prevalent genotype was G1P[8] (34/72; 47.2%), followed by the uncommon G1P[6] (21/72; 29.2%), and G2P[4] (9/72; 12.5%). Only two G-types were found: G1 (60/72; 83.3%) and G2 (11/72; 15.3%). Among the P-genotypes, P[8] was the most prevalent (34/72; 47.2%), followed by P[6] (22/72; 30.6%) and P[4] (9/72; 12.5%). In the phylogenetic trees, the identified G and P-types clustered tightly together and with reference sequences in specific monophyletic groups, with highly significant bootstrap values (≥92%). This pre-vaccination study revealed, for the first time for Bengo province (Angola), the RVA genotype profile, including phylogenetic relationships, and a high RVA detection rate, supporting the immediate introduction of a RVA vaccine in the national immunization programme.

Detection of Rare G3P[19] Porcine Rotavirus Strains in Chiang Mai, Thailand, Provides Evidence for Origin of the VP4 Genes of Mc323 and Mc345 Human Rotaviruses▿

PubMed Central

Maneekarn, Niwat; Khamrin, Pattara; Chan-it, Wisoot; Peerakome, Supatra; Sukchai, Sujin; Pringprao, Kidsadagon; Ushijima, Hiroshi

2006-01-01

Among 175 fecal specimens collected from diarrheic piglets during a surveillance of porcine rotavirus (PoRV) strains in Chiang Mai, Thailand, 39 (22.3%) were positive for group A rotaviruses. Of these, 33.3% (13 of 39) belonged to G3P[19], which was a rare P genotype seldom reported. Interestingly, their VP4 nucleotide sequences were most closely related to human P[19] strains (Mc323 and Mc345) isolated in 1989 from the same geographical area where these PoRV strains were isolated. These P[19] PoRV strains were also closely related to another human P[19] strain (RMC321), isolated from India in 1990. The VP4 sequence identities with human P[19] were 95.4% to 97.4%, while those to a porcine P[19] strain (4F) were only 87.6 to 89.1%. Phylogenetic analysis of the VP4 gene revealed that PoRV P[19] strains clustered with human P[19] strains in a monophyletic branch separated from strain 4F. Analysis of the VP7 gene confirmed that these strains belonged to the G3 genotype and shared 97.7% to 98.3% nucleotide identities with other G3 PoRV strains circulating in the regions. This close genetic relationship was also reflected in the phylogenetic analysis of their VP7 genes. Altogether, the findings provided peculiar evidence that supported the porcine origin of VP4 genes of Mc323 and Mc345 human rotaviruses. PMID:16988014

Comparative analysis of the Rotarix™ vaccine strain and G1P[8] rotaviruses detected before and after vaccine introduction in Belgium.

PubMed

Zeller, Mark; Heylen, Elisabeth; Tamim, Sana; McAllen, John K; Kirkness, Ewen F; Akopov, Asmik; De Coster, Sarah; Van Ranst, Marc; Matthijnssens, Jelle

2017-01-01

G1P[8] rotaviruses are responsible for the majority of human rotavirus infections worldwide. The effect of universal mass vaccination with rotavirus vaccines on circulating G1P[8] rotaviruses is still poorly understood. Therefore we analyzed the complete genomes of the Rotarix™ vaccine strain, and 70 G1P[8] rotaviruses, detected between 1999 and 2010 in Belgium (36 before and 34 after vaccine introduction) to investigate the impact of rotavirus vaccine introduction on circulating G1P[8] strains. All rotaviruses possessed a complete Wa-like genotype constellation, but frequent intra-genogroup reassortments were observed as well as multiple different cluster constellations circulating in a single season. In addition, identical cluster constellations were found to circulate persistently over multiple seasons. The Rotarix™ vaccine strain possessed a unique cluster constellation that was not present in currently circulating G1P[8] strains. At the nucleotide level, the VP6, VP2 and NSP2 gene segments of Rotarix™ were relatively distantly related to any Belgian G1P[8] strain, but other gene segments of Rotarix™ were found in clusters also containing circulating Belgian strains. At the amino acid level, the genetic distance between Rotarix™ and circulating Belgian strains was considerably lower, except for NSP1. When we compared the Belgian G1P[8] strains collected before and after vaccine introduction a reduction in the proportion of strains that were found in the same cluster as the Rotarix™ vaccine strain was observed for most gene segments. The reduction in the proportion of strains belonging to the same cluster may be the result of the vaccine introduction, although natural fluctuations cannot be ruled out.

Determinants of Parents' Decision to Vaccinate Their Children against Rotavirus: Results of a Longitudinal Study

ERIC Educational Resources Information Center

Dube, E.; Bettinger, J. A.; Halperin, B.; Bradet, R.; Lavoie, F.; Sauvageau, C.; Gilca, V.; Boulianne, N.

2012-01-01

Rotavirus disease is a common cause of health care utilization and almost all children are affected by the age of 5 years. In Canada, at the time of this survey (2008-09), immunization rates for rotavirus were less than 20%. We assessed the determinants of a parent's acceptance to have their child immunized against rotavirus. The survey…

Clinical and Molecular Characteristics of Human Rotavirus G8P[8] Outbreak Strain, Japan, 2014

PubMed Central

Kondo, Kenji; Ono, Mayumi; Ohara, Toshio; Fujibayashi, Shinsuke; Tahara, Yasuo; Kubo, Noriaki; Nakata, Shuji; Higashidate, Yoshihito; Fujii, Yoshiki; Katayama, Kazuhiko; Yoto, Yuko; Tsutsumi, Hiroyuki

2017-01-01

During March–July 2014, rotavirus G8P[8] emerged as the predominant cause of rotavirus gastroenteritis among children in Hokkaido Prefecture, Japan. Clinical characteristics were similar for infections caused by G8 and non-G8 strains. Sequence and phylogenetic analyses suggest the strains were generated by multiple reassortment events between DS-1–like P[8] strains and bovine strains from Asia. PMID:28518031

Changing molecular epidemiology of rotavirus infection after introduction of monovalent rotavirus vaccination in Scotland.

PubMed

Mukhopadhya, Indrani; Murdoch, Heather; Berry, Susan; Hunt, Alison; Iturriza-Gomara, Miren; Smith-Palmer, Alison; Cameron, J Claire; Hold, Georgina L

2017-01-03

Rotaviruses (RV) are the leading cause of gastroenteritis in children less than five years of age worldwide. Rotarix®, a live attenuated monovalent vaccine containing a RV strain of G1P[8] specificity has been included in the childhood immunisation schedule from June 2013 in Scotland. This study aimed to characterise the prevalent RV strains in Scotland before and after the introduction of the RV vaccine. RV positive faecal samples from Scottish virology laboratories covering the years 2012-2015 were genotyped. Viral RNA was extracted from faecal suspensions. VP7 and VP4 gene specific primers were used for multiplex hemi-nested PCRs and sequencing. Mann-Whitney U test and Chi-square test were used for statistical comparison. There was a decrease in RV positive samples from the Scottish virology laboratories from 7409 samples in the pre-vaccination years (2009-2013) to 760 in 2014-2015, with an annual reduction of RV infections by 74.4% (RR-3.95; 95%-CI, 3.53-4.42, p<0.001). 362 samples from the pre-vaccination period and 278 samples from the post-vaccination were genotyped. There was a drop in prevalence of G1P[8] strains (72.1%, 95%-CI, 67.42-76.33 to 15%, 95%-CI, 11.38-19.79) after introduction of the vaccine. In the post-vaccination period G2P[4] was the dominant strain in Scotland (21.9%, 95%-CI, 17.48-27.17) with increase in G9P[8] (12.9%, 95%-CI, 9.50-7.41), G12P[8] (12.2%, 95%-CI, 8.89-16.60) and G3P[8] (11.9%, 95%-CI, 8.58-16.20) infections. Phylogenetic analysis of the VP7 and VP4 genes showed no major differences between the pre and post-vaccination G1P[8] strains. This laboratory based surveillance study shows significant reduction in reported RV cases and a shift in proportion from G1P[8] to G2P[4] strains after introduction of RV vaccination in Scotland. The genotyping data from a subset of the total reported RV cases will be used to ascertain cross protection against strains and identify vaccine induced RV strain shifts in the years to come. Copyright © 2016 Elsevier Ltd. All rights reserved.

Modeling effect of cover condition and soil type on rotavirus transport in surface flow.

PubMed

Bhattarai, Rabin; Davidson, Paul C; Kalita, Prasanta K; Kuhlenschmidt, Mark S

2017-08-01

Runoff from animal production facilities contains various microbial pathogens which pose a health hazard to both humans and animals. Rotavirus is a frequently detected pathogen in agricultural runoff and the leading cause of death among children around the world. Diarrheal infection caused by rotavirus causes more than two million hospitalizations and death of more than 500,000 children every year. Very little information is available on the environmental factors governing rotavirus transport in surface runoff. The objective of this study is to model rotavirus transport in overland flow and to compare the model results with experimental observations. A physically based model, which incorporates the transport of infective rotavirus particles in both liquid (suspension or free-floating) and solid phase (adsorbed to soil particles), has been used in this study. Comparison of the model results with experimental results showed that the model could reproduce the recovery kinetics satisfactorily but under-predicted the virus recovery in a few cases when multiple peaks were observed during experiments. Similarly, the calibrated model had a good agreement between observed and modeled total virus recovery. The model may prove to be a promising tool for developing effective management practices for controlling microbial pathogens in surface runoff.

Group A Rotaviruses in Chinese Bats: Genetic Composition, Serology, and Evidence for Bat-to-Human Transmission and Reassortment.

PubMed

He, Biao; Huang, Xiaohong; Zhang, Fuqiang; Tan, Weilong; Matthijnssens, Jelle; Qin, Shaomin; Xu, Lin; Zhao, Zihan; Yang, Ling'en; Wang, Quanxi; Hu, Tingsong; Bao, Xiaolei; Wu, Jianmin; Tu, Changchun

2017-06-15

Bats are natural reservoirs for many pathogenic viruses, and increasing evidence supports the notion that bats can also harbor group A rotaviruses (RVAs), important causative agents of diarrhea in children and young animals. Currently, 8 RVA strains possessing completely novel genotype constellations or genotypes possibly originating from other mammals have been identified from African and Chinese bats. However, all the data were mainly based on detection of RVA RNA, present only during acute infections, which does not permit assessment of the true exposure of a bat population to RVA. To systematically investigate the genetic diversity of RVAs, 547 bat anal swabs or gut samples along with 448 bat sera were collected from five South Chinese provinces. Specific reverse transcription-PCR (RT-PCR) screening found four RVA strains. Strain GLRL1 possessed a completely novel genotype constellation, whereas the other three possessed a constellation consistent with the MSLH14-like genotype, a newly characterized group of viruses widely prevalent in Chinese insectivorous bats. Among the latter, strain LZHP2 provided strong evidence of cross-species transmission of RVAs from bats to humans, whereas strains YSSK5 and BSTM70 were likely reassortants between typical MSLH14-like RVAs and human RVAs. RVA-specific antibodies were detected in 10.7% (48/448) of bat sera by an indirect immunofluorescence assay (IIFA). Bats in Guangxi and Yunnan had a higher RVA-specific antibody prevalence than those from Fujian and Zhejiang provinces. These observations provide evidence for cross-species transmission of MSLH14-like bat RVAs to humans, highlighting the impact of bats as reservoirs of RVAs on public health. IMPORTANCE Bat viruses, such as severe acute respiratory syndrome (SARS), Middle East respiratory syndrome (MERS), Ebola, Hendra, and Nipah viruses, are important pathogens causing outbreaks of severe emerging infectious diseases. However, little is known about bat viruses capable of causing gastroenteritis in humans, even though 8 group A viruses (RVAs) have been identified from bats so far. In this study, another 4 RVA strains were identified, with one providing strong evidence for zoonotic transmission from bats to humans. Serological investigation has also indicated that RVA infection in bats is far more prevalent than expected based on the detection of viral RNA. Copyright © 2017 American Society for Microbiology.

VP8*P[8] lineages of group A rotaviruses circulating over 20 years in Brazil: proposal of six different sub-lineages for P[8]-3 clade.

PubMed

da Silva, Marcelle Figueira Marques; Gómez, Mariela Martínez; Rose, Tatiana Lundgren; Volotão, Eduardo de Mello; Carvalho-Costa, Filipe Anibal; Bello, Gonzalo; Leite, Jose Paulo Gagliardi

2013-06-01

Group A rotaviruses (RVA) is the most important cause of severe gastroenteritis among children worldwide. Vaccination is considered the best alternative among public health measures to reduce and prevent the global burden caused by RVA infections. Rotarix™, a monovalent vaccine based on a human strain with a G1P[8]-1 specificity, was introduced in the National Brazilian Immunization Programs (NIP) in March, 2006. RVA P[8] is the most prevalent P genotype worldwide and four distinct phylogenetic lineages: P[8]-1, -2, -3, and -4 have been described. In the current study phylogenetic analysis of the VP8(*) gene of 135 RVA P[8] Brazilian strains, in combination with G1, G3, G5 or G9 VP7 genotype, collected from 1986 to 2011 were carried out for a better understanding of the evolution of this viral genotype in Brazil. Lineages P[8]-1, P[8]-2, and P[8]-3 were observed circulating in Brazil. In 2001 these three P[8] lineages co-circulated simultaneously and this is the first report in South America to date. Considering the P[8] lineage and the G genotype, all G3 strains were related to lineage P[8]-3, whereas the G9 strains were related to P[8]-2 and P[8]-3 and G1 and G5 were related to P[8]-1, P[8]-2, and P[8]-3. In addition, the phylogenetic analysis based on estimate of genetic distances between P[8]-3 strains and the definition of a 1.5% cutoff value (with relevant statistical support) it was possible to propose a new classification for the P[8]-3 lineage into six different sub-lineages: P[8]-3.1 to P[8]-3.6. These findings reinforce the notion of the existence of constraints within specific RVA strains populations. The results obtained in this study reinforce the importance of a continuous RVA surveillance of circulating strains in order to predict the possible variants that will circulate in a country, assess the effects of vaccination on RVA circulating strains, and ultimately help in the design, challenges, and prospects of RVA vaccines. Copyright © 2013 Elsevier B.V. All rights reserved.

Human rotavirus vaccine is highly efficacious when coadministered with routine expanded program of immunization vaccines including oral poliovirus vaccine in Latin America.

PubMed

Tregnaghi, Miguel W; Abate, Héctor J; Valencia, Alejandra; Lopez, Pio; Da Silveira, Themis Reverbel; Rivera, Luis; Rivera Medina, Doris Maribel; Saez-Llorens, Xavier; Gonzalez Ayala, Silvia Elena; De León, Tirza; Van Doorn, Leen-Jan; Pilar Rubio, Maria Del; Suryakiran, Pemmaraju Venkata; Casellas, Javier M; Ortega-Barria, Eduardo; Smolenov, Igor V; Han, Htay-Htay

2011-06-01

The efficacy of a rotavirus vaccine against severe rotavirus gastroenteritis when coadministered with routine Expanded Program on Immunization (EPI) vaccines including oral polio vaccine (OPV) was evaluated in this study. Double-blind, randomized (2:1), placebo-controlled study conducted across 6 Latin American countries. Healthy infants (N = 6568) 6 to 12 weeks of age received 2 doses of RIX4414 vaccine or placebo following a 0, 1- to 2-month schedule. Routine vaccines including OPV were coadministered according to local EPI schedule. Vaccine efficacy (VE) against severe rotavirus gastroenteritis caused by circulating wild-type rotavirus from 2 weeks post-Dose 2 until 1 year of age was calculated with 95% confidence interval [CI]. Safety was assessed during the entire study period. Immunogenicity of RIX4414 and OPV was also assessed. During the efficacy follow-up period (mean duration = 7.4 months), 7 and 19 cases of severe rotavirus gastroenteritis were reported in the vaccine and placebo groups, respectively, with a VE of 81.6% (95% CI: 54.4-93.5). VE against severe rotavirus gastroenteritis caused by G1 type was 100% (95% CI: <0-100) and 80.6% (95% CI: 51.4-93.2) against the pooled non-G1 rotavirus types, respectively. There was no difference (P = 0.514) in the incidence of serious adverse events reported in the 2 groups. Antirotavirus IgA seropositivity rate at 1 to 2 months post-Dose 2 was 61.4% (95% CI: 53.7-68.6) in the RIX4414 group; similar seroprotection rates (≥96.0%) against the 3 antipoliovirus types was observed 1 month post-Dose 3 of OPV in both groups. RIX4414 was highly efficacious against severe rotavirus gastroenteritis caused by the circulating wild-type rotavirus (G1 and non-G1) when coadministered with routine EPI vaccines including OPV.

Rotavirus epidemiology and vaccine demand: considering Bangladesh chapter through the book of global disease burden.

PubMed

Mahmud-Al-Rafat, Abdullah; Muktadir, Abdul; Muktadir, Hasneen; Karim, Mahbubul; Maheshwari, Arpan; Ahasan, Mohammad Mainul

2018-02-01

Rotavirus is the major cause of gastroenteritis in children throughout the world. Every year, a large number of children aged < 5 years die from rotavirus-related diarrhoeal diseases. Though these infections are vaccine-preventable, the vast majority of children in low-income countries suffer from the infection. The situation leads to severe economic loss and constitutes a major public health problem. We searched electronic databases including PubMed and Google scholar using the following words: "features of rotavirus," "epidemiology of rotavirus," "rotavirus serotypes," "rotavirus in Bangladesh," "disease burden of rotavirus," "rotavirus vaccine," "low efficacy of rotavirus vaccine," "inactivated rotavirus vaccine". Publications until July 2017 have been considered for this work. Currently, two live attenuated vaccines are available throughout the world. Many countries have included rotavirus vaccines in national immunization program to reduce the disease burden. However, due to low efficacy of the available vaccines, satisfactory outcome has not yet been achieved in developing countries such as Bangladesh. Poor economic, public health, treatment, and sanitation status of the low-income countries necessitate the need for the most effective rotavirus vaccines. Therefore, the present scenario demands the development of a highly effective rotavirus vaccine. In this regard, inactivated rotavirus vaccine concept holds much promise for reducing the current disease burden. Recent advancements in developing an inactivated rotavirus vaccine indicate a significant progress towards disease prophylaxis and control.

Immunogenicity and protective efficacy of yeast extracts containing rotavirus-like particles: a potential veterinary vaccine.

PubMed

Rodríguez-Limas, William A; Pastor, Ana Ruth; Esquivel-Soto, Ernesto; Esquivel-Guadarrama, Fernando; Ramírez, Octavio T; Palomares, Laura A

2014-05-19

Rotavirus is the most common cause of severe diarrhea in many animal species of economic interest. A simple, safe and cost-effective vaccine is required for the control and prevention of rotavirus in animals. In this study, we evaluated the use of Saccharomyces cerevisiae extracts containing rotavirus-like particles (RLP) as a vaccine candidate in an adult mice model. Two doses of 1mg of yeast extract containing rotavirus proteins (between 0.3 and 3 μg) resulted in an immunological response capable of reducing the replication of rotavirus after infection. Viral shedding in all mice groups diminished in comparison with the control group when challenged with 100 50% diarrhea doses (DD50) of murine rotavirus strain EDIM. Interestingly, when immunizing intranasally protection against rotavirus infection was observed even when no increase in rotavirus-specific antibody titers was evident, suggesting that cellular responses were responsible of protection. Our results indicate that raw yeast extracts containing rotavirus proteins and RLP are a simple, cost-effective alternative for veterinary vaccines against rotavirus. Copyright © 2014 Elsevier Ltd. All rights reserved.

Rotavirus vaccines in Israel: Uptake and impact.

PubMed

Muhsen, Khitam; Cohen, Daniel

2017-07-03

We present an overview of the impact of universal rotavirus immunization with the pentavalent vaccine, RotaTeq, which was introduced in Israel in 2010. The vaccine is given free of charge at age 2, 4 and 6 months, with an 80% coverage that was shortly achieved during the universal immunization period. Compared to pre-universal immunization years (2008-2010), a reduction of 66-68% in the incidence of rotavirus gastroenteritis (RVGE) hospitalizations was observed in 2011-2015 among children aged 0-23 months in central and northern Israel. In southern Israel a reduction of 80-88% in RVGE hospital visit rate was found among Jewish children aged 0-23 months in 2011-2013. Among Bedouins, the respective decline was 62-75%. A significant reduction of 59% was also observed in RVGE clinic visits, presumably representing less severe illness. Indirect benefit was evident in children aged 24-59 months who were ineligible for universal immunization. Vaccine effectiveness against RVGE hospitalization was estimated at 86% in children aged 6-23 months. Changes in the circulating rotavirus genotypes occurred but the contribution of vaccine induced immune pressure is unclear. Universal rotavirus immunization was followed by an impressive decrease in the burden of RVGE in young children in Israel, likely attributed to good vaccine coverage and effectiveness.

SEASONALITY OF ROTAVIRUS IN SOUTH ASIA: A META-ANALYSIS APPROACH ASSESSING ASSOCIATIONS WITH TEMPERATURE, PRECIPTATION, AND VEGETATION INDEX

EPA Science Inventory

Background: Rotavirus infection causes a significant proportion of diarrhea in infants and young children worldwide leading to dehydration, hospitalization, and in some cases death. Rotavirus infection represents a significant burden of disease in developing countries, such as th...

Vaccines for preventing rotavirus diarrhoea: vaccines in use.

PubMed

Soares-Weiser, Karla; Maclehose, Harriet; Ben-Aharon, Irit; Goldberg, Elad; Pitan, Femi; Cunliffe, Nigel

2010-05-12

Rotavirus results in higher diarrhoea-related death in children less than five years of age than any other single agent, particularly in low- and middle-income countries. The World Health Organization has recommended the use of rotavirus vaccines in childhood immunization schedules. To evaluate rotavirus vaccines approved for use (Rotarix, RotaTeq, and Lanzhou Lamb Rotavirus (LLR)) for preventing rotavirus diarrhoea. In February 2010, we searched the Cochrane Infectious Diseases Group Specialized Register, CENTRAL (published in The Cochrane Library 2009, Issue 1), MEDLINE, EMBASE, LILACS, and BIOSIS. We also searched the ICTRP (January 2010) and checked reference lists of identified studies. Randomized controlled trials comparing rotavirus vaccines approved for use with placebo, no intervention, or another vaccine in children. Two authors independently assessed trial eligibility, extracted data, and assessed risk of bias. Dichotomous data were combined using the risk ratio (RR) and 95% confidence intervals (CI). Thirty-four trials that included 175,944 participants met the inclusion criteria. They evaluated Rotarix (26 trials; 99,841 participants) and RotaTeq (eight trials; 76,103 participants), and had variable risk of bias (where information provided). None of the identified trials used LLR or compared rotavirus vaccines. Compared to placebo, Rotarix and RotaTeq were both effective at reducing rotavirus diarrhoea (severe cases and cases of any severity). They also reduced all-cause diarrhoea (severe cases), and hospitalizations and need for medical attention caused by rotavirus diarrhoea. However, few data were available for Rotarix and all-cause diarrhoea. Versus the placebo groups, participants in each vaccine group had similar numbers of deaths, serious adverse events, reactogenicity profiles (fever, diarrhoea, and vomiting), and adverse events that required discontinuation of the vaccination schedule. Both vaccines were immunogenic (measured by virus shedding in stool and/or seroconversion). Subgroup analyses indicate that both vaccines are effective in countries with different incomes, but few data are available. Rotarix and RotaTeq are effective vaccines for the prevention of rotavirus diarrhoea. The balance between benefit and harm favours benefit. Ongoing safety monitoring should be continued. Trials comparing LLR with placebo should be conducted and the results made available.

A significant and consistent reduction in rotavirus gastroenteritis hospitalization of children under 5 years of age, following the introduction of universal rotavirus immunization in Israel.

PubMed

Muhsen, Khitam; Rubenstein, Uri; Kassem, Eias; Goren, Sophy; Schachter, Yaakov; Kremer, Adi; Shulman, Lester M; Ephros, Moshe; Cohen, Dani

2015-01-01

Universal rotavirus vaccination with RotaTeq was introduced in Israel in December 2010. We examined hospitalization rates of children under 5 years of age due to all-cause and rotavirus gastroenteritis, both before and 3 years after universal introduction of the vaccination. An ongoing hospital-based surveillance network that was established in November 2007, accessed information regarding hospitalization of children due to gastroenteritis (n = 6205) in 3 hospitals in northern Israel, with an annual average of about 60,000 children under 5 years of age living in the catchment area of these hospitals. Stool samples were tested for rotavirus by immunochromatography. Compared to the period preceding implementation of the universal rotavirus vaccination (2008-2010), hospitalizations due to rotavirus gastroenteritis in children <5 years of age decreased significantly, by 55% (95% CI 43%-67%) during the period of universal vaccination (2011-2013), a decrease that was sustained throughout the 3 year period. This reduction was greater in children aged 0-23 months (60-61%) than in toddlers aged 24-59 months (36%). A 32% (95% CI 21%-45%) decrease in the incidence of all-cause gastroenteritis was also observed. During the period preceding universal vaccination, rotavirus diarrhea showed typical winter seasonality, with highest incidence in December. However, the winter peak was substantially blunted during the period of universal immunization. Surveillance of rotavirus gastroenteritis should continue to assess the long-term impact of such a program. Our findings are of relevance to high and middle-income countries considering the introduction of a universal rotavirus immunization program.

Epidemiologic Association Between FUT2 Secretor Status and Severe Rotavirus Gastroenteritis in Children in the United States

PubMed Central

Payne, Daniel C.; Currier, Rebecca L.; Staat, Mary A.; Sahni, Leila C.; Selvarangan, Rangaraj; Halasa, Natasha B.; Englund, Janet A.; Weinberg, Geoffrey A.; Boom, Julie A.; Szilagyi, Peter G.; Klein, Eileen J.; Chappell, James; Harrison, Christopher J.; Davidson, Barbara S.; Mijatovic-Rustempasic, Slavica; Moffatt, Mary D.; McNeal, Monica; Wikswo, Mary; Bowen, Michael D.; Morrow, Ardythe L.; Parashar, Umesh D.

2016-01-01

IMPORTANCE A genetic polymorphism affecting FUT2 secretor status in approximately one-quarter of humans of European descent affects the expression of histo-blood group antigens on the mucosal epithelia of human respiratory, genitourinary, and digestive tracts. These histo-blood group antigens serve as host receptor sites necessary for attachment and infection of some pathogens, including norovirus. OBJECTIVE We investigated whether an association exists between FUT2 secretor status and laboratory-confirmed rotavirus infections in US children. DESIGN, SETTING, AND PARTICIPANTS Multicenter case-control observational study involving active surveillance at 6 US pediatric medical institutions in the inpatient and emergency department clinical settings. We enrolled 1564 children younger than 5 years with acute gastroenteritis (diarrhea and/or vomiting) and 818 healthy controls frequency matched by age and month, from December 1, 2011, through March 31, 2013. MAIN OUTCOMES AND MEASURES Paired fecal-saliva specimens were tested for rotavirus and for secretor status. Comparisons were made between rotavirus test–positive cases and healthy controls stratified by ethnicity and vaccination status. Adjusted multivariable analyses assessed the preventive association of secretor status against severe rotavirus gastroenteritis. RESULTS One (0.5%) of 189 rotavirus test–positive cases was a nonsecretor, compared with 188 (23%) of 818 healthy control participants (P < .001). Healthy control participants of Hispanic ethnicity were significantly less likely to be nonsecretors (13%) compared with healthy children who were not of Hispanic ethnicity (25%) (P < .001). After controlling for vaccination and other factors, children with the nonsecretor FUT2 polymorphism appeared statistically protected (98% [95% CI, 84%–100%]) against severe rotavirus gastroenteritis. CONCLUSIONS AND RELEVANCE Severe rotavirus gastroenteritis was virtually absent among US children who had a genetic polymorphism that inactivates FUT2 expression on the intestinal epithelium. We observed a strong epidemiologic association among children with rotavirus gastroenteritis compared with healthy control participants. The exact cellular mechanism behind this epidemiologic association remains unclear, but evidence suggests that it may be rotavirus genotype specific. The lower prevalence of nonsecretors among Hispanic children may translate to an enhanced burden of rotavirus gastroenteritis among this group. Our findings may have bearing on our full understanding of rotavirus infections and the effects of vaccination in diverse populations. PMID:26389824

Rotavirus vaccines

PubMed Central

Yen, Catherine; Tate, Jacqueline E; Hyde, Terri B; Cortese, Margaret M; Lopman, Benjamin A; Jiang, Baoming; Glass, Roger I; Parashar, Umesh D

2014-01-01

Rotavirus is the leading cause of severe diarrhea among children <5 years worldwide. Currently licensed rotavirus vaccines have been efficacious and effective, with many countries reporting substantial declines in diarrheal and rotavirus-specific morbidity and mortality. However, the full public health impact of these vaccines has not been realized. Most countries, including those with the highest disease burden, have not yet introduced rotavirus vaccines into their national immunization programs. Research activities that may help inform vaccine introduction decisions include (1) establishing effectiveness, impact, and safety for rotavirus vaccines in low-income settings; (2) identifying potential strategies to improve performance of oral rotavirus vaccines in developing countries, such as zinc supplementation; and (3) pursuing alternate approaches to oral vaccines, such as parenteral immunization. Policy- and program-level barriers, such as financial implications of new vaccine introductions, should be addressed to ensure that countries are able to make informed decisions regarding rotavirus vaccine introduction. PMID:24755452

VP7 and VP8* genetic characterization of group A rotavirus genotype G12P[8]: Emergence and spreading in the Eastern Brazilian coast in 2014.

PubMed

da Silva, Marcelle Figueira Marques; Fumian, Tulio Machado; de Assis, Rosane Maria Santos; Fialho, Alexandre Madi; Carvalho-Costa, Filipe Anibal; da Silva Ribeiro de Andrade, Juliana; Leite, José Paulo Gagliardi

2017-01-01

Group A rotavirus (RVA) genotype G12 is habitually associated with diarrhea disease (DD) in African children and recently its detection has increased worldwide. A total of 970 stool samples collected from individuals with DD in the Northeastern, Southeastern, and Southern Brazilian regions, Eastern coast, were analyzed and 321 (33%) were positive for RVA and of these, 241 (75%) genotyped as G12P[8]. The rate of RVA positivity was higher among children aged 5-10 years old (60%). All RVA infections observed in adults aged >21 years were G12P[8] (n = 27) showing that this genotype affected older age groups during the year of 2014 in Brazil. Phylogenetic analysis of VP7 and VP8* G12P[8] strains demonstrated an elevated similarity among Brazilian and G12-III prototypes strains circulating worldwide recently, suggesting that this lineage is associated with the global spread of the G12 genotype, considered as the 6th most prevalent human RVA genotype nowadays; while other G12 lineages remain sporadically detected and usually detected in association with other P genotypes. VP8* analysis revealed that Brazilian strains belong to P[8]-3 lineage, the single P[8] lineage presently detected in the country. No major nucleotide/amino acid disparities were observed among strains recovered from children and adults for VP7 and VP8* genes. These data are essential to support the surveillance studies, particularly in countries where the RVA vaccine was introduced in their National Immunization Program enabling identification of potential alterations in the epidemiological profile that can impact its efficacy in vaccination programs. J. Med. Virol. 89:64-70, 2017. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Analysis of Human Rotaviruses from a Single Location Over an 18-Year Time Span Suggests that Protein Coadaption Influences Gene Constellations

PubMed Central

Zhang, Shu; McDonald, Paul W.; Thompson, Travis A.; Dennis, Allison F.; Akopov, Asmik; Kirkness, Ewen F.; Patton, John T.

2014-01-01

ABSTRACT Rotaviruses (RVs) are 11-segmented, double-stranded RNA viruses that cause severe gastroenteritis in children. In addition to an error-prone genome replication mechanism, RVs can increase their genetic diversity by reassorting genes during host coinfection. Such exchanges allow RVs to acquire advantageous genes and adapt in the face of selective pressures. However, reassortment may also impose fitness costs if it unlinks genes/proteins that have accumulated compensatory, coadaptive mutations and that operate best when kept together. To better understand human RV evolutionary dynamics, we analyzed the genome sequences of 135 strains (genotype G1/G3/G4-P[8]-I1-C1-R1-A1-N1-T1-E1-H1) that were collected at a single location in Washington, DC, during the years 1974 to 1991. Intragenotypic phylogenetic trees were constructed for each viral gene using the nucleotide sequences, thereby defining novel allele level gene constellations (GCs) and illuminating putative reassortment events. The results showed that RVs with distinct GCs cocirculated during the vast majority of the collection years and that some of these GCs persisted in the community unchanged by reassortment. To investigate the influence of protein coadaptation on GC maintenance, we performed a mutual information-based analysis of the concatenated amino acid sequences and identified an extensive covariance network. Unexpectedly, amino acid covariation was highest between VP4 and VP2, which are structural components of the RV virion that are not thought to directly interact. These results suggest that GCs may be influenced by the selective constraints placed on functionally coadapted, albeit noninteracting, viral proteins. This work raises important questions about mutation-reassortment interplay and its impact on human RV evolution. IMPORTANCE Rotaviruses are devastating human pathogens that cause severe diarrhea and kill >450,000 children each year. The virus can evolve by accumulating mutations and by acquiring new genes from other strains via a process called reassortment. However, little is known about the relationship between mutation accumulation and gene reassortment for rotaviruses and how it impacts viral evolution. In this study, we analyzed the genome sequences of human strains found in clinical fecal specimens that were collected at a single hospital over an 18-year time span. We found that many rotaviruses did not reassort their genes but instead maintained them as specific sets (i.e., constellations). By analyzing the encoded proteins, we discovered concurrent amino acid changes among them, which suggests that they are functionally coadapted to operate best when kept together. This study increases our understanding of how rotaviruses evolve over time in the human population. PMID:24942570

Update on Rotarix: an oral human rotavirus vaccine.

PubMed

O'Ryan, Miguel; Linhares, Alexandre C

2009-12-01

Worldwide, rotaviruses are the single most important agents of severe gastroenteritis in infants and young children. Globally, it is estimated that every year rotavirus gastroenteritis causes more than 125 million episodes of diarrhea and nearly 527,000 deaths, mainly in developing countries. The development of new effective and safe rotavirus vaccines was recognized as the most effective intervention strategy that could yield a significant impact on the burden of rotavirus disease. Rotarix is an oral live-attenuated human rotavirus vaccine containing a single G1P[8] strain. The first oral dose may be administered as early as 6 weeks of age, with a minimum interval of 4 weeks prior to second dose; the vaccination course should be completed by the age of 24 weeks according to the manufacturer. In the USA, the upper age limit for the second dose has recently been recommended at 32 weeks of age by the Advisory Committee on Immunization Practices. The development program for Rotarix including Phase I, II and III multicenter studies involving over 100,000 infants has been established in Latin America, Europe, Asia and Africa. The vaccine proved to be well tolerated, immunogenic, efficacious, safe and not associated with intussusception. It provided 85-96% protection against severe rotavirus gastroenteritis caused by G1 and non-G1 serotypes in Latin American and European clinical trials; and of public health importance, Rotarix reduced hospitalizations of all-cause gastroenteritis by 40 and 75%, respectively. Efficacy against G2P[4] strains ranged from 41% in Latin America to 81% in Europe. In the former, Rotarix afforded sustained high protection (80.5%; 95% CI: 71.3-87.1) against severe rotavirus gastroenteritis during the first 2 years of life in a region with a changing pattern of wild-type rotavirus circulation. In a recently completed vaccine trial in South Africa and Malawi, Rotarix showed an overall efficacy of 61.2% (95% CI: 44.0-73.2) by 1 year of age. Although these rates are lower than those from developed and middle-income countries, they look promising given the lack of other effective interventions. With the expanding introduction of rotavirus vaccines into national immunization programs, postmarketing surveillance should be conducted to measure the impact of rotavirus vaccination, as well as continued monitoring of circulating rotavirus strains.

Comparative study on the mechanisms of rotavirus inactivation by sodium dodecyl sulfate and ethylenediaminetetraacetate

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ward, R.L.; Ashley, C.S.

1980-06-01

This report describes a comparative study on the effects of the anionic detergent sodium dodecyl sulfate and the chelating agent ethylenediaminetetraacetate on purified rotavirus SA-11 particles. Both chemicals readily inactivated rotavirus at quite low concentrations and under very mild conditions. In addition, both agents modified the viral capsid and prevented the adsorption of inactivated virions to cells. Capsid damage by ethylenediaminetetraacetate caused a shift in the densities of rotavirions from about l.35 to about 1.37 g/ml and a reduction in their sedimentation coefficients. Sodium dodcyl sulfate, on the other hand, did not detectably alter either of these physical properties ofmore » rotavirions. Both agents caused some alteration of the isoelectric points of the virions. Finally, analysis of rotavirus proteins showed that ethylenediaminetetraacetate caused the loss of two protein peaks from the electrophoretic pattern of virions but sodium dodecyl sulfate caused the loss of only one of these same protein peaks.« less

Association between mixed rotavirus vaccination types of infants and rotavirus acute gastroenteritis

PubMed Central

Mohammed, Anaam; Immergluck, Lilly; Parker, Trisha Chan; Jain, Shabnam; Leong, Traci; Anderson, Evan J.; Jerris, Robert C.

2017-01-01

Introduction Rotavirus remains the leading cause of severe diarrhea in children under 5 years worldwide. In the US, Rotarix® (RV1) and RotaTeq® (RV5), have been associated with reductions in and severity of rotavirus disease. Studies have evaluated the impact of RV1 or RV5 but little is known about the impact of incomplete or mixed vaccination upon vaccine effectiveness. Methods Case control study to examine association of combined RV1 and RV5 and rotavirus acute gastroenteritis, factoring severity of diarrheal disease. Children born after March 1, 2009 with acute gastroenteritis from three pediatric hospitals in Atlanta, Georgia were approached for enrollment. Survey was administered, stool specimen was collected, and vaccination records were obtained. Results 891 of 1127 children with acute gastroenteritis were enrolled. Stool specimens were collected from 708 for rotavirus testing; 215 stool samples tested positively for rotavirus. Children >12 months of age were more likely to have rotavirus. Children categorized with Vesikari score of >11 were almost twice as likely to be rotavirus positive. Prior rotavirus vaccination decreased the mean Vesikari score, p < 0.0001. Children with complete single type vaccination were protected against rotavirus (OR 0.21, 95% CI: 0.14–0.31, p < 0.0001). Conclusion Complete rotavirus vaccination with a single vaccine type resulted in protection against rotavirus diarrhea and decrease in severity of rotavirus gastroenteritis. Incomplete rotavirus vaccination either with a single vaccine or mixed vaccination types also provided some protection. PMID:26322843

Some infectious causes of diarrhea in young farm animals.

PubMed Central

Holland, R E

1990-01-01

Escherichia coli, rotaviruses, and Cryptosporidium parvum are discussed in this review as they relate to enteric disease in calves, lambs, and pigs. These microorganisms are frequently incriminated as causative agents in diarrheas among neonatal food animals, and in some cases different strains or serotypes of the same organism cause diarrhea in humans. E. coli causes diarrhea by mechanisms that include production of heat-labile or heat-stable enterotoxins and synthesis of potent cytotoxins, and some strains cause diarrhea by yet undetermined mechanisms. Rotaviruses and C. parvum induce various degrees of villous atrophy. Rotaviruses infect and replicate within the cytoplasm of enterocytes, whereas C. parvum resides in an intracellular, extracytoplasmic location. E. coli, rotavirus, and C. parvum infections are of concern to producers, veterinarians, and public health officials. These agents are a major cause of economic loss to the producer because of costs associated with therapy, reduced performance, and high morbidity and mortality rates. Moreover, diarrheic animals may harbor, incubate, and act as a source to healthy animals and humans of some of these agents. Images PMID:2224836

Resource utilization and costs of treating severe rotavirus diarrhea in young Mexican children from the health care provider perspective.

PubMed

Granados-García, Victor; Velázquez-Castillo, Raúl; Garduño-Espinosa, Juan; Torres-López, Javier; Muñoz-Hernández, Onofre

2009-01-01

Rotavirus is the most common cause of severe diarrhea in infants. The economic costs of treating severe rotavirus can be quite significant and are important to include in any evaluation of prevention programs. The aim of this study was to determine utilization of health care resources and costs incurred due to severe diarrhea associated with rotavirus infection in Mexican children < 5 years of age. The costs of rotavirus infection evaluated in this observational study consisted of hospital, emergency room care and out-patient visit expenses at three hospitals of the Mexican Institute of Social Security throughout 1999-2000. Service costs were estimated from costs of care for rotavirus versus non-rotavirus diarrhea obtained through a follow-up study data of 383 children and administrative records. Diarrhea cases due to rotavirus infection comprised 36% of the sample. Participants with rotavirus diarrhea spent an average of 3.2 days in the hospital, 5.9 hours in the emergency room, and had 1.3 visits to an outpatient physician's office. Some differences in the consumption of health care were found between rotavirus and non-rotavirus diarrhea cases, although the mean costs of rotavirus and nonrotavirus cases were not significantly different. The mean cost per case of severe rotavirus diarrhea was estimated to be US $936. The total cost of treating severe rotavirus diarrhea, including 5,955 rotavirus hospitalizations for 2004, was estimated at US $5.5 million. Health care costs due to treatment for severe rotavirus diarrhea are a significant economic burden to the Mexican Social Security system.

Effect of human rotavirus vaccine on severe diarrhea in African infants.

PubMed

Madhi, Shabir A; Cunliffe, Nigel A; Steele, Duncan; Witte, Desirée; Kirsten, Mari; Louw, Cheryl; Ngwira, Bagrey; Victor, John C; Gillard, Paul H; Cheuvart, Brigitte B; Han, Htay H; Neuzil, Kathleen M

2010-01-28

Rotavirus is the most common cause of severe gastroenteritis among young children worldwide. Data are needed to assess the efficacy of the rotavirus vaccine in African children. We conducted a randomized, placebo-controlled, multicenter trial in South Africa (3166 infants; 64.1% of the total) and Malawi (1773 infants; 35.9% of the total) to evaluate the efficacy of a live, oral rotavirus vaccine in preventing severe rotavirus gastroenteritis. Healthy infants were randomly assigned in a 1:1:1 ratio to receive two doses of vaccine (in addition to one dose of placebo) or three doses of vaccine--the pooled vaccine group--or three doses of placebo at 6, 10, and 14 weeks of age. Episodes of gastroenteritis caused by wild-type rotavirus during the first year of life were assessed through active follow-up surveillance and were graded with the use of the Vesikari scale. A total of 4939 infants were enrolled and randomly assigned to one of the three groups; 1647 infants received two doses of the vaccine, 1651 infants received three doses of the vaccine, and 1641 received placebo. Of the 4417 infants included in the per-protocol efficacy analysis, severe rotavirus gastroenteritis occurred in 4.9% of the infants in the placebo group and in 1.9% of those in the pooled vaccine group (vaccine efficacy, 61.2%; 95% confidence interval, 44.0 to 73.2). Vaccine efficacy was lower in Malawi than in South Africa (49.4% vs. 76.9%); however, the number of episodes of severe rotavirus gastroenteritis that were prevented was greater in Malawi than in South Africa (6.7 vs. 4.2 cases prevented per 100 infants vaccinated per year). Efficacy against all-cause severe gastroenteritis was 30.2%. At least one serious adverse event was reported in 9.7% of the infants in the pooled vaccine group and in 11.5% of the infants in the placebo group. Human rotavirus vaccine significantly reduced the incidence of severe rotavirus gastroenteritis among African infants during the first year of life. (ClinicalTrials.gov number, NCT00241644.) 2010 Massachusetts Medical Society

Haze is an important medium for the spread of rotavirus.

PubMed

Ye, Qing; Fu, Jun-Feng; Mao, Jian-Hua; Shen, Hong-Qiang; Chen, Xue-Jun; Shao, Wen-Xia; Shang, Shi-Qiang; Wu, Yi-Feng

2016-09-01

This study investigated whether the rotavirus infection rate in children is associated with temperature and air pollutants in Hangzhou, China. This study applied a distributed lag non-linear model (DLNM) to assess the effects of daily meteorological data and air pollutants on the rotavirus positive rate among outpatient children. There was a negative correlation between temperature and the rotavirus infection rate. The impact of temperature on the detection rate of rotavirus presented an evident lag effect, the temperature change shows the greatest impact on the detection rate of rotavirus approximate at lag one day, and the maximum relative risk (RR) was approximately 1.3. In 2015, the maximum cumulative RR due to the cumulative effect caused by the temperature drop was 2.5. Particulate matter (PM) 2.5 and PM10 were the primary air pollutants in Hangzhou. The highest RR of rotavirus infection occurred at lag 1-1.5 days after the increase in the concentration of these pollutants, and the RR increased gradually with the increase in concentration. Based on the average concentrations of PM2.5 of 53.9 μg/m(3) and PM10 of 80.6 μg/m(3) in Hangzhou in 2015, the cumulative RR caused by the cumulative effect was 2.5 and 2.2, respectively. The current study suggests that temperature is an important factor impacting the rotavirus infection rate of children in Hangzhou. Air pollutants significantly increased the risk of rotavirus infection, and dosage, lag and cumulative effects were observed. Copyright © 2016 Elsevier Ltd. All rights reserved.

Effectiveness and impact of rotavirus vaccines in Europe, 2006-2014.

PubMed

Karafillakis, Emilie; Hassounah, Sondus; Atchison, Christina

2015-04-27

Prior to the introduction of rotavirus vaccines in 2006, rotavirus was the leading cause of severe gastroenteritis among European children <5 years of age. We conducted a systematic review of the published literature to examine the effectiveness and impact of rotavirus vaccines in Europe following the first eight years of routine use. Four publication databases were searched, yielding 276 unique citations from February 1st, 2006 to July 31st, 2014. Twenty four studies on effectiveness (n=9) and impact (n=15) met the inclusion criteria. Across Europe, vaccine effectiveness against rotavirus-related healthcare utilisation ranged from 68% to 98%, consistent with efficacy data from clinical trials. Reductions in rotavirus hospitalisations ranged from 65% to 84%, consistent with findings from post-marketing studies from the US and Latin America. We confirm the significant public health benefit of rotavirus vaccination in Europe and provide further evidence to support implementation of universal rotavirus vaccination in all European countries. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

Rotavirus vaccines in Israel: Uptake and impact

PubMed Central

Muhsen, Khitam; Cohen, Daniel

2017-01-01

ABSTRACT We present an overview of the impact of universal rotavirus immunization with the pentavalent vaccine, RotaTeq, which was introduced in Israel in 2010. The vaccine is given free of charge at age 2, 4 and 6 months, with an 80% coverage that was shortly achieved during the universal immunization period. Compared to pre-universal immunization years (2008–2010), a reduction of 66–68% in the incidence of rotavirus gastroenteritis (RVGE) hospitalizations was observed in 2011–2015 among children aged 0–23 months in central and northern Israel. In southern Israel a reduction of 80–88% in RVGE hospital visit rate was found among Jewish children aged 0–23 months in 2011–2013. Among Bedouins, the respective decline was 62–75%. A significant reduction of 59% was also observed in RVGE clinic visits, presumably representing less severe illness. Indirect benefit was evident in children aged 24–59 months who were ineligible for universal immunization. Vaccine effectiveness against RVGE hospitalization was estimated at 86% in children aged 6–23 months. Changes in the circulating rotavirus genotypes occurred but the contribution of vaccine induced immune pressure is unclear. Universal rotavirus immunization was followed by an impressive decrease in the burden of RVGE in young children in Israel, likely attributed to good vaccine coverage and effectiveness. PMID:28281866

Hospitalizations associated with rotavirus gastroenteritis in Spain, 2001–2005

PubMed Central

López-de-Andrés, Ana; Jiménez-García, Rodrigo; Carrasco-Garrido, Pilar; Alvaro-Meca, Alejandro; Galarza, Patricia Graciela; de Miguel, Ángel Gil

2008-01-01

Background This study aims to describe and analyze hospital admissions in Spain due to rotavirus infections among children aged 5 years or under during the period 2001–2005, along with the associated health cost. Methods To update estimates of rotavirus hospitalizations rates in Spain, we conducted a retrospective study of 5 years of national hospitalization data associated with acute gastroenteritis using the Minimum Basic Data Set. Results During the study period, a total of 17.1% of all admissions due to acute gastroenteritis of any etiology in children aged ≤ 5 years were attributable to rotavirus infection as determined by the rotavirus-specific International Classification of Diseases, ninth revision, Clinical Modification code. A mean incidence of 135 hospital admissions attributable to rotavirus per 100,000 children aged ≤ 5 years was found. Hospitalizations associated with rotavirus had a marked winter-time seasonality. The estimated cost of hospital admission attributable to rotavirus has risen from 3 million euros estimated for 2001 to almost 7 million euros estimated in 2005. Conclusion Rotavirus gastroenteritis remains an important cause of hospitalizations in Spanish children, mostly during the winter season. PMID:18397512

Rotavirus Vaccines: an Overview

PubMed Central

Dennehy, Penelope H.

2008-01-01

Rotavirus infection is the most common cause of severe diarrhea disease in infants and young children worldwide and continues to have a major global impact on childhood morbidity and mortality. Vaccination is the only control measure likely to have a significant impact on the incidence of severe dehydrating rotavirus disease. In 1999, a highly efficacious rotavirus vaccine licensed in the United States, RotaShield, was withdrawn from the market after 14 months because of its association with intussusception. Two new live, oral, attenuated rotavirus vaccines were licensed in 2006: the pentavalent bovine-human reassortant vaccine (RotaTeq) and the monovalent human rotavirus vaccine (Rotarix). Both vaccines have demonstrated very good safety and efficacy profiles in large clinical trials in western industrialized countries and in Latin America. Careful surveillance has not revealed any increased risk of intussusception in the vaccinated groups with either vaccine. The new rotavirus vaccines are now introduced for routine use in a number of industrialized and developing countries. These new safe and effective rotavirus vaccines offer the best hope of reducing the toll of acute rotavirus gastroenteritis in both developed and developing countries. PMID:18202442

Rotarix in developing countries: paving the way for inclusion in national childhood immunization programs in Africa.

PubMed

Pawinski, Robert; Debrus, Serge; Delem, Andrée; Smolenov, Igor; Suryakiran, Pemmaraju V; Han, Htay Htay

2010-09-01

Rotavirus gastroenteritis causes more than half a million deaths annually among children aged <5 years, the great majority of which occur in Africa and Asia. Vaccination is considered to be the most effective public health strategy to prevent rotavirus disease and to reduce the significant global burden of rotavirus gastroenteritis. Rotarix (GlaxoSmithKline Biologicals) is an oral, live attenuated rotavirus vaccine derived from a human G1P[8] rotavirus strain. Results of phase III studies in Europe, Latin America, and Asia have shown that Rotarix offers sustained high protection against severe rotavirus gastroenteritis during the first 2 years of life, when disease burden is highest, with broad protection demonstrated against each of the 5 main rotavirus types that circulate globally (G1, G2, G3, G4, and G9). Coupled with the availability of local burden of disease data and promising interim efficacy data from an ongoing study in Malawi and South Africa, this further reinforces the case for introduction of this rotavirus vaccine in national childhood immunization programs in Africa, where rotavirus-related mortality is significant.

Options for improving effectiveness of rotavirus vaccines in developing countries.

PubMed

Tissera, Marion S; Cowley, Daniel; Bogdanovic-Sakran, Nada; Hutton, Melanie L; Lyras, Dena; Kirkwood, Carl D; Buttery, Jim P

2017-04-03

Rotavirus gastroenteritis is a leading global cause of mortality and morbidity in young children due to diarrhea and dehydration. Over 85% of deaths occur in developing countries. In industrialised countries, 2 live oral rotavirus vaccines licensed in 2006 quickly demonstrated high effectiveness, dramatically reducing severe rotavirus gastroenteritis admissions in many settings by more than 90%. In contrast, the same vaccines reduced severe rotavirus gastroenteritis by only 30-60% in developing countries, but have been proven life-saving. Bridging this "efficacy gap" offers the possibility to save many more lives of children under the age of 5. The reduced efficacy of rotavirus vaccines in developing settings may be related to differences in transmission dynamics, as well as host luminal, mucosal and immune factors. This review will examine strategies currently under study to target the issue of reduced efficacy and effectiveness of oral rotavirus vaccines in developing settings.

Options for improving effectiveness of rotavirus vaccines in developing countries

PubMed Central

Cowley, Daniel; Bogdanovic-Sakran, Nada; Hutton, Melanie L.; Lyras, Dena; Kirkwood, Carl D.; Buttery, Jim P.

2017-01-01

ABSTRACT Rotavirus gastroenteritis is a leading global cause of mortality and morbidity in young children due to diarrhea and dehydration. Over 85% of deaths occur in developing countries. In industrialised countries, 2 live oral rotavirus vaccines licensed in 2006 quickly demonstrated high effectiveness, dramatically reducing severe rotavirus gastroenteritis admissions in many settings by more than 90%. In contrast, the same vaccines reduced severe rotavirus gastroenteritis by only 30–60% in developing countries, but have been proven life-saving. Bridging this “efficacy gap” offers the possibility to save many more lives of children under the age of 5. The reduced efficacy of rotavirus vaccines in developing settings may be related to differences in transmission dynamics, as well as host luminal, mucosal and immune factors. This review will examine strategies currently under study to target the issue of reduced efficacy and effectiveness of oral rotavirus vaccines in developing settings. PMID:27835052

Molecular epidemiology of noroviruses associated with sporadic gastroenteritis in children in Novosibirsk, Russia, 2003-2012.

PubMed

Zhirakovskaia, Elena V; Tikunov, Artem Yu; Bodnev, Sergey A; Klemesheva, Vera V; Netesov, Sergey V; Tikunova, Nina V

2015-05-01

Noroviruses (NoVs) are an important cause of acute gastroenteritis worldwide. To monitor the molecular epidemiology of NoVs genogroup II (GII) in Novosibirsk, Russia, a total of 10,198 stool samples from young children hospitalized with acute gastroenteritis and two asymptomatic comparison groups were collected from 2003 to 2012. All samples were screened for the presence of NoV GII, rotavirus, and astrovirus by RT-PCR. The prevalence of NoV in gastroenteritis cases was 13.1%, varying from 7.1% to 21.3% in different seasons. Rotavirus and/or astrovirus were detectable in 25% of the NoV-positive samples. NoV was detected throughout the year with a seasonal increase during winter months. Based on sequence analysis of regions D and/or C within the VP1 gene, 892 identified NoV strains were divided into nine genotypes—GII.3 (51%), GII.4 (44%), GII.6 (2%), as well as GII.1, GII.2, GII.5, GII.7, GII.16, and GII.21 (totally, 3%). The prevalence of NoV in the comparison groups was considerably lower (∼2.5%); only GII.4 (n = 6), GII.21 (n = 2) and GII.1 (n = 1) genotypes were revealed. Based on phylogenetic analysis of the ORF1/ORF2 junction region sequences, GII.P21/GII.3 recombinant and GII.P4/GII.4 were prevalent genotypes (totally, 93%) and their ratio changed every season. The median age of children with NoV infection was 6.6 months (range, <1-35 months), but it was different depending on NoV genotype. Children infected with the NoV GII.3 were younger (median 6.2 months) than GII.4-positive patients (median 9.1 months). This is the first long-term systematic study of NoV molecular epidemiology in Russia. © 2015 Wiley Periodicals, Inc.

Decreased performance of live attenuated, oral rotavirus vaccines in low-income settings: causes and contributing factors.

PubMed

Velasquez, Daniel E; Parashar, Umesh; Jiang, Baoming

2018-02-01

Numerous studies have shown that the oral rotavirus vaccines are less effective in infants born in low income countries compared to those born in developed countries. Identifying the specific factors in developing countries that decrease and/or compromise the protection that rotavirus vaccines offer, could lead to a path for designing new strategies for the vaccines' improvement. Areas covered: We accessed PubMed to identify rotavirus vaccine performance studies (i.e., efficacy, effectiveness and immunogenicity) and correlated performance with several risk factors. Here, we review the factors that might contribute to the low vaccine efficacy, including passive transfer of maternal rotavirus antibodies, rotavirus seasonality, oral polio vaccine (OPV) administered concurrently, microbiome composition and concomitant enteric pathogens, malnutrition, environmental enteropathy, HIV, and histo blood group antigens. Expert commentary: We highlight two major factors that compromise rotavirus vaccines' efficacy: the passive transfer of rotavirus IgG antibodies to infants and the  co-administration of rotavirus vaccines with OPV. We also identify other potential risk factors that require further research because the data about their interference with the efficacy of rotavirus vaccines are inconclusive and at times conflicting.

Cytokines in the management of rotavirus infection: A systematic review of in vivo studies.

PubMed

Gandhi, Gopalsamy Rajiv; Santos, Victor Santana; Denadai, Marina; da Silva Calisto, Valdete Kaliane; de Souza Siqueira Quintans, Jullyana; de Oliveira E Silva, Ana Mara; de Souza Araújo, Adriano Antunes; Narain, Narendra; Cuevas, Luis Eduardo; Júnior, Lucindo José Quintans; Gurgel, Ricardo Queiroz

2017-08-01

Rotavirus is a leading cause of childhood diarrhoea. Rotavirus vaccines are effective against severe rotavirus gastroenteritis, but have lower efficacy in low income countries in Africa. Anti-rotavirus treatment is not available. This study reviews the literature of animal studies evaluating whether cytokine mediated pathways of immune activation could improve rotavirus therapy. We performed a systematic review of articles in English published from 2010 to 2016 reporting agents with in vivo antirotavirus activity for the management of rotavirus infection. The search was carried in PubMed, EMBASE, Scopus and Web of Science. Animal experiments where cytokines were investigated to assess the outcome of rotavirus therapy were included. A total of 869 publications were identified. Of these, 19 pertained the objectives of the review, and 11 articles described the effect of probiotics/commensals on rotavirus infection and immune responses in animals. Eight further in vivo studies evaluated the immunomodulating effects of herbs, secondary metabolites and food-derived products on cytokine responses of rotavirus-infected animals. Studies extensively reported the regulatory roles for T-helper (Th)1 (interferon gamma (IFN-γ), interleukin (IL)-2, IL-12) and Th2 (IL-4, IL-6, IL-10) cytokines responses to rotavirus pathogenesis and immunity, inhibiting rotavirus infection through suppression of inflammation by viral inhibition. Th1 and Th2 cytokines stimulate the immune system, inhibiting rotavirus binding and/or replication in animal models. Th1/Th2 cytokine responses have optimal immunomodulating effects to reduce rotavirus diarrhoea and enhance immune responses in experimental rotavirus infection. Copyright © 2017 Elsevier Ltd. All rights reserved.

Estimated reductions in hospitalizations and deaths from childhood diarrhea following implementation of rotavirus vaccination in Africa.

PubMed

Shah, Minesh P; Tate, Jacqueline E; Mwenda, Jason M; Steele, A Duncan; Parashar, Umesh D

2017-10-01

Rotavirus is the leading cause of hospitalizations and deaths from diarrhea. 33 African countries had introduced rotavirus vaccines by 2016. We estimate reductions in rotavirus hospitalizations and deaths for countries using rotavirus vaccination in national immunization programs and the potential of vaccine introduction across the continent. Areas covered: Regional rotavirus burden data were reviewed to calculate hospitalization rates, and applied to under-5 population to estimate baseline hospitalizations. Rotavirus mortality was based on 2013 WHO estimates. Regional pre-licensure vaccine efficacy and post-introduction vaccine effectiveness studies were used to estimate summary effectiveness, and vaccine coverage was applied to calculate prevented hospitalizations and deaths. Uncertainties around input parameters were propagated using boot-strapping simulations. In 29 African countries that introduced rotavirus vaccination prior to end 2014, 134,714 (IQR 112,321-154,654) hospitalizations and 20,986 (IQR 18,924-22,822) deaths were prevented in 2016. If all African countries had introduced rotavirus vaccines at benchmark immunization coverage, 273,619 (47%) (IQR 227,260-318,102) hospitalizations and 47,741 (39%) (IQR 42,822-52,462) deaths would have been prevented. Expert commentary: Rotavirus vaccination has substantially reduced hospitalizations and deaths in Africa; further reductions are anticipated as additional countries implement vaccination. These estimates bolster wider introduction and continued support of rotavirus vaccination programs.

Rotavirus vaccination within the South African Expanded Programme on Immunisation.

PubMed

Seheri, L Mapaseka; Page, Nicola A; Mawela, Mothahadini P B; Mphahlele, M Jeffrey; Steele, A Duncan

2012-09-07

Diarrhoeal diseases are ranked the third major cause of childhood mortality in South African children less than 5 years, where the majority of deaths are among black children. Acute severe dehydrating rotavirus diarrhoea remains an important contributor towards childhood mortality and morbidity and has been well documented in South Africa. As the preventive strategy to control rotavirus diarrhoea, South Africa became the first country in the WHO African Region to adopt the rotavirus vaccine in the national childhood immunisation programme in August 2009. The rotavirus vaccine in use, Rotarix, GSK Biologicals, is given at 6 and 14 weeks of age, along with other vaccines as part of Expanded Programme on Immunisation (EPI). Studies which facilitated the introduction of rotavirus vaccine in South Africa included the burden of rotavirus disease and strain surveillance, economic burden of rotavirus infection and clinical trials to assess the safety and efficacy of vaccine candidates. This paper reviews the epidemiology of rotavirus in South Africa, outlines some of the steps followed to introduce rotavirus vaccine in the EPI, and highlights the early positive impact of vaccination in reducing the rotavirus burden of disease based on the post-marketing surveillance studies at Dr George Mukhari hospital, a sentinel site at University of Limpopo teaching hospital in Pretoria, South Africa, which has conducted rotavirus surveillance for >20 years. Copyright © 2012 Elsevier Ltd. All rights reserved.

Solar and Temperature Treatments Affect the Ability of Human Rotavirus Wa To Bind to Host Cells and Synthesize Viral RNA

PubMed Central

Shisler, Joanna L.

2015-01-01

Rotavirus, the leading cause of diarrheal diseases in children under the age of five, is often resistant to conventional wastewater treatment and thus can remain infectious once released into the aquatic environment. Solar and heat treatments can inactivate rotavirus, but it is unknown how these treatments inactivate the virus on a molecular level. To answer this question, our approach was to correlate rotavirus inactivation with the inhibition of portions of the virus life cycle as a means to identify the mechanisms of solar or heat inactivation. Specifically, the integrity of the rotavirus NSP3 gene, virus-host cell interaction, and viral RNA synthesis were examined after heat (57°C) or solar treatment of rotavirus. Only the inhibition of viral RNA synthesis positively correlated with a loss of rotavirus infectivity; 57°C treatment of rotavirus resulted in a decrease of rotavirus RNA synthesis at the same rate as rotavirus infectivity. These data suggest that heat treatment neutralized rotaviruses primarily by targeting viral transcription functions. In contrast, when using solar disinfection, the decrease in RNA synthesis was responsible for approximately one-half of the decrease in infectivity, suggesting that other mechanisms, including posttranslational, contribute to inactivation. Nevertheless, both solar and heat inactivation of rotaviruses disrupted viral RNA synthesis as a mechanism for inactivation. PMID:25862222

Increased Rotavirus Prevalence in Diarrheal Outbreak Precipitated by Localized Flooding, Solomon Islands, 2014.

PubMed

Jones, Forrest K; Ko, Albert I; Becha, Chris; Joshua, Cynthia; Musto, Jennie; Thomas, Sarah; Ronsse, Axelle; Kirkwood, Carl D; Sio, Alison; Aumua, Audrey; Nilles, Eric J

2016-05-01

Flooding on 1 of the Solomon Islands precipitated a nationwide epidemic of diarrhea that spread to regions unaffected by flooding and caused >6,000 cases and 27 deaths. Rotavirus was identified in 38% of case-patients tested in the city with the most flooding. Outbreak potential related to weather reinforces the need for global rotavirus vaccination.

Diarrhea (For Parents)

MedlinePlus

... can't get enough fluids can become dehydrated . Rotavirus infection, a frequent cause of diarrhea in kids, ... months, especially in childcare centers. A very effective rotavirus vaccine is now recommended for infants. Enteroviruses, particularly ...

Sustained impact of rotavirus vaccine introduction on rotavirus gastroenteritis hospitalizations in children <5 years of age, Ghana, 2009-2016.

PubMed

Enweronu-Laryea, Christabel C; Armah, George; Sagoe, Kwamena W; Ansong, Daniel; Addo-Yobo, Emmanuel; Diamenu, Stanley K; Mwenda, Jason M; Parashar, Umesh D; Tate, Jacqueline E

2018-05-08

Ghana introduced monovalent rotavirus vaccine in April 2012. We sought to determine the long-term impact of routine rotavirus vaccination on rotavirus gastroenteritis hospitalizations in Ghana during the first 4 years following rotavirus vaccine introduction. Active sentinel surveillance for acute gastroenteritis hospitalizations among children <5 years of age was conducted at two sites from July 2009 through June 2016. Stool specimens were collected from enrolled children and tested by enzyme immunoassay. Changes in the proportion of all-cause gastroenteritis hospitalizations due to rotavirus pre- (July 2009-June 2012) and post-vaccine introduction (July 2012-June 2016) were compared using chi-square test. The proportion of acute gastroenteritis hospitalizations due to rotavirus among children <5 years of age significantly declined by 42% from a pre-vaccine median of 50% (343/684) to a post-vaccine median of 29% (118/396) (p < 0.001). The age distribution of rotavirus hospitalizations shifted toward older ages with 64% (759/1197) of rotavirus hospitalizations occurring in children <12 months of age pre-vaccine introduction to 47% (212/453) occurring in children <12 months of age post-vaccine introduction (p < 0.001). The decline in rotavirus hospitalizations following rotavirus vaccine introduction have been sustained over the first 4 years of the vaccination program in Ghana. Continued vaccination against rotavirus will ensure that this burden remains low. Copyright © 2018. Published by Elsevier Ltd.

Socio-demographic, Clinical and Laboratory Features of Rotavirus Gastroenteritis in Children Treated in Pediatric Clinic

PubMed Central

Azemi, Mehmedali; Berisha, Majlinda; Ismaili-Jaha, Vlora; Kolgeci, Selim; Avdiu, Muharrem; Jakupi, Xhevat; Hoxha, Rina; Hoxha-Kamberi, Teuta

2013-01-01

Aim: The aim of work was presentation of several socio-demographic, clinical and laboratory characteristics of gastroenteritis caused by rotavirus. The examinees and methods: The examinees were children under the age of five years treated at the Pediatric Clinic due to acute gastroenteritis caused by rotavirus. Rotavirus is isolated by method chromatographic immunoassay by Cer Test Biotec. Results: From the total number of patients (850) suffering from acute gastroenteritis, feces test on bacteria, viruses. protozoa and fungi was positive in 425 (49.76%) cases. From this number the test on bacteria was positive in 248 (58.62%) cases, on viruses it was positive in 165 (39.0%), on protozoa in 9 (2.12%) cases and on fungi only one case. Rotavirus was the most frequent one in viral test, it was isolated in 142 (86.06%) cases, adenoviruses were found in 9 (5.45%) cases and noroviruses in only one case. The same feces sample that contained rotavirus and adenoviruses were isolated in five cases, whereas rotavirus with bacteria was isolated in the same feces sample in five cases. The biggest number of cases 62 (43.66%) were of the age 6-12 months, whereas the smallest number 10 (7.04%) cases were of the age 37-60 months. There were 76 (53.52%) of cases of male gender, from rural areas there were 81 (57.04%) cases and there were 58 (40.80%) cases during the summer period. Among the clinical symptoms the most prominent were diarrhea, vomiting, high temperature, whereas the different degree of dehydration were present in all cases (the most common one was moderate dehydration). The most frequent one was isonatremic dehydration in 91 (64.08%) cases, less frequent one was hypernatremic dehydration in 14 (9.85%) cases. The majority of cases (97.89%) had lower blood pH values, whereas 67 (47.17%) cases had pH values that varied from 7.16 -7.20 (curve peak), normal values were registered in only 3 (2.11%) cases. Urea values were increased in 45 (31.07%) cases (the maximum value was 26.5 mmol/L), whereas creatinine value was increased in 41 (28.87%) cases (maximum value was 302 mmol/L). Conclusion: The results show the high frequency of rotavirus infections in children hospitalized with acute gastroenteritis. Rotavirus may cause different dehydration degree with electrolyte, acid-base and other biochemical disorders. Preventing the infection caused by rotavirus is of a great importance. PMID:23678334

Innate Immune Factors in Mothers' Breast Milk and Their Lack of Association With Rotavirus Vaccine Immunogenicity in Nicaraguan Infants.

PubMed

Becker-Dreps, Sylvia; Choi, Wan Suk; Stamper, Lisa; Vilchez, Samuel; Velasquez, Daniel E; Moon, Sung-Sil; Hudgens, Michael G; Jiang, Baoming; Permar, Sallie R

2017-03-01

To better understand underlying causes of lower rotavirus vaccine effectiveness in low-middle income countries (LMICs), we measured innate antiviral factors in Nicaraguan mothers' milk and immune response to the first dose of the pentavalent rotavirus vaccine in corresponding infants. No relationship was found between concentrations of innate factors and rotavirus vaccine response. © The Author 2015. Published by Oxford University Press on behalf of the Pediatric Infectious Diseases Society. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Therapeutics and Immunoprophylaxis Against Noroviruses and Rotaviruses: The Past, Present, and Future

PubMed Central

Ghosh, Souvik; Malik, Yashpal Singh; Kobayashi, Nobumichi

2018-01-01

Background: Noroviruses and rotaviruses are important viral etiologies of severe gastroenteritis. Noroviruses are the primary cause of nonbacterial diarrheal outbreaks in humans, whilst rotaviruses are a major cause of childhood diarrhea. Although both enteric pathogens substantially impact human health and economies, there are no approved drugs against noroviruses and rotaviruses so far. On the other hand, whilst the currently licensed rotavirus vaccines have been successfully implemented in over 100 countries, the most advanced norovirus vaccine has recently completed phase-I and II trials. Methods: We performed a structured search of bibliographic databases for peer-reviewed research litera-ture on advances in the fields of norovirus and rotavirus therapeutics and immunoprophylaxis. Results: Technological advances coupled with a proper understanding of viral morphology and replication over the past decade has facilitated pioneering research on therapeutics and immunoprophylaxis against noroviruses and rotaviruses, with promising outcomes in human clinical trials of some of the drugs and vaccines. This review focuses on the various developments in the fields of norovirus and rotavirus thera-peutics and immunoprophylaxis, such as potential antiviral drug molecules, passive immunotherapies (oral human immunoglobulins, egg yolk and bovine colostral antibodies, llama-derived nanobodies, and anti-bodies expressed in probiotics, plants, rice grains and insect larvae), immune system modulators, probiot-ics, phytochemicals and other biological substances such as bovine milk proteins, therapeutic nanoparti-cles, hydrogels and viscogens, conventional viral vaccines (live and inactivated whole virus vaccines), and genetically engineered viral vaccines (reassortant viral particles, virus-like particles (VLPs) and other sub-unit recombinant vaccines including multi-valent viral vaccines, edible plant vaccines, and encapsulated viral particles). Conclusions: This review provides important insights into the various approaches to therapeutics and im-munoprophylaxis against noroviruses and rotaviruses.. PMID:28901254

A Preliminary Assessment of Rotavirus Vaccine Effectiveness in Zambia.

PubMed

Beres, Laura K; Tate, Jacqueline E; Njobvu, Lungowe; Chibwe, Bertha; Rudd, Cheryl; Guffey, M Brad; Stringer, Jeffrey S A; Parashar, Umesh D; Chilengi, Roma

2016-05-01

Diarrhea is the third leading cause of child death in Zambia. Up to one-third of diarrhea cases resulting in hospitalization and/or death are caused by vaccine-preventable rotavirus. In January 2012, Zambia initiated a pilot introduction of the Rotarix live, oral rotavirus vaccine in all public health facilities in Lusaka Province. Between July 2012 and October 2013, we conducted a case-control study at 6 public sector sites to estimate rotavirus vaccine effectiveness (VE) in age-eligible children presenting with diarrhea. We computed the odds of having received at least 1 dose of Rotarix among children whose stool was positive for rotavirus antigen (cases) and children whose stool was negative (controls). We adjusted the resulting odds ratio (OR) for patient age, calendar month of presentation, and clinical site, and expressed VE as (1 - adjusted OR) × 100. A total of 91 rotavirus-positive cases and 298 rotavirus-negative controls who had under-5 card-confirmed vaccination status and were ≥6 months of age were included in the case-control analysis. Among rotavirus-positive children who were age-eligible to be vaccinated, 20% were hospitalized. Against rotavirus diarrhea of all severity, the adjusted 2-dose VE was 26% (95% confidence interval [CI], -30% to 58%) among children ≥6 months of age. VE against hospitalized children ≥6 months of age was 56% (95% CI, -34% to 86%). We observed a higher point estimate for VE against increased severity of illness compared with milder disease, but were not powered to detect a low level of VE against milder disease. © The Author 2016. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail journals.permissions@oup.com.

Therapeutics and Immunoprophylaxis Against Noroviruses and Rotaviruses: The Past, Present, and Future.

PubMed

Ghosh, Souvik; Malik, Yashpal Singh; Kobayashi, Nobumichi

2018-01-01

Noroviruses and rotaviruses are important viral etiologies of severe gastroenteritis. Noroviruses are the primary cause of nonbacterial diarrheal outbreaks in humans, whilst rotaviruses are a major cause of childhood diarrhea. Although both enteric pathogens substantially impact human health and economies, there are no approved drugs against noroviruses and rotaviruses so far. On the other hand, whilst the currently licensed rotavirus vaccines have been successfully implemented in over 100 countries, the most advanced norovirus vaccine has recently completed phase-I and II trials. We performed a structured search of bibliographic databases for peer-reviewed research literature on advances in the fields of norovirus and rotavirus therapeutics and immunoprophylaxis. Technological advances coupled with a proper understanding of viral morphology and replication over the past decade has facilitated pioneering research on therapeutics and immunoprophylaxis against noroviruses and rotaviruses, with promising outcomes in human clinical trials of some of the drugs and vaccines. This review focuses on the various developments in the fields of norovirus and rotavirus therapeutics and immunoprophylaxis, such as potential antiviral drug molecules, passive immunotherapies (oral human immunoglobulins, egg yolk and bovine colostral antibodies, llama-derived nanobodies, and antibodies expressed in probiotics, plants, rice grains and insect larvae), immune system modulators, probiotics, phytochemicals and other biological substances such as bovine milk proteins, therapeutic nanoparticles, hydrogels and viscogens, conventional viral vaccines (live and inactivated whole virus vaccines), and genetically engineered viral vaccines (reassortant viral particles, virus-like particles (VLPs) and other subunit recombinant vaccines including multi-valent viral vaccines, edible plant vaccines, and encapsulated viral particles). This review provides important insights into the various approaches to therapeutics and immunoprophylaxis against noroviruses and rotaviruses. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Live attenuated human rotavirus vaccine, Rotarix.

PubMed

Bernstein, David I

2006-10-01

Rotavirus infections are the leading cause of severe gastroenteritis in young children worldwide. Recently two new rotavirus vaccines have entered the world market. This review provides a summary of the rationale, development, and evaluation of one of these vaccines, Rotarix. Rotarix is a live oral rotavirus vaccine developed from a single protective human strain following multiple passages in tissue culture to attenuate the strain. The vaccine is administered as two oral doses at approximately 2 and 4 months of age. Large safety and efficacy trials have shown the vaccine is safe, not associated with intussusception, and effective against the most common circulating human serotypes. Efficacy against severe rotavirus gastroenteritis and hospitalization have ranged from 85 to 100 percent.

Human norovirus infection in Latin America.

PubMed

da Silva Poló, Tatiane; Peiró, Juliana R; Mendes, Luiz Cláudio Nogueira; Ludwig, Louisa F; de Oliveira-Filho, Edmilson F; Bucardo, Filemon; Huynen, Pascale; Melin, Pierrette; Thiry, Etienne; Mauroy, Axel

2016-05-01

Noroviruses are important enteric pathogens involved in non-bacterial gastroenteritis outbreaks worldwide. Noroviruses mainly occur from person to person via the fecal-oral route but also through contaminated food or water; indirect contamination is also possible due to the resistance of the virus in the environment. Latin American countries as a whole cover a vast North-to-South range, which is highly heterogeneous in terms of climate, ecosystem, human population distribution (urban areas with high human densities versus closed communities), economic development and genetic backgrounds resulting from each particular historical context. This review aims to present epidemiological and clinical patterns of human norovirus infections in Latin American countries. Divergent prevalences were observed depending on the country and the surveyed population. In particular, a shift in rotavirus/norovirus ratio in the etiologies of gastroenteritis was detected in some countries and could be attributed partly to rotavirus vaccine coverage in their infant population. While GII.4 noroviruses were seen to constitute the most common genotype, differences in genotype distribution were observed both in the environment (via sewage sampling proxy) and between genotypes circulating in healthy and diarrheic patients. Due to high climatic discrepancies, different patterns of seasonality were observed. Accordingly, this continent may condense the different particular epidemiological features encountered for HuNoV infections worldwide. Copyright © 2016 Elsevier B.V. All rights reserved.

An evaluation of the inhibitory effects against rotavirus infection of edible plant extracts

PubMed Central

2012-01-01

Background Rotaviruses are the single most important cause of severe diarrhea in young children worldwide. The developments of specific, potent and accessible antiviral treatments that restrain rotavirus infection remain important to control rotavirus disease. Methods 150 plant extracts with nutritional applications were screened in vitro on MA-104 cells for their antiviral activity against rhesus rotavirus (RRV). One extract (Aspalathus linearis (Burm.f.) R.Dahlgren) was also tested for its effect on the loss of transepithelial resistance (TER) of Caco-2 cells caused by simian rotavirus (SA-11) infection. Results Aqueous extracts of Nelumbo nucifera Gaertn. fruit, Urtica dioica L. root, Aspalathus linearis (Burm.f.) R.Dahlgren leaves, Glycyrrhiza glabra L. root and Olea europaea L. leaves were found to have strong significant antiviral activity with a 50% inhibitory concentration (IC50) < 300 μg/ml. The pure compound 18ß-glycyrrhetinic acid from Glycyrrhiza glabra was found to have the strongest antiviral activity (IC50 46 μM), followed by luteolin and vitexin from Aspalathus linearis (IC50 respectively 116 μM and 129 μM) and apigenin-7-O-glucoside from Melissa officinalis (IC50 150 μM). A combination of Glycyrrhiza glabra L. + Nelumbo nucifera Gaertn. and Urtica dioica L. + Nelumbo nucifera Gaertn. showed synergy in their anti-viral activities. Aspalathus linearis (Burm.f.) R.Dahlgren showed no positive effect on the maintenance of the TER. Conclusions These results indicate that nutritional intervention with extracts of Nelumbo nucifera Gaertn., Aspalathus linearis (Burm.f.) R.Dahlgren, Urtica dioica L., Glycyrrhiza glabra L. and Olea europaea L. might be useful in the treatment of diarrhea caused by rotavirus infection. PMID:22834653

An evaluation of the inhibitory effects against rotavirus infection of edible plant extracts.

PubMed

Knipping, Karen; Garssen, Johan; van't Land, Belinda

2012-07-26

Rotaviruses are the single most important cause of severe diarrhea in young children worldwide. The developments of specific, potent and accessible antiviral treatments that restrain rotavirus infection remain important to control rotavirus disease. 150 plant extracts with nutritional applications were screened in vitro on MA-104 cells for their antiviral activity against rhesus rotavirus (RRV). One extract (Aspalathus linearis (Burm.f.) R.Dahlgren) was also tested for its effect on the loss of transepithelial resistance (TER) of Caco-2 cells caused by simian rotavirus (SA-11) infection. Aqueous extracts of Nelumbo nucifera Gaertn. fruit, Urtica dioica L. root, Aspalathus linearis (Burm.f.) R.Dahlgren leaves, Glycyrrhiza glabra L. root and Olea europaea L. leaves were found to have strong significant antiviral activity with a 50% inhibitory concentration (IC50) < 300 μg/ml. The pure compound 18ß-glycyrrhetinic acid from Glycyrrhiza glabra was found to have the strongest antiviral activity (IC50 46 μM), followed by luteolin and vitexin from Aspalathus linearis (IC50 respectively 116 μM and 129 μM) and apigenin-7-O-glucoside from Melissa officinalis (IC50 150 μM). A combination of Glycyrrhiza glabra L. + Nelumbo nucifera Gaertn. and Urtica dioica L. + Nelumbo nucifera Gaertn. showed synergy in their anti-viral activities. Aspalathus linearis (Burm.f.) R.Dahlgren showed no positive effect on the maintenance of the TER. These results indicate that nutritional intervention with extracts of Nelumbo nucifera Gaertn., Aspalathus linearis (Burm.f.) R.Dahlgren, Urtica dioica L., Glycyrrhiza glabra L. and Olea europaea L. might be useful in the treatment of diarrhea caused by rotavirus infection.

Multiple norovirus infections in a birth cohort in a Peruvian Periurban community.

PubMed

Saito, Mayuko; Goel-Apaza, Sonia; Espetia, Susan; Velasquez, Daniel; Cabrera, Lilia; Loli, Sebastian; Crabtree, Jean E; Black, Robert E; Kosek, Margaret; Checkley, William; Zimic, Mirko; Bern, Caryn; Cama, Vitaliano; Gilman, Robert H

2014-02-01

Human noroviruses are among the most common enteropathogens globally, and are a leading cause of infant diarrhea in developing countries. However, data measuring the impact of norovirus at the community level are sparse. We followed a birth cohort of children to estimate norovirus infection and diarrhea incidence in a Peruvian community. Stool samples from diarrheal episodes and randomly selected nondiarrheal samples were tested by polymerase chain reaction for norovirus genogroup and genotype. Excretion duration and rotavirus coinfection were evaluated in a subset of episodes. Two hundred twenty and 189 children were followed to 1 and 2 years of age, respectively. By 1 year, 80% (95% confidence interval [CI], 75%-85%) experienced at least 1 norovirus infection and by 2 years, 71% (95% CI, 65%-77%) had at least 1 episode of norovirus-associated diarrhea. Genogroup II (GII) infections were 3 times more frequent than genogroup 1 (GI) infections. Eighteen genotypes were found; GII genotype 4 accounted for 41%. Median excretion duration was 34.5 days for GII vs 8.5 days for GI infection (P = .0006). Repeat infections by the same genogroup were common, but repeat infections by the same genotype were rare. Mean length-for-age z score at 12 months was lower among children with prior norovirus infection compared to uninfected children (coefficient: -0.33 [95% CI, -.65 to -.01]; P = .04); the effect persisted at 24 months. Norovirus infection occurs early in life and children experience serial infections with multiple genotypes, suggesting genotype-specific immunity. An effective vaccine would have a substantial impact on morbidity, but may need to target multiple genotypes.

Detection and distribution of rotavirus in raw sewage and creeks in Sao Paulo, Brazil

DOE Office of Scientific and Technical Information (OSTI.GOV)

Mehnert, D.U.; Stewien, K.E.

1993-01-01

Rotavirus invection is an important cause of hospitalization and mortality of infants and children in developing countries, especially where the water supply and sewage disposal systems are in precarious conditions. This report describes the detection, quantitation, and distribution of rotaviruses in domestic sewage and sewage polluted creeks in the city of San Paulo. 22 refs., 1 fig., 3 tabs.

Predominance of new G9P[8] rotaviruses closely related to Turkish strains in Nizhny Novgorod (Russia).

PubMed

Sashina, T A; Morozova, O V; Epifanova, N V; Novikova, N A

2017-08-01

Genotype G9P[8] rotaviruses are rare in the territory of Russia. They were found in Nizhny Novgorod only in 2011-2012 for the first time, when their proportion was 25.9%. During the next two seasons, G9P[8] strains were detected in only 1.8% of cases. Their proportion substantially increased again in 2014, and they became predominant in the city by 2016. Phylogenetic analysis on the basis of gene VP7 nucleotide sequences showed that this increase was accompanied by the emergence of new strains in the population. These isolates were related to Turkish strains, but not to Russian ones detected earlier.

Modulation of rotavirus severe gastroenteritis by the combination of probiotics and prebiotics.

PubMed

Gonzalez-Ochoa, Guadalupe; Flores-Mendoza, Lilian K; Icedo-Garcia, Ramona; Gomez-Flores, Ricardo; Tamez-Guerra, Patricia

2017-09-01

Annual mortality rates due to infectious diarrhea are about 2.2 million; children are the most vulnerable age group to severe gastroenteritis, representing group A rotaviruses as the main cause of disease. One of the main factors of rotavirus pathogenesis is the NSP4 protein, which has been characterized as a viral toxin involved in triggering several cellular responses leading to diarrhea. Furthermore, the rotavirus protein NSP1 has been associated with interferon production inhibition by inducing the degradation of interferon regulatory factors IRF3, IRF5, and IRF7. On the other hand, probiotics such as Bifidobacterium and Lactobacillus species in combination with prebiotics such as inulin, HMO, scGOS, lcFOS have been associated with improved generalized antiviral response and anti-rotavirus effect by the reduction of rotavirus infectivity and viral shedding, decreased expression of NSP4 and increased levels of specific anti-rotavirus IgAs. Moreover, these probiotics and prebiotics have been related to shorter duration and severity of rotavirus diarrhea, to the prevention of infection and reduced incidence of reinfections. In this review we will discuss in detail about the rotavirus pathogenesis and immunity, and how probiotics such as Lactobacillus and Bifidobacterium species in combination with prebiotics have been associated with the prevention or modulation of rotavirus severe gastroenteritis.

Generation of recombinant rotaviruses expressing fluorescent proteins using an optimized reverse genetics system.

PubMed

Komoto, Satoshi; Fukuda, Saori; Ide, Tomihiko; Ito, Naoto; Sugiyama, Makoto; Yoshikawa, Tetsushi; Murata, Takayuki; Taniguchi, Koki

2018-04-18

An entirely plasmid-based reverse genetics system for rotaviruses was established very recently. We improved the reverse genetics system to generate recombinant rotavirus by transfecting only 11 cDNA plasmids for its 11 gene segments under the condition of increasing the ratio of the cDNA plasmids for NSP2 and NSP5 genes. Utilizing this highly efficient system, we then engineered infectious recombinant rotaviruses expressing bioluminescent (NanoLuc luciferase) and fluorescent (EGFP and mCherry) reporters. These recombinant rotaviruses expressing reporters remained genetically stable during serial passages. Our reverse genetics approach and recombinant rotaviruses carrying reporter genes will be great additions to the tool kit for studying the molecular virology of rotavirus, and for developing future next-generation vaccines and expression vectors. IMPORTANCE Rotavirus is one of the most important pathogens causing severe gastroenteritis in young children worldwide. In this paper, we describe a robust and simple reverse genetics system based on only rotavirus cDNAs, and its application for engineering infectious recombinant rotaviruses harboring bioluminescent (NanoLuc) and fluorescent (EGFP and mCherry) protein genes. This highly efficient reverse genetics system and recombinant RVAs expressing reporters could be powerful tools for the study of different aspects of rotavirus replication. Furthermore, they may be useful for next-generation vaccine production for this medically important virus. Copyright © 2018 American Society for Microbiology.

Molecular characterization of rotavirus isolated from alpaca (Vicugna pacos) crias with diarrhea in the Andean Region of Cusco, Peru.

PubMed

Garmendia, Antonio E; Lopez, Wellington; Ortega, Nastassja; Chamorro, Marycris J

2015-10-22

Alpacas (Vicugna pacos), a species of South American camelids (SAC), suffer high morbidity and mortality from infectious diseases. Diarrhea is one of the leading causes of alpaca cria mortality in Peru and elsewhere. In order to develop appropriate control and/or treatment, it is necessary to identify infectious pathogens that cause diarrhea in crias. Rotavirus was isolated in cell culture from feces collected from crias with acute diarrhea that tested positive to rotaviral antigen by rapid immunochromatographic methods in an earlier study. The isolates were identified as rotaviruses by RT-PCR run with specific primers for human rotavirus VP7 coding sequences using total RNA extracted from cells displaying cytopathic effects as template. These alpaca isolates were further identified as group A rotaviruses by means of a VP6-specific PCR and were designated as ALRVA-K'ayra/Perú/3368-10 and ALRVA-K'ayra/Perú/3386-10. Molecular G and P typing, placed the former as G3/P11 and the latter as G3/P?. Sequence analysis of two genome segments (coding for VP4 and VP7) from the alpaca isolates revealed partial homologies to swine and human rotaviruses, respectively. These results demonstrate that rotaviruses are associated with a proportion of cases of diarrhea in crias, although prevalence and impact remain to be determined. The isolation of rotaviruses from alpaca crias with diarrhea will contribute positively to further understand the pathogen and its role in the diarrhea complex. Copyright © 2015 Elsevier B.V. All rights reserved.

Burden and epidemiology of rotavirus diarrhea in selected African countries: preliminary results from the African Rotavirus Surveillance Network.

PubMed

Mwenda, Jason M; Ntoto, Kinkela Mina; Abebe, Almaz; Enweronu-Laryea, Christabel; Amina, Ismail; Mchomvu, Jackson; Kisakye, Annet; Mpabalwani, Evans M; Pazvakavambwa, Isoro; Armah, George E; Seheri, L M; Kiulia, Nicholas M; Page, N; Widdowson, Marc-Alain; Steele, A Duncan

2010-09-01

Severe rotavirus diarrhea in children <5 years of age is a major public health problem; however, limited regional and country specific data on rotavirus disease burden are available from sub-Saharan Africa. In June 2006, the World Health Organization Regional Office for Africa initiated rotavirus surveillance in selected African countries. With use of standardized methodology developed by the World Health Organization, children <5 years of age who were hospitalized with severe diarrhea were enrolled, and stool specimens were collected for detection of rotavirus strains with use of a commercial enzyme immunoassay. Rotavirus strains were further characterized for G and P types with use of a reverse-transcriptase polymerase chain reaction. From June 2006 through December 2008, rotavirus surveillance was established at 14 sites in 11 African countries. Of 5461 stool samples collected from children enrolled in 8 countries with 1 or 2 complete years of data, 2200 (40%) were positive for rotavirus. Ninety percent of all rotavirus hospitalizations occurred among children aged 3-12 months. Predominant types included G1P[8] (21%), G2P[4] (7%), and P [8] (29%); however, unusual types were also detected, including G8P[6] (5%), G8P[8] (1%), G12P[6] (1%), and G12P[6] (1%). A high percentage of mixed rotavirus infections was also detected. These preliminary results indicate that rotavirus is a major cause of severe diarrheal disease in African children.

Rotavirus gastroenteritis surveillance in Azerbaijan, 2011-2016.

PubMed

Mursalova, Nazifa; Shugayev, Nazim; Suleymanova, Javahir; Daniels, Danni S; Wasley, Annemarie; Cohen, Adam L; Aliabadi, Negar

2018-05-18

Rotavirus is a leading cause of acute gastroenteritis and mortality among children worldwide but data describing rotavirus disease in Azerbaijan are lacking. This analysis describes the rotavirus disease burden in Baku, the largest city in Azerbaijan. We conducted active, prospective, sentinel hospital surveillance with laboratory confirmation for rotavirus among children under 5 years of age hospitalized at a large pediatric hospital in Baku during 2011-2016. Children with bloody diarrhea, or prior use of antibiotics or intravenous fluids were excluded. The guardians of enrolled children completed a questionnaire documenting clinical and demographic information. A stool specimen was collected from each enrolled child. We report the number and proportion of rotavirus positive hospitalizations during the surveillance period and a clinical description of rotavirus-positive and rotavirus-negative children. From July 2011 through June 2016, 3139 children <5 years of age were enrolled into the surveillance system. Of these, 523 (17%) were positive for rotavirus, varying from 13% to 21% by surveillance year, with a median of 16% over the surveillance period. Increase in rotavirus detections occurred during December-May. Most rotavirus infections (303/523; 58%) occurred in children aged 6-23 months. Rotavirus is responsible for approximately 16% of annual hospital admissions for acute gastroenteritis in children <5 years of age in Baku. This is lower than regional estimates. Exclusion of children with a history of antibiotic use or intravenous fluids may be accounting for this lower prevalence, and expansion of surveillance to include these groups could provide a more comprehensive picture of acute rotavirus gastroenteritis in Baku. Published by Elsevier Ltd.

Rotavirus vaccines: safety, efficacy and public health impact.

PubMed

Gray, J

2011-09-01

Rotaviruses are the cause of acute gastroenteritis, and disease is widespread amongst infants and young children throughout the world. Also, rotavirus is associated with significant mortality in developing countries with more than 500 000 children dying each year as a result of the severe dehydration associated with rotavirus disease. Efforts have been ongoing for more than 30 years to develop a safe and effective rotavirus vaccine. Currently, two vaccines, RotaRix and RotaTeq, have been licensed for use in many countries throughout the world following comprehensive safety and efficiency trials. Monitoring their effectiveness after licensure has confirmed that their incorporation into early childhood vaccination schedules can significantly prevent severe rotavirus diarrhoea, which would have resulted in hospitalizations, emergency room visits or increased diarrhoea-related mortality. Although the efficacy of both vaccines is lower at approximately 40-59% in developing countries, their use could significantly reduce the mortality associated with rotavirus disease that is concentrated in these countries. © 2011 The Association for the Publication of the Journal of Internal Medicine.

Secondary efficacy endpoints of the pentavalent rotavirus vaccine against gastroenteritis in sub-Saharan Africa.

PubMed

Tapia, Milagritos D; Armah, George; Breiman, Robert F; Dallas, Michael J; Lewis, Kristen D C; Sow, Samba O; Rivers, Stephen B; Levine, Myron M; Laserson, Kayla F; Feikin, Daniel R; Victor, John C; Ciarlet, Max; Neuzil, Kathleen M; Steele, A Duncan

2012-04-27

The efficacy of the pentavalent rotavirus vaccine (PRV), RotaTeq(®), was evaluated in a double-blind, placebo-controlled, multicenter Phase III clinical trial conducted (April 2007-March 2009) in 3 low-income countries in Africa: Ghana, Kenya, and Mali. In total, 5468 infants were randomized 1:1 to receive 3 doses of PRV/placebo at approximately 6, 10, and 14 weeks of age; concomitant administration with routine EPI vaccines, including OPV, was allowed. HIV-infected infants were not excluded. The primary endpoint, vaccine efficacy (VE) against severe-rotavirus gastroenteritis (RVGE), as measured by Vesikari scoring system (VSS, score ≥11), from ≥14 days following Dose 3 through a follow-up period of nearly 2 years in the combined 3 African countries, and secondary endpoints by total follow-up period have been previously reported. In this study, we report post hoc subgroup analyses on secondary endpoints of public health importance. VE against RVGE of any severity was 49.2% (95%CI: 29.9, 63.5) through the first year of life and 30.5% (95%CI: 16.7, 42.2) through the complete follow-up period. VE against severe-gastroenteritis of any etiology was 21.5% (95%CI: <0, 38.4) through the first year of life and 10.6% (95%CI: <0, 24.9) through the complete follow-up period. Through the complete follow-up period, VE against severe-RVGE caused by (i) vaccine-contained G and P types (G1-G4, P1A[8]), (ii) non-vaccine G types (G8, G9, G10), and (iii) non-vaccine P types (P1B[4], P2A[6]) was 34.0% (95%CI:11.2, 51.2), 81.8% (95%CI:16.5, 98.0) and 40.7% (95%CI:8.4, 62.1), respectively. There was a trend towards higher VE with higher disease severity, although in some cases the numbers were small. In African countries with high under-5 mortality rates, PRV significantly reduced RVGE through nearly 2 years of follow-up; more modest reductions were observed against gastroenteritis of any etiology. PRV provides protection against severe-RVGE caused by diverse rotavirus genotypes, including those not contained in the vaccine. Copyright © 2012 Elsevier Ltd. All rights reserved.

Rotavirus vaccine effectiveness in Hong Kong children.

PubMed

Yeung, Karene Hoi Ting; Tate, Jacqueline E; Chan, Ching Ching; Chan, Martin C W; Chan, Paul K S; Poon, Kin Hung; Siu, Sylvia Luen Yee; Fung, Genevieve Po Gee; Ng, Kwok Leung; Chan, Iris Mei Ching; Yu, Pui Tak; Ng, Chi Hang; Lau, Yu Lung; Nelson, E Anthony S

2016-09-22

Rotavirus is a common infectious cause of childhood hospitalisation in Hong Kong. Rotavirus vaccines have been used in the private sector since licensure in 2006 but have not been incorporated in the government's universal Childhood Immunisation Programme. This study aimed to evaluate rotavirus vaccine effectiveness against hospitalisation. This case-control study was conducted in the 2014/2015 rotavirus season in six public hospitals. Hospitalised acute gastroenteritis patients meeting inclusion criteria were recruited and copies of their immunisation records were collected. Case-patients were defined as enrolled subjects with stool specimens obtained in the first 48h of hospitalisation that tested positive for rotavirus, whereas control-patients were those with stool specimens obtained in the first 48h of hospitalisation testing negative for rotavirus. Vaccine effectiveness for administration of at least one dose of either Rotarix(®) (GlaxoSmithKline Biologicals) or RotaTeq(®) (Merck Research Laboratories) was calculated as 1 minus the odds ratio for rotavirus vaccination history for case-patients versus control-patients. Among the 525 eligible subjects recruited, immunisation records were seen in 404 (77%) subjects. 31% (162/525 and 126/404) tested positive for rotavirus. In the 404 subjects assessed for vaccine effectiveness, 2.4% and 24% received at least 1 dose of either rotavirus vaccine in case- and control-patients respectively. The unmatched vaccine effectiveness against hospitalisation for administration of at least one dose of either rotavirus vaccines was 92% (95% confidence interval [CI]: 75%, 98%). The matched analyses by age only and both age and admission date showed 96% (95% CI: 72%, 100%) and 89% (95% CI: 51%, 97%) protection against rotavirus hospitalisation respectively. Rotavirus vaccine is highly effective in preventing hospitalisation from rotavirus disease in young Hong Kong children. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

Structural basis of glycan specificity of P[19] VP8*: Implications for rotavirus zoonosis and evolution.

PubMed

Liu, Yang; Xu, Shenyuan; Woodruff, Andrew L; Xia, Ming; Tan, Ming; Kennedy, Michael A; Jiang, Xi

2017-11-01

Recognition of specific cell surface glycans, mediated by the VP8* domain of the spike protein VP4, is the essential first step in rotavirus (RV) infection. Due to lack of direct structural information of virus-ligand interactions, the molecular basis of ligand-controlled host ranges of the major human RVs (P[8] and P[4]) in P[II] genogroup remains unknown. Here, through characterization of a minor P[II] RV (P[19]) that can infect both animals (pigs) and humans, we made an important advance to fill this knowledge gap by solving the crystal structures of the P[19] VP8* in complex with its ligands. Our data showed that P[19] RVs use a novel binding site that differs from the known ones of other genotypes/genogroups. This binding site is capable of interacting with two types of glycans, the mucin core and type 1 histo-blood group antigens (HBGAs) with a common GlcNAc as the central binding saccharide. The binding site is apparently shared by other P[II] RVs and possibly two genotypes (P[10] and P[12]) in P[I] as shown by their highly conserved GlcNAc-interacting residues. These data provide strong evidence of evolutionary connections among these human and animal RVs, pointing to a common ancestor in P[I] with a possible animal host origin. While the binding properties to GlcNAc-containing saccharides are maintained, changes in binding to additional residues, such as those in the polymorphic type 1 HBGAs may occur in the course of RV evolution, explaining the complex P[II] genogroup that mainly causes diseases in humans but also in some animals.

A porcine G9 rotavirus strain shares neutralization and VP7 phylogenetic sequence lineage 3 characteristics with contemporary human G9 rotavirus strains.

PubMed

Hoshino, Yasutaka; Honma, Shinjiro; Jones, Ronald W; Ross, Jerri; Santos, Norma; Gentsch, Jon R; Kapikian, Albert Z; Hesse, Richard A

2005-02-05

Of five globally important VP7 (G) serotypes (G1-4 and 9) of group A rotaviruses (the single most important etiologic agents of infantile diarrhea worldwide), G9 continues to attract considerable attention because of its unique natural history. Serotype G9 rotavirus was isolated from a child with diarrhea first in the United States in 1983 and subsequently in Japan in 1985. Curiously, soon after their detection, G9 rotaviruses were not detected for about a decade in both countries and then reemerged in both countries in the mid-1990s. Unexpectedly, however, such reemerged G9 strains were distinct genetically and molecularly from those isolated in the 1980s. Thus, the origin of the reemerged G9 viruses remains an enigma. Sequence analysis has demonstrated that the G9 rotavirus VP7 gene belongs to one of at least three phylogenetic lineages: lineage 1 (strains isolated in the 1980s in the United States and Japan), lineage 2 (strains first isolated in 1986 and exclusively in India thus far), and lineage 3 (strains that emerged/reemerged in the mid-1990s). Currently, lineage 3 G9 viruses are the most frequently detected G9 strains globally. We characterized a porcine rotavirus (A2 strain) isolated in the United States that was known to belong to the P[7] genotype but had not been serotyped by neutralization. The A2 strain was found to bear serotype G9 and P9 specificities as well as NSP4 [B] and subgroup I characteristics. By VP7-specific neutralization, the porcine G9 strain was more closely related to lineage 3 viruses than to lineage 1 or 2 viruses. Furthermore, by sequence analysis, the A2 VP7 was shown to belong to lineage 3 G9. These findings raise intriguing questions regarding possible explanations for the emergence of variations among the G9 strains.

Effectiveness of rotavirus pentavalent vaccine under a universal immunization programme in Israel, 2011-2015: a case-control study.

PubMed

Muhsen, K; Anis, E; Rubinstein, U; Kassem, E; Goren, S; Shulman, L M; Ephros, M; Cohen, D

2018-01-01

The use of rotavirus pentavalent vaccine (RotaTeq ® ) as a sole vaccine within rotavirus universal immunization programmes remains limited. We examined the effectiveness of RotaTeq in preventing rotavirus gastroenteritis (RVGE) hospitalization in Israel, after the introduction of universal immunization against the disease. A test-negative case-control study included age-eligible children for universal RotaTeq immunization (aged 2-59 months, born in 2011-2015). Cases (n = 98) were patients who tested positive for rotavirus by immunochromatography; those who tested negative (n = 628) comprised the control group. Information on rotavirus immunization history was obtained through linkage with a national immunization registry. Vaccination status was compared between cases and controls, adjusted odds ratios (aORs) were obtained from logistic regression models, and vaccine effectiveness calculated as (1 - aOR)*100. Immunization with RotaTeq was less frequent in RVGE cases (73.5%) than in controls (90.1%), p < 0.001; this association persisted after controlling for potential confounders. Effectiveness of the complete vaccine series was estimated at 77% (95% confidence interval (CI): 49-90) in children aged 6-59 months, and 86% (95% CI: 65-94) in children aged 6-23 months; whereas for the incomplete series, the respective estimates were 72% (95% CI: 28-89) and 75% (95% CI: 30-91). Vaccine effectiveness was estimated at 79% (95% CI: 45-92) against G1P[8]-associated RVGE hospitalizations and 69% (95% CI: 11-89) against other genotype-RVGE hospitalizations. High effectiveness of RotaTeq as the sole rotavirus vaccine in a universal immunization programme was demonstrated in a high-income country. Although partial vaccination conferred protection, completing the vaccine series is warranted to maximize the benefit. Copyright © 2017 European Society of Clinical Microbiology and Infectious Diseases. Published by Elsevier Ltd. All rights reserved.

Nosocomial outbreak of neonatal gastroenteritis caused by a new serotype 4, subtype 4B human rotavirus.

PubMed

Gerna, G; Forster, J; Parea, M; Sarasini, A; Di Matteo, A; Baldanti, F; Langosch, B; Schmidt, S; Battaglia, M

1990-07-01

A nosocomial outbreak of rotavirus gastroenteritis involving 52 newborns occurred between June and September 1988 at the University Children's Hospital of Freiburg, Federal Republic of Germany. Stools from 27 representative patients were examined for rotavirus serotypes, using a monoclonal antibody-based enzyme-linked immunosorbent assay. The electropherotype was also examined by polyacrylamide gel electrophoresis of genomic RNA. As many as 18 patients were found to be infected by serotype 4, subtype 4B strain, and in all of them the same electropherotype was detected. Although rotavirus from the remaining nine patients could not be typed, the electropherotype in four was identical to that of the serotype 4, subtype 4B strain. Thus, most of the patients in the outbreak were infected by the same rotavirus strain. Retrospective epidemiological studies showed that the 4B strain began to circulate at the hospital in January 1988, whereas only rotavirus serotypes 1, 3, and 4A were detected in 1985-1987. The primary case of the outbreak was presumably a newborn with acute gastroenteritis, admitted to the hospital from a small maternity unit in the same urban area. During the outbreak, 12 of 44 healthy newborns in the nurseries of the Children's Hospital and other maternity hospitals were found to be asymptomatic rotavirus carriers, and in three of the newborns the same 4B strain was detected. This is the first reported outbreak caused by a serotype 4, subtype 4B strain.

Anticipating rotavirus vaccines: hospital-based surveillance for rotavirus diarrhea and estimates of disease burden in Bangladesh.

PubMed

Unicomb, L E; Kilgore, P E; Faruque, S G; Hamadani, J D; Fuchs, G J; Albert, M J; Glass, R I

1997-10-01

Rotavirus is the most common cause of severe diarrhea in children worldwide, and a vaccine may soon be licensed and available for use in immunization programs. To assess the need for a rotavirus vaccine in Bangladesh, we estimated the disease burden of rotavirus diarrhea from national vital statistics for births and diarrheal deaths, together with hospital surveillance data on the proportion of severe childhood diarrhea attributed to rotavirus. From 1990 through 1993, hospital surveillance was conducted of a systematic, random 4% sample of >80,000 patients with diarrhea who sought care each year at the International Centre for Diarrhoeal Disease Research, Bangladesh (ICDDR,B). Rotavirus was detected in 20% (1561 of 7709) of fecal specimens from children with diarrhea <5 years of age; 92% of all cases (1436) occurred in children <2 years of age, but only 3% (50) of cases occurred in infants <3 months of age. Children infected with rotavirus were more likely to have watery stools (P < 0.001), severe vomiting (P < 0.001) but less severe dehydration (P = 0.007) than children infected with other enteropathogens. We estimate that in this setting, where 18% of children die by age 5 and about 25% of these succumb to diarrhea, between 14,850 and 27,000 of the 3 million Bangladeshi children born in 1994 will die of rotavirus by the age of 5 years, equivalent to 1 rotavirus death per 111 to 203 children. The estimated burden of rotavirus diarrhea in Bangladesh is sufficiently great to warrant field testing of rotavirus vaccines for possible inclusion in the current immunization program.

A hospital-based surveillance of rotavirus gastroenteritis in children <5 years of age in Singapore.

PubMed

Phua, Kong Boo; Tee, Nancy; Tan, Nancy; Ramakrishnan, Gunasekaran; Teoh, Yee-Leong; Bock, Hans; Liu, Yanfang

2013-12-01

In Singapore, 2 rotavirus vaccines were licensed in October 2005 and July 2007, respectively, for vaccinating infants aged ≥ 6 weeks against rotavirus gastroenteritis. These vaccines are optional and are not included in the National Childhood Immunization Program. This study aimed to determine the incidence of rotavirus gastroenteritis-associated hospitalizations among children <5 years of age. Children <5 years, who were hospitalized for acute gastro enteritis, were enrolled between September 2005 and April 2008. Stool samples were tested for the presence and serotyping of rotavirus. Incidence and proportion of gastroenteritis and rotavirus gastroenteritis cases were calculated with 95% confidence intervals. Among 1976 children included in the according-to-protocol cohort, 781 were rotavirus positive with a median age of 24 months (range: 0-59 months). The overall incidence of rotavirus gastroenteritis hospitalizations during the entire study period in children <5 years of age was 4.6 (95% confidence interval: 4.3-4.9) per 1000 person-years with the highest number of cases observed in children 13-24 months of age (26.5%). G1P[8] (18.3%) and G9P[8] (9.9%) were the most common rotavirus types. Rotavirus gastroenteritis hospitalizations peaked between January and March. Rotavirus infection was the primary cause of acute gastro enteritis hospitalizations among children <5 years of age, constituting nearly one-third of gastroenteritis hospitalizations in Singapore. The predominant strain observed in Singapore was G1P[8]. Results of this study suggest the need for implementation of rotavirus vaccination into National Childhood Immunization Program in Singapore.

Engineering and expression of a human rotavirus candidate vaccine in Nicotiana benthamiana.

PubMed

Pêra, Francisco F P G; Mutepfa, David L R; Khan, Ayesha M; Els, Johann H; Mbewana, Sandiswa; van Dijk, Alberdina A A; Rybicki, Edward P; Hitzeroth, Inga I

2015-12-02

Human rotaviruses are the main cause of severe gastroenteritis in children and are responsible for over 500 000 deaths annually. There are two live rotavirus vaccines currently available, one based on human rotavirus serotype G1P[8], and the other a G1-G4 P[8] pentavalent vaccine. However, the recent emergence of the G9 and other novel rotavirus serotypes in Africa and Asia has prompted fears that current vaccines might not be fully effective against these new varieties. We report an effort to develop an affordable candidate rotavirus vaccine against the new emerging G9P[6] (RVA/Human-wt/ZAF/GR10924/1999/G9P[6]) strain. The vaccine is based on virus-like particles which are both highly immunogenic and safe. The vaccine candidate was produced in Nicotiana benthamiana by transient expression, as plants allow rapid production of antigens at lower costs, without the risk of contamination by animal pathogens. Western blot analysis of plant extracts confirmed the successful expression of two rotavirus capsid proteins, VP2 and VP6. These proteins assembled into VLPs resembling native rotavirus particles when analysed by transmission electron microscopy (TEM). Expression of the rotavirus glycoprotein VP7 and the spike protein VP4 was also tried. However, VP7 expression caused plant wilting during the course of the time trial and expression could never be detected for either protein. We therefore created three fusion proteins adding the antigenic part of VP4 (VP8*) to VP6 in an attempt to produce more appropriately immunogenic particles. Fusion protein expression in tobacco plants was detected by western blot using anti-VP6 and anti-VP4 antibodies, but no regular particles were observed by TEM, even when co-expressed with VP2. Our results suggest that the rotavirus proteins produced in N. benthamiana are candidates for a subunit vaccine specifically for the G9P[6] rotavirus strain. This could be more effective in developing countries, thereby possibly providing a higher overall efficacy for the existing vaccines. The production of rotavirus proteins in plants would probably result in lower manufacturing costs, making it more affordable for developing countries. Further investigation is required to evaluate the immunogenic potential of the VLPs and fusion proteins created in this study.

Rotavirus diarrhea disease burden in Peru: the need for a rotavirus vaccine and its potential cost savings.

PubMed

Ehrenkranz, P; Lanata, C F; Penny, M E; Salazar-Lindo, E; Glass, R I

2001-10-01

To assess the disease burden of rotavirus diarrhea in Peru as well the need for and the potential cost savings with a rotavirus vaccine in that country. To assess the burden of rotavirus diarrhea in Peru, we reviewed published and unpublished reports where rotavirus was sought as the etiologic agent of diarrhea in children. Rotavirus detection rates obtained from these studies were combined with diarrhea incidence rates from a number of national surveys in order to estimate both the burden of rotavirus diarrhea in the country and its associated medical costs. Rotavirus is a significant cause of morbidity and mortality in Peruvian children. In their first 5 years of life, an estimated 1 in 1.6 children will experience an episode of rotavirus diarrhea, 1 in 9.4 will seek medical care, 1 in 19.7 will require hospitalization, and 1 in 375 will die of the disease. Per year, this represents approximately 384,000 cases, 64,000 clinic visits, 30,000 hospitalizations, and 1,600 deaths. The annual cost of medical care alone for these children is approximately US$ 2.6 million--and that does not take into account the indirect or societal costs of the illness and the deaths. Rotavirus immunization provides the prospect of decreasing the morbidity and mortality from diarrhea in Peru, but a vaccine regimen would have to be relatively inexpensive, a few dollars or less per child. Future cost-effectiveness analyses should explore the total costs (medical as well as indirect or societal) associated with rotavirus diarrhea. Newly licensed vaccines should be tested according to both their ability to avert deaths and their efficacy with fewer than three doses. All three of these factors could increase the cost savings associated with a rotavirus vaccine.

Influence of birth rates and transmission rates on the global seasonality of rotavirus incidence.

PubMed

Pitzer, Virginia E; Viboud, Cécile; Lopman, Ben A; Patel, Manish M; Parashar, Umesh D; Grenfell, Bryan T

2011-11-07

Rotavirus is a major cause of mortality in developing countries, and yet the dynamics of rotavirus in such settings are poorly understood. Rotavirus is typically less seasonal in the tropics, although recent observational studies have challenged the universality of this pattern. While numerous studies have examined the association between environmental factors and rotavirus incidence, here we explore the role of intrinsic factors. By fitting a mathematical model of rotavirus transmission dynamics to published age distributions of cases from 15 countries, we obtain estimates of local transmission rates. Model-predicted patterns of seasonal incidence based solely on differences in birth rates and transmission rates are significantly correlated with those observed (Spearman's ρ = 0.65, p < 0.05). We then examine seasonal patterns of rotavirus predicted across a range of different birth rates and transmission rates and explore how vaccination may impact these patterns. Our results suggest that the relative lack of rotavirus seasonality observed in many tropical countries may be due to the high birth rates and transmission rates typical of developing countries rather than being driven primarily by environmental conditions. While vaccination is expected to decrease the overall burden of disease, it may increase the degree of seasonal variation in the incidence of rotavirus in some settings.

An evaluation of the Australian Rotavirus Surveillance Program.

PubMed

Roberts-Witteveen, April R; Patel, Mahomed S; Roche, Paul W

2008-09-01

The Australian Rotavirus Serotyping Program (ARSP) serotypes rotavirus isolates obtained from stool samples sent from Australian laboratories. In collaboration with ARSP the Australian Government Department of Health and Ageing evaluated the program for its utility and capacity to monitor effectiveness of the rotavirus vaccines recently introduced into the Australian National Immunisation Program. The system was described using ARSP annual reports and staff interviews. The attributes of the system were assessed by adapting standard guidelines for evaluating a surveillance system. Email surveys or face to face interviews were conducted with staff of ARSP, participating laboratories, rotavirus vaccine manufacturing companies and representatives of the Communicable Diseases Network Australia. The ability of the ARSP to monitor changes in rotavirus serotype epidemiology was assessed. ARSP serotypes rotavirus isolates received from participating laboratories at least bi-annually, with results being reported at least as often. Serotype analyses have informed formulation of rotavirus vaccines and contributed to forecasting the extent of outbreaks caused by novel serotypes. The ARSP will be able to monitor changes in rotavirus serotype epidemiology and identify probable vaccination failures. Enhancement of the representativeness and sensitivity of the system are needed for the data to remain useful in the public health context. Methods for transferring data between the program and state and territory health departments need to be developed.

Use of population-based surveillance to determine the incidence of rotavirus gastroenteritis in an urban slum and a rural setting in Kenya.

PubMed

Breiman, Robert F; Cosmas, Leonard; Audi, Allan; Mwiti, William; Njuguna, Henry; Bigogo, Godfrey M; Olack, Beatrice; Ochieng, John B; Wamola, Newton; Montgomery, Joel M; Williamson, John; Parashar, Umesh D; Burton, Deron C; Tate, Jacqueline E; Feikin, Daniel R

2014-01-01

Rotavirus gastroenteritis is a major cause of mortality among children <2 years of age. Disease burden data are important for introducing and sustaining new rotavirus vaccines in immunization programs. We analyzed population-based infectious disease surveillance data from 2007 to 2010 from Kenyan sites in rural and urban slum areas. Stool specimens were collected from patients of all ages presenting to study clinics with diarrheal disease and tested for rotavirus by enzyme immunoassay. Incidence rates were adjusted using data on healthcare utilization (from biweekly home visits) and proportion of stools collected at study clinics from patients meeting case definitions. Rotavirus was detected in 285 (9.0%) of 3174 stools tested, including 122 (11.9%) from children <5 years of age and 162 (7.6%) from participants ≥5 years of age. Adjusted incidence rates for infants were 13,419 and 12,135 per 100,000 person-years of observation in rural and urban areas, respectively. Adjusted incidence rates were high in adults across age ranges. The rates suggest that annually, among children <5 years of age, there are >54,500 cases of rotavirus-associated gastroenteritis in rural Nyanza Province and >16,750 cases in Nairobi urban slums. Community-based surveillance in urban and rural Kenya suggests that rotavirus plays an important role as a cause of acute gastroenteritis in adults, as well as in children. In addition to substantially preventing illness and complications from diarrheal disease in children, rotavirus infant immunization has the potential of indirectly preventing diarrheal disease in older children and adults, assuming children are the predominant sources of transmission.

Zinc and Diarrheal Disease: Current Status and Future Perspectives

DTIC Science & Technology

2008-01-01

Rotavirus infection is the most common cause of severe diarrhea disease in children less than 5 years worldwide and continues to have a major global...impact on childhood morbidity and mortality. In 2006, two new (live, oral. attenuated) vaccines against rotavirus werc licensed, Zinc and diarrheal...8217fhese new rota virus vaccines offer thc best hope of reducing the toll of acute rotavirus gastroenteritis in both developed and dcvc10ping countries

Serologic Correlates of Protection against Enterotoxigenic Escherichia coli Diarrhea

DTIC Science & Technology

2005-01-14

strain expressed either LT, CFA/I, CFA/II, or CFA/IV. Episodes in which Shigella spe- cies, Campylobacter species, rotavirus , or astrovirus were iso- lated...serum antibody levels cor- relate with protection against diarrheal illness caused by cholera and rotavirus [29–33]. Serum vibriocidal antibodies...cholera. J Infect Dis 1991; 163:1235–42. 31. Clemens JD, Ward RL, Rao MR, et al. Seroepidemiologic evaluation of antibodies to rotavirus as correlates of

Global issues related to enteric viral infections.

PubMed

Desselberger, Ulrich

2014-01-01

Acute viral gastroenteritis is a major health issue worldwide and is associated with high annual mortality, particularly in children of developing countries. Rotaviruses, caliciviruses and astroviruses are the main causes. Accurate diagnoses are possible by recently developed molecular techniques. In many setups, zoonotic transmission is an important epidemiological factor. Treatment consists of rehydration and is otherwise symptomatic. The worldwide introduction of universal rotavirus vaccination of infants has significantly reduced rotavirus disease and mortality.

Development of a rotavirus vaccine: clinical safety, immunogenicity, and efficacy of the pentavalent rotavirus vaccine, RotaTeq.

PubMed

Ciarlet, Max; Schödel, Florian

2009-12-30

Initial approaches for rotavirus vaccines were based on the classical "Jennerian" approach and utilized simian and bovine rotavirus strains, which provided cross-protection against human rotavirus strains but did not cause illness in infants and young children because of their species-specific tropism. The demonstrated efficacy of these vaccines was not consistent across studies. Thus, human-animal reassortants containing an animal rotavirus backbone with human rotavirus surface G and/or P proteins were developed, which demonstrated more consistent efficacy than that observed with the non-reassortant rotavirus strains. The pentavalent rotavirus vaccine, RotaTeq, contains 5 human-bovine reassortant rotaviruses consisting of a bovine (WC3) backbone with human rotavirus surface proteins representative of the most common G (G1, G2, G3, G4) or P (P1A[8]) types worldwide. The present review focuses on the development of the pentavalent rotavirus vaccine RotaTeq. Results of a large-scale Phase III clinical study showed that three doses of RotaTeq were immunogenic, efficacious, and well tolerated with no increased clinical risk of intussusception. RotaTeq was efficacious against rotavirus gastroenteritis of any severity (74%) and severe disease (98-100%), using a validated clinical scoring system. Reductions in rotavirus-associated hospitalizations and emergency department (ED) visits, for up to 2 years post-vaccination, were 95% in Europe, 97% in the United States, and 90% in the Latin American/Caribbean regions. RotaTeq was recently shown to be up to 100% effective in routine use in the US in reducing hospitalizations and ED visits and 96% effective in reducing physician visits. Additional studies in 8 different locations in the US have shown 85-95% reduction in rotavirus-associated hospitalizations and/or ED visits in the first 2-2.5 years of routine use.

Correlates of protection against human rotavirus disease and the factors influencing protection in low-income settings.

PubMed

Clarke, E; Desselberger, U

2015-01-01

Rotaviruses (RV) are the leading cause of gastroenteritis in infants and children worldwide and are associated with high mortality predominately in low-income settings. The virus is classified into G and P serotypes and further into P genotypes based on differences in the surface-exposed proteins VP7 and VP4, respectively. Infection results in a variable level of protection from subsequent reinfection and disease. This protection is predominantly homotypic in some settings, whereas broader heterotypic protection is reported in other cohorts. Two antigenically distinct oral RV vaccines are licensed and are being rolled out widely, including in resource-poor setting, with funding provided by the GAVI alliance. First is a monovalent vaccine derived from a live-attenuated human RV strain, whereas the second is a pentavalent bovine-human reassortment vaccine. Both vaccines are highly efficacious in high-income settings, but greatly reduced levels of protection are reported in low-income countries. Here, the current challenges facing mucosal immunologists and vaccinologists aiming to define immunological correlates and to understand the variable levels of protection conferred by these vaccines in humans is considered. Such understanding is critical to maximize the public health impact of the current vaccines and also to the development of the next generation of RV vaccines, which are needed.

Involvement of main diarrheagenic Escherichia coli, with emphasis on enteroaggregative E. coli, in severe non-epidemic pediatric diarrhea in a high-income country.

PubMed

Tobias, Joshua; Kassem, Eias; Rubinstein, Uri; Bialik, Anya; Vutukuru, Sreekanth-Reddy; Navaro, Armando; Rokney, Assaf; Valinsky, Lea; Ephros, Moshe; Cohen, Dani; Muhsen, Khitam

2015-02-21

Bacterial and viral enteric pathogens are the leading cause of diarrhea in infants and children. We aimed to identify and characterize the main human diarrheagenic E. coli (DEC) in stool samples obtained from children less than 5 years of age, hospitalized for acute gastroenteritis in Israel, and to examine the hypothesis that co-infection with DEC and other enteropathogens is associated with the severity of symptoms. Stool specimens obtained from 307 patients were tested by multiplex PCR (mPCR) to identify enteroaggregative E. coli (EAEC), enterohemorrhagic (EHEC), enteropathogenic E. coli (EPEC) and enterotoxigenic E. coli (ETEC). Specimens were also examined for the presence of rotavirus by immunochromatography, and of Shigella, Salmonella and Campylobacter by stool culture; clinical information was also obtained. Fifty nine (19%) children tested positive for DEC; EAEC and atypical EPEC were most common, each detected in 27 (46%), followed by ETEC (n = 3; 5%), EHEC and typical EPEC (each in 1 child; 1.5%). Most EAEC isolates were resistant to cephalexin, cefixime, cephalothin and ampicillin, and genotypic characterization of EAEC isolates by O-typing and pulsed-field gel electrophoresis showed possible clonal relatedness among some. The likelihood of having > 10 loose/watery stools on the most severe day of illness was significantly increased among patients with EAEC and rotavirus co-infection compared to children who tested negative for both pathogens: adjusted odds ratio 7.0 (95% CI 1.45-33.71, P = 0.015). DEC was common in this pediatric population, in a high-income country, and mixed EAEC and rotavirus infection was characterized by especially severe diarrhea.

Multiple Norovirus Infections in a Birth Cohort in a Peruvian Periurban Community

PubMed Central

Saito, Mayuko; Goel-Apaza, Sonia; Espetia, Susan; Velasquez, Daniel; Cabrera, Lilia; Loli, Sebastian; Crabtree, Jean E.; Black, Robert E.; Kosek, Margaret; Checkley, William; Zimic, Mirko; Bern, Caryn; Cama, Vitaliano; Gilman, Robert H.; Xiao, L.; Kelleher, D.; Windle, H. J.; van Doorn, L. J.; Varela, M.; Verastegui, M.; Calderon, M.; Alva, A.; Roman, K.

2014-01-01

Background. Human noroviruses are among the most common enteropathogens globally, and are a leading cause of infant diarrhea in developing countries. However, data measuring the impact of norovirus at the community level are sparse. Methods. We followed a birth cohort of children to estimate norovirus infection and diarrhea incidence in a Peruvian community. Stool samples from diarrheal episodes and randomly selected nondiarrheal samples were tested by polymerase chain reaction for norovirus genogroup and genotype. Excretion duration and rotavirus coinfection were evaluated in a subset of episodes. Results. Two hundred twenty and 189 children were followed to 1 and 2 years of age, respectively. By 1 year, 80% (95% confidence interval [CI], 75%–85%) experienced at least 1 norovirus infection and by 2 years, 71% (95% CI, 65%–77%) had at least 1 episode of norovirus-associated diarrhea. Genogroup II (GII) infections were 3 times more frequent than genogroup 1 (GI) infections. Eighteen genotypes were found; GII genotype 4 accounted for 41%. Median excretion duration was 34.5 days for GII vs 8.5 days for GI infection (P = .0006). Repeat infections by the same genogroup were common, but repeat infections by the same genotype were rare. Mean length-for-age z score at 12 months was lower among children with prior norovirus infection compared to uninfected children (coefficient: −0.33 [95% CI, −.65 to −.01]; P = .04); the effect persisted at 24 months. Conclusions. Norovirus infection occurs early in life and children experience serial infections with multiple genotypes, suggesting genotype-specific immunity. An effective vaccine would have a substantial impact on morbidity, but may need to target multiple genotypes. PMID:24300042

Effectiveness of monovalent rotavirus vaccine (Rotarix) against severe diarrhea caused by serotypically unrelated G2P[4] strains in Brazil.

PubMed

Correia, Jailson B; Patel, Manish M; Nakagomi, Osamu; Montenegro, Fernanda M U; Germano, Eliane M; Correia, Nancy B; Cuevas, Luis E; Parashar, Umesh D; Cunliffe, Nigel A; Nakagomi, Toyoko

2010-02-01

BACKGROUND. In a Latin American trial, a monovalent G1P[8] rotavirus vaccine showed high efficacy against severe rotavirus diarrhea. Protection was lower against serotypically unrelated G2P[4] strains, which circulated infrequently. This case-control study was undertaken to assess the effectiveness of this monovalent G1P[8] rotavirus vaccine against G2P[4] strains in Brazil. METHODS. Case patients were children with severe G2P[4] rotavirus diarrhea who presented at a hospital in Recife, Brazil, from March 2006 through September 2008. Vaccination rates among case patients were compared with rates among 2 groups of control participants-children with rotavirus-negative diarrhea and children admitted for acute respiratory tract infection (ARI)-to calculate vaccine effectiveness, after controlling for the birth month and year. RESULTS. We enrolled 70 G2P[4] rotavirus-positive case patients with severe diarrhea, 484 rotavirus-negative control participants with diarrhea, and 416 control participants with ARI, aged 6 months. Among children aged 6-11 months, the effectiveness of the vaccine against G2P[4] diarrhea was 77% (95% confidence interval [CI], 42%-91%) and 77% (95% CI, 43%-90%) among the rotavirus-negative control participants with diarrhea and control participants with ARI, respectively. Vaccine effectiveness in children aged 12 months decreased to -24% (95% CI, -190% to 47%) and 15% (95% CI, -101 to 64) among the rotavirus-negative control groups with diarrhea and ARI, respectively. CONCLUSIONS. This monovalent G1P[8] rotavirus vaccine was effective against severe G2P[4] rotavirus diarrhea among children aged 6-11 months. Effectiveness declined among children aged 12 months, which suggests waning immunity.

Human rotavirus strain Wa downregulates NHE1 and NHE6 expressions in rotavirus-infected Caco-2 cells.

PubMed

Chen, Honglang; Song, Lijun; Li, Guixian; Chen, Wenfeng; Zhao, Shumin; Zhou, Ruoxia; Shi, Xiaoying; Peng, Zhenying; Zhao, Wenchang

2017-06-01

Rotavirus (RV) is the most common cause of severe gastroenteritis and fatal dehydration in human infants and neonates of different species. However, the pathogenesis of rotavirus-induced diarrhea is poorly understood. Secretory diarrhea caused by rotavirus may lead to a combination of excessive secretion of fluid and electrolytes into the intestinal lumen. Fluid absorption in the small intestine is driven by Na + -coupled transport mechanisms at the luminal membrane, including Na + /H + exchanger (NHE). Here, we performed qRT-PCR to detect the transcription of NHEs. Western blotting was employed for protein detection. Furthermore, immunocytochemistry was used to validate the NHE's protein expression. Finally, intracellular Ca 2+ concentration was detected by confocal laser scanning microscopy. The results demonstrated that the NHE6 mRNA and protein expressed in the human colon adenocarcinoma cell line (Caco-2). Furthermore, RV-Wa induced decreased expression of the NHE1 and NHE6 in Caco-2 cell in a time-dependent manner. In addition, intracellular Ca 2+ concentration in RV-Wa-infected Caco-2 cells was higher than that in the mock-infected cells. Furthermore, RV-Wa also can downregulate the expression of calmodulin (CaM) and calmodulin kinase II (CaMKII) in Caco-2 cells. These findings provides important insights into the mechanisms of rotavirus-induced diarrhea. Further studies on the underlying pathophysiological mechanisms that downregulate NHEs in RV-induced diarrhea are required.

Cost-effectiveness of Rotavirus vaccination in Vietnam

PubMed Central

Kim, Sun-Young; Goldie, Sue J; Salomon, Joshua A

2009-01-01

Background Rotavirus is the most common cause of severe diarrhea leading to hospitalization or disease-specific death among young children. New rotavirus vaccines have recently been approved. Some previous studies have provided broad qualitative insights into the health and economic consequences of introducing the vaccines into low-income countries, representing several features of rotavirus infection, such as varying degrees of severity and age-dependency of clinical manifestation, in their model-based analyses. We extend this work to reflect additional features of rotavirus (e.g., the possibility of reinfection and varying degrees of partial immunity conferred by natural infection), and assess the influence of the features on the cost-effectiveness of rotavirus vaccination. Methods We developed a Markov model that reflects key features of rotavirus infection, using the most recent data available. We applied the model to the 2004 Vietnamese birth cohort and re-evaluated the cost-effectiveness (2004 US dollars per disability-adjusted life year [DALY]) of rotavirus vaccination (Rotarix®) compared to no vaccination, from both societal and health care system perspectives. We conducted univariate sensitivity analyses and also performed a probabilistic sensitivity analysis, based on Monte Carlo simulations drawing parameter values from the distributions assigned to key uncertain parameters. Results Rotavirus vaccination would not completely protect young children against rotavirus infection due to the partial nature of vaccine immunity, but would effectively reduce severe cases of rotavirus gastroenteritis (outpatient visits, hospitalizations, or deaths) by about 67% over the first 5 years of life. Under base-case assumptions (94% coverage and $5 per dose), the incremental cost per DALY averted from vaccination compared to no vaccination would be $540 from the societal perspective and $550 from the health care system perspective. Conclusion Introducing rotavirus vaccines would be a cost-effective public health intervention in Vietnam. However, given the uncertainty about vaccine efficacy and potential changes in rotavirus epidemiology in local settings, further clinical research and re-evaluation of rotavirus vaccination programs may be necessary as new information emerges. PMID:19159483

Lymphotoxin Alpha-Deficient Mice Clear Persistent Rotavirus Infection after Local Generation of Mucosal IgA

PubMed Central

Lopatin, Uri; Blutt, Sarah E.; Conner, Margaret E.

2013-01-01

Rotavirus is a major cause of pediatric diarrheal illness worldwide. To explore the role of organized intestinal lymphoid tissues in infection by and immunity to rotavirus, lymphotoxin alpha-deficient (LTα−/−) mice that lack Peyer's patches and mesenteric lymph nodes were orally infected with murine rotavirus. Systemic rotavirus was cleared within 10 days in both LTα−/− and wild-type mice, and both strains developed early and sustained serum antirotavirus antibody responses. However, unlike wild-type mice, which resolved the intestinal infection within 10 days, LTα−/− mice shed fecal virus for approximately 50 days after inoculation. The resolution of fecal virus shedding occurred concurrently with induction of intestinal rotavirus-specific IgA in both mouse strains. Induction of intestinal rotavirus-specific IgA in LTα−/− mice correlated with the (late) appearance of IgA-producing plasma cells in the small intestine. This, together with the absence of rotavirus-specific serum IgA, implies that secretory rotavirus-specific IgA was produced locally. These findings indicate that serum IgG responses are insufficient and imply that local intestinal IgA responses are important for the clearance of rotavirus from intestinal tissues. Furthermore, they show that while LTα-dependent lymphoid tissues are important for the generation of IgA-producing B cells in the intestine, they are not absolutely required in the setting of rotavirus infection. Moreover, the induction of local IgA-producing B cell responses can occur late after infection and in an LTα-independent manner. PMID:23097456

Evaluating the potential risks and benefits of infant rotavirus vaccination in England.

PubMed

Clark, Andy; Jit, Mark; Andrews, Nick; Atchison, Christina; Edmunds, W John; Sanderson, Colin

2014-06-17

Rotarix(®), a vaccine for the prevention of gastroenteritis in young children, was introduced in England in July 2013. At around this time, an elevated risk of intussusception (a cause of bowel obstruction) was reported among infants vaccinated in Australia and the USA. A risk-benefit analysis compared potential vaccine-related risks (additional intussusception admissions and deaths) with estimated vaccine benefits (prevented rotavirus general practitioner visits, emergency visits, admissions and deaths) in the 2012 birth cohort. Detailed data from England included the incidence of intussusception events aged <2 years by week of age, the coverage of vaccination aged <2 years by week of age, and the incidence of rotavirus gastroenteritis (RVGE) events aged <5 years by week of age. Recent estimates of vaccine-related risk from Australia were applied during the 1-21 day period after the first and second dose of vaccination. Rotarix(®) is estimated to cause one additional intussusception admission in every 18,551 vaccinated English infants (5th and 95th percentiles, 6728-93,952), equivalent to 35 (7-98) additional intussusception admissions each year. The vaccine is estimated to prevent three rotavirus deaths, 13,000 rotavirus admissions, 27,000 rotavirus emergency visits and 74,000 rotavirus GP consultations in children aged <5 years, and lead to annual savings of over £11 million, each year. We estimate 375 (136-1900) fewer RVGE admissions for every additional intussusception admission, and 88 (18-852) fewer RVGE deaths for every additional intussusception death. The estimated benefits of Rotarix(®) vaccination would greatly exceed the potential risk in England. Copyright © 2014. Published by Elsevier Ltd.

Global, Regional, and National Estimates of Rotavirus Mortality in Children <5 Years of Age, 2000-2013.

PubMed

Tate, Jacqueline E; Burton, Anthony H; Boschi-Pinto, Cynthia; Parashar, Umesh D

2016-05-01

Rotavirus vaccine is recommended for routine use in all countries globally. To facilitate decision making on rotavirus vaccine adoption by countries, help donors prioritize investments in health interventions, and monitor vaccine impact, we estimated rotavirus mortality for children <5 years of age from 2000 to 2013. We searched PubMed using the keyword "rotavirus" to identify studies that met each of the following criteria: data collection midpoint in year 1998 or later, study period of a 12-month increment, and detection of rotavirus infection by enzyme immunoassay in at least 100 children <5 years of age who were hospitalized with diarrhea and systematically enrolled through active surveillance. We also included data from countries that participated in the World Health Organization (WHO)-coordinated rotavirus surveillance network between 2008 and 2013 that met these criteria. To predict the proportion of diarrhea due to rotavirus, we constructed a multiple linear regression model. To determine the number of rotavirus deaths in children <5 years of age from 2000 to 2013, we multiplied annual, country-specific estimates of the proportion of diarrhea due to rotavirus from the regression model by the annual number of WHO-estimated child deaths caused by diarrhea in each country. Globally, we estimated that the number of rotavirus deaths in children <5 years of age declined from 528 000 (range, 465 000-591 000) in 2000 to 215 000 (range, 197 000-233 000) in 2013. The predicted annual rotavirus detection rate from these studies declined slightly over time from 42.5% (95% confidence interval [CI], 37.4%-47.5%) in 2000 to 37.3% (95% CI, 34.2%-40.5%) in 2013 globally. In 2013, an estimated 47 100 rotavirus deaths occurred in India, 22% of all rotavirus deaths that occurred globally. Four countries (India, Nigeria, Pakistan, and Democratic Republic of Congo) accounted for approximately half (49%) of all estimated rotavirus deaths in 2013. While rotavirus vaccine had been introduced in >60 countries worldwide by the end of 2013, the majority of countries using rotavirus vaccine during the review period were low-mortality countries and the impact of rotavirus vaccine on global estimates of rotavirus mortality has been limited. Continued monitoring of rotavirus mortality rates and deaths through rotavirus surveillance will aid in monitoring the impact of vaccination. Published by Oxford University Press for the Infectious Diseases Society of America 2016. This work is written by (a) US Government employee(s) and is in the public domain in the US.

Rotarix (RIX4414): an oral human rotavirus vaccine.

PubMed

O'Ryan, Miguel

2007-02-01

Rotavirus is the most common cause of severe gastroenteritis in children younger than 3 years of age worldwide. New rotavirus vaccine candidates were required to confer early protection against the most common rotavirus serotypes and to be well tolerated and not associated with intussusception. RIX4414 is a human-attenuated G1(P8) oral rotavirus vaccine administered in two doses at approximately 6-24 weeks of age. The first dose may be administered from the age of 6 weeks. There should be an interval of at least 4 weeks between doses and the vaccination course should preferably be given before 16 weeks of age and must be completed, according to the manufacturer, by the age of 24 weeks. In a worldwide development program involving more than 70,000 children in six Phase I-III field trials, this vaccine proved to be nonreactogenic, well tolerated and not associated with intussusception. The vaccine provides over 85-96% protection against moderate-to-severe gastroenteritis caused by G1 and non-G1 serotypes, as demonstrated in Latin American and European clinical trial settings, respectively; and reduces gastroenteritis-related hospitalizations by more than 40% in Latin America and by 75% in European settings.

Rotavirus Surveillance in Kisangani, the Democratic Republic of the Congo, Reveals a High Number of Unusual Genotypes and Gene Segments of Animal Origin in Non-Vaccinated Symptomatic Children

PubMed Central

Heylen, Elisabeth; Batoko Likele, Bibi; Zeller, Mark; Stevens, Stijn; De Coster, Sarah; Conceição-Neto, Nádia; Van Geet, Christel; Jacobs, Jan; Ngbonda, Dauly; Van Ranst, Marc; Matthijnssens, Jelle

2014-01-01

Group A rotavirus (RVA) infections form a major public health problem, especially in low-income countries like the Democratic Republic of the Congo (COD). However, limited data on RVA diversity is available from sub-Saharan Africa in general and the COD in particular. Therefore, the first aim of this study was to determine the genetic diversity of 99 RVAs detected during 2007–2010 in Kisangani, COD. The predominant G-type was G1 (39%) and the most predominant P-type was P[6] (53%). A total of eight different G/P-combinations were found: G1P[8] (28%), G8P[6] (26%), G2P[4] (14%), G12P[6] (13%), G1P[6] (11%), G9P[8] (4%), G4P[6] (2%) and G8P[4] (1%). The second aim of this study was to gain insight into the diversity of P[6] RVA strains in the COD. Therefore, we selected five P[6] RVA strains in combination with the G1, G4, G8 (2x) or G12 genotype for complete genome analysis. Complete genome analysis showed that the genetic background of the G1P[6] and G12P[6] strains was entirely composed of genotype 1 (Wa-like), while the segments of the two G8P[6] strains were identified as genotype 2 (DS-1-like). Interestingly, all four strains possessed a NSP4 gene of animal origin. The analyzed G4P[6] RVA strain was found to possess the unusual G4-P[6]-I1-R1-C1-M1-A1-N1-T7-E1-H1 constellation. Although the majority of its genes (if not all), were presumably of porcine origin, this strain was able to cause gastro-enteritis in humans. The high prevalence of unusual RVA strains in the COD highlights the need for continued surveillance of RVA diversity in the COD. These results also underline the importance of complete genetic characterization of RVA strains and indicate that reassortments and interspecies transmission among human and animal RVAs strains occur regularly. Based on these data, RVA vaccines will be challenged with a wide variety of different RVA strain types in the COD. PMID:24968018

Rotavirus vaccination and intussusception – Science, surveillance, and safety: A review of evidence and recommendations for future research priorities in low and middle income countries

PubMed Central

Yen, Catherine; Healy, Kelly; Tate, Jacqueline E.; Parashar, Umesh D.; Bines, Julie; Neuzil, Kathleen; Santosham, Mathuram; Steele, A. Duncan

2016-01-01

ABSTRACT As of January 2016, 80 countries have introduced rotavirus vaccines into their national immunization programs. Many have documented significant declines in rotavirus-specific and all-cause diarrheal illnesses following vaccine introduction. Two globally licensed rotavirus vaccines have been associated with a low risk of intussusception in several studies. In July 2014, the Rotavirus Organization of Technical Allies Council convened a meeting of research and advocacy organizations, public health experts, funders, and vaccine manufacturers to discuss post-marketing intussusception surveillance and rotavirus vaccine impact data. Meeting objectives were to evaluate updated data, identify and prioritize research gaps, discuss best practices for intussusception monitoring in lower-income settings and risk communication, and provide insight to country-level stakeholders on best practices for intussusception monitoring and communication. Meeting participants agreed with statements from expert bodies that the benefits of vaccination with currently available rotavirus vaccines outweigh the low risk of vaccination-associated intussusception. However, further research is needed to better understand the relationship of intussusception to wild-type rotavirus and rotavirus vaccines and delineate potential etiologies and mechanisms of intussusception. Additionally, evidence from research and post-licensure evaluations should be presented with evidence of the benefits of vaccination to best inform policymakers deciding on vaccine introduction or vaccination program sustainability. PMID:27322835

Rotavirus Infection in the Auckland Region After the Implementation of Universal Infant Rotavirus Vaccination: Impact on Hospitalizations and Laboratory Implications.

PubMed

McAuliffe, Gary N; Taylor, Susan L; Drinković, Dragana; Roberts, Sally A; Wilson, Elizabeth M; Best, Emma J

2018-01-01

In July 2014, New Zealand introduced universal infant vaccination with RotaTeq (Merk & Co.) administered as 3 doses at 6 weeks, 3 and 5 months of age. We sought to assess the impact of rotavirus vaccination on gastroenteritis (GE) hospitalizations in the greater Auckland region and analyze changes in rotavirus testing in the period around vaccine introduction. Hospitalizations, laboratory testing rates and methods were compared between the pre-vaccine period (2009-2013), post-vaccine period (January 2015 to December 2015) and year of vaccine introduction (2014). There was a 68% decline in rotavirus hospitalizations of children <5 years of age after vaccine introduction (from 258/100,000 to 83/100,000) and a 17% decline in all-cause gastroenteritis admissions (from 1815/100,000 to 1293/100,000). Reductions were also seen in pediatric groups too old to have received vaccine. Despite these changes, rotavirus testing rates in our region remained static in the year after vaccine introduction compared with the 2 prior years, and after vaccine introduction, we observed a high rate of false positives 19/58 (33%) in patients with reactive rotavirus tests. Rotavirus vaccine has had a significant early impact on gastroenteritis hospitalizations for children in the Auckland region. However, continued rotavirus testing at pre-vaccine rates risks generating false positive results. Laboratories and clinicians should consider reviewing their testing algorithms before vaccine introduction.

Emergence of Double- and Triple-Gene Reassortant G1P[8] Rotaviruses Possessing a DS-1-Like Backbone after Rotavirus Vaccine Introduction in Malawi.

PubMed

Jere, Khuzwayo C; Chaguza, Chrispin; Bar-Zeev, Naor; Lowe, Jenna; Peno, Chikondi; Kumwenda, Benjamin; Nakagomi, Osamu; Tate, Jacqueline E; Parashar, Umesh D; Heyderman, Robert S; French, Neil; Cunliffe, Nigel A; Iturriza-Gomara, Miren

2018-02-01

To combat the high burden of rotavirus gastroenteritis, multiple African countries have introduced rotavirus vaccines into their childhood immunization programs. Malawi incorporated a G1P[8] rotavirus vaccine (Rotarix) into its immunization schedule in 2012. Utilizing a surveillance platform of hospitalized rotavirus gastroenteritis cases, we examined the phylodynamics of G1P[8] rotavirus strains that circulated in Malawi before (1998 to 2012) and after (2013 to 2014) vaccine introduction. Analysis of whole genomes obtained through next-generation sequencing revealed that all randomly selected prevaccine G1P[8] strains sequenced ( n = 32) possessed a Wa-like genetic constellation, whereas postvaccine G1P[8] strains ( n = 18) had a DS-1-like constellation. Phylodynamic analyses indicated that postvaccine G1P[8] strains emerged through reassortment events between human Wa- and DS-1-like rotaviruses that circulated in Malawi from the 1990s and hence were classified as atypical DS-1-like reassortants. The time to the most recent common ancestor for G1P[8] strains was from 1981 to 1994; their evolutionary rates ranged from 9.7 × 10 -4 to 4.1 × 10 -3 nucleotide substitutions/site/year. Three distinct G1P[8] lineages chronologically replaced each other between 1998 and 2014. Genetic drift was the likely driver for lineage turnover in 2005, whereas replacement in 2013 was due to reassortment. Amino acid substitution within the outer glycoprotein VP7 of G1P[8] strains had no impact on the structural conformation of the antigenic regions, suggesting that it is unlikely that they would affect recognition by vaccine-induced neutralizing antibodies. While the emergence of DS-1-like G1P[8] rotavirus reassortants in Malawi was therefore likely due to natural genotype variation, vaccine effectiveness against such strains needs careful evaluation. IMPORTANCE The error-prone RNA-dependent RNA polymerase and the segmented RNA genome predispose rotaviruses to genetic mutation and genome reassortment, respectively. These evolutionary mechanisms generate novel strains and have the potential to lead to the emergence of vaccine escape mutants. While multiple African countries have introduced a rotavirus vaccine, there are few data describing the evolution of rotaviruses that circulated before and after vaccine introduction. We report the emergence of atypical DS-1-like G1P[8] strains during the postvaccine era in Malawi. Three distinct G1P[8] lineages circulated chronologically from 1998 to 2014; mutation and reassortment drove lineage turnover in 2005 and 2013, respectively. Amino acid substitutions within the outer capsid VP7 glycoprotein did not affect the structural conformation of mapped antigenic sites, suggesting a limited effect on the recognition of G1-specific vaccine-derived antibodies. The genes that constitute the remaining genetic backbone may play important roles in immune evasion, and vaccine effectiveness against such atypical strains needs careful evaluation. Copyright © 2018 Jere et al.

Emergence of Double- and Triple-Gene Reassortant G1P[8] Rotaviruses Possessing a DS-1-Like Backbone after Rotavirus Vaccine Introduction in Malawi

PubMed Central

2017-01-01

ABSTRACT To combat the high burden of rotavirus gastroenteritis, multiple African countries have introduced rotavirus vaccines into their childhood immunization programs. Malawi incorporated a G1P[8] rotavirus vaccine (Rotarix) into its immunization schedule in 2012. Utilizing a surveillance platform of hospitalized rotavirus gastroenteritis cases, we examined the phylodynamics of G1P[8] rotavirus strains that circulated in Malawi before (1998 to 2012) and after (2013 to 2014) vaccine introduction. Analysis of whole genomes obtained through next-generation sequencing revealed that all randomly selected prevaccine G1P[8] strains sequenced (n = 32) possessed a Wa-like genetic constellation, whereas postvaccine G1P[8] strains (n = 18) had a DS-1-like constellation. Phylodynamic analyses indicated that postvaccine G1P[8] strains emerged through reassortment events between human Wa- and DS-1-like rotaviruses that circulated in Malawi from the 1990s and hence were classified as atypical DS-1-like reassortants. The time to the most recent common ancestor for G1P[8] strains was from 1981 to 1994; their evolutionary rates ranged from 9.7 × 10−4 to 4.1 × 10−3 nucleotide substitutions/site/year. Three distinct G1P[8] lineages chronologically replaced each other between 1998 and 2014. Genetic drift was the likely driver for lineage turnover in 2005, whereas replacement in 2013 was due to reassortment. Amino acid substitution within the outer glycoprotein VP7 of G1P[8] strains had no impact on the structural conformation of the antigenic regions, suggesting that it is unlikely that they would affect recognition by vaccine-induced neutralizing antibodies. While the emergence of DS-1-like G1P[8] rotavirus reassortants in Malawi was therefore likely due to natural genotype variation, vaccine effectiveness against such strains needs careful evaluation. IMPORTANCE The error-prone RNA-dependent RNA polymerase and the segmented RNA genome predispose rotaviruses to genetic mutation and genome reassortment, respectively. These evolutionary mechanisms generate novel strains and have the potential to lead to the emergence of vaccine escape mutants. While multiple African countries have introduced a rotavirus vaccine, there are few data describing the evolution of rotaviruses that circulated before and after vaccine introduction. We report the emergence of atypical DS-1-like G1P[8] strains during the postvaccine era in Malawi. Three distinct G1P[8] lineages circulated chronologically from 1998 to 2014; mutation and reassortment drove lineage turnover in 2005 and 2013, respectively. Amino acid substitutions within the outer capsid VP7 glycoprotein did not affect the structural conformation of mapped antigenic sites, suggesting a limited effect on the recognition of G1-specific vaccine-derived antibodies. The genes that constitute the remaining genetic backbone may play important roles in immune evasion, and vaccine effectiveness against such atypical strains needs careful evaluation. PMID:29142125

Group A Rotavirus Infection and Age-Dependent Diarrheal Disease in Rats: a New Animal Model To Study the Pathophysiology of Rotavirus Infection

PubMed Central

Ciarlet, Max; Conner, Margaret E.; Finegold, Milton J.; Estes, Mary K.

2002-01-01

Group A rotaviruses are major pathogens causing acute gastroenteritis in children and animals. To determine if group A rotavirus replicates and induces disease in rats, antibody-negative Lewis neonatal or adult rats were inoculated orally with tissue culture-adapted human (Wa, WI61, and HAL1166), simian (rhesus rotavirus [RRV] and SA11), bovine (WC3), lapine (ALA), or porcine (OSU) rotavirus strains, wild-type murine (ECwt) rotavirus strain, or phosphate-buffered saline (PBS). Rotavirus infection in rats was evaluated by (i) clinical findings, (ii) virus antigen shedding or infectious virus titers in the feces or intestinal contents measured by enzyme-linked immunosorbent assay or fluorescent-focus assay, (iii) histopathological changes in the small intestine, (iv) distribution of rotavirus antigen in small-intestine sections by immunofluorescence, and (v) growth rate. Rotavirus infection of 5-day-old but not ≥21-day-old rats resulted in diarrhea that lasted from 1 to 10 days postinoculation. The severity of disease and spread of infection to naÏve littermates differed depending on the virus strain used for inoculation. The duration of virus antigen shedding following infection was considerably prolonged (up to 10 days) in neonatal rats compared to that in 21-day-old rats (1 or 2 days). Based on lack of virus antigen shedding and disease induction, the murine ECwt rotavirus was the only strain tested that did not infect rats. Histopathological changes in the small-intestine mucosa of 5-day-old RRV-inoculated rats but not of PBS-inoculated rats was limited to extensive enterocyte vacuolation in the ileum. In RRV-inoculated neonatal rats, rotavirus antigen was detected in the epithelial cells on the upper half of the intestinal villi of the jejunum and ileum. In addition, infection of neonatal rats with RRV but not with PBS resulted in reduced weight gain. Rats infected with group A rotaviruses provide a new animal model with unique features amenable to investigate rotavirus pathogenesis and the molecular mechanisms of intestinal development, including physiological factors that may regulate age-dependent rotavirus-induced diarrhea. PMID:11739670

Estimating global, regional and national rotavirus deaths in children aged <5 years: Current approaches, new analyses and proposed improvements.

PubMed

Clark, Andrew; Black, Robert; Tate, Jacqueline; Roose, Anna; Kotloff, Karen; Lam, Diana; Blackwelder, William; Parashar, Umesh; Lanata, Claudio; Kang, Gagandeep; Troeger, Christopher; Platts-Mills, James; Mokdad, Ali; Sanderson, Colin; Lamberti, Laura; Levine, Myron; Santosham, Mathuram; Steele, Duncan

2017-01-01

Rotavirus is a leading cause of diarrhoeal mortality in children but there is considerable disagreement about how many deaths occur each year. We compared CHERG, GBD and WHO/CDC estimates of age under 5 years (U5) rotavirus deaths at the global, regional and national level using a standard year (2013) and standard list of 186 countries. The global estimates were 157,398 (CHERG), 122,322 (GBD) and 215,757 (WHO/CDC). The three groups used different methods: (i) to select data points for rotavirus-positive proportions; (ii) to extrapolate data points to individual countries; (iii) to account for rotavirus vaccine coverage; (iv) to convert rotavirus-positive proportions to rotavirus attributable fractions; and (v) to calculate uncertainty ranges. We conducted new analyses to inform future estimates. We found that acute watery diarrhoea was associated with 87% (95% CI 83-90%) of U5 diarrhoea hospitalisations based on data from 84 hospital sites in 9 countries, and 65% (95% CI 57-74%) of U5 diarrhoea deaths based on verbal autopsy reports from 9 country sites. We reanalysed data from the Global Enteric Multicenter Study (GEMS) and found 44% (55% in Asia, and 32% in Africa) rotavirus-positivity among U5 acute watery diarrhoea hospitalisations, and 28% rotavirus-positivity among U5 acute watery diarrhoea deaths. 97% (95% CI 95-98%) of the U5 diarrhoea hospitalisations that tested positive for rotavirus were entirely attributable to rotavirus. For all clinical syndromes combined the rotavirus attributable fraction was 34% (95% CI 31-36%). This increased by a factor of 1.08 (95% CI 1.02-1.14) when the GEMS results were reanalysed using a more sensitive molecular test. We developed consensus on seven proposals for improving the quality and transparency of future rotavirus mortality estimates.

Estimating global, regional and national rotavirus deaths in children aged <5 years: Current approaches, new analyses and proposed improvements

PubMed Central

Black, Robert; Tate, Jacqueline; Roose, Anna; Kotloff, Karen; Parashar, Umesh; Lanata, Claudio; Kang, Gagandeep; Troeger, Christopher; Platts-Mills, James; Mokdad, Ali; Sanderson, Colin; Lamberti, Laura; Santosham, Mathuram; Steele, Duncan

2017-01-01

Background Rotavirus is a leading cause of diarrhoeal mortality in children but there is considerable disagreement about how many deaths occur each year. Methods and findings We compared CHERG, GBD and WHO/CDC estimates of age under 5 years (U5) rotavirus deaths at the global, regional and national level using a standard year (2013) and standard list of 186 countries. The global estimates were 157,398 (CHERG), 122,322 (GBD) and 215,757 (WHO/CDC). The three groups used different methods: (i) to select data points for rotavirus-positive proportions; (ii) to extrapolate data points to individual countries; (iii) to account for rotavirus vaccine coverage; (iv) to convert rotavirus-positive proportions to rotavirus attributable fractions; and (v) to calculate uncertainty ranges. We conducted new analyses to inform future estimates. We found that acute watery diarrhoea was associated with 87% (95% CI 83–90%) of U5 diarrhoea hospitalisations based on data from 84 hospital sites in 9 countries, and 65% (95% CI 57–74%) of U5 diarrhoea deaths based on verbal autopsy reports from 9 country sites. We reanalysed data from the Global Enteric Multicenter Study (GEMS) and found 44% (55% in Asia, and 32% in Africa) rotavirus-positivity among U5 acute watery diarrhoea hospitalisations, and 28% rotavirus-positivity among U5 acute watery diarrhoea deaths. 97% (95% CI 95–98%) of the U5 diarrhoea hospitalisations that tested positive for rotavirus were entirely attributable to rotavirus. For all clinical syndromes combined the rotavirus attributable fraction was 34% (95% CI 31–36%). This increased by a factor of 1.08 (95% CI 1.02–1.14) when the GEMS results were reanalysed using a more sensitive molecular test. Conclusions We developed consensus on seven proposals for improving the quality and transparency of future rotavirus mortality estimates. PMID:28892480

A population based study comparing changes in rotavirus burden on the Island of Ireland between a highly vaccinated population and an unvaccinated population.

PubMed

Armstrong, Gillian; Gallagher, Naomh; Cabrey, Paul; Graham, Adele M; McKeown, Paul J; Jackson, Sarah; Dallat, Mary; Smithson, Richard D

2016-09-07

Rotavirus infection is a leading cause of gastroenteritis in infants and children globally. Reductions in rotavirus activity have been observed following introduction of rotavirus vaccination programmes, however a reductions have also been reported in some unvaccinated countries. The Island of Ireland incorporates the two jurisdictions Northern Ireland (NI) and the Republic of Ireland (IE). Both have similarities in climate, demography, morbidity and mortality but distinct health administrations and vaccination policies. Rotarix was added to the childhood immunisation programme in NI on the 1 July 2013. IE have not introduced routine rotavirus vaccination to date. The aim of this population based ecological study was to evaluate the impact of the rotavirus vaccine on burden of rotavirus disease in NI, and to compare with IE as an unvaccinated control population. This will help determine if the changes seen were due to the rotavirus vaccine, or due to confounding factors. A number of population based measures of disease burden were compared in both jurisdictions pre-vaccine (six years; 2007/08-2012/13) and post-vaccine (two years; 2013/14-2014/15). The data sources included national rotavirus surveillance data based on laboratory reports/notifications; hospital admission data; and notifications of gastroenteritis in under 2year olds. In the post-vaccination period, rotavirus incidence in NI dropped by 54% while in IE it increased by 19% compared to the pre-vaccine period. Notifications of gastroenteritis in under 2s in NI declined by 53% and hospital admissions in under 5year olds in NI declined by 40% in the post vaccine period. This natural experiment demonstrated a significant reduction in rotavirus disease activity post-vaccine introduction in NI with associated reductions in healthcare utilisation, with a concurrent increase in rotavirus disease activity in the non-vaccinated population in IE. These findings support rotavirus vaccination as an effective measure to reduce childhood morbidity. Copyright © 2016 Elsevier Ltd. All rights reserved.

Cost-effectiveness analysis of rotavirus vaccination among Libyan children using a simple economic model

PubMed Central

Alkoshi, Salem; Maimaiti, Namaitijiang; Dahlui, Maznah

2014-01-01

Background Rotavirus infection is a major cause of childhood diarrhea in Libya. The objective of this study is to evaluate the cost-effectiveness of rotavirus vaccination in that country. Methods We used a published decision tree model that has been adapted to the Libyan situation to analyze a birth cohort of 160,000 children. The evaluation of diarrhea events in three public hospitals helped to estimate the rotavirus burden. The economic analysis was done from two perspectives: health care provider and societal. Univariate sensitivity analyses were conducted to assess uncertainty in some values of the variables selected. Results The three hospitals received 545 diarrhea patients aged≤5 with 311 (57%) rotavirus positive test results during a 9-month period. The societal cost for treatment of a case of rotavirus diarrhea was estimated at US$ 661/event. The incremental cost-effectiveness ratio with a vaccine price of US$ 27 per course was US$ 8,972 per quality-adjusted life year gained from the health care perspective. From a societal perspective, the analysis shows cost savings of around US$ 16 per child. Conclusion The model shows that rotavirus vaccination could be economically a very attractive intervention in Libya. PMID:25499622

[Nosocomial rotavirus gastroenteritis].

PubMed

Marinosci, A; Doit, C; Koehl, B; Belhacel, K; Mariani Kurkdjian, P; Melki, I; Renaud, A; Lemaitre, C; Ammar Khodja, N; Blachier, A; Bonacorsi, S; Faye, A; Lorrot, M

2016-11-01

Rotavirus is the most common cause of gastroenteritis in children requiring hospitalization. It is a very resistant and contagious virus causing nosocomial gastroenteritis. In France, the vaccine against rotavirus has been available since 2006, but the vaccine is not recommended for infant vaccination. The aim of this retrospective study was to describe nosocomial rotavirus gastroenteritis (NRGE) and to assess its impact on children hospitalized in the General Pediatrics Department of Robert-Debré Hospital (Paris) between 1 January 2009 and 31 December 2013. We analyzed the demographic characteristics of children (age, term birth, underlying diseases) and the severity of the NRGE (oral or intravenous hydration), and assessed whether these children could benefit from vaccination against rotavirus. One hundred thirty-six children presented nosocomial rotavirus infection, with an incidence of 2.5 NRGE per 1000 days of hospitalization. The incidence of NRGE was stable between 2009 and 2013 despite the introduction of specific hygiene measures. The average age of the children was 7 months (range: 0.5-111 months). Most often NRGE occurred in children hospitalized for respiratory diseases (65% of cases) and requiring prolonged hospitalization (median: 18 days). One-third of children were born premature (25%). Hydration was oral in 80 patients (59%), by intravenous infusion in 18 patients (13%), and intraosseous in one patient. Half of the patients were aged less than 5 months and could benefit from the protection afforded by vaccination. NRGE are common. Rotavirus mass vaccination should have a positive impact on the incidence of NRGE by reducing the number of children hospitalized for gastroenteritis, therefore indirectly reducing the number of hospital cross-infections of hospitalized children who are too young to be vaccinated. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

Aetiology of diarrhoeal disease and evaluation of viral-bacterial coinfection in children under 5 years old in China: a matched case-control study.

PubMed

Li, L L; Liu, N; Humphries, E M; Yu, J M; Li, S; Lindsay, B R; Stine, O C; Duan, Z J

2016-04-01

Globally, diarrhoeal diseases are the second leading cause of death among children under 5 years old. Few case-control studies on the aetiology of diarrhoea have been conducted in China. A case-control study on 922 children under 5 years old who presented with diarrhoea and individually matched controls was conducted in China between May 2011 and January 2013. Quantitative PCR was used to analyze stool samples for 10 diarrhoeal pathogens. Potential enteric pathogens were detected in 377 (81.8%) of 461 children with diarrhoea and 215 controls (46.6%, p <0.001). Rotavirus, norovirus GII, Shigella and adenovirus were qualitatively associated with diarrhoea. Using receiver operating characteristic curves, the optimal cutoff threshold for defining a symptomatic individual was 72, 5840, and 10(4) copies per reaction for rotavirus (odds ratio 259), norovirus GII (odds ratio 10.6) and Shigella (odds ratio 5.1). The attributable fractions were 0.18 for rotavirus, 0.08 for norovirus GII, 0.01 for Shigella and 0.04 for adenovirus. Coinfections between pathogens were common. Two pairs, rotavirus and adenovirus, and norovirus GII and Salmonella were positively associated. The co-occurrence of rotavirus and sapovirus, astrovirus, enterotoxigenic Escherichia coli or Campylobacter jejuni only occurred in children with disease. Coinfection was not correlated with clinical symptoms. Quantitative data are critical. Our results indicate that increased pathogen loads increase the OR between diarrhoea and rotavirus, norovirus GII and Shigella. Coinfections with rotavirus and norovirus GII are common and occur in a nonrandom distribution. Despite testing for ten diarrhoeal pathogens, over two-thirds of cases do not have a recognized attributable cause. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

Prevention of childhood rotavirus disease through the use of Rotarix and RotaTeq vaccines.

PubMed

Lepage, Philippe; Vergison, Anne

2007-12-01

Rotaviruses are the most common enteric pathogens to cause acute diarrhoea in infants and young children throughout the world. Two new live, orally administered vaccines (Rotarix and RotaTeq) that provide protection against rotavirus infections are now available and have been licensed in many countries in Europe, North and Latin America. Two recent large clinical trials have demonstrated that their efficacy, immunogenicity and safety, including absence of vaccine-associated intussusception in young infants, are remarkably similar. The protection against severe rotavirus gastroenteritis extends into the second year of follow up for both vaccines. Rotarix and RotaTeq vaccines can be coadministered with routine childhood vaccines. However, more data on the efficacy of these two new vaccines in low-income nations are needed, particularly in Asia and Africa, before global inclusion of rotavirus vaccines into national immunisation programmes can be recommended.

[Identification of rotavirus associated to serotype G2 in Yucatan, Mexico].

PubMed

Gonzales-Loza, M del R; Polanco-Marín, G G; Puerto-Solis, M

2000-01-01

In the present study, rotavirus G2 serotype was identified from fecal samples of children with gastroenteritis from the city of Merida, Yucatan, Mexico. Virological diagnosis of disease was performed using polycrylamide gel electrophoresis and immunoenzymatic assay. Out of 149 analyzed samples 25 (16.7%) gave positive reaction to rotavirus groups A, of these 23 (92%) were identified as serotype g2, subgroup i and electrophoretic short pattern, whereas 2 (8%) were identified as subgroups II and electrophoretic long pattern, however, the G serotype was not possible to determine. Rotavirus G serotype has not been detected in more than 90% of samples since 1985. This indicates that the number of people susceptible to G2 serotype within the population has increased over recent years, which perhaps indicates that an important outbreak of acute infectious diarrhea caused by the rotavirus G2 serotype may be forthcoming.

Antigenic and Genomic Diversity of Human Rotavirus VP4 in Two Consecutive Epidemic Seasons in Mexico

PubMed Central

Padilla-Noriega, Luis; Méndez-Toss, Martha; Menchaca, Griselda; Contreras, Juan F.; Romero-Guido, Pedro; Puerto, Fernando I.; Guiscafré, Héctor; Mota, Felipe; Herrera, Ismael; Cedillo, Roberto; Muñoz, Onofre; Calva, Juan; Guerrero, María de Lourdes; Coulson, Barbara S.; Greenberg, Harry B.; López, Susana; Arias, Carlos F.

1998-01-01

In the present investigation we characterized the antigenic diversity of the VP4 and VP7 proteins in 309 and 261 human rotavirus strains isolated during two consecutive epidemic seasons, respectively, in three different regions of Mexico. G3 was found to be the prevalent VP7 serotype during the first year, being superseded by serotype G1 strains during the second season. To antigenically characterize the VP4 protein of the strains isolated, we used five neutralizing monoclonal antibodies (MAbs) which showed specificity for VP4 serotypes P1A, P1B, and P2 in earlier studies. Eight different patterns of reactivity with these MAbs were found, and the prevalence of three of these patterns varied from one season to the next. The P genotype of a subset of 52 samples was determined by PCR. Among the strains characterized as genotype P[4] and P[8] there were three and five different VP4 MAb reactivity patterns, respectively, indicating that the diversity of neutralization epitopes in VP4 is greater than that previously appreciated by the genomic typing methods. PMID:9620401

Identification of Equine Lactadherin-derived Peptides That Inhibit Rotavirus Infection via Integrin Receptor Competition.

PubMed

Civra, Andrea; Giuffrida, Maria Gabriella; Donalisio, Manuela; Napolitano, Lorenzo; Takada, Yoshikazu; Coulson, Barbara S; Conti, Amedeo; Lembo, David

2015-05-08

Human rotavirus is the leading cause of severe gastroenteritis in infants and children under the age of 5 years in both developed and developing countries. Human lactadherin, a milk fat globule membrane glycoprotein, inhibits human rotavirus infection in vitro, whereas bovine lactadherin is not active. Moreover, it protects breastfed infants against symptomatic rotavirus infections. To explore the potential antiviral activity of lactadherin sourced by equines, we undertook a proteomic analysis of milk fat globule membrane proteins from donkey milk and elucidated its amino acid sequence. Alignment of the human, bovine, and donkey lactadherin sequences revealed the presence of an Asp-Gly-Glu (DGE) α2β1 integrin-binding motif in the N-terminal domain of donkey sequence only. Because integrin α2β1 plays a critical role during early steps of rotavirus host cell adhesion, we tested a minilibrary of donkey lactadherin-derived peptides containing DGE sequence for anti-rotavirus activity. A 20-amino acid peptide containing both DGE and RGD motifs (named pDGE-RGD) showed the greatest activity, and its mechanism of antiviral action was characterized; pDGE-RGD binds to integrin α2β1 by means of the DGE motif and inhibits rotavirus attachment to the cell surface. These findings suggest the potential anti-rotavirus activity of equine lactadherin and support the feasibility of developing an anti-rotavirus peptide that acts by hindering virus-receptor binding. © 2015 by The American Society for Biochemistry and Molecular Biology, Inc.

The burden of hospitalizations and clinic visits for rotavirus disease in children aged <5 years in the Philippines.

PubMed

Carlos, Celia C; Inobaya, Marianette T; Bresee, Joseph S; Lagrada, Marietta L; Olorosa, Agnettah M; Kirkwood, Carl D; Widdowson, Marc-Alain

2009-11-01

Recent data on the burden of hospitalization and clinic visits for rotavirus gastroenteritis are needed to support the decision to introduce rotavirus vaccine in the Philippines. From 2005 through 2006, children aged <5 years with acute diarrhea who attended 1 of 7 clinics and/or hospitals in Muntinlupa City, the Philippines, were enrolled. Clinical and demographic data were collected, and a stool specimen was obtained for rotavirus testing and typing for G and P antigens. The incidences of different clinical outcomes of rotavirus gastroenteritis were determined for 3 townships under surveillance and were extrapolated to the Philippines with use of national data sets. The prevalence of rotavirus was 31% (171/560) among children hospitalized with diarrhea, 30% (155/520) among those who presented to the emergency department, and 15% (56/385) among those who presented to a clinic. The annual estimated incidence (per 100,000 children aged <5 years) of rotavirus gastroenteritis in outpatient, emergency department, and inpatient settings was 755, 451, and 279, respectively. Of 274 strains, 50 (18%) were nontypeable. Of the 128 strains that underwent G and P typing, 98% belong to the globally common strains G3P[P], G2P[4], and G1P[8]. The burden of rotavirus gastroenteritis in the Philippines is high and is predominantly caused by strains against which current vaccines have shown good efficacy, suggesting that routine immunization will have a large impact on rotavirus disease burden.

Stem cell-derived human intestinal organoids as an infection model for rotaviruses.

PubMed

Finkbeiner, Stacy R; Zeng, Xi-Lei; Utama, Budi; Atmar, Robert L; Shroyer, Noah F; Estes, Mary K

2012-01-01

Directed differentiation of stem cell lines into intestine-like tissue called induced human intestinal organoids (iHIOs) is now possible (J. R. Spence, C. N. Mayhew, S. A. Rankin, M. F. Kuhar, J. E. Vallance, K. Tolle, E. E. Hoskins, V. V. Kalinichenko, S. I. Wells, A. M. Zorn, N. F. Shroyer, and J. M. Wells, Nature 470:105-109, 2011). We tested iHIOs as a new model to cultivate and study fecal viruses. Protocols for infection of iHIOs with a laboratory strain of rotavirus, simian SA11, were developed. Proof-of-principle analyses showed that iHIOs support replication of a gastrointestinal virus, rotavirus, on the basis of detection of nonstructural viral proteins (nonstructural protein 4 [NSP4] and NSP2) by immunofluorescence, increased levels of viral RNA by quantitative reverse transcription-PCR (qRT-PCR), and production of infectious progeny virus. iHIOs were also shown to support replication of 12/13 clinical rotavirus isolates directly from stool samples. An unexpected finding was the detection of rotavirus infection not only in the epithelial cells but also in the mesenchymal cell population of the iHIOs. This work demonstrates that iHIOs offer a promising new model to study rotaviruses and other gastrointestinal viruses. Gastrointestinal viral infections are a major cause of illness and death in children and adults. The ability to fully understand how viruses interact with human intestinal cells in order to cause disease has been hampered by insufficient methods for growing many gastrointestinal viruses in the laboratory. Induced human intestinal organoids (iHIOs) are a promising new model for generating intestine-like tissue. This is the first report of a study using iHIOs to cultivate any microorganism, in this case, an enteric virus. The evidence that both laboratory and clinical rotavirus isolates can replicate in iHIOs suggests that this model would be useful not only for studies of rotaviruses but also potentially of other infectious agents. Furthermore, detection of rotavirus proteins in unexpected cell types highlights the promise of this system to reveal new questions about pathogenesis that have not been previously recognized or investigated in other intestinal cell culture models.

Molecular characterization of two rare human G8P[14] rotavirus strains, detected in Italy in 2012.

PubMed

Delogu, Roberto; Ianiro, Giovanni; Morea, Anna; Chironna, Maria; Fiore, Lucia; Ruggeri, Franco M

2016-10-01

Since 2007, the Italian Rotavirus Surveillance Program (RotaNet-Italy) has monitored the diversity and distribution of genotypes identified in children hospitalized with rotavirus acute gastroenteritis. We report the genomic characterization of two rare human G8P[14] rotavirus strains, identified in two children hospitalized with acute gastroenteritis in the southern Italian region of Apulia during rotavirus strain surveillance in 2012. Both strains showed a G8-P[14]-I2-R2-C2-M2-A11-N2-T6-E2-H3 genomic constellation (DS-1-like genomic background). Phylogenetic analysis of each genome segment revealed a mixed configuration of genes of animal and zoonotic human origin, indicating that genetic reassortment events generated these unusual human strains. Eight out of 11 genes (VP1, VP2, VP3, VP6, VP7, NSP3, NSP4 and NSP5) of the Italian G8P[14] strains exhibited close identity with a Spanish sheep strain, whereas the remaining genes (VP4, NSP1 and NSP2) were more closely related to human strains. The amino acid sequences of the antigenic regions of outer capsid proteins VP4 and VP7 were compared with vaccine and field strains, showing high conservation between the amino acid sequences of Apulia G8P[14] strains and human and animal strains bearing G8 and/or P[14] proteins, and revealing many substitutions with respect to the RotaTeq™ and Rotarix™ vaccine strains. Conversely, the amino acid analysis of the four antigenic sites of VP6 revealed a high degree of conservation between the two Apulia strains and the human and animal strains analyzed. These results reinforce the potential role of interspecies transmission and reassortment in generating novel rotavirus strains that might not be fully contrasted by current vaccines. Copyright © 2016 Elsevier B.V. All rights reserved.

Hospital surveillance of rotavirus infection and nosocomial transmission of rotavirus disease among children in Guinea-Bissau.

PubMed

Rodrigues, Amaélia; de Carvalho, Melo; Monteiro, Serifo; Mikkelsen, Carsten Sauer; Aaby, Peter; Molbak, Kåre; Fischer, Thea Kølsen

2007-03-01

Vaccination against rotavirus is protective against severe disease. Surveillance of rotavirus infection in developing countries might direct vaccination policy more efficiently. We implemented WHO's generic protocols for hospital-and community-based surveillance of rotavirus gastroenteritis. From April 2001 to May 2002, and from January 2003 to June 2003, we conducted hospital surveillance for rotavirus infection at the only pediatric ward in the capital of Guinea-Bissau. Children less than 5 years of age admitted with diarrhea or developing diarrhea during hospitalization were enrolled in the study. Rotavirus infection was detected in the feces samples using an ELISA assay. Rectal swabs were also obtained and its use was validated against stool specimen. During the surveillance period, 161 cases of rotavirus infection were registered. During the season, rotavirus accounted for 35% of all hospitalized diarrhea cases. The rate of nosocomial disease was 1.6 per 1000 child-days (95% confidence interval [CI] = 1.02-2.51) with high rates for children aged 12 to 23 months of age (rate: 3.09; 95% CI = 1.47-6.48). Most of the rotavirus cases (93%) were in children less than 2 years of age and only 10 children aged less than 3 months were infected. Fever (risk ratio (RR) 1.56; 95% CI = 1.16-2.10) and vomiting (RR 1.38; 95% CI = 1.11-1.73) were more common in patients with rotavirus than in patients with nonrotavirus diarrhea. The case-fatality was 8%. Results from stool samples and rectal swabs were concordant in 96% of the pairs. Rectal swabs increased the detection of rotavirus cases by 6% and deaths by 33% over stool sample results. Rotavirus infections were confined to a 4-month period each year. It is an important cause of childhood diarrhea with high case-fatality ratio in Guinea-Bissau. The use of rectal swab appeared to increase the detection rate of rotavirus infection and the case-fatality rate. The high rate of nosocomial infections in hospitalized children emphasizes the need for prevention of disease.

The impact of the recommendation of routine rotavirus vaccination in Germany: An interrupted time-series analysis.

PubMed

Kittel, Phillip Alexander

2018-01-04

Rotavirus is a highly contagious virus causing gastroenteritis, mostly in children under the age of 5. Since 2006, two vaccines are available in Germany. In 2013, these were included into the German national vaccination schedule. The aim of this intervention is to reduce the incidence and hospitalization among children under 5 years caused by rotavirus. The effectiveness of the intervention was analyzed in this study. National surveillance data of laboratory confirmed rotavirus infections among children under the age of 5 were analyzed using interrupted time-series analysis. Weekly incidence from 2011 to 2017 and monthly hospital discharge rates from 2005 to 2015 were analyzed using a segmented generalized linear model with Poisson distribution. After adjusting for seasonal effects the incidence were approximately 22% (95% CI: 13.2-30.1) lower than expected following the intervention. The hospitalizations were approximately 27% (95% CI: 14.9-39.7) lower than expected following the intervention. The long-term effects of the intervention were nearly zero. The incidence changed in trend by -0.2% (95% CI: -0.1 to (-0.3)) and the hospitalizations by +0.2% (95% CI: 1.2-(-0.8)) following the intervention. After the inclusion of the vaccines into the national vaccination schedule significant immediate effects of this intervention were found. The weekly incidences and monthly hospitalization caused by the rotavirus were more than 20% lower than expected. The long-term effects of the intervention however were found to be nearly zero. This could be caused by a low vaccination rate in the German population. Copyright © 2017 Elsevier Ltd. All rights reserved.

Ice-associated norovirus outbreak predominantly caused by GII.17 in Taiwan, 2015.

PubMed

Cheng, Hao-Yuan; Hung, Min-Nan; Chen, Wan-Chin; Lo, Yi-Chun; Su, Ying-Shih; Wei, Hsin-Yi; Chen, Meng-Yu; Tuan, Yen-Chang; Lin, Hui-Chen; Lin, Hsu-Yang; Liu, Tsung-Yen; Wang, Yu-Ying; Wu, Fang-Tzy

2017-11-07

On 5 March 2015, Taiwan Centers for Disease Control was notified of more than 200 students with gastroenteritis at a senior high school during excursion to Kenting. We conducted an outbreak investigation to identify the causative agent and possible vehicle of the pathogen. We conducted a retrospective cohort study by using a structured questionnaire to interview all students for consumed food items during their stay at the resort. Students were defined as a gastroenteritis case while having vomiting or diarrhea after the breakfast on 4 March. We inspected the environment to identify possible contamination route. We collected stool or vomitus samples from ill students, food handlers and environmental specimens for bacterial culture for common enteropathogens, reverse transcription polymerase chain reaction (RT-PCR) for norovirus and enzyme-linked immunosorbent assay (ELISA) for rotavirus. Norovirus PCR-positive products were then sequenced and genotyped. Of 267 students enrolled, 144 (54%) met our case definition. Regression analysis revealed elevated risk associated with iced tea, which was made from tea powder mixed with hot water and self-made ice (risk ratio 1.54, 95% confidence interval 1.22-1.98). Ice used for beverages, water before and after water filter of the ice machine and 16 stool and vomitus samples from ill students were tested positive for norovirus; Multiple genotypes were identified including GI.2, GI.4 and GII.17. GII.17 was the predominant genotype and phylogenetic analyses showed that noroviruses identified in ice, water and human samples were clustered into the same genotypes. Environmental investigation revealed the ice was made by inadequate-filtered and un-boiled water. We identified the ice made by norovirus-contaminated un-boiled water caused the outbreak and the predominant genotype was GII.17. Adequately filtered or boiled water should be strongly recommended for making ice to avoid possible contamination.

Impact and Effectiveness of Monovalent Rotavirus Vaccine in Armenian Children.

PubMed

Sahakyan, Gayane; Grigoryan, Svetlana; Wasley, Annemarie; Mosina, Liudmila; Sargsyan, Shushan; Asoyan, Ara; Gevorgyan, Zaruhi; Kocharyan, Karine; Avagyan, Tigran; Lopman, Benjamin; Vanyan, Artavazd; Khactatryan, Sergey; Parashar, Umesh D; Cortese, Margaret M

2016-05-01

The Republic of Armenia was 1 of the 2 earliest countries in the Newly Independent States to introduce rotavirus vaccine into its national immunization program to reduce the burden of rotavirus disease (documented to cause 38% of acute gastroenteritis hospitalizations [AGE] among children aged <5 years). In November 2012, RV1 (Rotarix) was introduced for Armenian infants at ages 6 and 12 weeks. The established active surveillance system at 2 hospitals in the capital, Yerevan, whereby children aged <5 years hospitalized for AGE have stool sample tested for rotavirus antigen, was used to assess trends in rotavirus hospitalizations. Immunization records on children enrolled after vaccine introduction were obtained from clinics, and vaccine effectiveness (VE) was estimated using children with AGE who test negative for rotavirus as controls for the rotavirus-positive cases. Among infants, rotavirus hospitalizations were reduced by 48% within the first year after introduction, and by ≥75% in years 2 and 3 following introduction. Reductions of ≥30% in other young children too old to have been vaccinated suggest additional benefit through indirect protection; overall in year 3, rotavirus hospitalizations were reduced by 69% among children aged <5 years. The overall VE of 2 RV1 doses in protecting against rotavirus hospitalization (any severity) was 62% (95% confidence interval [CI], 36%-77%) among children aged 6-23 months; 68% (95% CI, 24%-86%) among those aged 6-11 months, and 60% (95% CI, 20%-80%) in children aged 12-23 months. Against more severe rotavirus disease, VE was 79% (95% CI, 55%-90%) and similarly high in both age groups. RV1 is effective in young Armenian children and substantially reduced rotavirus hospitalizations shortly after introduction. Published by Oxford University Press for the Infectious Diseases Society of America 2016. This work is written by (a) US Government employee(s) and is in the public domain in the US.

Burden of rotavirus in India--is rotavirus vaccine an answer to it?

PubMed

Taneja, Davendra K; Malik, Akash

2012-01-01

Rotavirus is currently by far the most common cause of severe diarrhea in infants and young children worldwide and of diarrheal deaths in developing countries. Worldwide Rotavirus is responsible for 611,000 childhood deaths out of which more than 80% occur in low-income countries. The resistance of rotavirus to commonly used disinfectants and ineffectiveness of oral rehydration therapy due to severe vomiting indicates that if an effective vaccine is the preferred option. WHO has recommended inclusion of rotavirus vaccine in the National Schedules where under 5 mortality due to diarrheal diseases is ≥ 10%. Currently two vaccines are available against rotavirus. Rotarix (GlaxoSmithKline) is a monovalent vaccine recommended to be orally administered in two doses at 6-12 weeks. Rota Teq (Merck) is a pentavalent vaccine recommended to be orally administered in three doses starting at 6-12 weeks of age. Serodiversity of rotavirus in India and its regional variation favor either a monovalent vaccine that can induce heterotypic immunity or a polyvalent vaccine incorporating majority of serotypes prevalent in the country. However, the efficacy of available rotavirus vaccines is less in low-income countries. Both the candidate vaccines when coadministered with OPV, immune response to first dose of these vaccines is reduced. However, immune responses to subsequent rotavirus vaccine doses are not affected. In view of this, WHO recommends three doses of either vaccine to be given to children in developing countries to produce the optimum response. Indigenous vaccine, 116E (Bharat Biotech) based on human rotavirus of serotype G9P [11] is still under Phase 2 trials. Another multivalent vaccine is being developed by Shantha Biotechnics in India. The cost effectiveness of the three dose schedule of the available and the rsults of the field trials of the indigenous vaccines should be assessed before inclusion of rotavirus vaccine in the National Immunization Schedule.

Disease burden and related medical costs of rotavirus infections in Taiwan

PubMed Central

Lu, Chun-Yi; Lauderdale, Tsai-Ling; Fang, Yin-Hua; Wang, Chung-Yi; Ho, Yu-Huai; Hung, Che-Lun; Chang, Luan-Yin; Lee, Chin-Yun; Huang, Li-Min

2006-01-01

Background The disease burden and associated medical costs of rotavirus infections in inpatient and outpatient sectors in Taiwan were examined in anticipation of the availability of new rotavirus vaccines. Methods The yearly national case number and medical costs for all for inpatients and outpatients with acute gastroenteritis (AGE) were extracted from the Bureau of National Health Insurance database in Taiwan according to ICD-9-CM codes. A retrospective study was also performed using records of children with AGE seen at three hospitals in Taiwan in 2001 to identify laboratory confirmed rotavirus infection cases. The annual incidence and related medical costs of AGE due to rotavirus infection were then estimated. Results Children <5 years old comprised 83.6% of inpatient and 62.0% of outpatient pediatric AGE cases in Taiwan in 2001. Rotavirus was the most common agent detected among AGE patients in this age group in the three hospitals, and was detected in 32.9% (221/672) of inpatient and 24% (23/96) of outpatient stool specimens tested for microbial etiologies. An estimated 277,400 to 624,892 cases of rotavirus infections sought medical care in Taiwan in 2001, equaling one in 2 to 5 children <5 years old required medical care due to rotavirus infection. The incidence of hospitalization due to rotavirus infections was 1,528–1,997/100,000 for children <5 years old. The total associated medical costs due to rotavirus infection were estimated at US $10–16 millions in Taiwan in 2001. Although the per-capita medical cost of rotavirus infection was lower in Taiwan than in the United States or Hong Kong, the personal economic burden was similar among the three places when normalized for gross national incomes per capita. Conclusion Infections caused by rotavirus constitute an important human and economic burden among young children in Taiwan. A safe and effective vaccine is urgently needed. PMID:17173677

Accelerating the introduction of rotavirus immunization in Indonesia.

PubMed

Suwantika, Auliya A; Zakiyah, Neily; Lestari, Keri; Postma, Maarten J

2014-04-01

The introduction of the rotavirus vaccine in Indonesia is currently in its infancy. Delay in its development might be caused by factors related to the perceived value of the vaccine, health system characteristics and policy considerations. Other factors, which may also interfere with optimizing the introduction, are financial barriers because Indonesia is a lower-middle-income country. Creating fiscal space to finance new immunization programs, such as for the rotavirus immunization, is very important to ensure the sustainability of new programs so that such programs would be financed over the long term and not endanger the sustainability of the Indonesian government's financial position. This article provides an illustration of the various steps needed to accelerate the introduction of the rotavirus immunization.

Aetiology of acute paediatric gastroenteritis in Bulgaria during summer months: prevalence of viral infections.

PubMed

Mladenova, Zornitsa; Steyer, Andrej; Steyer, Adela Fratnik; Ganesh, Balasubramanian; Petrov, Petar; Tchervenjakova, Tanja; Iturriza-Gomara, Miren

2015-03-01

Paediatric acute gastroenteritis is a global public health problem. Comprehensive laboratory investigation for viral, bacterial and parasitic agents is helpful for improving management of acute gastroenteritis in health care settings and for monitoring and controlling the spread of these infections. Our study aimed to investigate the role of various pathogens in infantile diarrhoea in Bulgaria outside the classical winter epidemics of rotavirus and norovirus. Stool samples from 115 hospitalized children aged 0-3 years collected during summer months were tested for presence of 14 infectious agents - group A rotavirus, astrovirus, Giardia, Cryptosporidium and Entamoeba using ELISAs; norovirus by real-time RT-PCR; picobirnavirus and sapovirus by RT-PCR; adenovirus using PCR, and Salmonella, Shigella, Escherichia coli, Yersinia and Campylobacter using standard bacterial cultures. Infectious origin was established in a total of 92 cases and 23 samples remained negative. A single pathogen was found in 67 stools, of which rotaviruses were the most prevalent (56.7 %), followed by noroviruses (19.4 %), enteric adenoviruses (7.5 %), astroviruses (6.0 %), bacteria and parasites (4.5 % each) and sapoviruses (1.4 %). Rotavirus predominant genotypes were G4P[8] (46.3 %) and G2P[4] (21.4 %); for astroviruses, type 1a was the most common, while the GII.4/2006b variant was the most prevalent among noroviruses. Bacteria were observed in five cases, with Salmonella sp. as the most prevalent, while parasites were found in ten stool samples, with Giardia intestinalis in five cases. The results demonstrated high morbidity associated with viral infections and that rotavirus and norovirus remain the most common pathogens associated with severe gastroenteritis during summer months in Bulgaria, a country with a temperate climate, and significant molecular diversity among circulating virus strains. © 2015 The Authors.

Chicken Egg Yolk Antibodies (IgY) for Prophylaxis and Treatment of Rotavirus Diarrhea in Human and Animal Neonates: A Concise Review

PubMed Central

Thu, Hlaing Myat; Myat, Theingi Win; Win, Mo Mo; Thant, Kyaw Zin; Rahman, Shofiqur; Umeda, Kouji; Nguyen, Sa Van; Icatlo, Faustino C.; Higo-Moriguchi, Kyoko; Taniguchi, Koki; Tsuji, Takao; Oguma, Keiji; Kim, Sang Jong; Bae, Hyun Suk

2017-01-01

The rotavirus-induced diarrhea of human and animal neonates is a major public health concern worldwide. Until recently, no effective therapy is available to specifically inactivate the rotavirion particles within the gut. Passive immunotherapy by oral administration of chicken egg yolk antibody (IgY) has emerged of late as a fresh alternative strategy to control infectious diseases of the alimentary tract and has been applied in the treatment of diarrhea due to rotavirus infection. The purpose of this concise review is to evaluate evidence on the properties and performance of anti-rotavirus immunoglobulin Y (IgY) for prevention and treatment of rotavirus diarrhea in human and animal neonates. A survey of relevant anti-rotavirus IgY basic studies and clinical trials among neonatal animals (since 1994-2015) and humans (since 1982-2015) have been reviewed and briefly summarized. Our analysis of a number of rotavirus investigations involving animal and human clinical trials revealed that anti-rotavirus IgY significantly reduced the severity of clinical manifestation of diarrhea among IgY-treated subjects relative to a corresponding control or placebo group. The accumulated information as a whole depicts oral IgY to be a safe and efficacious option for treatment of rotavirus diarrhea in neonates. There is however a clear need for more randomized, placebo controlled and double-blind trials with bigger sample size to further solidify and confirm claims of efficacy and safety in controlling diarrhea caused by rotavirus infection especially among human infants with health issues such as low birth weights or compromised immunity in whom it is most needed. PMID:28316465

The validation and utility of a quantitative one-step multiplex RT real-time PCR targeting Rotavirus A and Norovirus

PubMed Central

Dung, Tran Thi Ngoc; Phat, Voong Vinh; Nga, Tran Vu Thieu; My, Phan Vu Tra; Duy, Pham Thanh; Campbell, James I.; Thuy, Cao Thu; Hoang, Nguyen Van Minh; Van Minh, Pham; Le Phuc, Hoang; Tuyet, Pham Thi Ngoc; Vinh, Ha; Kien, Duong Thi Hue; Huy, Huynh Le Anh; Vinh, Nguyen Thanh; Nga, Tran Thi Thu; Hau, Nguyen Thi Thu; Chinh, Nguyen Tran; Thuong, Tang Chi; Tuan, Ha Manh; Simmons, Cameron; Farrar, Jeremy J.; Baker, Stephen

2013-01-01

Rotavirus (RoV) and Norovirus (NoV) are the main causes of viral gastroenteritis. Currently, there is no validated multiplex real-time PCR that can detect and quantify RoV and NoV simultaneously. The aim of the study was to develop, validate, and internally control a multiplex one-step RT real-time PCR to detect and quantify RoV and NoV in stool samples. PCR sensitivity was assessed by comparing amplification against the current gold standard, enzyme immunoassay (EIA), on stool samples from 94 individuals with diarrhea and 94 individuals without diarrhea. PCR detected 10% more RoV positive samples than EIA in stools samples from patients with diarrhea. PCR detected 23% more NoV genogroup II positive samples from individuals with diarrhea and 9% more from individuals without diarrhea than EIA, respectively. Genotyping of the PCR positive/EIA negative samples suggested the higher rate of PCR positivity, in comparison to EIA, was due to increased sensitivity, rather than nonspecific hybridization. Quantitation demonstrated that the viral loads of RoV and NoV in the stools of diarrheal patients were an order of magnitude greater than in individuals without diarrhea. This internally controlled real-time PCR method is robust, exhibits a high degree of reproducibility, and may have a greater utility and sensitivity than commercial EIA kits. PMID:23046990

Mycophenolic acid potently inhibits rotavirus infection with a high barrier to resistance development.

PubMed

Yin, Yuebang; Wang, Yijin; Dang, Wen; Xu, Lei; Su, Junhong; Zhou, Xinying; Wang, Wenshi; Felczak, Krzysztof; van der Laan, Luc J W; Pankiewicz, Krzysztof W; van der Eijk, Annemiek A; Bijvelds, Marcel; Sprengers, Dave; de Jonge, Hugo; Koopmans, Marion P G; Metselaar, Herold J; Peppelenbosch, Maikel P; Pan, Qiuwei

2016-09-01

Rotavirus infection has emerged as an important cause of complications in organ transplantation recipients. Immunosuppressants used to prevent alloreactivity can also interfere with virus infection, but the direct effects of the specific type of immunosuppressants on rotavirus infection are still unclear. Here we profiled the effects of different immunosuppressants on rotavirus using a 2D culture model of Caco2 human intestinal cell line and a 3D model of human primary intestinal organoids inoculated with laboratory and patient-derived rotavirus strains. We found that the responsiveness of rotavirus to Cyclosporine A treatment was moderate and strictly regulated in an opposite direction by its cellular targets cyclophilin A and B. Treatment with mycophenolic acid (MPA) resulted in a 99% inhibition of viral RNA production at the clinically relevant concentration (10 μg/ml) in Caco2 cells. This effect was further confirmed in organoids. Importantly, continuous treatment with MPA for 30 passages did not attenuate its antiviral potency, indicating a high barrier to drug resistance development. Mechanistically, the antiviral effects of MPA act via inhibiting the IMPDH enzyme and resulting in guanosine nucleotide depletion. Thus for transplantation patients at risk for rotavirus infection, the choice of MPA as an immunosuppressive agent appears rational. Copyright © 2016 Elsevier B.V. All rights reserved.

Influence of Epicuticular Physicochemical Properties on Porcine Rotavirus Adsorption to 24 Leafy Green Vegetables and Tomatoes

PubMed Central

Palma-Salgado, Sindy Paola; Storm, Andrew Page; Feng, Hao; Juvik, John A.; Nguyen, Thanh H.

2015-01-01

Foodborne diseases are a persistent problem in the United States and worldwide. Fresh produce, especially those used as raw foods like salad vegetables, can be contaminated, causing illness. In this study, we determined the number of rotaviruses adsorbed on produce surfaces using group A porcine rotaviruses and 24 cultivars of leafy vegetables and tomato fruits. We also characterized the physicochemical properties of each produce’s outermost surface layer, known as the epicuticle. The number of rotaviruses found on produce surfaces varied among cultivars. Three-dimensional crystalline wax structures on the epicuticular surfaces were found to significantly contribute to the inhibition of viral adsorption to the produce surfaces (p = 0.01). We found significant negative correlations between the number of rotaviruses adsorbed on the epicuticular surfaces and the concentrations of alkanes, fatty acids, and total waxes on the epicuticular surfaces. Partial least square model fitting results suggest that alkanes, ketones, fatty acids, alcohols, contact angle and surface roughness together can explain 60% of the variation in viral adsorption. The results suggest that various fresh produce surface properties need to be collectively considered for efficient sanitation treatments. Up to 10.8% of the originally applied rotaviruses were found on the produce surfaces after three washing treatments, suggesting a potential public health concern regarding rotavirus contamination. PMID:26181904

DEVELOPMENT OF MULTIPLEX RT-PCR FOR THE DETECTION OF REOVIRUS, HEPATITIS A VIRUS, POLIOVIRUS, NORWALK VIRUS AND ROTAVIRUS

EPA Science Inventory

Water sources are often found to be contaminated by enteric viruses. This is a public health concern as food and waterborne outbreaks caused by enteric viruses such as noroviruses, rotaviruses, hepatitis A virus (HAV) and enteroviruses are a common occurrence. All of these viru...

75 FR 48706 - Proposed Vaccine Information Materials for Rotavirus Vaccine

Federal Register 2010, 2011, 2012, 2013, 2014

2010-08-11

... the parent or legal representative in the case of a child) receiving vaccines covered under the... who intends to administer one of these covered vaccines is required to provide copies of the relevant... accompanied by vomiting and fever. Rotavirus is not the only cause of severe diarrhea, but it is one of the...

[Nosocomial virus infections].

PubMed

Eggers, H J

1986-12-01

Enveloped viruses, e.g. influenza- or varicella viruses may cause highly contagious airborne infections. Their spread is difficult to control, also in hospitals. In the case of influenza and varicella immune prophylaxis and chemotherapy/chemoprophylaxis are possible. This is of particular significance, since varicella and zoster are of increasing importance for immunocompromized patients. Diarrhea is caused to a large extent by viruses. Rotavirus infections play an important role in infancy, and are frequently acquired in the hospital. In a study on infectious gastroenteritis of infants in a hospital we were able to show that 30 percent of all rotavirus infections were of nosocomial origin. Admission of a rotavirus-excreting patient (or personnel) may start a long chain of rotavirus infections on pediatric wards. Even careful hygienic measures in the hospital can hardly prevent the spread of enterovirus infections. Such infections may be severe and lethal for newborns, as shown by us in a study on an outbreak of echovirus 11 disease on a maternity ward. We have recently obtained data on the "stickiness" of enteroviruses on human skin. This could explain essential features of the spread of enteroviruses in the population.

Intra-genotypic Diversity of Archival G4P[8] Human Rotaviruses from Washington, DC

PubMed Central

McDonald, Sarah M.; Davis, Kristin; McAllen, John K.; Spiro, David J.; Patton, John T.

2011-01-01

Group A human rotaviruses (RVs) remain the most frequently detected viral agents associated with acute gastroenteritis in infants and young children. Despite their medical importance, relatively few complete genome sequences have been determined for commonly circulating G/P-type strains (i.e., G1P[8], G2P[4], G3P[8], G4P[8], and G9P[8]). In the current study, we sequenced the genomes of 11 G4P[8] isolates from stool specimens that were collected in Washington, DC during the years of 1974-1991. We found that the VP7-VP4-VP6-VP1-VP2-VP3-NSP1-NSP2-NSP3-NSP4-NSP5/6-encoding genes of all 11 G4P[8] RVs have the genotypes of G4-P[8]-I1-R1-C1-M1-A1-N1-T1-E1-H1. By constructing phylogenetic trees for each gene, extensive intra-genotypic diversity was revealed among the G4P[8] RVs, and new sub-genotype gene alleles were identified. Several of these alleles are nearly identical to those of G3P[8] isolates previously sequenced from this same Washington, DC collection, strongly suggesting that the RVs underwent gene reassortment. On the other hand, we observed that some G4P[8] RVs exhibit completely different allele-based genome constellations, despite being collected during the same epidemic season; there was no evidence of gene reassortment between these strains. This observation extends our previous findings and supports the notion that stable, genetically-distinct clades of human RVs with the same G/P-type can co-circulate in a community. Interestingly, the sub-genotype gene alleles found in some of the DC RVs share a close evolutionary relationship with genes of more contemporary human strains. Thus, archival human RVs sequenced in this study might represent evolutionary precursors to modern-day strains. PMID:21712102

Detection and genotyping of group A rotaviruses isolated from sewage samples in Monastir, Tunisia between April 2007 and April 2010.

PubMed

Hassine-Zaafrane, M; Kaplon, J; Ben Salem, I; Sdiri-Loulizi, K; Sakly, N; Pothier, P; Aouni, M; Ambert-Balay, K

2015-11-01

To ascertain the viral load, the distribution of G and P types of group A rotaviruses (RV-A) in sewage samples and to compare strains in clinical, animal and environmental samples. During our study from April 2007 to April 2010, 518 samples of raw and treated sewage were collected from two biological sewage treatment plants (STPs) located in the Monastir region, Tunisia. RV-A was detected by real-time RT-PCR in 375 (72·4%) sewage samples. According to the quantification results of RV-A, it appears that the viral load in raw and treated sewage of the two STPs was quite similar (P = 0·735). The genotyping of RV-A strains detected in sewage samples showed a great diversity with 10 G types and 8 P types. Most of them were described as common in humans, but we also detected genotypes commonly found in animals. All the genotypes detected in two previous studies performed in our laboratory on clinical and bovine samples were also found in environmental samples. However, some genotypes commonly found in animal were only found in sewage samples. The comparison of environmental, clinical and animal data suggests that STPs may convey not only human sewage but also animal wastes, both of them contaminated with numerous RV-A strains which are not efficiently eliminated by the sewage treatment process and may spread to surface waters. This work demonstrates the potential release of human and animal RV-A into water sources, representing a public health risk, by inducing gastroenteritis in population, but also by increasing the risk of zoonotic transmission and formation of reassortant viruses which could get a higher infectious potential. Our findings also suggest that monitoring of sewage may provide an additional tool to determine the epidemiology of RV-A circulating in a given community. © 2015 The Society for Applied Microbiology.

A cost effectiveness and capacity analysis for the introduction of universal rotavirus vaccination in Kenya: comparison between Rotarix and RotaTeq vaccines.

PubMed

van Hoek, Albert Jan; Ngama, Mwanajuma; Ismail, Amina; Chuma, Jane; Cheburet, Samuel; Mutonga, David; Kamau, Tatu; Nokes, D James

2012-01-01

Diarrhoea is an important cause of death in the developing world, and rotavirus is the single most important cause of diarrhoea associated mortality. Two vaccines (Rotarix and RotaTeq) are available to prevent rotavirus disease. This analysis was undertaken to aid the decision in Kenya as to which vaccine to choose when introducing rotavirus vaccination. Cost-effectiveness modelling, using national and sentinel surveillance data, and an impact assessment on the cold chain. The median estimated incidence of rotavirus disease in Kenya was 3015 outpatient visits, 279 hospitalisations and 65 deaths per 100,000 children under five years of age per year. Cumulated over the first five years of life vaccination was predicted to prevent 34% of the outpatient visits, 31% of the hospitalizations and 42% of the deaths. The estimated prevented costs accumulated over five years totalled US$1,782,761 (direct and indirect costs) with an associated 48,585 DALYs. From a societal perspective Rotarix had a cost-effectiveness ratio of US$142 per DALY (US$5 for the full course of two doses) and RotaTeq US$288 per DALY ($10.5 for the full course of three doses). RotaTeq will have a bigger impact on the cold chain compared to Rotarix. Vaccination against rotavirus disease is cost-effective for Kenya irrespective of the vaccine. Of the two vaccines Rotarix was the preferred choice due to a better cost-effectiveness ratio, the presence of a vaccine vial monitor, the requirement of fewer doses and less storage space, and proven thermo-stability.

Pharmacoeconomic spotlight on rotavirus vaccine RIX4414 (Rotarix™) in developed countries.

PubMed

Plosker, Greg L

2012-12-01

The most common cause of severe diarrhea in infants and young children is rotavirus gastroenteritis (RVGE), which is associated with significant morbidity, healthcare resource use, and direct and indirect costs in industrialized nations. The monovalent rotavirus vaccine RIX4414 (Rotarix™) is administered as a two-dose oral series in infants and has demonstrated protective efficacy against RVGE in clinical trials conducted in developed countries. In addition, various naturalistic studies have demonstrated 'real-world' effectiveness after the introduction of widespread rotavirus vaccination programs in the community setting. Numerous cost-effectiveness analyses have been conducted in developed countries in which a universal rotavirus vaccination program using RIX4414 was compared with no universal rotavirus vaccination program. There was a high degree of variability in base-case results across studies even when the studies were conducted in the same country, often reflecting differences in the selection of data sources or assumptions used to populate the models. In addition, results were sensitive to plausible changes in a number of key input parameters. As such, it is not possible to definitively state whether a universal rotavirus vaccination program with RIX4414 is cost effective in developed countries, although results of some analyses in some countries suggest this is the case. In addition, international guidelines advocate universal vaccination of infants and children against rotavirus. It is also difficult to draw conclusions regarding the cost effectiveness of rotavirus vaccine RIX4414 relative to that of the pentavalent rotavirus vaccine, which is administered as a three-dose oral series. Although indirect comparisons in cost-effectiveness analyses indicate that RIX4414 provided more favorable incremental cost-effectiveness ratios when each vaccine was compared with no universal rotavirus vaccination program, results were generally sensitive to vaccine costs. Actual tender prices of a full vaccination course for each vaccine were not known at the time of the analyses and therefore had to be estimated.

Hospitalization of childhood rotavirus infection from Kuala Lumpur, Malaysia.

PubMed

Lee, W S; Veerasingam, P D; Goh, A Y T; Chua, K B

2003-01-01

To determine the epidemiology of rotavirus gastroenteritis in children admitted to an urban hospital in a developing country from South-East Asia. Retrospective review of cases of acute gastroenteritis admitted to the children's ward of the University of Malaya Medical Centre, Kuala Lumpur, Malaysia, between 1996 and 1999. During the study period, 333 cases (24%) of 1362 stool samples, obtained from children admitted with acute diarrhoea, were positive for rotavirus. Acute gastroenteritis constituted 8.2%, and rotavirus infection 1.6% of all the paediatric admissions each year. Of the 271 cases analysed, 72% of the affected population were less than 2 years of age. Peak incidence of admissions was between January to March, and September to October. Dehydration was common (92%) but electrolyte disturbances, lactose intolerance (5.2%), prolonged diarrhoea (2.6%) and cow's milk protein intolerance was uncommon. No deaths were recorded. Rotavirus infection was a common cause of childhood diarrhoea that required hospital admission in an urban setting in Malaysia.

Rotarix: a rotavirus vaccine for the world.

PubMed

Ward, Richard L; Bernstein, David I

2009-01-15

Single rotavirus infections have been reported to protect humans against subsequent illnesses caused by both homotypic and heterotypic rotaviruses. On the basis of these observations, a G1P[8] strain of human rotavirus named 89-12 was attenuated by multiple passages in cell culture and was developed into a vaccine candidate (herein referred to as the RIX4414 vaccine). This vaccine is currently licensed in >100 countries worldwide, many of which have a universal recommendation for all infants. The US Food and Drug Administration approved the RIX4414 vaccine for use in the United States in April 2008. This vaccine has been found to provide a reduction in the incidence of severe rotavirus disease of >80% in all trials including a developing country. No increased risk of intussusception has been associated with this vaccine, nor has the vaccine been found to interfere with responses to other routine immunizations. This article describes the history of the development of the RIX4414 vaccine.

The Control of Rotavirus Gastroenteritis in The United States

PubMed Central

Glass, Roger I.; Parashar, Umesh; Patel, Manish; Tate, Jacqueline; Jiang, Baoming; Gentsch, Jon

2012-01-01

Since 2006, two new vaccines have been licensed to prevent rotavirus, the cause of 20% to 50% of severe acute gastroenteritis in young children worldwide. These vaccines have been implemented in national immunization programs in about 30 high- and middle-income countries, including the United States, and vaccine use has led to substantial decreases in diarrhea-related health care visits. In addition to reductions in diarrhea burden in vaccinated children, decreases have been observed in older, unvaccinated age groups in many settings, suggesting indirect benefits (i.e., herd immunity) from vaccination. Although the efficacy of these oral rotavirus vaccines is expectedly lower in developing countries in Asia and Africa, the public health benefits of vaccination in these settings, where more than 90% of the estimated 453,000 annual deaths from rotavirus occur, are likely to be substantial. Efforts continue to develop alternative rotavirus vaccines that could have a better efficacy and safety profile and may be less expensive. PMID:23303967

Effective prophylaxis against rotavirus diarrhea using a combination of Lactobacillus rhamnosus GG and antibodies

PubMed Central

Pant, Neha; Marcotte, Harold; Brüssow, Harald; Svensson, Lennart; Hammarström, Lennart

2007-01-01

Background Rotavirus is a worldwide cause of infectious infantile diarrhea that claims over 600,000 lives annually. Recently, two new vaccine candidates have been developed but their efficacy in developing countries, still remains to be proven. Oral delivery of specific immunoglobulins provides passive immunity and is a fast acting treatment for rotavirus diarrhea. Probiotic bacteria have also gained considerable attention lately as treatment for rotavirus diarrhea. Here we report an evaluation of the therapeutic potential of different probiotics and their combination with anti – rotavirus antibodies in a mouse model of rotavirus diarrhea. Results Of the six probiotic bacteria tested, Lactobacillus rhamnosus strain GG had the strongest influence in reducing prevalence, duration and severity of diarrhea and was therefore chosen for combination treatment with immunoglobulins. The combination treatment reduced the diarrhea outcome measures significantly, prevented histopathological changes and reduced the virus load in the intestines. Conclusion The advantages associated with immunoglobulins and probiotics based therapy is that the treatment provides a rapid therapeutic effect and is cost efficient. These components do not require special storage conditions and could potentially complement the rehydration therapy that is currently used. PMID:17900343

Heterogeneity of Rotavirus Vaccine Efficacy Among Infants in Developing Countries.

PubMed

Gruber, Joann F; Hille, Darcy A; Liu, G Frank; Kaplan, Susan S; Nelson, Micki; Goveia, Michelle G; Mast, T Christopher

2017-01-01

Rotavirus is the leading cause of severe diarrhea worldwide in young children. Although rotavirus vaccine efficacy is high in developed countries, efficacy is lower in developing countries. Here, we investigated heterogeneity of rotavirus vaccine efficacy by infant characteristics in developing countries. An exploratory, post hoc analysis was conducted using randomized controlled trial data of the pentavalent rotavirus vaccine (RV5) conducted in Africa and Asia (NCT00362648). Infants received either 3 doses of vaccine/placebo and were followed for up to 2 years. Within subgroups, vaccine efficacies and 95% confidence intervals (CIs) against rotavirus gastroenteritis (RVGE) were estimated using Poisson regression. We assessed heterogeneity of efficacy by age at first dose, gender, breastfeeding status and nutrition status. African children receiving the first dose at <8 weeks had lower efficacy (23.7%; 95% CI: -8.2%-46.3%) than those vaccinated at ≥8 weeks (59.1%; 95% CI: 34.0%-74.6%). Marginally statistically significant differences were observed by age at first dose, gender and underweight status in Ghana and gender in Asian countries. Heterogeneity of efficacy was observed for age at first dose in African countries. This was an exploratory analysis; additional studies are needed to validate these results.

Prospective evaluation of indirect costs due to acute rotavirus gastroenteritis in Spain: the ROTACOST study.

PubMed

Bouzón-Alejandro, Marta; Redondo-Collazo, Lorenzo; Sánchez-Lastres, Juan Manuel; Martinón-Torres, Nazareth; Martinón-Sánchez, José María; Martinón-Torres, Federico

2011-09-14

The effect of rotavirus in developed countries is mainly economic. This study aimed to assess the indirect costs induced by rotavirus acute gastroenteritis (RVAGE) in Spain. A prospective observational study was conducted from October 2008 to June 2009. It included 682 children up to 5 years of age with acute gastroenteritis (AGE) who attended primary care (n = 18) and emergency room/hospital settings (n = 10), covering the regions of Galicia and Asturias (North-west Spain). All non-medical expenses incurred throughout the episode were recorded in detail using personal interviews and telephone contact. Among the 682 enrolled children, 207 (30.4%) were rotavirus positive and 170 (25%) had received at least one dose of rotavirus vaccine. The mean (standard deviation) indirect cost caused by an episode of AGE was estimated at 135.17 (182.70) Euros. Costs were 1.74-fold higher when AGE was caused by rotavirus compared with other etiologies: 192.7 (219.8) Euros vs. 111.6 (163.5) Euros (p < .001). The costs for absenteeism were the most substantial with a mean of 91.41 (134.76) Euros per family, resulting in a loss of 2.45 (3.17) days of work. In RVAGE patients, the absenteeism cost was 120.4 (154) Euros compared with 75.8 (123) for the other etiologies (p = .002), because of loss of 3.5 (3.6) vs 1.9 (2.9) days of work (p < .001). Meals costs were 2-fold-higher (48.5 (55) vs 24.3 (46) Euros, p < .001) and travel costs were 2.6-fold-higher (32 (92) vs 12.5 (21.1) Euros, p = .005) in RVAGE patients compared with those with other etiologies. There were no differences between RVAGE and other etiologies groups regarding costs of hiring of caregivers or purchase of material. Patients with RVAGE were admitted to hospital more frequently than those with other etiologies (47.8% vs 14%, p < .001). Rotavirus generates a significant indirect economic burden. Our data should be considered in the decision-making process of the eventual inclusion of rotavirus vaccine in the national immunization schedule of well developed countries.

A Prospective Hospital-based Surveillance to Estimate Rotavirus Disease Burden in Bhutanese Children under 5 Years of Age.

PubMed

Wangchuk, Sonam; Dorji, Tshering; Tsheten; Tshering, Karchung; Zangmo, Sangay; Pem Tshering, Kunzang; Dorji, Tandin; Nishizono, Akira; Ahmed, Kamruddin

2015-03-01

As part of efforts to develop an informed policy for rotavirus vaccination, this prospective study was conducted to estimate the burden of rotavirus diarrhea among children less than 5 years old attended to the Department of Pediatrics, Jigme Dorji Wangchuk National Referral Hospital (JDWNRH), Thimphu, Bhutan. The duration of the study was three years, extending from February 2010 through December 2012. We estimated the frequency of hospitalization in the pediatric ward and dehydration treatment unit (DTU) for diarrhea and the number of events attributable to rotavirus infection among children under 5 years of age. During the study period, a total of 284 children (1 in 45) were hospitalized in the pediatric ward, and 2,220 (1 in 6) in the DTU with diarrhea among children residing in the Thimphu district. Group A rotavirus was detected in 32.5% and 18.8% of the stool samples from children hospitalized in the pediatric ward, respectively. Overall, 22.3% of the stool samples were rotavirus-positive, and the majority (90.8%) of them was detected in children under 2 years of age. From this study, we estimated that the annual incidence of hospitalization in the pediatric ward and DTU due to rotavirus diarrhea was 2.4/1000 (95% CI 1.7-3.4) and 10.8/1000 (95% CI 9.1-12.7) children, respectively. This study revealed that rotavirus is a major cause of diarrhea in Bhutanese children in Thimphu district and since no study has been performed previously, represents an important finding for policy discussions regarding the adoption of a rotavirus vaccine in Bhutan.

Changing epidemiology of rotavirus G-types circulating in Hong Kong, China.

PubMed

Lo, Janice Yee Chi; Szeto, Kai Cheung; Tsang, Dominic Ngai Chong; Leung, Kwok Hung; Lim, Wilina Wei Ling

2005-01-01

Group A rotaviruses are the most common cause of severe diarrhoeal disease in young children worldwide. The development of a vaccine is advocated by the World Health Organization. Obtaining local baseline information regarding rotavirus strain variation is important to ensure matching of circulating and vaccine strains. The current study was undertaken to determine the epidemiology of rotavirus G-types in Hong Kong in anticipation of a vaccination program. From 2001 to 2002 over a period of one year, diarrhoeal stool specimens known to be positive for rotavirus were subjected to G-typing by reverse transcriptase-polymerase chain reaction using nested type-specific primers. Rotavirus G-type distribution was correlated with patient demographics. Among 747 rotavirus positive stool specimens, 723 strains could be G-typed as G1 (302, 40.4%), G2 (128, 17.1%), G3 (231, 30.9%), G4 (24, 3.2%), and G9 (38, 5.1%). G1 strains were found predominantly in those 5 years old or younger (P < 0.0001), while G2 strains were more prevalent among those over 5 years of age (P < 0.001). When compared with similar studies in 1983 to 1984 and 1999 to 2000, there were significant changes in the prevalence of various G-types, with consistent detection of G9 strains in the current study. It is concluded that rotavirus G-type distribution in Hong Kong has varied with time. Continuous monitoring of the epidemiology of rotavirus is important, especially in anticipation of the introduction of a vaccine, in order to document its impact and to ensure its continued effectiveness. Copyright 2005 Wiley-Liss, Inc.

Burden of paediatric Rotavirus Gastroenteritis (RVGE) and potential benefits of a universal Rotavirus vaccination programme with a pentavalent vaccine in Spain

PubMed Central

2010-01-01

Background Rotavirus is the most common cause of gastroenteritis in young children worldwide. The aim of the study was to assess the health outcomes and the economic impact of a universal rotavirus vaccination programme with RotaTeq, the pentavalent rotavirus vaccine, versus no vaccination programme in Spain. Methods A birth cohort was followed up to the age of 5 using a cohort model. Epidemiological parameters were taken from the REVEAL study (a prospective epidemiological study conducted in Spain, 2004-2005) and from the literature. Direct and indirect costs were assessed from the national healthcare payer and societal perspectives by combining health care resource utilisation collected in REVEAL study and unit costs from official sources. RotaTeq per protocol efficacy data was taken from a large worldwide rotavirus clinical trial (70,000 children). Health outcomes included home care cases, General Practioner (GP)/Paediatrician, emergency department visits, hospitalisations and nosocomial infections. Results The model estimates that the introduction of a universal rotavirus vaccination programme with RotaTeq (90% coverage rate) would reduce the rotavirus gastroenteritis (RVGE) burden by 75% in Spain; 53,692 home care cases, 35,187 GP/Paediatrician visits, 34,287 emergency department visits, 10,987 hospitalisations and 2,053 nosocomial infections would be avoided. The introduction of RotaTeq would avoid about 76% of RVGE-related costs from both perspectives: €22 million from the national health system perspective and €38 million from the societal perspective. Conclusions A rotavirus vaccination programme with RotaTeq would reduce significantly the important medical and economic burden of RVGE in Spain. PMID:20698958

Cost-effectiveness analysis of diarrhoea management approaches in Nigeria: A decision analytical model

PubMed Central

Ekwunife, Obinna I.

2017-01-01

Background Diarrhoea is a leading cause of death in Nigerian children under 5 years. Implementing the most cost-effective approach to diarrhoea management in Nigeria will help optimize health care resources allocation. This study evaluated the cost-effectiveness of various approaches to diarrhoea management namely: the ‘no treatment’ approach (NT); the preventive approach with rotavirus vaccine; the integrated management of childhood illness for diarrhoea approach (IMCI); and rotavirus vaccine plus integrated management of childhood illness for diarrhoea approach (rotavirus vaccine + IMCI). Methods Markov cohort model conducted from the payer’s perspective was used to calculate the cost-effectiveness of the four interventions. The markov model simulated a life cycle of 260 weeks for 33 million children under five years at risk of having diarrhoea (well state). Disability adjusted life years (DALYs) averted was used to quantify clinical outcome. Incremental cost-effectiveness ratio (ICER) served as measure of cost-effectiveness. Results Based on cost-effectiveness threshold of $2,177.99 (i.e. representing Nigerian GDP/capita), all the approaches were very cost-effective but rotavirus vaccine approach was dominated. While IMCI has the lowest ICER of $4.6/DALY averted, the addition of rotavirus vaccine was cost-effective with an ICER of $80.1/DALY averted. Rotavirus vaccine alone was less efficient in optimizing health care resource allocation. Conclusion Rotavirus vaccine + IMCI approach was the most cost-effective approach to childhood diarrhoea management. Its awareness and practice should be promoted in Nigeria. Addition of rotavirus vaccine should be considered for inclusion in the national programme of immunization. Although our findings suggest that addition of rotavirus vaccine to IMCI for diarrhoea is cost-effective, there may be need for further vaccine demonstration studies or real life studies to establish the cost-effectiveness of the vaccine in Nigeria. PMID:29261649

Genetic diversity of G1P[8] rotavirus VP7 and VP8* antigens in Finland over a 20-year period: No evidence for selection pressure by universal mass vaccination with RotaTeq® vaccine.

PubMed

Hemming, Maria; Vesikari, Timo

2013-10-01

Two live-attenuated oral vaccines (Rotarix™ and Rotateq®) against rotavirus gastroenteritis were licensed in 2006 and have been introduced into National Immunization Programs (NIPs) of several countries. Large scale use of rotavirus vaccines might cause antigenic pressure on circulating rotavirus types or lead to selection of new rotaviruses thus decreasing vaccine efficacy. We examined the nucleotide and amino acid sequences of the surface proteins VP7 and VP4 (cleaved to VP8(*) and VP5(*)) of a total of 108 G1P[8] rotavirus strains collected over a 20-year period from 1992, including the years 2006-2009 when rotavirus vaccine (mainly Rotarix™) was available, and the years 2009-2012 after implementation of RotaTeq® vaccine into the NIP of Finland. In G1 VP7 no changes at amino acid level were observed. In VP8(*) periodical fluctuation of the sublineage over the study period was found with multiple changes both at nucleotide and amino acid levels. Most amino acid changes were in the dominant antigenic epitopes of VP8(*). A change in VP8(*) sublineage occurred between 2008 and 2009, with a temporal correlation to the use of Rotarix™ up to 30% coverage in the period. In contrast, no antigenic changes in the VP8(*) protein appeared to be correlated to the exclusive use of RotaTeq® vaccine after 2009. Nevertheless, long-term surveillance of antigenic changes in VP4 and also VP7 proteins in wild-type rotavirus strains is warranted in countries with large scale use of the currently licensed live oral rotavirus vaccines. Copyright © 2013 Elsevier B.V. All rights reserved.

Rotavirus Vaccine will Improve Child Survival by More than Just Preventing Diarrhea: Evidence from Bangladesh.

PubMed

Saha, Senjuti; Santosham, Mathuram; Hussain, Manzoor; Black, Robert E; Saha, Samir K

2018-02-01

Despite the high burden of rotavirus diarrhea, uptake of rotavirus vaccines in Asia remains low. This primarily stems from a perception of rotavirus as a non-life-threatening pathogen amidst a background of competing health priorities and limited resources. In the largest pediatric hospital of Bangladesh, where there is a fierce competition for beds, we found that between November 2015 and October 2016, 12% of 23,064 admissions were due to gastrointestinal infections, 54% of which were caused by rotavirus. One in four cases requiring hospitalization, or 5,879 cases, was refused because of unavailability of beds. Most refused cases were of pneumonia (22%), severe perinatal asphyxia (17%), preterm birth complications (7%), and meningitis (2%), all of which bear high risks of death or disability, if not treated timely. When determining vaccine policies and conducting vaccine impact studies, it would be shortsighted to not consider the impact on morbidity and mortality of cases that are refused admission because of the hospitalization of children with a preventable disease as rotavirus diarrhea. In our hospital, routine use of a rotavirus vaccine with 41% efficacy will release 629 beds per year to accommodate previously refused cases. Based on evidence, we make the case that introduction of this vaccine in Bangladesh and the surrounding region will prevent morbidity and mortality, both directly and indirectly, and help us ensure survival and well-being of all children.

Structure-function analysis of rotavirus NSP2 octamer by using a novel complementation system.

PubMed

Taraporewala, Zenobia F; Jiang, Xiaofang; Vasquez-Del Carpio, Rodrigo; Jayaram, Hariharan; Prasad, B V Venkataram; Patton, John T

2006-08-01

Viral inclusion bodies, or viroplasms, that form in rotavirus-infected cells direct replication and packaging of the segmented double-stranded RNA (dsRNA) genome. NSP2, one of two rotavirus proteins needed for viroplasm assembly, possesses NTPase, RNA-binding, and helix-unwinding activities. NSP2 of the rotavirus group causing endemic infantile diarrhea (group A) was shown to self-assemble into large doughnut-shaped octamers with circumferential grooves and deep clefts containing nucleotide-binding histidine triad (HIT)-like motifs. Here, we demonstrate that NSP2 of group C rotavirus, a group that fails to reassort with group A viruses, retains the unique architecture of the group A octamer but differs in surface charge distribution. By using an NSP2-dependent complementation system, we show that the HIT-dependent NTPase activity of NSP2 is necessary for dsRNA synthesis, but not for viroplasm formation. The complementation system also showed that despite the retention of the octamer structure and the HIT-like fold, group C NSP2 failed to rescue replication and viroplasm formation in NSP2-deficient cells infected with group A rotavirus. The distinct differences in the surface charges on the Bristol and SA11 NSP2 octamers suggest that charge complementarity of the viroplasm-forming proteins guides the specificity of viroplasm formation and, possibly, reassortment restriction between rotavirus groups.

Rotavirus gastroenteritis in children under 5 years in the Kingdom of Bahrain: hospital-based surveillance

PubMed Central

Musawi, Muna Al; Zainaldeen, Hassan; Shafi, Fakrudeen; Anis, Sameh; DeAntonio, Rodrigo

2013-01-01

Purpose Rotavirus (RV) is the leading cause of morbidity and mortality in children under 5 years of age worldwide. This study assessed the role of RV as a cause of gastroenteritis (GE)-associated hospitalization in children, generating baseline information to evaluate the potential impact of the RV vaccine in reducing RVGE disease burden in the Kingdom of Bahrain. Methods This single, pediatric hospital-based surveillance study was conducted over a period of 12 months beginning April 1, 2006. A total of 314 children aged under 5 years and hospitalized due to GE were enrolled in the study, following collection of written informed consent from parents/guardians. Stool samples were tested for the presence of RV using enzyme immunoassay, and a random subset of RV-positive samples was further genotyped using reverse transcriptase-polymerase chain reaction and reverse hybridization assay. Results Of 314 enrolled children, 239 were included in the final analysis. RV was detected in 107 children (44.8%), mostly in the 6–23 months age group (82/107; 76.6%). RVGE occurred throughout the year, with the highest proportion occurring during April (26/42; 61.9%). G1P[8[ was the most commonly detected RV strain (10/17; 58.8%) in the limited number of samples analyzed. Vomiting and severe RVGE were more commonly observed in RV-positive than RV-negative children before hospitalization (P = 0.0008 and 0.0204, respectively). Conclusion In our study, RV accounted for over 40% of GE-associated hospitalizations and particularly affected children under 2 years of age. These data will serve as a baseline for assessing the potential changes in the epidemiology of RV disease and for evaluating the potential impact of the introduction of RV vaccination. PMID:23950659

Impact of community-acquired paediatric rotavirus gastroenteritis on family life: data from the REVEAL study.

PubMed

Van der Wielen, Marie; Giaquinto, Carlo; Gothefors, Leif; Huelsse, Christel; Huet, Frédéric; Littmann, Martina; Maxwell, Melanie; Talayero, José M P; Todd, Peter; Vila, Miguel T; Cantarutti, Luigi; Van Damme, Pierre

2010-03-15

Rotavirus is the leading cause of acute gastroenteritis (AGE) and the most frequent cause of severe diarrhoea in children aged less than 5 years. Although the epidemiology of rotavirus gastroenteritis (RVGE) is well documented, there are few data on the impact of RVGE on the families of affected children. Data associated with the burden of RVGE, including number of working days lost, levels of parental stress, the need for alternative childcare arrangements and additional nappies used, were extracted from questionnaires completed by parents of children participating in a prospective, multicentre, observational study (Rotavirus gastroenteritis Epidemiology and Viral types in Europe Accounting for Losses in public health and society, REVEAL), conducted during 2004-2005 in selected areas of Belgium, France, Germany, Italy, Spain, Sweden, and the United Kingdom to estimate the incidence of RVGE in children aged less than 5 years seeking medical care as a result of AGE. 1102 children with RVGE were included in the present analysis. The proportion of RVGE cases that required at least one parent or other person to be absent from work was 39%-91% in the hospital setting, 44%-64% in the emergency department, and 20%-64% in primary care. Self-reported levels of parental stress were generally high (mean stress levels, > or = 5 on a 10-point visual analogue scale). Additional childcare arrangements were required in up to 21% of RVGE episodes. The mean number of nappies used per day during RVGE episodes was approximately double that used when the child was not ill. Paediatric RVGE cases cause disruption to families and parental stress. The burden of RVGE on children and their families could be substantially reduced by routine rotavirus vaccination of infants.

Impact of community-acquired paediatric rotavirus gastroenteritis on family life: data from the REVEAL study

PubMed Central

2010-01-01

Background Rotavirus is the leading cause of acute gastroenteritis (AGE) and the most frequent cause of severe diarrhoea in children aged less than 5 years. Although the epidemiology of rotavirus gastroenteritis (RVGE) is well documented, there are few data on the impact of RVGE on the families of affected children. Methods Data associated with the burden of RVGE, including number of working days lost, levels of parental stress, the need for alternative childcare arrangements and additional nappies used, were extracted from questionnaires completed by parents of children participating in a prospective, multicentre, observational study (Rotavirus gastroenteritis Epidemiology and Viral types in Europe Accounting for Losses in public health and society, REVEAL), conducted during 2004-2005 in selected areas of Belgium, France, Germany, Italy, Spain, Sweden, and the United Kingdom to estimate the incidence of RVGE in children aged less than 5 years seeking medical care as a result of AGE. Results 1102 children with RVGE were included in the present analysis. The proportion of RVGE cases that required at least one parent or other person to be absent from work was 39%-91% in the hospital setting, 44%-64% in the emergency department, and 20%-64% in primary care. Self-reported levels of parental stress were generally high (mean stress levels, ≥ 5 on a 10-point visual analogue scale). Additional childcare arrangements were required in up to 21% of RVGE episodes. The mean number of nappies used per day during RVGE episodes was approximately double that used when the child was not ill. Conclusions Paediatric RVGE cases cause disruption to families and parental stress. The burden of RVGE on children and their families could be substantially reduced by routine rotavirus vaccination of infants. PMID:20230601

A Cost Effectiveness and Capacity Analysis for the Introduction of Universal Rotavirus Vaccination in Kenya: Comparison between Rotarix and RotaTeq Vaccines

PubMed Central

van Hoek, Albert Jan; Ngama, Mwanajuma; Ismail, Amina; Chuma, Jane; Cheburet, Samuel; Mutonga, David; Kamau, Tatu; Nokes, D. James

2012-01-01

Background Diarrhoea is an important cause of death in the developing world, and rotavirus is the single most important cause of diarrhoea associated mortality. Two vaccines (Rotarix and RotaTeq) are available to prevent rotavirus disease. This analysis was undertaken to aid the decision in Kenya as to which vaccine to choose when introducing rotavirus vaccination. Methods Cost-effectiveness modelling, using national and sentinel surveillance data, and an impact assessment on the cold chain. Results The median estimated incidence of rotavirus disease in Kenya was 3015 outpatient visits, 279 hospitalisations and 65 deaths per 100,000 children under five years of age per year. Cumulated over the first five years of life vaccination was predicted to prevent 34% of the outpatient visits, 31% of the hospitalizations and 42% of the deaths. The estimated prevented costs accumulated over five years totalled US$1,782,761 (direct and indirect costs) with an associated 48,585 DALYs. From a societal perspective Rotarix had a cost-effectiveness ratio of US$142 per DALY (US$5 for the full course of two doses) and RotaTeq US$288 per DALY ($10.5 for the full course of three doses). RotaTeq will have a bigger impact on the cold chain compared to Rotarix. Conclusion Vaccination against rotavirus disease is cost-effective for Kenya irrespective of the vaccine. Of the two vaccines Rotarix was the preferred choice due to a better cost-effectiveness ratio, the presence of a vaccine vial monitor, the requirement of fewer doses and less storage space, and proven thermo-stability. PMID:23115650

A Point Mutation in the Rhesus Rotavirus VP4 Protein Generated through a Rotavirus Reverse Genetics System Attenuates Biliary Atresia in the Murine Model.

PubMed

Mohanty, Sujit K; Donnelly, Bryan; Dupree, Phylicia; Lobeck, Inna; Mowery, Sarah; Meller, Jaroslaw; McNeal, Monica; Tiao, Greg

2017-08-01

Rotavirus infection is one of the most common causes of diarrheal illness in humans. In neonatal mice, rhesus rotavirus (RRV) can induce biliary atresia (BA), a disease resulting in inflammatory obstruction of the extrahepatic biliary tract and intrahepatic bile ducts. We previously showed that the amino acid arginine (R) within the sequence SRL (amino acids 445 to 447) in the RRV VP4 protein is required for viral binding and entry into biliary epithelial cells. To determine if this single amino acid (R) influences the pathogenicity of the virus, we generated a recombinant virus with a single amino acid mutation at this site through a reverse genetics system. We demonstrated that the RRV mutant (RRV VP4-R446G ) produced less symptomatology and replicated to lower titers both in vivo and in vitro than those seen with wild-type RRV, with reduced binding in cholangiocytes. Our results demonstrate that a single amino acid change in the RRV VP4 gene influences cholangiocyte tropism and reduces pathogenicity in mice. IMPORTANCE Rotavirus is the leading cause of diarrhea in humans. Rhesus rotavirus (RRV) can also lead to biliary atresia (a neonatal human disease) in mice. We developed a reverse genetics system to create a mutant of RRV (RRV VP4-R446G ) with a single amino acid change in the VP4 protein compared to that of wild-type RRV. In vitro , the mutant virus had reduced binding and infectivity in cholangiocytes. In vivo , it produced fewer symptoms and lower mortality in neonatal mice, resulting in an attenuated form of biliary atresia. Copyright © 2017 American Society for Microbiology.

Molecular epidemiology of rotavirus gastroenteritis in Central Kenya before vaccine introduction, 2009-2014.

PubMed

Wandera, Ernest A; Mohammad, Shah; Komoto, Satoshi; Maeno, Yoshimasa; Nyangao, James; Ide, Tomihiko; Kathiiko, Cyrus; Odoyo, Erick; Tsuji, Takao; Taniguchi, Koki; Ichinose, Yoshio

2017-05-01

Between July 2009 and June 2014, a total of 1,546 fecal specimens were collected from children <5 years of age with acute gastroenteritis admitted to Kiambu County Hospital, Central Kenya. The specimens were screened for group A rotavirus (RVA) using ELISA, and RVA-positive specimens were subjected to semi-nested RT-PCR to determine the G and P genotypes. RVA was detected in 429/1,546 (27.5%) fecal specimens. RVA infections occurred in all age groups <59 months, with an early peak at 6-17 months. The infections persisted year-round with distinct seasonal peaks depending on the year. G1P[8] (28%) was the most predominant genotype, followed by G9P[8] (12%), G8P[4] (7%), G1P[4] (5%), G9P[4] (4%), and G12P[6] (3%). In the yearly change of G and P genotypes, a major shift from G9P[8] to G1P[8] was found in 2012. Phylogenetic analysis of the nucleotide sequences of the VP7 and VP4 genes of seven strains with unusual G8 or P[6] showed that the VP7 nucleotide sequences of G8 were clustered in lineage 6 in which African strains are included, and that there are at least two distinct VP4 nucleotide sequences of P[6] strains. These results represent basic data on RVA strains circulating in this region before vaccine introduction. J. Med. Virol. 89:809-817, 2017. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

ROTAVIRUS GENOTYPES CIRCULATING IN BRAZIL, 2007-2012: IMPLICATIONS FOR THE VACCINE PROGRAM

PubMed Central

LUCHS, Adriana; CILLI, Audrey; MORILLO, Simone Guadagnucci; CARMONA, Rita de Cássia Compagnoli; TIMENETSKY, Maria do Carmo Sampaio Tavares

2015-01-01

SUMMARY Regarding public health in Brazil, a new scenario emerged with the establishment of universal rotavirus (RV) vaccination programs. Herein, the data from the five years of surveillance (2007-2012) of G- and P-type RV strains isolated from individuals with acute gastroenteritis in Brazil are reported. A total of 6,196 fecal specimens were investigated by ELISA and RT-PCR. RVs were detected in 19.1% (1,181/6,196). The peak of RV incidence moved from June-August to September. RV was detected less frequently (19.5%) among children ≤ 5 years than in older children and adolescents (6-18 years) (40.6%). Genotype distribution showed a different profile for each year: G2P[4] strains were most prevalent during 2007-2010, G9P[8] in 2011, and G12P[8] in 2012. Mixed infections (G1+G2P[4], G2+G3P[4]+P[8], G2+G12P[8]), unusual combinations (G1P[4], G2P[6]), and rare strains (G3P[3]) were also identified throughout the study period. Widespread vaccination may alter the RV seasonal pattern. The finding of RV disease affecting older children and adolescents after vaccine implementation has been reported worldwide. G2P[4] emergence most likely follows a global trend seemingly unrelated to vaccination, and G12, apparently, is emerging in the Brazilian population. The rapidly changing RV genotype patterns detected during this study illustrate a dynamic population of co-circulating wildtype RVs in Brazil. PMID:26422154

Impact and cost-effectiveness of rotavirus vaccination in Bangladesh.

PubMed

Pecenka, Clint; Parashar, Umesh; Tate, Jacqueline E; Khan, Jahangir A M; Groman, Devin; Chacko, Stephen; Shamsuzzaman, Md; Clark, Andrew; Atherly, Deborah

2017-07-13

Diarrheal disease is a leading cause of child mortality globally, and rotavirus is responsible for more than a third of those deaths. Despite substantial decreases, the number of rotavirus deaths in children under five was 215,000 per year in 2013. Of these deaths, approximately 41% occurred in Asia and 3% of those in Bangladesh. While Bangladesh has yet to introduce rotavirus vaccination, the country applied for Gavi support and plans to introduce it in 2018. This analysis evaluates the impact and cost-effectiveness of rotavirus vaccination in Bangladesh and provides estimates of the costs of the vaccination program to help inform decision-makers and international partners. This analysis used Pan American Health Organization's TRIVAC model (version 2.0) to examine nationwide introduction of two-dose rotavirus vaccination in 2017, compared to no vaccination. Three mortality scenarios (low, high, and midpoint) were assessed. Benefits and costs were examined from the societal perspective over ten successive birth cohorts with a 3% discount rate. Model inputs were locally acquired and complemented by internationally validated estimates. Over ten years, rotavirus vaccination would prevent 4000 deaths, nearly 500,000 hospitalizations and 3 million outpatient visits in the base scenario. With a Gavi subsidy, cost/disability adjusted life year (DALY) ratios ranged from $58/DALY to $142/DALY averted. Without a Gavi subsidy and a vaccine price of $2.19 per dose, cost/DALY ratios ranged from $615/DALY to $1514/DALY averted. The discounted cost per DALY averted was less than the GDP per capita for nearly all scenarios considered, indicating that a routine rotavirus vaccination program is highly likely to be cost-effective. Even in a low mortality setting with no Gavi subsidy, rotavirus vaccination would be cost-effective. These estimates exclude the herd immunity benefits of vaccination, so represent a conservative estimate of the cost-effectiveness of rotavirus vaccination in Bangladesh. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

Cost-Effectiveness of Monovalent Rotavirus Vaccination of Infants in Malawi: A Postintroduction Analysis Using Individual Patient–Level Costing Data

PubMed Central

Bar-Zeev, Naor; Tate, Jacqueline E.; Pecenka, Clint; Chikafa, Jean; Mvula, Hazzie; Wachepa, Richard; Mwansambo, Charles; Mhango, Themba; Chirwa, Geoffrey; Crampin, Amelia C.; Parashar, Umesh D.; Costello, Anthony; Heyderman, Robert S.; French, Neil; Atherly, Deborah; Cunliffe, Nigel A.

2016-01-01

Background. Rotavirus vaccination reduces childhood hospitalization in Africa, but cost-effectiveness has not been determined using real-world effectiveness and costing data. We sought to determine monovalent rotavirus vaccine cost-effectiveness in Malawi, one of Africa's poorest countries and the first Gavi-eligible country to report disease reduction following introduction in 2012. Methods. This was a prospective cohort study of children with acute gastroenteritis at a rural primary health center, a rural first referral–level hospital and an urban regional referral hospital in Malawi. For each participant we itemized household costs of illness and direct medical expenditures incurred. We also collected Ministry of Health vaccine implementation costs. Using a standard tool (TRIVAC), we derived cost-effectiveness. Results. Between 1 January 2013 and 21 November 2014, we recruited 530 children aged <5 years with gastroenteritis. Costs did not differ by rotavirus test result, but were significantly higher for admitted children and those with increased severity on Vesikari scale. Adding rotavirus vaccine to the national schedule costs Malawi $0.42 per dose in system costs. Vaccine copayment is an additional $0.20. Over 20 years, the vaccine program will avert 1 026 000 cases of rotavirus gastroenteritis, 78 000 inpatient admissions, 4300 deaths, and 136 000 disability-adjusted-life-years (DALYs). For this year's birth cohort, it will avert 54 000 cases of rotavirus and 281 deaths in children aged <5 years. The program will cost $10.5 million and save $8.0 million in averted healthcare costs. Societal cost per DALY averted was $10, and the cost per rotavirus case averted was $1. Conclusions. Gastroenteritis causes substantial economic burden to Malawi. The rotavirus vaccine program is highly cost-effective. Together with the demonstrated impact of rotavirus vaccine in reducing population hospitalization burden, its cost-effectiveness makes a strong argument for widespread utilization in other low-income, high-burden settings. PMID:27059360

Protein-energy malnutrition alters IgA responses to rotavirus vaccination and infection but does not impair vaccine efficacy in mice

PubMed Central

Maier, Elizabeth A.; Weage, Kristina J.; Guedes, Marjorie M; Denson, Lee A.; McNeal, Monica M.; Bernstein, David I.; Moore, Sean R.

2013-01-01

Background Conflicting evidence links malnutrition to the reduced efficacy of rotavirus vaccines in developing countries, where diarrhea and undernutrition remain leading causes of child deaths. Here, we adapted mouse models of rotavirus vaccination (rhesus rotavirus, RRV), rotavirus infection (EDIM), and protein-energy malnutrition (PEM) to test the hypothesis that undernutrition reduces rotavirus vaccine immunogenicity and efficacy. Methods We randomized wild type Balb/C dams with 3-day-old pups to a control diet (CD) or an isocaloric, multideficient regional basic diet (RBD) that produces PEM. At 3 weeks of age, we weaned CD and RBD pups to their dams’ diet and subrandomized weanlings to receive a single dose of either live oral rotavirus vaccine (RRV) or PBS. At 6 weeks of age, we orally challenged all groups with murine rotavirus (EDIM). Serum and stool specimens were collected before and after RRV and EDIM administration to measure viral shedding and antibody responses by ELISA. Results RBD pups and weanlings exhibited significant failure to thrive compared to age-matched CD mice (P<.0001). RRV vaccination induced higher levels of serum anti-RV IgA responses in RBD vs. CD mice (P<.0001). Vaccination protected CD and RBD mice equally against EDIM infection, as measured by viral shedding. In unvaccinated RBD mice, EDIM shedding peaked 1 day earlier (P<.05), however we detected no effects of undernutrition on viral clearance nor of infection on bodyweight. EDIM infection provoked higher anti-RV serum IgA levels in RBD vs. CD mice, regardless of vaccination (P<.0001). Last, RRV vaccination mitigated stool IgA responses to EDIM more in CD vs. RBD mice (P<.0001). Conclusions Despite modulated IgA responses to vaccination and infection, undernutrition does not impair rotavirus vaccine efficacy nor exacerbate infection in this mouse model of protein-energy malnutrition. Alternative models are needed to elucidate host-pathogen factors undermining rotavirus vaccine effectiveness in high-risk global settings. PMID:24200975

Cost-Effectiveness of Monovalent Rotavirus Vaccination of Infants in Malawi: A Postintroduction Analysis Using Individual Patient-Level Costing Data.

PubMed

Bar-Zeev, Naor; Tate, Jacqueline E; Pecenka, Clint; Chikafa, Jean; Mvula, Hazzie; Wachepa, Richard; Mwansambo, Charles; Mhango, Themba; Chirwa, Geoffrey; Crampin, Amelia C; Parashar, Umesh D; Costello, Anthony; Heyderman, Robert S; French, Neil; Atherly, Deborah; Cunliffe, Nigel A

2016-05-01

Rotavirus vaccination reduces childhood hospitalization in Africa, but cost-effectiveness has not been determined using real-world effectiveness and costing data. We sought to determine monovalent rotavirus vaccine cost-effectiveness in Malawi, one of Africa's poorest countries and the first Gavi-eligible country to report disease reduction following introduction in 2012. This was a prospective cohort study of children with acute gastroenteritis at a rural primary health center, a rural first referral-level hospital and an urban regional referral hospital in Malawi. For each participant we itemized household costs of illness and direct medical expenditures incurred. We also collected Ministry of Health vaccine implementation costs. Using a standard tool (TRIVAC), we derived cost-effectiveness. Between 1 January 2013 and 21 November 2014, we recruited 530 children aged <5 years with gastroenteritis. Costs did not differ by rotavirus test result, but were significantly higher for admitted children and those with increased severity on Vesikari scale. Adding rotavirus vaccine to the national schedule costs Malawi $0.42 per dose in system costs. Vaccine copayment is an additional $0.20. Over 20 years, the vaccine program will avert 1 026 000 cases of rotavirus gastroenteritis, 78 000 inpatient admissions, 4300 deaths, and 136 000 disability-adjusted-life-years (DALYs). For this year's birth cohort, it will avert 54 000 cases of rotavirus and 281 deaths in children aged <5 years. The program will cost $10.5 million and save $8.0 million in averted healthcare costs. Societal cost per DALY averted was $10, and the cost per rotavirus case averted was $1. Gastroenteritis causes substantial economic burden to Malawi. The rotavirus vaccine program is highly cost-effective. Together with the demonstrated impact of rotavirus vaccine in reducing population hospitalization burden, its cost-effectiveness makes a strong argument for widespread utilization in other low-income, high-burden settings. © The Author 2016. Published by Oxford University Press for the Infectious Diseases Society of America.

A systematic review of anti-rotavirus serum IgA antibody titer as a potential correlate of rotavirus vaccine efficacy.

PubMed

Patel, Manish; Glass, Roger I; Jiang, Baoming; Santosham, Mathuram; Lopman, Ben; Parashar, Umesh

2013-07-15

Identifying an immunological correlate of protection for rotavirus vaccines (Rotarix [RV1] and RotaTeq [RV5]) would substantially facilitate testing of interventions for improving efficacy in developing countries and evaluating additional candidate rotavirus vaccines. We accessed PubMed and ClinicalTrials.gov to identify immunogenicity and efficacy trials for RV1 and RV5 to correlate anti-rotavirus serum immunoglobulin A (IgA) antibody titers vs efficacy in regions stratified by all-cause under-5 mortality rates (u5MR). We established a cutoff point for IgA geometric mean concentration or titer (GMC) that predicted lower efficacy and calculated pooled vaccine efficacy among countries with high vs low IgA titers. We observed an inverse correlation between u5MR and IgA titers for RV1 (r(2) = 0.72; P < .001 and RV5 (r(2) = 0.66; P < .001) and between efficacy and IgA titers for both vaccines (r(2) = 0.56; P = .005). Postimmunization anti-rotavirus IgA GMC <90 were associated with decline in vaccine efficacy. Efficacy during first 2 years of life was significantly lower among countries with IgA GMC < 90 (44%; 95% confidence interval [CI], 30-55) compared to countries with GMC > 90 (85%; 95% CI, 82-88). We observed a significant correlation between IgA titers and rotavirus vaccine efficacy and hypothesize that a critical level of IgA antibody titer is associated with a sufficient level of sustained protection after rotavirus vaccination.

Astrovirus, reovirus and rotavirus concomitant infection causes decreased weight gain in broad-breasted white poults

USDA-ARS?s Scientific Manuscript database

Turkey astrovirus type-2 (TAstV-2), turkey rotavirus (TRotV) and turkey reovirus (TReoV) were evaluated for pathogenesis in 3 day-old turkey poults in all possible combinations of one, two or three viruses. Body-weights were recorded at 2, 4, 7, 10 and 14 days post inoculation (PI) and were decreas...

Chimaeric Virus-Like Particles Derived from Consensus Genome Sequences of Human Rotavirus Strains Co-Circulating in Africa

PubMed Central

Jere, Khuzwayo C.; O'Neill, Hester G.; Potgieter, A. Christiaan; van Dijk, Alberdina A.

2014-01-01

Rotavirus virus-like particles (RV-VLPs) are potential alternative non-live vaccine candidates due to their high immunogenicity. They mimic the natural conformation of native viral proteins but cannot replicate because they do not contain genomic material which makes them safe. To date, most RV-VLPs have been derived from cell culture adapted strains or common G1 and G3 rotaviruses that have been circulating in communities for some time. In this study, chimaeric RV-VLPs were generated from the consensus sequences of African rotaviruses (G2, G8, G9 or G12 strains associated with either P[4], P[6] or P[8] genotypes) characterised directly from human stool samples without prior adaptation of the wild type strains to cell culture. Codon-optimised sequences for insect cell expression of genome segments 2 (VP2), 4 (VP4), 6 (VP6) and 9 (VP7) were cloned into a modified pFASTBAC vector, which allowed simultaneous expression of up to four genes using the Bac-to-Bac Baculovirus Expression System (BEVS; Invitrogen). Several combinations of the genome segments originating from different field strains were cloned to produce double-layered RV-VLPs (dRV-VLP; VP2/6), triple-layered RV-VLPs (tRV-VLP; VP2/6/7 or VP2/6/7/4) and chimaeric tRV-VLPs. The RV-VLPs were produced by infecting Spodoptera frugiperda 9 and Trichoplusia ni cells with recombinant baculoviruses using multi-cistronic, dual co-infection and stepwise-infection expression strategies. The size and morphology of the RV-VLPs, as determined by transmission electron microscopy, revealed successful production of RV-VLPs. The novel approach of producing tRV-VLPs, by using the consensus insect cell codon-optimised nucleotide sequence derived from dsRNA extracted directly from clinical specimens, should speed-up vaccine research and development by by-passing the need to adapt rotaviruses to cell culture. Other problems associated with cell culture adaptation, such as possible changes in epitopes, can also be circumvented. Thus, it is now possible to generate tRV-VLPs for evaluation as non-live vaccine candidates for any human or animal field rotavirus strain. PMID:25268783

Qualitative Effects of Monovalent Vaccination Against Rotavirus: A Comparison of North America and South America.

PubMed

Young, Glenn; Shim, Eunha; Ermentrout, G Bard

2015-10-01

Rotavirus is the most common cause of severe gastroenteritis in young children worldwide. The introduction of vaccination programs has led to a significant reduction in number of hospitalizations due to rotavirus in North and South American countries. Little work has been done, however, to examine the differential impact of vaccination as a function of strain distribution and strain-specific vaccine efficacy. We developed a two-strain epidemiological model of rotavirus transmission, and used it to examine the effects of a monovalent vaccine (Rotarix) on the qualitative behaviors of infection levels in a population. For contrast, we parameterized our model with strain distribution data from North America and from South America. In all cases, the introduction of the vaccine led to significant decreases in the prevalence of primary infection due to both strains for a decade or more, after which the overall prevalence recovers to near pre-vaccination levels. The prevalence of G1P[8] is significantly higher in North America (73 % of all rotavirus infections) compared to that in South America (34 %). Our model predicts that the introduction of Rotarix might result in major strain replacement in regions such as North America where the prevalence of G1P[8] is relatively high, due to higher efficacy of Rotarix against infection caused by G1P[8], while regions with lower prevalence of G1P[8], such as South America, are not susceptible to major strain replacement.

Acute gastroenteritis associated with rotavirus in adults.

PubMed

del Refugio González-Losa, M; Polanco-Marín, G G; Manzano-Cabrera, L; Puerto-Solís, M

2001-01-01

Rotavirus (RV) is an important cause of acute infectious diarrhea in children all over the world. In adults, RV infection tends to be subclinical; however, outbreaks of gastroenteritis have been reported in emergency situations and in closed communities. The aim of this study was to characterize electrophoretically and antigenically the strains of rotavirus that caused acute gastroenteritis in adults and correlate them with the clinical manifestations. A laboratory-based survey was carried out in which fecal samples from 44 patients over 18 years of age with acute gastroenteritis were studied. Polyacrylamide gels electrophoresis and immunoenzymatic assay with specific antibodies to group A rotavirus, serotypes G1-4, P1A, and P1B were carried out on all the samples. Twenty-eight (63.63%) of the 44 samples were positive for group A rotavirus. Of these, 19 (68%) had long pattern and nine (32%) short pattern. Of all positive samples, 15 (54%) were serotype G1, seven (25%) were G2, two (7%) were G4, and four (14%) had no monoclonal reaction; all were serotype P1A. Among the patients with RV infection, 13 (46.4%) required hospitalization and the remaining 15 (53.6%) showed moderate symptoms. The strains that infected the adults were electrophoretically and antigenically the same as those that infected infants in Mérida, Yucatán over the last 10 years. No relationship between the severity of the symptoms and any specific serotype was found.

Efficacy and immunogenicity of live-attenuated human rotavirus vaccine in breast-fed and formula-fed European infants.

PubMed

Vesikari, Timo; Prymula, Roman; Schuster, Volker; Tejedor, Juan-C; Cohen, Robert; Bouckenooghe, Alain; Damaso, Silvia; Han, Htay Htay

2012-05-01

Rotavirus is the main cause of severe gastroenteritis and diarrhea in infants and young children less than 5 years of age. Potential impact of breast-feeding on the efficacy and immunogenicity of human rotavirus G1P[8] vaccine was examined in this exploratory analysis. Healthy infants (N = 3994) aged 6-14 weeks who received 2 doses of human rotavirus vaccine/placebo according to a 0-1 or 0-2 month schedule were followed for rotavirus gastroenteritis during 2 epidemic seasons. Rotavirus IgA seroconversion rate (anti-IgA antibody concentration ≥ 20 mIU/mL) and geometric mean concentrations were measured prevaccination and 1-2 months post-dose 2. Vaccine efficacy against any and severe rotavirus gastroenteritis was analyzed according to the infants being breast-fed or exclusively formula-fed at the time of vaccination. Antirotavirus IgA seroconversion rate was 85.5% (95% confidence interval [CI]: 82.4-88.3) in breast-fed and 89.2% (95% CI: 84.2-93) in exclusively formula-fed infants; geometric mean concentrations in the respective groups were 185.8 U/mL (95% CI: 161.4-213.9) and 231.5 U/mL (95% CI: 185.9-288.2). Vaccine efficacy was equally high in breast-fed and exclusively formula-fed children in the first season but fell in breast-fed infants in the second rotavirus season. During the combined 2-year efficacy follow-up period, vaccine efficacy against any rotavirus gastroenteritis was 76.2% (95% CI: 68.7-82.1) and 89.8% (95% CI: 77.6-95.9) and against severe rotavirus gastroenteritis 88.4% (95% CI: 81.6-93) and 98.1% (95% CI: 88.2-100) in the breast-fed and exclusively formula-fed infants, respectively. The difference in immunogenicity of human rotavirus vaccine in breast-fed and exclusively formula-fed infants was small. Vaccine efficacy was equally high in breast-fed and exclusively formula-fed children in the first season. Breast-feeding seemed to reduce slightly the efficacy in the second season.

Variation in rotavirus vaccine coverage by sub-counties in Kenya.

PubMed

Wandera, Ernest Apondi; Mohammad, Shah; Ouko, John Odhiambo; Yatitch, James; Taniguchi, Koki; Ichinose, Yoshio

2017-01-01

Rotavirus gastroenteritis is an important cause of childhood morbidity and mortality in Kenya. In July 2014, Kenya introduced the rotavirus vaccine into her national immunization program. Although immunization coverage is crucial in assessing the real-world impact of this vaccine, variability in the vaccine coverage across the country is likely to occur. In view of this, we estimated the extent of coverage for the rotavirus vaccine at two socio-economically different sub-counties using the administrative data. The findings indicate disparities in vaccine coverage and access between the sub-counties and, thus, underscore the need to strengthen immunization systems to facilitate timely, accessible, and equitable vaccine delivery across the country. Both sub-counties recorded high vaccine dropout, suggestive of poor utilization of the vaccine. In this regard, increased social mobilization is needed to encourage vaccine compliance and to enhance tracking of vaccine defaulters. While efforts to improve the accuracy of the administrative coverage estimates are crucial, vaccination coverage surveys will be needed to verify the administrative coverage data and help identify specific factors relating to rotavirus vaccine coverage in the country.

Therapeutics Insight with Inclusive Immunopharmacology Explication of Human Rotavirus A for the Treatment of Diarrhea.

PubMed

Hossain, Mohammad Uzzal; Hashem, Abu; Keya, Chaman Ara; Salimullah, Md

2016-01-01

Rotavirus is the most common cause of severe infant and childhood diarrhea worldwide, and the morbidity and mortality rate is going to be outnumbered in developing countries like Bangladesh. To mitigate this substantial burden of disease, new therapeutics such as vaccine and drug are swiftly required against rotavirus. The present therapeutics insight study was performed with comprehensive immunoinformatics and pharmacoinformatics approach. T and B-cell epitopes were assessed in the conserved region of outer capsid protein VP4 among the highly reviewed strains from different countries including Bangladesh. The results suggest that epitope SU1 (TLKNLNDNY) could be an ideal candidate among the predicted five epitopes for both T and B-cell epitopes for the development of universal vaccine against rotavirus. This research also suggests five novel drug compounds from medicinal plant Rhizophora mucronata Lamk. for better therapeutics strategies against rotavirus diarrhea based on 3D structure building, pharmacophore, ADMET, and QSAR properties. The exact mode of action between drug compounds and target protein VP4 were revealed by molecular docking analysis. Drug likeness and oral bioavailability further confirmed the effectiveness of the proposed drugs against rotavirus diarrhea. This study might be implemented for experimental validation to facilitate the novel vaccine and drug design.

Incorporation of a rotavirus vaccine into the national immunisation schedule in the United Kingdom: a review.

PubMed

Nakagomi, Osamu; Iturriza-Gomara, Miren; Nakagomi, Toyoko; Cunliffe, Nigel A

2013-11-01

Rotavirus, the commonest cause of severe acute gastroenteritis in infants and young children worldwide, imposes a large health and economic burden on the British society, accounting for an estimated 14,300 hospitalisations and 133,000 general practitioner consultations each year among children aged < 5 years in England and Wales alone. Following a tender process, an attenuated human rotavirus vaccine, Rotarix (GlaxoSmithKline Biologicals, Belgium), was introduced into the UK childhood immunisation programme in 2013. This article provides a review of the product profile of the Rotarix vaccine for use in the national immunisation programme in the UK from an expert perspective. This single G1P[8] strain-based human rotavirus vaccine has demonstrated high efficacy in preventing severe rotavirus gastroenteritis in the first 3 years of life in middle- and high-income countries. In countries that have adopted rotavirus vaccine in childhood immunisation programmes, indirect benefits (herd protection) have been observed among older, unvaccinated children and adults. When the first dose is administered between 6 and 14 weeks of age and the last dose by 24 weeks of age, Rotarix carries a small risk of intussusception within the week of vaccination. However, this small risk may at most result in a negligible population attributable risk at the end of the first year of life. Overall, the rotavirus immunisation programme is expected to provide substantial health benefits to the UK population.

Zoonotic transmission of reassortant porcine G4P[6] rotaviruses in Hungarian pediatric patients identified sporadically over a 15 year period.

PubMed

Papp, Hajnalka; Borzák, Réka; Farkas, Szilvia; Kisfali, Péter; Lengyel, György; Molnár, Péter; Melegh, Béla; Matthijnssens, Jelle; Jakab, Ferenc; Martella, Vito; Bányai, Krisztián

2013-10-01

Genotype G4P[6] Rotavirus A (RVA) strains collected from children admitted to hospital with gastroenteritis over a 15 year period in the pre rotavirus vaccine era in Hungary were characterized in this study. Whole genome sequencing and phylogenetic analysis was performed on eight G4P[6] RVA strains. All these RVA strains shared a fairly conservative genomic configuration (G4-P[6]-I1/I5-R1-C1-M1-A1/A8-N1-T1/T7-E1-H1) and showed striking similarities to porcine and porcine-derived human RVA strains collected worldwide, although genetic relatedness to some common human RVA strains was also seen. The resolution of phylogenetic relationship between porcine and human RVA genes was occasionally low, making the evaluation of host species origin of individual genes sometimes difficult. Yet the whole genome constellations and overall phylogenetic analyses indicated that these eight Hungarian G4P[6] RVA strains may have originated by independent zoonotic transmission, probably from pigs. Future surveillance studies of human and animal RVA should go parallel to enable the distinction between direct interspecies transmission events and those that are coupled with reassortment of cognate genes. Copyright © 2013 Elsevier B.V. All rights reserved.

Projected health and economic impact of rotavirus vaccination in GAVI-eligible countries: 2011-2030.

PubMed

Atherly, Deborah E; Lewis, Kristen D C; Tate, Jacqueline; Parashar, Umesh D; Rheingans, Richard D

2012-04-27

Rotavirus is the leading cause of diarrheal disease in children under 5 years of age. It is responsible for more than 450,000 deaths each year, with more than 90% of these deaths occurring in low-resource countries eligible for support by the GAVI Alliance. Significant efforts made by the Alliance and its partners are providing countries with the opportunity to introduce rotavirus vaccines into their national immunization programs, to help prevent childhood illness and death. We projected the cost-effectiveness and health impact of rotavirus vaccines in GAVI-eligible countries, to assist decision makers in prioritizing resources to achieve the greatest health benefits for their populations. A decision-analytic model was used to project the health outcomes and direct costs of a birth cohort in the target population, with and without a rotavirus vaccine. Current data on disease burden, vaccine efficacy, immunization rates, and costs were used in the model. Vaccination in GAVI-eligible countries would prevent 2.46 million childhood deaths and 83 million disability-adjusted life years (DALYs) from 2011 to 2030, with annual reductions of 180,000 childhood deaths at peak vaccine uptake. The cost per DALY averted is $42 for all GAVI countries combined, over the entire period. Rotavirus vaccination would be considered very cost-effective for the entire cohort of GAVI countries, and in each country individually, as cost-effectiveness ratios are less than the gross domestic product (GDP) per capita. Vaccination is most cost-effective and has the greatest impact in regions with high rotavirus mortality. Rotavirus vaccination in GAVI-eligible countries is very cost-effective and is projected to substantially reduce childhood mortality in this population. Copyright © 2012. Published by Elsevier Ltd.

[Characterisation of viral agents with potential to cause diarrhea in Djibouti].

PubMed

Maslin, J; Kohli, E; Leveque, N; Chomel, J J; Nicand, E; Fouet, C; Haus, R; Depina, J J; Mathecowitsch, P; Dampierre, H

2007-06-01

Due to limited laboratory facilities in the tropics, the exact role of enteric viruses in causing diarrhea among adults in the tropics is unknown. The purpose of this report is to describe a multicenter study undertaken in Djibouti to determine the prevalence of a large panel of enteric viruses using immunochromatography; antigenic detection by ELISA, RT-PCR cellular inoculation, sequence analysis; and indirect serology. Study samples were collected from 108 patients presenting acute and sporadic diarrhea. Although they are well known causes of diarrhea in children, rotavirus and adenovirus were identified in only 2 and 5% of adults respectively. In contrast human caliciviruses (HuCVs) and enterovirus were identified in 25 and 42% of adult cases respectively. Uncommon genotypes of HuCVs and recombinant forms (junction pol/l cap) as well as a significant number of sapovirus (30%) were identified. Further study is needed to clarify the role of enterovirus (echovirus) in the etiology of acute diarrhea in adults. No polivirus was identified. These new data from the Horn of Africa increase our knowledge about the epidemiology of acute infectious diarrhea that is a major public health problem and potential danger for travelers.

Effectiveness of Monovalent and Pentavalent Rotavirus Vaccines in Guatemala.

PubMed

Gastañaduy, Paul A; Contreras-Roldán, Ingrid; Bernart, Chris; López, Beatriz; Benoit, Stephen R; Xuya, Marvin; Muñoz, Fredy; Desai, Rishi; Quaye, Osbourne; Tam, Ka Ian; Evans-Bowen, Diana K; Parashar, Umesh D; Patel, Manish; McCracken, John P

2016-05-01

Concerns remain about lower effectiveness and waning immunity of rotavirus vaccines in resource-poor populations. We assessed vaccine effectiveness against rotavirus in Guatemala, where both the monovalent (RV1; 2-dose series) and pentavalent (RV5; 3-dose series) vaccines were introduced in 2010. A case-control evaluation was conducted in 4 hospitals from January 2012 to August 2013. Vaccine status was compared between case patients (children with laboratory-confirmed rotavirus diarrhea) and 2 sets of controls: nondiarrhea "hospital" controls (matched by birth date and site) and nonrotavirus "test-negative" diarrhea controls (adjusted for age, birth month/year, and site). Vaccine effectiveness ([1 - odds ratio of vaccination] × 100%) was computed using logistic regression models. We evaluated 213 case patients, 657 hospital controls, and 334 test-negative controls. Effectiveness of 2-3 doses of a rotavirus vaccine against rotavirus requiring emergency department visit or hospitalization was 74% (95% confidence interval [CI], 58%-84%) with hospital controls, and 52% (95% CI, 26%-69%) with test-negative controls. Using hospital controls, no significant difference in effectiveness was observed between infants 6-11 months (74% [95% CI, 18%-92%]) and children ≥12 months of age (71% [95% CI, 44%-85%]) (P= .85), nor between complete courses of RV1 (63% [95% CI, 23%-82%]) and RV5 (69% [95% CI, 29%-87%]) (P= .96). An uncommon G12P[8] strain, partially heterotypic to strains in both vaccines, was identified in 89% of cases. RV1 and RV5 were similarly effective against severe rotavirus diarrhea caused by a heterotypic strain in Guatemala. This supports broader implementation of rotavirus vaccination in low-income countries where >90% global deaths from rotavirus occur. Published by Oxford University Press for the Infectious Diseases Society of America 2016. This work is written by (a) US Government employee(s) and is in the public domain in the US.

Cost-effectiveness of childhood rotavirus vaccination in Taiwan.

PubMed

Wu, Chia-Ling; Yang, Yi-Ching; Huang, Li-Min; Chen, Kow-Tong

2009-03-04

Rotavirus is the most common cause of severe diarrhea in children. Two rotavirus vaccines (RotaTeq and Rotarix) have been licensed in Taiwan. We have investigated whether routine infant immunization with either vaccine could be cost-effective in Taiwan. We modeled specific disease outcomes including hospitalization, emergency department visits, hospital outpatient visits, physician office visits, and death. Cost-effectiveness was analyzed from the perspectives of the health care system and society. A decision tree was used to estimate the disease burden and costs based on data from published and unpublished sources. A routine rotavirus immunization program would prevent 146,470 (Rotarix) or 149,937 (RotaTeq) cases of rotavirus diarrhea per year, and would prevent 21,106 (Rotarix) and 23,057 (RotaTeq) serious cases (hospitalizations, emergency department visits, and death). At US$80 per dose for the Rotarix vaccine, the program would cost US$32.7 million, provided an increasing cost offset of US$19.8 million to the health care system with $135 per case averted. Threshold analysis identified a break-even price per dose of US$27 from the health care system perspective and US$41 from a societal perspective. At US$60.0 per dose of RotaTeq vaccine, the program would cost US$35.4 million and provide an increasing cost offset of US$22.5 million to the health care system, or US$150 per case averted. Threshold analysis identified a break-even price per dose of US$20.0 from the health care system perspective and $29 from the societal perspective. Greater costs of hospitalization and lower vaccine price could increase cost-effectiveness. Despite a higher burden of serious rotavirus disease than estimated previously, routine rotavirus vaccination would unlikely be cost-saving in Taiwan at present unless the price fell to US$41 (Rotarix) or US$29 (RotaTeq) per dose from societal perspective, respectively. Nonetheless, rotavirus immunization could reduce the substantial burden of short-term morbidity due to rotavirus.

Induction of homologous and cross-reactive GII.4-specific blocking antibodies in children after GII.4 New Orleans norovirus infection.

PubMed

Blazevic, Vesna; Malm, Maria; Vesikari, Timo

2015-10-01

Noroviruses (NoVs) are major causative agents of acute gastroenteritis (AGE) in children worldwide and the most common viral cause of AGE in countries where rotavirus incidence has been eliminated by vaccination. Previous infections with the dominant GII.4 NoV genotype confer only partial protection against evolving immune escape variants that emerge every few years. The objective of this work was to investigate GII.4-specific homologous and cross-reactive antibody responses in young children after NoV GII.4-2009 New Orleans (NO) infection. Virus-like particles (VLPs) representing GII.4-1999, GII.4-2009 NO, and GII.4-2012 Sydney genotypes were used in ELISA and histo-blood group antigen blocking assays to examine acute and convalescent sera of five children <2 years of age infected with GII.4-2009 NO. GII.4-2009 NO infection induced IgG seroconversion to all three tested NoV GII.4 variants. Homologous blocking antibodies to GII.4-2009 NO were detected in each convalescent sera. Fourfold increase in cross-blocking antibodies to GII.4-2012 Sydney was observed in 4/5 subjects, but no child developed cross-blocking antibodies to GII.4-1999. In conclusion, antibodies induced in young children after norovirus GII.4 infection are targeted against the causative variant and may cross-protect against strains that are closely related, but not with more distinct and earlier GII.4 genotypes. © 2015 Wiley Periodicals, Inc.

Hospitalizations due to rotavirus gastroenteritis in Catalonia, Spain, 2003-2008

PubMed Central

2011-01-01

Background Rotavirus is the most common cause of severe gastroenteritis among young children in Spain and worldwide. We evaluated hospitalizations due to community and hospital-acquired rotavirus gastroenteritis (RVGE) and estimated related costs in children under 5 years old in Catalonia, Spain. Results We analyzed hospital discharge data from the Catalan Health Services regarding hospital admissions coded as infectious gastroenteritis in children under 5 for the period 2003-2008. In order to estimate admission incidence, we used population estimates for each study year published by the Statistic Institut of Catalonia (Idescat). The costs associated with hospital admissions due to rotavirus diarrhea were estimated for the same years. A decision tree model was used to estimate the threshold cost of rotavirus vaccine to achieve cost savings from the healthcare system perspective in Catalonia. From 2003 through 2008, 10655 children under 5 years old were admitted with infectious gastroenteritis (IGE). Twenty-two percent of these admissions were coded as RVGE, yielding an estimated average annual incidence of 104 RVGE hospitalizations per 100000 children in Catalonia. Eighty seven percent of admissions for RVGE occurred during December through March. The mean hospital stay was 3.7 days, 0.6 days longer than for other IGE. An additional 892 cases of presumed nosocomial RVGE were detected, yielding an incidence of 2.5 cases per 1000 child admissions. Total rotavirus hospitalization costs due to community acquired RVGE for the years 2003 and 2008 were 431,593 and 809,224 €, respectively. According to the estimated incidence and hospitalization costs, immunization would result in health system cost savings if the cost of the vaccine was 1.93 € or less. At a vaccine cost of 187 € the incremental cost per hospitalization prevented is 195,388 € (CI 95% 159,300; 238,400). Conclusions The burden of hospitalizations attributable to rotavirus appeared to be lower in Catalonia than in other regions of Spain and Europe. The relatively low incidence of hospitalization due to rotavirus makes rotavirus vaccination less cost-effective in Catalonia than in other areas with higher rotavirus disease burden. PMID:22013948

Ecological assessment of the direct and indirect effects of routine rotavirus vaccination in Merseyside, UK using data from multiple health systems: a study protocol.

PubMed

Hungerford, Daniel; Vivancos, Roberto; French, Neil; Iturriza-Gomara, Miren; Cunliffe, Nigel

2014-11-25

Rotavirus is the most common cause of severe gastroenteritis in infants and young children worldwide. Currently 67 countries include rotavirus vaccine in childhood immunisation programmes, but uptake in Western Europe has been slow. In July 2013, rotavirus vaccine was introduced into the UK's routine childhood immunisation programme. Prior to vaccine introduction in the UK, rotavirus was estimated to result in 750,000 diarrhoea episodes and 80,000 general practice (GP) consultations each year, together with 45% and 20% of hospital admissions and emergency department attendances for acute gastroenteritis, in children under 5 years of age. This paper describes a protocol for an ecological study that will assess rotavirus vaccine impact in the UK, to inform rotavirus immunisation policy in the UK and in other Western European countries. In Merseyside, UK, we will conduct an ecological study using a 'before and after' approach to examine changes in gastroenteritis and rotavirus incidence following the introduction of rotavirus vaccination. Data will be collected on mortality, hospital admissions, nosocomial infection, emergency department attendances, GP consultations and community health consultations to capture all healthcare providers in the region. We will assess both the direct and indirect effects of the vaccine on the study population. Comparisons of outcome indicator rates will be made in relation to vaccine uptake and socioeconomic status. The study has been approved by NHS Research Ethics Committee, South Central-Berkshire REC Reference: 14/SC/1140. Study outputs will be disseminated through scientific conferences and peer-reviewed publications. The study will demonstrate the impact of rotavirus vaccination on the burden of disease from a complete health system perspective. It will identify key areas that require improved data collection tools to maximise the usefulness of this surveillance approach and will provide a template for vaccine evaluations using ecological methods in the UK. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

Efficacy and immunogenicity of two or three dose rotavirus-vaccine regimen in South African children over two consecutive rotavirus-seasons: a randomized, double-blind, placebo-controlled trial.

PubMed

Madhi, S A; Kirsten, M; Louw, C; Bos, P; Aspinall, S; Bouckenooghe, A; Neuzil, K M; Steele, A D

2012-04-27

Human rotavirus vaccine (HRV; i.e., Rotarix) reduced the incidence of severe rotavirus gastroenteritis (RVGE) by 77% (95% Confidence interval: 56-88%) during the first year of life in South Africa. Persistence of HRV-derived protection against RVGE during subsequent rotavirus seasons, although evident in industrialized settings, remains to be established in African settings. This study reports on the efficacy of HRV against severe RVGE over two consecutive rotavirus seasons in South African children. A prospective, double-blind, placebo controlled multi-centered trial in South Africa and Malawi randomly assigned infants in a 1:1:1 ratio to receive either two (10 and 14 weeks; HRV_2D) or three (6, 10 and 14 weeks; HRV_3D) doses of HRV or placebo. The primary analysis involved pooling of HRV_2D and HRV_3D arms. Episodes of gastroenteritis caused by wild-type rotavirus were identified through active follow-up surveillance and graded by the Vesikari scale. 1339 infants (447 in the HRV_2D group, 447 in the HRV_3D group and 445 in the placebo group) were enrolled in Year 2 of the study, including 1035 (77.3%) who were followed up over two consecutive rotavirus seasons (i.e., Cohort 2 subjects). Rotarix was associated with ongoing protection against severe RVGE, preventing 2.5 episodes per 100 vaccinated children over two consecutive rotavirus seasons; vaccine efficacy: 59% (95% Confidence interval: 1-83%). An exploratory analysis indicated better immunogenicity (among Cohort 1 subjects) and a higher point-efficacy estimate over two seasons in the HRV_3D compared to HRV_2D arms of the study in Cohort 2 subjects. Rotarix is associated with significant reductions in severe gastroenteritis episodes through 2 years of life among South African children. Further research is needed to determine the optimal dosing schedule of Rotarix in providing long-term protection against rotavirus illness in African children. Copyright © 2011 Elsevier Ltd. All rights reserved.

Protein-energy malnutrition alters IgA responses to rotavirus vaccination and infection but does not impair vaccine efficacy in mice.

PubMed

Maier, Elizabeth A; Weage, Kristina J; Guedes, Marjorie M; Denson, Lee A; McNeal, Monica M; Bernstein, David I; Moore, Sean R

2013-12-17

Conflicting evidence links malnutrition to the reduced efficacy of rotavirus vaccines in developing countries, where diarrhea and undernutrition remain leading causes of child deaths. Here, we adapted mouse models of rotavirus vaccination (rhesus rotavirus, RRV), rotavirus infection (EDIM), and protein-energy malnutrition (PEM) to test the hypothesis that undernutrition reduces rotavirus vaccine immunogenicity and efficacy. We randomized wild type Balb/C dams with 3-day-old pups to a control diet (CD) or an isocaloric, multideficient regional basic diet (RBD) that produces PEM. At 3 weeks of age, we weaned CD and RBD pups to their dams' diet and subrandomized weanlings to receive a single dose of either live oral rotavirus vaccine (RRV) or PBS. At 6 weeks of age, we orally challenged all groups with murine rotavirus (EDIM). Serum and stool specimens were collected before and after RRV and EDIM administration to measure viral shedding and antibody responses by ELISA. RBD pups and weanlings exhibited significant failure to thrive compared to age-matched CD mice (P<.0001). RRV vaccination induced higher levels of serum anti-RV IgA responses in RBD vs. CD mice (P<.0001). Vaccination protected CD and RBD mice equally against EDIM infection, as measured by viral shedding. In unvaccinated RBD mice, EDIM shedding peaked 1 day earlier (P<.05), however we detected no effects of undernutrition on viral clearance nor of infection on bodyweight. EDIM infection provoked higher anti-RV serum IgA levels in RBD vs. CD mice, regardless of vaccination (P<.0001). Last, RRV vaccination mitigated stool IgA responses to EDIM more in CD vs. RBD mice (P<.0001). Despite modulated IgA responses to vaccination and infection, undernutrition does not impair rotavirus vaccine efficacy nor exacerbate infection in this mouse model of protein-energy malnutrition. Alternative models are needed to elucidate host-pathogen factors undermining rotavirus vaccine effectiveness in high-risk global settings. Copyright © 2013 The Authors. Published by Elsevier Ltd.. All rights reserved.

Cost-effectiveness of rotavirus vaccination in Bolivia from the state perspective.

PubMed

Smith, Emily R; Rowlinson, Emily E; Iniguez, Volga; Etienne, Kizee A; Rivera, Rosario; Mamani, Nataniel; Rheingans, Rick; Patzi, Maritza; Halkyer, Percy; Leon, Juan S

2011-09-02

In Bolivia, in 2008, the under-five mortality rate is 54 per 1000 live births. Diarrhea causes 15% of these deaths, and 40% of pediatric diarrhea-related hospitalizations are caused by rotavirus illness (RI). Rotavirus vaccination (RV), subsidized by international donors, is expected to reduce morbidity, mortality, and economic burden to the Bolivian state. Estimates of illness and economic burden of RI and their reduction by RV are essential to the Bolivian state's policies on RV program financing. The goal of this report is to estimate the economic burden of RI and the cost-effectiveness of the RV program. To assess treatment costs incurred by the healthcare system, we abstracted medical records from 287 inpatients and 6751 outpatients with acute diarrhea between 2005 and 2006 at 5 sentinel hospitals in 4 geographic regions. RI prevalence rates were estimated from 4 years of national hospital surveillance. We used a decision-analytic model to assess the potential cost-effectiveness of universal RV in Bolivia. Our model estimates that, in a 5-year birth cohort, Bolivia will incur over US$3 million in direct medical costs due to RI. RV reduces, by at least 60%, outpatient visits, hospitalizations, deaths, and total direct medical costs associated with rotavirus diarrhea. Further, RV was cost-savings below a price of US$3.81 per dose and cost-effective below a price of US$194.10 per dose. Diarrheal mortality and hospitalization inputs were the most important drivers of rotavirus vaccine cost-effectiveness. Our data will guide Bolivia's funding allocation for RV as international subsidies change. Copyright © 2011 Elsevier Ltd. All rights reserved.

Whole-genome characterization of a Peruvian alpaca rotavirus isolate expressing a novel VP4 genotype.

PubMed

Rojas, Miguel; Gonçalves, Jorge Luiz S; Dias, Helver G; Manchego, Alberto; Pezo, Danilo; Santos, Norma

2016-11-30

The SA44 isolate of Rotavirus A (RVA) was identified from a neonatal Peruvian alpaca presenting with diarrhea, and the full-length genome sequence of the isolate (designated RVA/Alpaca-tc/PER/SA44/2014/G3P[40]) was determined. Phylogenetic analyses showed that the isolate possessed the genotype constellation G3-P[40]-I8-R3-C3-M3-A9-N3-T3-E3-H6, which differs considerably from those of RVA strains isolated from other species of the order Artiodactyla. Overall, the genetic constellation of the SA44 strain was quite similar to those of RVA strains isolated from a bat in Asia (MSLH14 and MYAS33). Nonetheless, phylogenetic analyses of each genome segment identified a distinct combination of genes. Several sequences were closely related to corresponding gene sequences in RVA strains from other species, including human (VP1, VP2, NSP1, and NSP2), simian (VP3 and NSP5), bat (VP6 and NSP4), and equine (NSP3). The VP7 gene sequence was closely related to RVA strains from a Peruvian alpaca (K'ayra/3368-10; 99.0% nucleotide and 99.7% amino acid identity) and from humans (RCH272; 95% nucleotide and 99.0% amino acid identity). The nucleotide sequence of the VP4 gene was distantly related to other VP4 sequences and was designated as the reference strain for the new P[40] genotype. This unique genetic makeup suggests that the SA44 strain emerged from multiple reassortment events between bat-, equine-, and human-like RVA strains. Copyright © 2016 Elsevier B.V. All rights reserved.

Simian Rotaviruses Possess Divergent Gene Constellations That Originated from Interspecies Transmission and Reassortment▿

PubMed Central

Matthijnssens, Jelle; Taraporewala, Zenobia F.; Yang, Hongyan; Rao, Shujing; Yuan, Lijuan; Cao, Dianjun; Hoshino, Yasutaka; Mertens, Peter P. C.; Carner, Gerry R.; McNeal, Monica; Sestak, Karol; Van Ranst, Marc; Patton, John T.

2010-01-01

Although few simian rotaviruses (RVs) have been isolated, such strains have been important for basic research and vaccine development. To explore the origins of simian RVs, the complete genome sequences of strains PTRV (G8P[1]), RRV (G3P[3]), and TUCH (G3P[24]) were determined. These data allowed the genotype constellations of each virus to be determined and the phylogenetic relationships of the simian strains with each other and with nonsimian RVs to be elucidated. The results indicate that PTRV was likely transmitted from a bovine or other ruminant into pig-tailed macaques (its host of origin), since its genes have genotypes and encode outer-capsid proteins similar to those of bovine RVs. In contrast, most of the genes of rhesus-macaque strains, RRV and TUCH, have genotypes more typical of canine-feline RVs. However, the sequences of the canine and/or feline (canine/feline)-like genes of RRV and TUCH are only distantly related to those of modern canine/feline RVs, indicating that any potential transmission of a progenitor of these viruses from a canine/feline host to a simian host was not recent. The remaining genes of RRV and TUCH appear to have originated through reassortment with bovine, human, or other RV strains. Finally, comparison of PTRV, RRV, and TUCH genes with those of the vervet-monkey RV SA11-H96 (G3P[2]) indicates that SA11-H96 shares little genetic similarity to other simian strains and likely has evolved independently. Collectively, our data indicate that simian RVs are of diverse ancestry with genome constellations that originated largely by interspecies transmission and reassortment with nonhuman animal RVs. PMID:19939934

Medicinal plants and natural molecules with in vitro and in vivo activity against rotavirus: A systematic review.

PubMed

Gandhi, Gopalsamy Rajiv; Barreto, Paula Gurgel; Lima, Bruno Dos Santos; Quintans, Jullyana de Souza Siqueira; Araújo, Adriano Antunes de Souza; Narain, Narendra; Quintans-Júnior, Lucindo Jose; Gurgel, Ricardo Queiroz

2016-12-15

Rotaviruses can cause life-threatening health disorders, such as severe dehydrating gastroenteritis and diarrhea in children. Vaccination is the main preventive strategy to reduce rotavirus diarrhea and the severity of episodes, but vaccines are not fully effective and new episodes may occur, even in vaccinated children. The WHO recommends oral rehydration therapy and zinc supplementation for rotavirus-induced diarrhea management. There is little preclinical evidence to support the use of phytotherapeutics in the management of rotaviral infections. We aim to review the use of medicinal plants and natural molecules in the management of rotavirus infections in experimental studies. Articles, published in the English language between 1991 and 2016, were retrieved from PubMed, Scopus and Web of Science using relevant keywords. The scientific literature mainly focusing on plant natural products with therapeutic efficacies against experimental models of rotavirus, were identified and tabulated. In addition, an assessment of the reliability of animal experiments was determined under ``Risk of Bias'' criteria. After an initial search and a revision of the inclusion criteria, 41 reports satisfied the objectives of the study. 36 articles were found concerning the anti-rotaviral potential in rotavirus infected cell lines. Among the active secondary metabolites screened for rotavirus inhibition, the polyphenols of flavonoid structure had acquired the highest number of studies in our survey, compared to phenolic acids, stilbenoids, tannins, pectins, terpenoids and flavonoid glycosides. Also, many phytochemicals reduced the efficacy of viral capsid proteins foremost to their elimination and improved the tendency of host-cell inhibiting virus absorption or by prevention of viral replication. Furthermore, five in vivo studies reported that herbs, as well its components, reduced the duration and severity of diarrhea in mice and piglets. The anti-rotavirus efficacy were highlighted based on improvements in reduction on liquid stool, fecal virus shedding, small intestinal histology, levels of inflammation related cytokines and signaling receptors. However, the quality of the experiments in animal studies contained certain types of bias in terms of how they were conducted and reported. We identified and summarized studies on medicinal plants and natural molecules having anti-rotavirus activity in order to further future developments of cures for rotavirus gastroenteritis. Copyright © 2016 Elsevier GmbH. All rights reserved.

Nlrp9b inflammasome restricts rotavirus infection in intestinal epithelial cells.

PubMed

Zhu, Shu; Ding, Siyuan; Wang, Penghua; Wei, Zheng; Pan, Wen; Palm, Noah W; Yang, Yi; Yu, Hua; Li, Hua-Bing; Wang, Geng; Lei, Xuqiu; de Zoete, Marcel R; Zhao, Jun; Zheng, Yunjiang; Chen, Haiwei; Zhao, Yujiao; Jurado, Kellie A; Feng, Ningguo; Shan, Liang; Kluger, Yuval; Lu, Jun; Abraham, Clara; Fikrig, Erol; Greenberg, Harry B; Flavell, Richard A

2017-06-29

Rotavirus, a leading cause of severe gastroenteritis and diarrhoea in young children, accounts for around 215,000 deaths annually worldwide. Rotavirus specifically infects the intestinal epithelial cells in the host small intestine and has evolved strategies to antagonize interferon and NF-κB signalling, raising the question as to whether other host factors participate in antiviral responses in intestinal mucosa. The mechanism by which enteric viruses are sensed and restricted in vivo, especially by NOD-like receptor (NLR) inflammasomes, is largely unknown. Here we uncover and mechanistically characterize the NLR Nlrp9b that is specifically expressed in intestinal epithelial cells and restricts rotavirus infection. Our data show that, via RNA helicase Dhx9, Nlrp9b recognizes short double-stranded RNA stretches and forms inflammasome complexes with the adaptor proteins Asc and caspase-1 to promote the maturation of interleukin (Il)-18 and gasdermin D (Gsdmd)-induced pyroptosis. Conditional depletion of Nlrp9b or other inflammasome components in the intestine in vivo resulted in enhanced susceptibility of mice to rotavirus replication. Our study highlights an important innate immune signalling pathway that functions in intestinal epithelial cells and may present useful targets in the modulation of host defences against viral pathogens.

Cost-effectiveness of live oral attenuated human rotavirus vaccine in Tanzania.

PubMed

Ruhago, George M; Ngalesoni, Frida N; Robberstad, Bjarne; Norheim, Ole F

2015-01-01

Globally, diarrhoea is the second leading cause of morbidity and mortality, responsible for the annual loss of about 10% of the total global childhood disease burden. In Tanzania, Rotavirus infection is the major cause of severe diarrhoea and diarrhoeal mortality in children under five years. Immunisation can reduce the burden, and Tanzania added rotavirus vaccine to its national immunisation programme in January 2013. This study explores the cost effectiveness of introducing rotavirus vaccine within the Tanzania Expanded Programme on Immunisation (EPI). We quantified all health system implementation costs, including programme costs, to calculate the cost effectiveness of adding rotavirus immunisation to EPI and the existing provision of diarrhoea treatment (oral rehydration salts and intravenous fluids) to children. We used ingredients and step down costing methods. Cost and coverage data were collected in 2012 at one urban and one rural district hospital and a health centre in Tanzania. We used Disability Adjusted Life Years (DALYs) as the outcome measure and estimated incremental costs and health outcomes using a Markov transition model with weekly cycles up to a five-year time horizon. The average unit cost per vaccine dose at 93% coverage is US$ 8.4, with marked difference between the urban facility US$ 5.2; and the rural facility US$ 9.8. RV1 vaccine added to current diarrhoea treatment is highly cost effective compared to diarrhoea treatment given alone, with incremental cost effectiveness ratio of US$ 112 per DALY averted, varying from US$ 80-218 in sensitivity analysis. The intervention approaches a 100% probability of being cost effective at a much lower level of willingness-to-pay than the US$609 per capita Tanzania gross domestic product (GDP). The combination of rotavirus immunisation with diarrhoea treatment is likely to be cost effective when willingness to pay for health is higher than USD 112 per DALY. Universal coverage of the vaccine will accelerate progress towards achievement of the child health Millennium Development Goals.

Time Series Analysis of the Microbiota of Children Suffering From Acute Infectious Diarrhea and Their Recovery After Treatment.

PubMed

Dinleyici, Ener C; Martínez-Martínez, Daniel; Kara, Ates; Karbuz, Adem; Dalgic, Nazan; Metin, Ozge; Yazar, Ahmet S; Guven, Sirin; Kurugol, Zafer; Turel, Ozden; Kucukkoc, Mehmet; Yasa, Olcay; Eren, Makbule; Ozen, Metehan; Martí, Jose Manuel; P Garay, Carlos; Vandenplas, Yvan; Moya, Andrés

2018-01-01

Gut microbiota is closely related to acute infectious diarrhea, one of the leading causes of mortality and morbidity in children worldwide. Understanding the dynamics of the recovery from this disease is of clinical interest. This work aims to correlate the dynamics of gut microbiota with the evolution of children who were suffering from acute infectious diarrhea caused by a rotavirus, and their recovery after the administration of a probiotic, Saccharomyces boulardii CNCM I-745. The experiment involved 10 children with acute infectious diarrhea caused by a rotavirus, and six healthy children, all aged between 3 and 4 years. The children who suffered the rotavirus infection received S. boulardii CNCM I-745 twice daily for the first 5 days of the experiment. Fecal samples were collected from each participant at 0, 3, 5, 10, and 30 days after probiotic administration. Microbial composition was characterized by 16S rRNA gene sequencing. Alpha and beta diversity were calculated, along with dynamical analysis based on Taylor's law to assess the temporal stability of the microbiota. All children infected with the rotavirus stopped having diarrhea at day 3 after the intervention. We observed low alpha diversities in the first 5 days ( p -value < 0.05, Wilcoxon test), larger at 10 and 30 days after probiotic treatment. Canonical correspondence analysis (CCA) showed differences in the gut microbiota of healthy children and of those who suffered from acute diarrhea in the first days ( p -value < 0.05, ADONIS test), but not in the last days of the experiment. Temporal variability was larger in children infected with the rotavirus than in healthy ones. In particular, Gammaproteobacteria class was found to be abundant in children with acute diarrhea. We identified the microbiota transition from a diseased state to a healthy one with time, whose characterization may lead to relevant clinical data. This work highlights the importance of using time series for the study of dysbiosis related to diarrhea.

Epidemiology of sapovirus infections in a birth cohort in Peru.

PubMed

Sánchez, Gerardo J; Mayta, Holger; Pajuelo, Monica J; Neira, Karen; Xiaofang, Liu; Cabrera, Lilia; Ballard, Sarah Blythe; Crabtree, Jean E; Kelleher, Dermot; Cama, Vitaliano; Bern, Caryn; Oshitani, Hitoshi; Gilman, Robert H; Saito, Mayuko

2017-12-22

Sapovirus is one of the primary viral causes of acute gastroenteritis, especially in settings where rotavirus vaccination has been implemented. The characteristics and impact of natural infection at the community level, however, have not been well documented. Stool samples were analyzed from 100 children randomly selected from a community-based birth cohort study in Peru. All diarrheal and one non-diarrheal stools collected trimonthly from children up to two years of age (n=1669) were tested for sapovirus detection. Viral shedding duration was determined by testing additional weekly samples (n=440), collected before and after a sapovirus positive sample. The incidence of sapovirus infection in the first and second year of life was 4.3 and 11.1 per 100-child months, respectively. By two years of age, 82% of children had at least one sapovirus infection, and 64% had at least one sapovirus-associated diarrhea episode. The median shedding period was 18.5 days. In 112 of 175 infections, 14 genotypes from four genogroups (GI, GII, GIV and GV) were determined. Among genogroups, GI viruses were more frequently found in symptomatic infections than in asymptomatic infections (OR: 3.1 [CI: 1.3-7.4]). Fifty-nine children had serial sapovirus infections but only three had repeated infection of the same genotype. Sapovirus was frequently detected in children with acute gastroenteritis at the community level during the first two years of life. Serial sapovirus infections by multiple genotypes in a child suggest genotype-specific immunity from each infection, which need to be taken into account for vaccine development. © The Author(s) 2017. Published by Oxford University Press for the Infectious Diseases Society of America.

Diversity in VP3, NSP3, and NSP4 of rotavirus B detected from Japanese cattle.

PubMed

Hayashi-Miyamoto, Michiko; Murakami, Toshiaki; Minami-Fukuda, Fujiko; Tsuchiaka, Shinobu; Kishimoto, Mai; Sano, Kaori; Naoi, Yuki; Asano, Keigo; Ichimaru, Toru; Haga, Kei; Omatsu, Tsutomu; Katayama, Yukie; Oba, Mami; Aoki, Hiroshi; Shirai, Junsuke; Ishida, Motohiko; Katayama, Kazuhiko; Mizutani, Tetsuya; Nagai, Makoto

2017-04-01

Bovine rotavirus B (RVB) is an etiological agent of diarrhea mostly in adult cattle. Currently, a few sequences of viral protein (VP)1, 2, 4, 6, and 7 and nonstructural protein (NSP)1, 2, and 5 of bovine RVB are available in the DDBJ/EMBL/GenBank databases, and none have been reported for VP3, NSP3, and NSP4. In order to fill this gap in the genetic characterization of bovine RVB strains, we used a metagenomics approach and sequenced and analyzed the complete coding sequences (CDS) of VP3, NSP3, and NSP4 genes, as well as the partial or complete CDS of other genes of RVBs detected from Japanese cattle. VP3, NSP3, and NSP4 of bovine RVBs shared low nucleotide sequence identities (63.3-64.9% for VP3, 65.9-68.2% for NSP3, and 52.6-56.2% for NSP4) with those of murine, human, and porcine RVBs, suggesting that bovine RVBs belong to a novel genotype. Furthermore, significantly low amino acid sequence identities were observed for NSP4 (36.1-39.3%) between bovine RVBs and the RVBs of other species. In contrast, hydrophobic plot analysis of NSP4 revealed profiles similar to those of RVBs of other species and rotavirus A (RVA) strains. Phylogenetic analyses of all gene segments revealed that bovine RVB strains formed a cluster that branched distantly from other RVBs. These results suggest that bovine RVBs have evolved independently from other RVBs but in a similar manner to other rotaviruses. These findings provide insights into the evolution and diversity of RVB strains. Copyright © 2017 Elsevier B.V. All rights reserved.

Molecular and biological characterization of the 5 human-bovine rotavirus (WC3)-based reassortant strains of the pentavalent rotavirus vaccine, RotaTeq (registered)

DOE Office of Scientific and Technical Information (OSTI.GOV)

Matthijnssens, Jelle; Joelsson, Daniel B.; Warakomski, Donald J.

RotaTeq (registered) is a pentavalent rotavirus vaccine that contains five human-bovine reassortant strains (designated G1, G2, G3, G4, and P1) on the backbone of the naturally attenuated tissue culture-adapted parental bovine rotavirus (BRV) strain WC3. The viral genomes of each of the reassortant strains were completely sequenced and compared pairwise and phylogenetically among each other and to human rotavirus (HRV) and BRV reference strains. Reassortants G1, G2, G3, and G4 contained the VP7 gene from their corresponding HRV parent strains, while reassortants G1 and G2 also contained the VP3 gene (genotype M1) from the HRV parent strain. The P1 reassortantmore » contained the VP4 gene from the HRV parent strain and all the other gene segments from the BRV WC3 strain. The human VP7s had a high level of overall amino acid identity (G1: 95-99%, G2: 94-99% G3: 96-100%, G4: 93-99%) when compared to those of representative rotavirus strains of their corresponding G serotypes. The VP4 of the P1 reassortant had a high identity (92-97%) with those of serotype P1A[8] HRV reference strains, while the BRV VP7 showed identities ranging from 91% to 94% to those of serotype G6 HRV strains. Sequence analyses of the BRV or HRV genes confirmed that the fundamental structure of the proteins in the vaccine was similar to those of the HRV and BRV references strains. Sequences analyses showed that RotaTeq (registered) exhibited a high degree of genetic stability as no mutations were identified in the material of each reassortant, which undergoes two rounds of replication cycles in cell culture during the manufacturing process, when compared to the final material used to fill the dosing tubes. The infectivity of each of the reassortant strains of RotaTeq (registered) , like HRV strains, did not require the presence of sialic acid residues on the cell surface. The molecular and biologic characterization of RotaTeq (registered) adds to the significant body of clinical data supporting the consistent efficacy, immunogenicity, and safety of RotaTeq (registered) .« less

Efficacy of pentavalent rotavirus vaccine against severe rotavirus gastroenteritis in infants in developing countries in sub-Saharan Africa: a randomised, double-blind, placebo-controlled trial.

PubMed

Armah, George E; Sow, Samba O; Breiman, Robert F; Dallas, Michael J; Tapia, Milagritos D; Feikin, Daniel R; Binka, Fred N; Steele, A Duncan; Laserson, Kayla F; Ansah, Nana A; Levine, Myron M; Lewis, Kristen; Coia, Michele L; Attah-Poku, Margaret; Ojwando, Joel; Rivers, Stephen B; Victor, John C; Nyambane, Geoffrey; Hodgson, Abraham; Schödel, Florian; Ciarlet, Max; Neuzil, Kathleen M

2010-08-21

Rotavirus gastroenteritis causes many deaths in infants in sub-Saharan Africa. Because rotavirus vaccines have proven effective in developed countries but had not been tested in developing countries, we assessed efficacy of a pentavalent rotavirus vaccine against severe disease in Ghana, Kenya, and Mali between April, 2007, and March, 2009. In our multicentre, double-blind, placebo-controlled trial, undertaken in rural areas of Ghana and Kenya and an urban area of Mali, we randomly assigned infants aged 4-12 weeks without symptoms of gastrointestinal disorders in a 1:1 ratio to receive three oral doses of pentavalent rotavirus vaccine 2 mL or placebo at around 6 weeks, 10 weeks, and 14 weeks of age. Infants with HIV infection were not excluded. Randomisation was done by computer-generated randomisation sequence in blocks of six. We obtained data for gastrointestinal symptoms from parents on presentation to health-care facilities and clinical data were obtained prospectively by clinicians. The primary endpoint was severe rotavirus gastroenteritis (Vesikari score >or=11), detected by enzyme immunoassay, arising 14 days or more after the third dose of placebo or vaccine to end of study (March 31, 2009; around 21 months of age). Analysis was per protocol; infants who received scheduled doses of vaccine or placebo without intervening laboratory-confirmed naturally occurring rotavirus disease earlier than 14 days after the third dose and had complete clinical and laboratory results were included in the analysis. This study is registered with ClinicalTrials.gov, number NCT00362648. 5468 infants were randomly assigned to receive pentavalent rotavirus vaccine (n=2733) or placebo (n=2735). 2357 infants assigned to vaccine and 2348 assigned to placebo were included in the per-protocol analysis. 79 cases of severe rotavirus gastroenteritis were reported in 2610.6 person-years in the vaccine group, compared with 129 cases in 2585.9 person-years in the placebo group, resulting in a vaccine efficacy against severe rotavirus gastroenteritis of 39.3% (95% CI 19.1-54.7, p=0.0003 for efficacy >0%). Median follow-up in both groups was 527 days starting 14 days after the third dose of vaccine or placebo was given. 42 (1.5%) of 2723 infants assigned to receive vaccine and 45 (1.7%) of 2724 infants assigned to receive placebo had a serious adverse event within 14 days of any dose. The most frequent serious adverse event was gastroenteritis (vaccine 17 [0.6%]; placebo 17 [0.6%]). Pentavalent rotavirus vaccine is effective against severe rotavirus gastroenteritis in the first 2 years of life in African countries with high mortality in infants younger than 5 years. We support WHO's recommendation for adoption of rotavirus vaccine into national expanded programmes on immunisation in Africa. PATH (GAVI Alliance grant) and Merck. Copyright 2010 Elsevier Ltd. All rights reserved.

Predominant prevalence of human rotaviruses with the G1P[8] and G8P[8] genotypes with a short RNA profile in 2013 and 2014 in Sukhothai and Phetchaboon provinces, Thailand.

PubMed

Guntapong, Ratigorn; Tacharoenmuang, Ratana; Singchai, Phakapun; Upachai, Sompong; Sutthiwarakom, Karun; Komoto, Satoshi; Tsuji, Takao; Tharmaphornpilas, Piyanit; Yoshikawa, Tetsushi; Sangkitporn, Somchai; Taniguchi, Koki

2017-04-01

Of 2,754 stool specimens collected from children with acute gastroenteritis during 2013-2014 in Sukhothai and Phetchaboon provinces, Thailand, 666 (24.2%) were positive for rotavirus A (RVA) in polyacrylamide gel electrophoresis (PAGE). The G and P types of all RVA-positive specimens were determined by semi-nested RT-PCR. G1P[8] (56.5%) was most prevalent, followed by G2P[4] (22.1%). Unusual G8P[8] human RVAs (HuRVAs) were detected at a high frequency (20.0%). Interestingly, 171 of the 376 G1P[8] HuRVAs and all of the 133 G8P[8] HuRVAs showed a short RNA pattern in PAGE. Thus, it was shown that the properties of HuRVAs have been markedly unusual in recent years in Thailand. J. Med. Virol. 89:615-620, 2017. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

An infant with acute gastroenteritis caused by a secondary infection with a Rotarix-derived strain.

PubMed

Sakon, Naomi; Miyamoto, Ryohei; Komano, Jun

2017-09-01

Rotavirus vaccines have been successful in controlling severe diarrhea and have decreased deaths of young children globally. Rotarix and RotaTeq are the two currently available live-attenuated rotavirus vaccines. The vaccine virus can grow in a recipient's gut and spread from the vaccinee to naïve individuals. The potential for the emergence of revertant viruses is a concern with live-attenuated vaccines. We identified a previously healthy infant with severe acute gastroenteritis that was positive for rotavirus in a non-endemic season. A whole genome sequencing revealed that all of the viral genome segments were highly similar to those of the Rotarix virus, with the exception of five amino acid mutations in viral genes that could be associated with virulence. The younger sibling of this patient was administered Rotarix before the onset of disease in this patient, although no gastrointestinal symptoms were reported. Epidemiological data, circumstantial evidence, and the genome analysis suggest that the vaccine virus was transmitted from the vaccinee to the patient. This is a severe acute gastroenteritis case most probably attributed to the secondary infection of Rotarix-related virus without underlying diseases. The importance of molecular surveillance of rotavirus infections is discussed. What is Known: • The live-attenuated rotavirus vaccines, Rotarix and RotaTeq, have been successful in controlling severe diarrhea and have decreased deaths of young children globally. • Attenuated vaccine virus can grow in a recipient's gut and spread to naïve individuals and may revert to cause secondary symptomatic infections. What is New: • This is the first report describing a Rotarix-associated secondary infection resulting in severe acute gastroenteritis in an infant without underlying diseases. • Amino acid mutations that might contribute to viral pathogenesis were identified by whole genome sequencing.

Efficacy and safety of pentavalent rotavirus vaccine in Japan: a randomized, double-blind, placebo-controlled, multicenter trial.

PubMed

Iwata, Satoshi; Nakata, Shuji; Ukae, Susumu; Koizumi, Yoshitugu; Morita, Yasuyuki; Kuroki, Haruo; Tanaka, Yoshiyuki; Shizuya, Toshiyuki; Schödel, Florian; Brown, Michelle L; Lawrence, Jody

2013-08-01

Rotavirus is the most common cause of severe gastroenteritis in children under 5 y of age. Estimates of disease burden in Japan suggest that between 26,500 and 78,000 children in this age group need hospitalization each year, resulting in a direct medical cost of 10 to 24 billion Yen. Since being introduced in routine infant immunization schedules in the United States in 2006, the oral live pentavalent rotavirus vaccine RV5 (RotaTeq™) has contributed to dramatic reductions in the incidence of rotavirus gastroenteritis (RVGE) and in health care resource utilization. This was a multicenter, randomized, double-blind, placebo-controlled, parallel-group study to evaluate the efficacy and safety of a 3-dose regimen of RV5 in healthy infants, age 6 to 12 weeks, at 32 sites across Japan. The results indicate that RV5 was significantly efficacious in preventing any severity [74.5% (95% confidence interval [CI]: 39.9%, 90.6%; p<0.001)], moderate-to-severe [80.2% (95% CI: 47.4%, 94.1%)], and severe [100% (95% CI: 55.4%, 100%)] RVGE caused by viruses with serotypes contained in the vaccine. The observed cases of RVGE included rotavirus types G1 (n=19), G3 (n=9), G9 (n=5) and one unspecified G serotype with P1A[8]. No G2 or G4 RVGE cases were observed, and this study was not powered to evaluate efficacy against individual serotypes. RV5 was generally safe and well tolerated in Japanese infants. These results are comparable to those observed in clinical studies conducted in other developed countries. Introduction of the vaccine in Japan may reduce disease burden and associated health care costs.

Delayed Dosing of Oral Rotavirus Vaccine Demonstrates Decreased Risk of Rotavirus Gastroenteritis Associated With Serum Zinc: A Randomized Controlled Trial.

PubMed

Colgate, E Ross; Haque, Rashidul; Dickson, Dorothy M; Carmolli, Marya P; Mychaleckyj, Josyf C; Nayak, Uma; Qadri, Firdausi; Alam, Masud; Walsh, Mary Claire; Diehl, Sean A; Zaman, K; Petri, William A; Kirkpatrick, Beth D

2016-09-01

Rotavirus is the world's leading cause of childhood diarrheal death. Despite successes, oral rotavirus vaccines are less effective in developing countries. In an urban slum of Dhaka, we performed active diarrhea surveillance to evaluate monovalent G1P[8] rotavirus vaccine (RV1) efficacy and understand variables contributing to risk of rotavirus diarrhea (RVD). We performed a randomized controlled trial of monovalent oral rotavirus vaccine (RV1). Seven hundred healthy infants received RV1 or no RV1 (1:1) using delayed dosing (10 and 17 weeks) and were followed for 1 year. Intensive diarrhea surveillance was performed. The primary outcome was ≥1 episode of RVD. Nutritional, socioeconomic, and immunologic factors were assessed by logistic regression best-subsets analysis for association with risk of RVD and interactions with vaccine arm. Incidence of all RVD was 38.3 cases per 100 person-years. Per-protocol RV1 efficacy was 73.5% (95% confidence interval [CI], 45.8%-87.0%) against severe RVD and 51% (95% CI, 33.8%-63.7%) against all RVD. Serum zinc level (odds ratio [OR], 0.77; P = .002) and lack of rotavirus immunoglobulin A (IgA) seroconversion (OR, 1.95; P = .018) were associated with risk of RVD, independent of vaccination status. Water treatment and exclusive breastfeeding were of borderline significance. Factors not associated with RVD included height for age at 10 weeks, vitamin D, retinol binding protein, maternal education, household income, and sex. In an urban slum with high incidence of RVD, the efficacy of RV1 against severe RVD was higher than anticipated in the setting of delayed dosing. Lower serum zinc level and lack of IgA seroconversion were associated with increased risk of RVD independent of vaccination. NCT01375647. © The Author 2016. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail journals.permissions@oup.com.

The cost effectiveness of rotavirus vaccination in Iran.

PubMed

Mousavi Jarrahi, Yasaman; Zahraei, Seyed Mohsen; Sadigh, Nader; Esmaeelpoor Langeroudy, Keyhan; Khodadost, Mahmoud; Ranjbaran, Mehdi; Sanjari Moghaddam, Ali; Besharat, Mehdi; Mosavi Jarrahi, Alireza

2016-03-03

Rotavirus is the most common cause of severe diarrhea leading to hospitalization or disease-specific death among young children. Effective vaccines have recently been approved and successful vaccination program implemented. The aim of this study was to evaluate the cost effectiveness of mass rotavirus vaccination program in Iran. We developed a Markov model that reflects key features of rotavirus natural history. Parameters of the model were assessed by field study or developed through literature search and published data. We applied the model to the 2009 Iranian birth cohort and evaluated the cost-effectiveness of including the rotavirus vaccine (Rotarix®) into Iranian expanded immunization program (EPI). With an estimated hospitalization rate of 0.05 and outpatient rate of 0.23 cases per person-year, vaccinating cohort of 1231735 infants in Iran with 2 doses of (Rotarix®), would prevent 32092 hospitalizations, 158750 outpatient visits, and 1591 deaths during 5 y of follow-up. Under base-case assumption of $10 cost per course of vaccine, the vaccination would incur an extra cost of $1,019,192 from health care perspective and would avert 54680 DALYs. From societal perspective, there would be $15,192,568 saving for the society with the same averted DALYs. The incremental cost effectiveness ratio showed a cost of $19 US dollars per averted DALY from health care perspective and a saving of $278 US dollars for each averted DALY from societal perspective. Introducing rotavirus vaccine into EPI program would be highly cost-effective public health intervention in Iran.

Cost-effectiveness analysis of rotavirus vaccination in China: Projected possibility of scale-up from the current domestic option.

PubMed

Cui, Shuhui; Tobe, Ruoyan Gai; Mo, Xiuting; Liu, Xiaoyan; Xu, Lingzhong; Li, Shixue

2016-11-15

Rotavirus infection causes considerable disease burden of acute gastroenteritis (AGE) hospitalization and death among children less than 5 years in China. Although two rotavirus vaccines (Rotarix and RotaTeq) have been licensed in more than 100 countries in the world, the Lanzhou Lamb rotavirus vaccine (LLR) is the only vaccine licensed in China. This study aims to forecast the potential impacts of the two international vaccines compared to domestic LLR. An economic evaluation was performed using a Markov simulation model. We compared costs at the societal aspect and health impacts with and without a vaccination program by LLR, Rotarix or RotaTeq. Parameters including demographic, epidemiological data, costs and efficacy of vaccines were obtained from literature review. The model incorporated the impact of vaccination on reduction of incidence of rotavirus infection and severity of AGE indicated by hospitalization, inpatient visits and deaths. Outcomes are presented in terms of quality-adjusted life years (QALYs) gained and incremental cost-effectiveness ratio (ICER) compared to status quo. In a hypothetical cohort of 100,000 infants, the two international vaccines showed very good cost-effectiveness, with ICER of Rotateq and Rotarix shifting from LLR of $1715.11/QALY and $2105.66/QALY, respectively. Rotateq and Rotarix had significantly decreased incidence compared to LLR, particularly among infants aged 6 months to 2 years. RotaTeq is expected to introduce in the national routine immunization program to reduce disease burden of rotavirus infection with universal coverage.

Epidemiology, Seasonality and Factors Associated with Rotavirus Infection among Children with Moderate-to-Severe Diarrhea in Rural Western Kenya, 2008–2012: The Global Enteric Multicenter Study (GEMS)

PubMed Central

Omore, Richard; Tate, Jacqueline E.; O’Reilly, Ciara E.; Ayers, Tracy; Williamson, John; Moke, Feny; Schilling, Katie A.; Awuor, Alex O.; Jaron, Peter; Ochieng, John B.; Oundo, Joseph; Parashar, Umesh D.; Parsons, Michele B.; Bopp, Cheryl C.; Nasrin, Dilruba; Farag, Tamer H.; Kotloff, Karen L.; Nataro, James P.; Panchalingam, Sandra; Levine, Myron M.; Laserson, Kayla F.; Nuorti, J. Pekka; Mintz, Eric D.; Breiman, Robert F.

2016-01-01

Objective To evaluate factors associated with rotavirus diarrhea and to describe severity of illness among children <5 years old with non-dysenteric, moderate-to-severe diarrhea (MSD) in rural western Kenya. Methods We analyzed data from children <5 years old with non-dysenteric MSD enrolled as cases in the Global Enteric Multicenter Study (GEMS) in Kenya. A non-dysenteric MSD case was defined as a child with ≥3 loose stools in 24 hrs. and one or more of the following: sunken eyes, skin tenting, intravenous rehydration, or hospitalization, who sought care at a sentinel health center within 7 days of illness onset. Rotavirus antigens in stool samples were detected by ELISA. Demographic and clinical information was collected at enrollment and during a single follow-up home visit at approximately 60 days. We analyzed diarrhea severity using a GEMS 17 point numerical scoring system adapted from the Vesikari score. We used logistic regression to evaluate factors associated with rotavirus infection. Results From January 31, 2008 to September 30, 2012, among 1,637 (92%) non-dysenteric MSD cases, rotavirus was detected in stools of 245 (15.0%). Rotavirus-positive compared with negative cases were: younger (median age, 8 vs. 13 months; p<0.0001), had more severe illness (median severity score, 9 vs 8; p<0.0001) and had to be hospitalized more frequently (37/245 [15.1%] vs. 134/1,392 [9.6%]), p <0.013). Independent factors associated with rotavirus infection included age 0–11 months old (aOR = 5.29, 95% CI 3.14–8.89) and presenting with vomiting ≥3 times/24hrs (aOR = 2.58, 95% CI [1.91–3.48]). Rotavirus was detected more commonly in warm and dry months than in the cool and rainy months (142/691 [20%] vs 70/673 [10%]) p<0.0001). Conclusions Diarrhea caused by rotavirus is associated with severe symptoms leading to hospitalization. Consistent with other settings, infants had the greatest burden of disease. PMID:27494517

A Multi-Center, Qualitative Assessment of Pediatrician and Maternal Perspectives on Rotavirus Vaccines and the Detection of Porcine circovirus

PubMed Central

2011-01-01

Background In 2010, researchers using novel laboratory techniques found that US-licensed rotavirus vaccines contain DNA or DNA fragments from Porcine circovirus (PCV), a virus common among pigs but not believed to cause illness in humans. We sought to understand pediatricians' and mothers' perspectives on this finding. Methods We conducted three iterations of focus groups for pediatricians and non-vaccine hesitant mothers in Seattle, WA, Cincinnati, OH, and Rochester, NY. Focus groups explored perceptions of rotavirus disease, rotavirus vaccination, and attitudes about the detection of PCV material in rotavirus vaccines. Results Pediatricians understood firsthand the success of rotavirus vaccines in preventing severe acute gastroenteritis among infants and young children. They measured this benefit against the theoretical risk of DNA material from PCV in rotavirus vaccines, determining overall that the PCV finding was of no clinical significance. Particularly influential was the realization that the large, randomized clinical trials that found both vaccines to be highly effective and safe were conducted with DNA material from PCV already in the vaccines. Most mothers supported the ideal of full disclosure regarding vaccination risks and benefits. However, with a scientific topic of this complexity, simplified information regarding PCV material in rotavirus vaccines seemed frightening and suspicious, and detailed information was frequently overwhelming. Mothers often remarked that if they did not understand a medical or technical topic regarding their child's health, they relied on their pediatrician's guidance. Many mothers and pediatricians were also concerned that persons who abstain from pork consumption for religious or personal reasons may have unsubstantiated fears of the PCV finding. Conclusions Pediatricians considered the detection of DNA material from PCV in rotavirus vaccines a "non-issue" and reported little hesitation in continuing to recommend the vaccines. Mothers desired transparency, but ultimately trusted their pediatrician's recommendation. Both vaccines are currently approved for their intended use, and no risk of human PCV illness has been reported. Communicating this topic to pediatricians and mothers requires sensitivity to a broad range of technical understanding and personal concerns. PMID:21943237

Impact of maternal antibodies and infant gut microbiota on the immunogenicity of rotavirus vaccines in African, Indian and European infants: protocol for a prospective cohort study.

PubMed

Sindhu, Kuladaipalayam Natarajan C; Cunliffe, Nigel; Peak, Matthew; Turner, Mark; Darby, Alistair; Grassly, Nicholas; Gordon, Melita; Dube, Queen; Babji, Sudhir; Praharaj, Ira; Verghese, Valsan; Iturriza-Gómara, Miren; Kang, Gagandeep

2017-03-29

Gastroenteritis is the leading cause of morbidity and mortality among young children living in resource-poor settings, majority of which is attributed to rotavirus. Rotavirus vaccination can therefore have a significant impact on infant mortality. However, rotavirus vaccine efficacy in Sub-Saharan Africa and Southeast Asia is significantly lower than in high-income countries. Maternally derived antibodies, infant gut microbiota and concomitant oral polio vaccination have been proposed as potential reasons for poor vaccine performance in low-income settings. The overall aim of this study is to compare the role of maternally derived antibodies and infant gut microbiota in determining immune response to rotavirus vaccine in high-income and low-income settings, using the same vaccine and a similar study protocol. The study is an observational cohort in three countries-Malawi, India and UK. Mothers will be enrolled in third trimester of pregnancy and followed up, along with infants after delivery, until the infant completes two doses of oral rotavirus vaccine (along with routine immunisation). The levels of prevaccination maternally derived rotavirus-specific antibodies (IgG) will be correlated with infant seroconversion and antibody titres, 4 weeks after the second dose of rotavirus vaccine. Both within-country and between-country comparisons of gut microbiome will be carried out between children who seroconvert and those who do not. The impact of oral polio vaccine coadministration on rotavirus vaccine response will be studied in Indian infants. Ethical approvals have been obtained from Integrated Research Application System (IRAS, NHS ethics) in UK, College of Medicine Research and Ethics Committee (COMREC) in Malawi and Institutional Review Board (IRB), Christian Medical College, Vellore in India. Participant recruitment and follow-up is ongoing at all three sites. Analysis of data, followed by publication of the results, is expected in 2018. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

Phylogenetic analysis of human G9P[8] rotavirus strains circulating in Jiangsu, China between 2010 and 2016.

PubMed

Xu, Cheng; Fu, Jianguang; Ai, Jing; Zhang, Jun; Liu, Cheng; Huo, Xiang; Bao, Changjun; Zhu, Yefei

2018-05-02

Rotavirus A (RVA) is the leading cause of acute viral gastroenteritis in children under 5 years of age worldwide. G9P[8] is a common RVA genotype that has been persistently prevalent in Jiangsu, China. To determine the genetic diversity of G9P[8] RVAs, 7 representative G9P[8] strains collected from Suzhou Children's Hospital between 2010 and 2016 (named JS2010-JS2016) were analyzed through whole-genome sequencing. All evaluated strains showed the Wa-like constellation G9-P[8]-I1-R1-C1-M1-A1-N1-T1-E1-H1. Furthermore, phylogenetic analysis revealed that the VP7 genes of all strains clustered into lineage G9-III and G9-VI. With the exception of strain JS2012 (P[8]-4), the VP4 sequences of all strains belonged to the P[8]-3 lineage. Sequencing further revealed that amino acid substitutions were present in the antigenic regions of the VP7 and VP4 genes of all strains. Moreover, there were multiple substitutions in antigenic sites I and II of the nonstructural protein 4 (NSP4) genes, whereas the other NSP genes were relatively conserved. In conclusion, our phylogenetic analysis of these 7 G9P[8] strains suggests that RVA varied across regions and time. Therefore, our findings suggest that continued surveillance is necessary to explore the molecular evolutionary characteristics of RVA for better prevention and treatment of acute viral gastroenteritis. © 2018 Wiley Periodicals, Inc.

Prevalence and Genetic Diversity of Norovirus Among Patients With Acute Diarrhea in Guatemala

PubMed Central

Estévez, Alejandra; Arvelo, Wences; Hall, Aron J.; López, María R.; López, Beatriz; Reyes, Lissette; Moir, Juan Carlos; Gregoricus, Nicole; Vinjé, Jan; Parashar, Umesh D.; Lindblade, Kim A.

2015-01-01

Noroviruses (NoVs) are a leading cause of acute gastroenteritis outbreaks and sporadic cases of diarrhea in industrialized countries. To study the prevalence and genetic diversity of NoVs in Guatemala, stool specimens were collected from hospitalized and ambulatory patients presenting with diarrhea (≥3 loose or liquid stools in a 24-hr period) who were enrolled in a prospective surveillance system in the Departments of Santa Rosa (October 2007 to August 2010) and Quetzaltenango (August 2009 to August 2010), Guatemala. Specimens were tested for rotavirus, enteric bacteria, and parasites by routine methods and for genogroups I and II NoV by real-time reverse transcription-PCR. A total of 2,403 stool specimens were collected from hospitalized (n = 528) and ambulatory patients (n = 1,875). Overall, 341 (14%) samples tested positive for NoVs including 114 (22%) hospitalized and 227 (12%) ambulatory patients. NoVs disease peaked during the winter (November–January) months. Among the 341 NoVs-positive patients, 32 (9%) were also positive for rotavirus, 32 (9%) for bacteria, and 9 (3%) for protozoa. Nucleotide sequences were obtained from 84 samples collected from hospitalized children aged <5 years of age, which could be grouped into nine GII and three GI genotypes with GII.4 (74%) and GI.8 (10%) being the most common. This is the first study on the prevalence of NoVs among hospitalized and ambulatory patients with diarrhea in Guatemala. The findings highlight the need to implement laboratory diagnostics for NoVs to improve appropriate clinical management of diarrheal diseases and guide vaccine development. PMID:23595770

Nlrp9b inflammasome restricts rotavirus infection in intestinal epithelial cells

PubMed Central

Zhu, Shu; Ding, Siyuan; Wang, Penghua; Wei, Zheng; Pan, Wen; Palm, Noah W; Yang, Yi; Yu, Hua; Li, Hua-Bing; Wang, Geng; Lei, Xuqiu; de Zoete, Marcel R.; Zhao, Jun; Zheng, Yunjiang; Chen, Haiwei; Zhao, Yujiao; Jurado, Kellie A.; Feng, Ningguo; Shan, Liang; Kluger, Yuval; Lu, Jun; Abraham, Clara; Fikrig, Erol; Greenberg, Harry B.; Flavell, Richard A.

2018-01-01

Rotavirus, a leading cause of severe gastroenteritis and diarrhoea in young children, accounts for around 215,000 deaths annually worldwide1. Rotavirus specifically infects the intestinal epithelial cells in the host small intestine and has evolved strategies to antagonize interferon and NF-κB signalling2–5, raising the question as to whether other host factors participate in antiviral responses in intestinal mucosa. The mechanism by which enteric viruses are sensed and restricted in vivo, especially by NOD-like receptor (NLR) inflammasomes, is largely unknown. Here we uncover and mechanistically characterize the NLR Nlrp9b that is specifically expressed in intestinal epithelial cells and restricts rotavirus infection. Our data show that, via RNA helicase Dhx9, Nlrp9b recognizes short double-stranded RNA stretches and forms inflammasome complexes with the adaptor proteins Asc and caspase-1 to promote the maturation of interleukin (Il)-18 and gasdermin D (Gsdmd)-induced pyroptosis. Conditional depletion of Nlrp9b or other inflammasome components in the intestine in vivo resulted in enhanced susceptibility of mice to rotavirus replication. Our study highlights an important innate immune signalling pathway that functions in intestinal epithelial cells and may present useful targets in the modulation of host defences against viral pathogens. PMID:28636595

Oral immunization with rotavirus VP7-CTB fusion expressed in transgenic Arabidopsis thaliana induces antigen-specific IgA and IgG and passive protection in mice

PubMed Central

Li, Yuxian; Guan, Lili; Liu, Xiuming; Liu, Weican; Yang, Jing; Zhang, Xiaomei; Wang, Fawei; Guo, Yongxin; Li, Haiyan; Li, Xiaokun

2018-01-01

Human rotavirus (HRV) is the primary cause of severe gastroenteritis in children. However, there is currently no protective virus for rotavirus available. In the present study, an HRVVP7-cholera toxin B subunit (CTB) fusion protein was expressed in Arabidopsis thaliana. To determine the adjuvant effect of HRVVP7-CTB, HRVVP7 without CTB was expressed in the same manner. HRVVP7-CTB accounted for 0.39% of the total soluble protein (TSP) in the transgenic seeds and 52.65 µg/g of HRVVP7 protein was expressed in these seeds. Mice were immunized with TSP from the transformed seeds and produced serum immunoglobulin G (IgG) and mucosal IgA specifically directed against HRVVP7. Antibody titers were highest in mice orally immunized with the plant-expressed HRVVP7-CTB protein, whereas HRVVP7-CTB-specific IgG neutralized the rotavirus. Suckling pups born from dams immunized with the HRVVP7-CTB fusion protein were protected against challenge with virulent rotavirus. The results of the present study suggest that the HRVVP7-CTB fusion protein produced in A. thaliana may be a rotaviral-specific candidate subunit vaccine. PMID:29805507

Comparative In Vitro and In Vivo Studies of Porcine Rotavirus G9P[13] and Human Rotavirus Wa G1P[8

PubMed Central

Shao, Lulu; Fischer, David D.; Kandasamy, Sukumar; Rauf, Abdul; Langel, Stephanie N.; Wentworth, David E.; Stucker, Karla M.; Halpin, Rebecca A.; Lam, Ham Ching; Marthaler, Douglas

2015-01-01

ABSTRACT The changing epidemiology of group A rotavirus (RV) strains in humans and swine, including emerging G9 strains, poses new challenges to current vaccines. In this study, we comparatively assessed the pathogenesis of porcine RV (PRV) G9P[13] and evaluated the short-term cross-protection between this strain and human RV (HRV) Wa G1P[8] in gnotobiotic pigs. Complete genome sequencing demonstrated that PRV G9P[13] possessed a human-like G9 VP7 genotype but shared higher overall nucleotide identity with historic PRV strains. PRV G9P[13] induced longer rectal virus shedding and RV RNAemia in pigs than HRV Wa G1P[8] and generated complete short-term cross-protection in pigs challenged with HRV or PRV, whereas HRV Wa G1P[8] induced only partial protection against PRV challenge. Moreover, PRV G9P[13] replicated more extensively in porcine monocyte-derived dendritic cells (MoDCs) than did HRV Wa G1P[8]. Cross-protection was likely not dependent on serum virus-neutralizing (VN) antibodies, as the heterologous VN antibody titers in the sera of G9P[13]-inoculated pigs were low. Thus, our results suggest that heterologous protection by the current monovalent G1P[8] HRV vaccine against emerging G9 strains should be evaluated in clinical and experimental studies to prevent further dissemination of G9 strains. Differences in the pathogenesis of these two strains may be partially attributable to their variable abilities to replicate and persist in porcine immune cells, including dendritic cells (DCs). Additional studies are needed to evaluate the emerging G9 strains as potential vaccine candidates and to test the susceptibility of various immune cells to infection by G9 and other common HRV/PRV genotypes. IMPORTANCE The changing epidemiology of porcine and human group A rotaviruses (RVs), including emerging G9 strains, may compromise the efficacy of current vaccines. An understanding of the pathogenesis and genetic, immunological, and biological features of the new emerging RV strains will contribute to the development of new surveillance and prevention tools. Additionally, studies of cross-protection between the newly identified emerging G9 porcine RV strains and a human G1 RV vaccine strain in a susceptible host (swine) will allow evaluation of G9 strains as potential novel vaccine candidates to be included in porcine or human vaccines. PMID:26468523

Effects of Lactobacillus rhamnosus GG on the maturation and differentiation of dendritic cells in rotavirus-infected mice.

PubMed

Jiang, Y; Ye, L; Cui, Y; Yang, G; Yang, W; Wang, J; Hu, J; Gu, W; Shi, C; Huang, H; Wang, C

2017-08-24

Rotavirus-related diarrhoea is considered one of the most important diseases in field animal production. In addition to the classic vaccine strategy, a number of studies have utilised probiotics, such as Lactobacillus rhamnosus GG (LGG), to prevent rotavirus-induced diarrhoea. Although it has been partially revealed that Toll-like receptors (TLRs) are involved in the LGG-mediated protection against rotavirus infection, the details of the underlying immunologic mechanisms remain largely unknown. In this study, three-to-four-week-old female BALB/c mice were divided into three groups and orally administered phosphate buffered saline (PBS), PBS plus rotavirus or LGG plus rotavirus, respectively. The differentiation and maturation of dendritic cells (DCs) were then determined by FACS, the expression levels of TLR-3 and nuclear factor kappa beta (NF-κB) were evaluated using real time PCR, and the production of inflammatory cytokines in mesenteric lymph nodes (MLNs) were determined by ELISA. The results demonstrated that rotavirus infection significantly increased the percentage of CD11c + CD11b + CD8a - DCs and decreased the percentage of CD11c + CD11b - CD8a + DCs in MLNs. By contrast, the presence of LGG significantly decreased the percentage of CD11c + CD11b + CD8a - DCs and increased the percentage of CD11c + CD11b - CD8a + DCs, which indicates that the differentiation of DCs is involved in the protective effects of LGG. Rotavirus infection also resulted in the increased expression of surface markers such as CD40, CD80 and MHC-II in DCs, and the administration of LGG significantly increased the expression level further. The mRNA levels of TLR-3 and NF-κB in the intestine and MLNs were also significantly increased in the presence of rotavirus, which was further increased in the presence of LGG. The production of inflammatory cytokines was also determined, and the results showed that rotavirus caused the increased production of interleukin (IL)-12 and tumour necrosis factor alpha; this effect was further enhanced by LGG. Meanwhile, although rotavirus infection led to the increased production of IL-6 and IL-10, the presence of LGG significantly decreased the mRNA levels of these cytokines. By contrast, rotavirus infection resulted in the decreased production of interferon gamma (IFN-γ), and the administration of LGG significantly increased the levels of IFN-γ. Taken together, the protective effects of LGG were partially due to the modulation of the differentiation and maturation of DCs, the increased production of TLR-3 and NF-κB, and the modulation of inflammatory cytokines.

The Battle between Rotavirus and Its Host for Control of the Interferon Signaling Pathway

PubMed Central

Arnold, Michelle M.; Sen, Adrish; Greenberg, Harry B.; Patton, John T.

2013-01-01

Viral pathogens must overcome innate antiviral responses to replicate successfully in the host organism. Some of the mechanisms viruses use to interfere with antiviral responses in the infected cell include preventing detection of viral components, perturbing the function of transcription factors that initiate antiviral responses, and inhibiting downstream signal transduction. RNA viruses with small genomes and limited coding space often express multifunctional proteins that modulate several aspects of the normal host response to infection. One such virus, rotavirus, is an important pediatric pathogen that causes severe gastroenteritis, leading to ∼450,000 deaths globally each year. In this review, we discuss the nature of the innate antiviral responses triggered by rotavirus infection and the viral mechanisms for inhibiting these responses. PMID:23359266

Characterisation of a rare, reassortant human G10P[14] rotavirus strain detected in Honduras

PubMed Central

Quaye, Osbourne; Roy, Sunando; Rungsrisuriyachai, Kunchala; Esona, Mathew D; Xu, Ziqian; Tam, Ka Ian; Banegas, Dina J Castro; Rey-Benito, Gloria; Bowen, Michael D

2018-01-01

BACKGROUND Although first detected in animals, the rare rotavirus strain G10P[14] has been sporadically detected in humans in Slovenia, Thailand, United Kingdom and Australia among other countries. Earlier studies suggest that the strains found in humans resulted from interspecies transmission and reassortment between human and bovine rotavirus strains. OBJECTIVES In this study, a G10P[14] rotavirus genotype detected in a human stool sample in Honduras during the 2010-2011 rotavirus season, from an unvaccinated 30-month old boy who reported at the hospital with severe diarrhea and vomiting, was characterised to determine the possible evolutionary origin of the rare strain. METHODS For the sample detected as G10P[14], 10% suspension was prepared and used for RNA extraction and sequence independent amplification. The amplicons were sequenced by next-generation sequencing using the Illumina MiSeq 150 paired end method. The sequence reads were analysed using CLC Genomics Workbench 6.0 and phylogenetic trees were constructed using PhyML version 3.0. FINDINGS The next generation sequencing and phylogenetic analyses of the 11-segmented genome of the G10P[14] strain allowed classification as G10-P[14]-I2-R2-C2-M2-A3-N2-T6-E2-H3. Six of the genes (VP1, VP2, VP3, VP6, NSP2 and NSP4) were DS-1-like. NSP1 and NSP5 were AU-1-like and NSP3 was T6, which suggests that multiple reassortment events occurred in the evolution of the strain. The phylogenetic analyses and genetic distance calculations showed that the VP7, VP4, VP6, VP1, VP3, NSP1, NSP3 and NSP4 genes clustered predominantly with bovine strains. NSP2 and VP2 genes were most closely related to simian and human strains, respectively, and NSP5 was most closely related to a rhesus strain. MAIN CONCLUSIONS The genetic characterisation of the G10P[14] strain from Honduras suggests that its genome resulted from multiple reassortment events which were possibly mediated through interspecies transmissions. PMID:29211103

Characterisation of a rare, reassortant human G10P[14] rotavirus strain detected in Honduras.

PubMed

Quaye, Osbourne; Roy, Sunando; Rungsrisuriyachai, Kunchala; Esona, Mathew D; Xu, Ziqian; Tam, Ka Ian; Banegas, Dina J Castro; Rey-Benito, Gloria; Bowen, Michael D

2018-01-01

Although first detected in animals, the rare rotavirus strain G10P[14] has been sporadically detected in humans in Slovenia, Thailand, United Kingdom and Australia among other countries. Earlier studies suggest that the strains found in humans resulted from interspecies transmission and reassortment between human and bovine rotavirus strains. In this study, a G10P[14] rotavirus genotype detected in a human stool sample in Honduras during the 2010-2011 rotavirus season, from an unvaccinated 30-month old boy who reported at the hospital with severe diarrhea and vomiting, was characterised to determine the possible evolutionary origin of the rare strain. For the sample detected as G10P[14], 10% suspension was prepared and used for RNA extraction and sequence independent amplification. The amplicons were sequenced by next-generation sequencing using the Illumina MiSeq 150 paired end method. The sequence reads were analysed using CLC Genomics Workbench 6.0 and phylogenetic trees were constructed using PhyML version 3.0. The next generation sequencing and phylogenetic analyses of the 11-segmented genome of the G10P[14] strain allowed classification as G10-P[14]-I2-R2-C2-M2-A3-N2-T6-E2-H3. Six of the genes (VP1, VP2, VP3, VP6, NSP2 and NSP4) were DS-1-like. NSP1 and NSP5 were AU-1-like and NSP3 was T6, which suggests that multiple reassortment events occurred in the evolution of the strain. The phylogenetic analyses and genetic distance calculations showed that the VP7, VP4, VP6, VP1, VP3, NSP1, NSP3 and NSP4 genes clustered predominantly with bovine strains. NSP2 and VP2 genes were most closely related to simian and human strains, respectively, and NSP5 was most closely related to a rhesus strain. The genetic characterisation of the G10P[14] strain from Honduras suggests that its genome resulted from multiple reassortment events which were possibly mediated through interspecies transmissions.

Highly sensitive detection of the group A Rotavirus using Apolipoprotein H-coated ELISA plates compared to quantitative real-time PCR.

PubMed

Adlhoch, Cornelia; Kaiser, Marco; Hoehne, Marina; Mas Marques, Andreas; Stefas, Ilias; Veas, Francisco; Ellerbrok, Heinz

2011-02-10

The principle of a capture ELISA is binding of specific capture antibodies (polyclonal or monoclonal) to the surface of a suitable 96 well plate. These immobilized antibodies are capable of specifically binding a virus present in a clinical sample. Subsequently, the captured virus is detected using a specific detection antibody. The drawback of this method is that a capture ELISA can only function for a single virus captured by the primary antibody. Human Apolipoprotein H (ApoH) or β2-glycoprotein 1 is able to poly-specifically bind viral pathogens. Replacing specific capture antibodies by ApoH should allow poly-specific capture of different viruses that subsequently could be revealed using specific detection antibodies. Thus, using a single capture ELISA format different viruses could be analysed depending on the detection antibody that is applied. In order to demonstrate that this is a valid approach we show detection of group A rotaviruses from stool samples as a proof of principle for a new method of capture ELISA that should also be applicable to other viruses. Stool samples of different circulating common human and potentially zoonotic group A rotavirus strains, which were pretested in commercial EIAs and genotyped by PCR, were tested in parallel in an ApoH-ELISA set-up and by quantitative real-time PCR (qPCR). Several control samples were included in the analysis. The ApoH-ELISA was suitable for the capture of rotavirus-particles and the detection down to 1,000 infectious units (TCID(50/ml)). Subsets of diagnostic samples of different G- and P-types were tested positive in the ApoH-ELISA in different dilutions. Compared to the qPCR results, the analysis showed high sensitivity, specificity and low cross-reactivity for the ApoH-ELISA, which was confirmed in receiver operating characteristics (ROC) analysis. In this study the development of a highly sensitive and specific capture ELISA was demonstrated by combining a poly-specific ApoH capture step with specific detection antibodies using group A rotaviruses as an example.

Whole genome sequences of Japanese porcine species C rotaviruses reveal a high diversity of genotypes of individual genes and will contribute to a comprehensive, generally accepted classification system.

PubMed

Niira, Kazutaka; Ito, Mika; Masuda, Tsuneyuki; Saitou, Toshiya; Abe, Tadatsugu; Komoto, Satoshi; Sato, Mitsuo; Yamasato, Hiroshi; Kishimoto, Mai; Naoi, Yuki; Sano, Kaori; Tuchiaka, Shinobu; Okada, Takashi; Omatsu, Tsutomu; Furuya, Tetsuya; Aoki, Hiroshi; Katayama, Yukie; Oba, Mami; Shirai, Junsuke; Taniguchi, Koki; Mizutani, Tetsuya; Nagai, Makoto

2016-10-01

Porcine rotavirus C (RVC) is distributed throughout the world and is thought to be a pathogenic agent of diarrhea in piglets. Although, the VP7, VP4, and VP6 gene sequences of Japanese porcine RVCs are currently available, there is no whole-genome sequence data of Japanese RVC. Furthermore, only one to three sequences are available for porcine RVC VP1-VP3 and NSP1-NSP3 genes. Therefore, we determined nearly full-length whole-genome sequences of nine Japanese porcine RVCs from seven piglets with diarrhea and two healthy pigs and compared them with published RVC sequences from a database. The VP7 genes of two Japanese RVCs from healthy pigs were highly divergent from other known RVC strains and were provisionally classified as G12 and G13 based on the 86% nucleotide identity cut-off value. Pairwise sequence identity calculations and phylogenetic analyses revealed that candidate novel genotypes of porcine Japanese RVC were identified in the NSP1, NSP2 and NSP3 encoding genes, respectively. Furthermore, VP3 of Japanese porcine RVCs was shown to be closely related to human RVCs, suggesting a gene reassortment event between porcine and human RVCs and past interspecies transmission. The present study demonstrated that porcine RVCs show greater genetic diversity among strains than human and bovine RVCs. Copyright © 2016 Elsevier B.V. All rights reserved.

Molecular epidemiology of enteric viruses in patients with acute gastroenteritis in Aichi prefecture, Japan, 2008/09-2013/14.

PubMed

Nakamura, Noriko; Kobayashi, Shinichi; Minagawa, Hiroko; Matsushita, Tadashi; Sugiura, Wataru; Iwatani, Yasumasa

2016-07-01

Acute gastroenteritis is a critical infectious disease that affects infants and young children throughout the world, including Japan. This retrospective study was conducted from September 2008 to August 2014 (six seasons: 2008/09-2013/14) to investigate the incidence of enteric viruses responsible for 1,871 cases of acute gastroenteritis in Aichi prefecture, Japan. Of the 1,871 cases, 1,100 enteric viruses were detected in 978 samples, of which strains from norovirus (NoV) genogroup II (60.9%) were the most commonly detected, followed by strains of rotavirus A (RVA) (23.2%), adenovirus (AdV) type 41 (8.2%), sapovirus (SaV) (3.6%), human astrovirus (HAstV) (2.8%), and NoV genogroup I (1.3%). Sequencing of the NoV genogroup II (GII) strains revealed that GII.4 was the most common genotype, although four different GII.4 variants were also identified. The most common G-genotype of RVA was G1 (63.9%), followed by G3 (27.1%), G2 (4.7%) and G9 (4.3%). Three genogroups of SaV strains were found: GI (80.0%), GII (15.0%), and GV (5.0%). HAstV strains were genotyped as HAstV-1 (80.6%), HAstV-8 (16.1%), and HAstV-3 (3.2%). These results show that NoV GII was the leading cause of sporadic acute viral gastroenteritis, although a variety of enteric viruses were detected during the six-season surveillance period. © 2015 Wiley Periodicals, Inc.

ADEQUACY OF DISINFECTION FOR CONTROL OF NEWLY RECOGNIZED WATERBORNE PATHOGENS

EPA Science Inventory

Agents recently recognized as causes or potential causes of waterborne outbreaks include pathogenic bacteria (Campylobacter jejuni, Yersinia enterocoliticia), viruses (rotavirus, Norwalk virus and other poorly defined viral agents) and Giardia lamblia, a protozoan agent. Although...

Epidemiology and burden of rotavirus-associated hospitalizations in Ferrara, Italy.

PubMed

Gabutti, G; Marsella, M; Lazzara, C; Fiumana, E; Cavallaro, A; Borgna-Pignatti, C

2007-03-01

Objective of this study was to provide data on hospitalizations for rotavirus gastroenteritis (RVGE) in Ferrara, Italy. The study was conducted analyzing the hospital discharge forms of all children admitted to the Pediatric Department of the University of Ferrara, Arcispedale Sant'Anna, from January 2001 through December 2005. The database was searched for all gastrointestinal diseases and in particular RVGE. During the period under study 3277 children, of which 2038 <60 months of age, were hospitalized; 247 children < 5 years old were admitted for acute gastroenteritis and 89 (4.4% of all and 36% of gastroenteritis-related hospitalizations) had rapid screening tests positive for rotavirus. A seasonal pattern was observed for RVGE with an increase in winter and early spring. The average length of hospital stay was 5.7 days. The median cost of each hospitalized case of RVGE ranged between 1417 and 1595 Euros. The present research confirms that rotavirus gastroenteritis represents an important cause of hospitalization in children and is responsible for significant costs for the Public Health Care System. An effective vaccination program could significantly reduce the incidence of hospitalization and the associated costs.

Pectic polysaccharides from Panax ginseng as the antirotavirus principals in ginseng.

PubMed

Baek, Seung-Hoon; Lee, Jin Gyun; Park, Seo Young; Bae, Ok Nam; Kim, Dong-Hyun; Park, Jeong Hill

2010-08-09

To evaluate the antidiarrheal effect of ginseng, the active principals of ginseng were studied in vitro model of rotavirus infection, the leading cause of severe diarrhea. Two pectic polysaccharides, named as GP50-dHR (56.0 kDa) and GP50-eHR (77.0 kDa), were purified from hot water extract of ginseng by bioassay-linked fractionation. Both polysaccharides rescued cell viability from rotavirus infection dose-dependently (IC50 are 15 and 10 microg/mL, respectively). Both polysaccharides had common structural features of homogalacturonan backbone with hairy regions of rhamnogalacturonan type I. Arabinose-rich side chains with abundant branch points were unique in GP50-eHR and may contribute to a greater antirotavirus effect of GP50-eHR than GP50-dHR. Because homogalacturonan itself did not show an antirotavirus effect, hairy regions might be functional sites. Of note, the antirotavirus effect of both polysaccharides resulted from inhibiting rotavirus attachment to cells. Together with a wide range of noncytotoxicity, these findings suggest that ginseng polysaccharides are viable therapeutic options for rotavirus diarrhea.

Trends in Rate of Seizure-Associated Hospitalizations Among Children <5 Years Old Before and After Rotavirus Vaccine Introduction in the United Sates, 2000-2013.

PubMed

Pringle, Kimberly D; Burke, Rachel M; Steiner, Claudia A; Parashar, Umesh D; Tate, Jacqueline E

2018-01-30

Rotavirus is a common cause of acute gastroenteritis and has also been associated with generalized tonic-clonic afebrile seizures. Since rotavirus vaccine introduction, hospitalizations for treatment of acute gastroenteritis have decreased. We assess whether there has been an associated decrease in seizure-associated hospitalizations. We used discharge codes to abstract data on seizure hospitalizations among children <5 years old from the State Inpatient Databases of the Healthcare Cost and Utilization Project. We compared seizure hospitalization rates before and after vaccine introduction, using Poisson regression, stratifying by age and by month and year of admission. We performed a time-series analysis with negative binomial models, constructed using prevaccine data from 2000 to 2006 and controlling for admission month and year. We examined 962899 seizure hospitalizations among children <5 years old during 2000-2013. Seizure rates after vaccine introduction were lower than those before vaccine introduction by 1%-8%, and rate ratios decreased over time. Time-series analyses demonstrated a decrease in the number of seizure-coded hospitalizations in 2012 and 2013, with notable decreases in children 12-17 months and 18-23 months. Our analysis provides evidence for a decrease in seizure hospitalizations following rotavirus vaccine introduction in the United States, with the greatest impact in age groups with a high rotavirus-associated disease burden and during rotavirus infection season. Published by Oxford University Press for the Infectious Diseases Society of America 2018. This work is written by (a) US Government employee(s) and is in the public domain in the US.

Study of the Ability of Bifidobacteria of Human Origin to Prevent and Treat Rotavirus Infection Using Colonic Cell and Mouse Models

PubMed Central

Darveau, André; Fliss, Ismaïl

2016-01-01

Rotavirus is the leading cause of severe acute gastroenteritis among children worldwide. Despite effective vaccines, inexpensive alternatives such as probiotics are needed. The aim of this study was to assess the ability of probiotic candidate Bifidobacterium thermophilum RBL67 to inhibit rotavirus infection. Bacterial adhesion to intestinal cells and interference with viral attachment were evaluated in vitro. B. thermophilum RBL67 displayed adhesion indexes of 625 ± 84 and 1958 ± 318 on Caco-2 and HT-29 cells respectively and was comparable or superior to four other bifidobacteria, including B. longum ATCC 15707 and B. pseudolongum ATCC 25526 strains. Incubation of B. thermophilum RBL67 for 30 min before (exclusion) and simultaneously (competition) with human rotavirus strain Wa decreased virus attachment by 2.0 ± 0.1 and 1.5 ± 0.1 log10 (by 99.0% and 96.8% respectively). Displacement of virus already present was negligible. In CD-1 suckling mice fed B. thermophilum RBL67 challenged with simian rotavirus SA-11, pre-infection feeding with RBL 67 was more effective than post-infection feeding, reducing the duration of diarrhea, limiting epithelial lesions, reducing viral replication in the intestine, accelerating recovery, and stimulating the humoral specific IgG and IgM response, without inducing any adverse effect. B. thermophilum RBL67 had little effect on intestinal IgA titer. These results suggest that humoral immunoglobulin might provide protection against the virus and that B. thermophilum RBL67 has potential as a probiotic able to inhibit rotavirus infection and ultimately reduce its spread. PMID:27727323

Development of an in situ magnetic beads based RT-PCR method for electrochemiluminescent detection of rotavirus

NASA Astrophysics Data System (ADS)

Zhan, Fangfang; Zhou, Xiaoming

2012-12-01

Rotaviruses are double-stranded RNA viruses belonging to the family of enteric pathogens. It is a major cause of diarrhoeal disease in infants and young children worldwide. Consequently, rapid and accurate detection of rotaviruses is of great importance in controlling and preventing food- and waterborne diseases and outbreaks. Reverse transcription-polymerase chain reaction (RT-PCR) is a reliable method that possesses high specificity and sensitivity. It has been widely used to detection of viruses. Electrochemiluminescence (ECL) can be considered as an important and powerful tool in analytical and clinical application with high sensitivity, excellent specificity, and low cost. Here we have developed a method for the detection of rotavirus by combining in situ magnetic beads (MBs) based RT-PCR with ECL. RT of rotavirus RNA was carried out in a traditional way and the resulting cDNA was directly amplified on MBs. Forward primers were covalently bounded to MBs and reverse primers were labeled with tris-(2, 2'-bipyridyl) ruthenium (TBR). During the PCR cycling, the TBR labeled products were directly loaded and enriched on the surface of MBs. Then the MBs-TBR complexes could be analyzed by a magnetic ECL platform without any post-modification or post-incubation which avoid some laborious manual operations and achieve rapid yet sensitive detection. In this study, rotavirus from fecal specimens was successfully detected within 2 h, and the limit of detection was estimated to be 104copies/μL. This novel in situ MBs based RT-PCR with ECL detection method can be used for pathogen detection in food safety field and clinical diagnosis.

Active Viremia in Rotavirus-Infected Mice

PubMed Central

Blutt, Sarah E.; Fenaux, Martijn; Warfield, Kelly L.; Greenberg, Harry B.; Conner, Margaret E.

2006-01-01

Rotavirus circulates extraintestinally in animals used as models for rotavirus infection and in children. Rotavirus infection in mice was used to define host or viral factors that affect rotavirus viremia. Antigenemia was observed with homologous and heterologous rotaviruses, and neither age nor mouse strain genetics altered the occurrence of rotavirus antigenemia or viremia. Rotavirus RNA and infectious virus were present in sera and associated with the plasma fraction of blood in all infected mice. These findings indicate that antigenemia/viremia occurs routinely in rotavirus infections and imply that infectious rotavirus has access to any extraintestinal cell within contact of blood. PMID:16775359

Species C Rotaviruses in Children with Diarrhea in India, 2010-2013: A Potentially Neglected Cause of Acute Gastroenteritis.

PubMed

Bhat, Sudipta; Kattoor, Jobin Jose; Malik, Yashpal Singh; Sircar, Shubhankar; Deol, Pallavi; Rawat, Vinita; Rakholia, Ritu; Ghosh, Souvik; Vlasova, Anastasia N; Nadia, Touil; Dhama, Kuldeep; Kobayashi, Nobumichi

2018-02-17

All over the world, children and adults are severely affected by acute gastroenteritis, caused by one of the emerging enteric pathogens, rotavirus C (RVC). At present, no extensive surveillance program is running for RVC in India, and its prevalence is largely unknown except cases of local outbreaks. Here, we intended to detect the presence of RVC in diarrheic children visiting or admitted to hospitals in Haldwani (state of Uttarakhand, India), a city located in the foothills of the Himalayas. During 2010-2013, we screened 119 samples for RVC by an RVC VP6 gene-specific RT-PCR. Of these, 38 (31.93%) were found positive, which is higher than the incidence rates reported so far from India. The phylogenetic analysis of the derived nucleotide sequences from one of the human RVC (HuRVC) isolates, designated as HuRVC/H28/2013/India, showed that the study isolate belongs to genotype I2, P2 and E2 for RVC structural genes 6 and 4 (VP6, and VP4) and non-structural gene 4 (NSP4), respectively. Furthermore, the VP6 gene of HuRVC/H28/2013/India shows the highest similarity to a recently-reported human-like porcine RVC (PoRVC/ASM140/2013/India, KT932963) from India suggesting zoonotic transmission. We also report a full-length NSP4 gene sequence of human RVC from India. Under the One-health platforms there is a need to launch combined human and animal RVC surveillance programs for a better understanding of the epidemiology of RVC infections and for implementing control strategies. Reoviridae , possess 11 double-stranded segments of RNA that encode six structural viral proteins (VP1, VP2, VP3, VP4, VP6, VP7) and five/six non-structural proteins (NSP1-NSP5/6) [7]. Based on the antigenic properties of the major inner capsid protein (VP6), RVs are subdivided into eight well-characterized species (A-H) and two putative species viz. I and J [8-10]. Humans and other mammalian species are affected by species A, B, C and H rotaviruses and birds by species D, F and G, and species E has been reported exclusively in pigs [7,8,11-17]. The newly-proposed species I is reported in dogs [18] and cats [19], whereas species J is found in bats [10].

Rotavirus (For Parents)

MedlinePlus

... Staying Safe Videos for Educators Search English Español Rotavirus KidsHealth / For Parents / Rotavirus What's in this article? ... the Doctor Print en español El rotavirus About Rotavirus Almost all kids have had a rotavirus infection ...

Screening of Viral Pathogens from Pediatric Ileal Tissue Samples after Vaccination

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hewitson, Laura; Thissen, James B.; Gardner, Shea N.

In 2010, researchers reported that the two US-licensed rotavirus vaccines contained DNA or DNA fragments from porcine circovirus (PCV). Although PCV, a common virus among pigs, is not thought to cause illness in humans, these findings raised several safety concerns. In this study, we sought to determine whether viruses, including PCV, could be detected in ileal tissue samples of children vaccinated with one of the two rotavirus vaccines. A broad spectrum, novel DNA detection technology, the Lawrence Livermore Microbial Detection Array (LLMDA), was utilized, and confirmation of viral pathogens using the polymerase chain reaction (PCR) was conducted. The LLMDA technologymore » was recently used to identify PCV from one rotavirus vaccine. Ileal tissue samples were analyzed from 21 subjects, aged 15–62 months. PCV was not detected in any ileal tissue samples by the LLMDA or PCR. LLMDA identified a human rotavirus A from one of the vaccinated subjects, which is likely due to a recent infection from a wild type rotavirus. LLMDA also identified human parechovirus, a common gastroenteritis viral infection, from two subjects. Additionally, LLMDA detected common gastrointestinal bacterial organisms from the Enterobacteriaceae , Bacteroidaceae , and Streptococcaceae families from several subjects. This study provides a survey of viral and bacterial pathogens from pediatric ileal samples, and may shed light on future studies to identify pathogen associations with pediatric vaccinations.« less

Screening of Viral Pathogens from Pediatric Ileal Tissue Samples after Vaccination

DOE PAGES

Hewitson, Laura; Thissen, James B.; Gardner, Shea N.; ...

2014-01-01

In 2010, researchers reported that the two US-licensed rotavirus vaccines contained DNA or DNA fragments from porcine circovirus (PCV). Although PCV, a common virus among pigs, is not thought to cause illness in humans, these findings raised several safety concerns. In this study, we sought to determine whether viruses, including PCV, could be detected in ileal tissue samples of children vaccinated with one of the two rotavirus vaccines. A broad spectrum, novel DNA detection technology, the Lawrence Livermore Microbial Detection Array (LLMDA), was utilized, and confirmation of viral pathogens using the polymerase chain reaction (PCR) was conducted. The LLMDA technologymore » was recently used to identify PCV from one rotavirus vaccine. Ileal tissue samples were analyzed from 21 subjects, aged 15–62 months. PCV was not detected in any ileal tissue samples by the LLMDA or PCR. LLMDA identified a human rotavirus A from one of the vaccinated subjects, which is likely due to a recent infection from a wild type rotavirus. LLMDA also identified human parechovirus, a common gastroenteritis viral infection, from two subjects. Additionally, LLMDA detected common gastrointestinal bacterial organisms from the Enterobacteriaceae , Bacteroidaceae , and Streptococcaceae families from several subjects. This study provides a survey of viral and bacterial pathogens from pediatric ileal samples, and may shed light on future studies to identify pathogen associations with pediatric vaccinations.« less

Long-term impact of changing childhood malnutrition on rotavirus diarrhoea: Two decades of adjusted association with climate and socio-demographic factors from urban Bangladesh.

PubMed

Das, Sumon Kumar; Chisti, Mohammod Jobayer; Sarker, Mohammad Habibur Rahman; Das, Jui; Ahmed, Shawnawaz; Shahunja, K M; Nahar, Shamsun; Gibbons, Nora; Ahmed, Tahmeed; Faruque, Abu Syed Golam; Rahman, Mustafizur; J Fuchs, George; Al Mamun, Abdullah; John Baker, Peter

2017-01-01

There is strong association between childhood rotavirus, diarrhoea, climate factors and malnutrition. Conversely, a significant nutritional transition (reduced under-nutrition) with a concurrent increasing trend of rotavirus infection in last decade was also observed among under 5 children, especially in developing countries including Bangladesh. Considering the pathophysiology of rotavirus, there might be an interaction of this nutrition transition which plays a pivotal role in increasing rotavirus infection in addition to climate and other man-made factors in urban areas such as Dhaka, Bangladesh. Relevant monthly data from 1993-2012 were extracted from the archive of the Diarrhoeal Disease Surveillance System of icddr, b and linked with data collected from the Dhaka station of the Bangladesh Meteorological Department (mean temperature, rainfall, sea level pressure and humidity). Seasonal autoregressive integrated moving average time series models were deployed to determine the association between the monthly proportion of rotavirus infection and underweight, stunting and wasting adjusting for climate, socio-demographic and sanitation factors. The proportion of rotavirus cases among all causes diarrhoea increased from 20% in 1993 to 43% in 2012 (Chi squared for trend p = 0.010). In contrast, underweight, stunting and wasting decreased from 59%-29% (p<0.001); 53%-21% (p<0.001) and 32%-22% (p<0.001) respectively over the same period. Mean ambient temperature increased from 25.76°C-26.62°C (p = 0.07); mean rainfall, sea level pressure and mean humidity decreased from 234.92-111.75 mm (p = 0.5), 1008.30-1006.61 mm of hg (p = 0.02) and 76.63%-70.26% (p<0.001), respectively. In the adjusted model, a decrease in monthly proportion of underweight [coef.: -0.189 (95% CI:-0.376, -0.003)] and wasting [-0.265 (-0.455, -0.075)] were significantly and inversely associated with rotavirus infection. However, an inverse but insignificant association was observed for stunting [-0.070 (-0.249, 0.109)]. The reduction of acute childhood malnutrition is significantly associated with increasing rotavirus diarrhoea among under-5 children. Thus mass vaccination in addition to interventions directed at man-made modifiable predictors for prevention and control is warranted.

Long-term impact of changing childhood malnutrition on rotavirus diarrhoea: Two decades of adjusted association with climate and socio-demographic factors from urban Bangladesh

PubMed Central

Das, Sumon Kumar; Chisti, Mohammod Jobayer; Sarker, Mohammad Habibur Rahman; Das, Jui; Ahmed, Shawnawaz; Shahunja, K. M.; Nahar, Shamsun; Gibbons, Nora; Ahmed, Tahmeed; Faruque, Abu Syed Golam; Rahman, Mustafizur; J Fuchs, George; Al Mamun, Abdullah; John Baker, Peter

2017-01-01

Background There is strong association between childhood rotavirus, diarrhoea, climate factors and malnutrition. Conversely, a significant nutritional transition (reduced under-nutrition) with a concurrent increasing trend of rotavirus infection in last decade was also observed among under 5 children, especially in developing countries including Bangladesh. Considering the pathophysiology of rotavirus, there might be an interaction of this nutrition transition which plays a pivotal role in increasing rotavirus infection in addition to climate and other man-made factors in urban areas such as Dhaka, Bangladesh. Methods Relevant monthly data from 1993–2012 were extracted from the archive of the Diarrhoeal Disease Surveillance System of icddr, b and linked with data collected from the Dhaka station of the Bangladesh Meteorological Department (mean temperature, rainfall, sea level pressure and humidity). Seasonal autoregressive integrated moving average time series models were deployed to determine the association between the monthly proportion of rotavirus infection and underweight, stunting and wasting adjusting for climate, socio-demographic and sanitation factors. Finding The proportion of rotavirus cases among all causes diarrhoea increased from 20% in 1993 to 43% in 2012 (Chi squared for trend p = 0.010). In contrast, underweight, stunting and wasting decreased from 59%-29% (p<0.001); 53%-21% (p<0.001) and 32%-22% (p<0.001) respectively over the same period. Mean ambient temperature increased from 25.76°C-26.62°C (p = 0.07); mean rainfall, sea level pressure and mean humidity decreased from 234.92–111.75 mm (p = 0.5), 1008.30–1006.61 mm of hg (p = 0.02) and 76.63%-70.26% (p<0.001), respectively. In the adjusted model, a decrease in monthly proportion of underweight [coef.: -0.189 (95% CI:-0.376, -0.003)] and wasting [-0.265 (-0.455, -0.075)] were significantly and inversely associated with rotavirus infection. However, an inverse but insignificant association was observed for stunting [-0.070 (-0.249, 0.109)]. Interpretation The reduction of acute childhood malnutrition is significantly associated with increasing rotavirus diarrhoea among under-5 children. Thus mass vaccination in addition to interventions directed at man-made modifiable predictors for prevention and control is warranted. PMID:28877163

Evaluating Rotavirus and Norovirus transport processes in standardised and natural soil-water columns experiments

NASA Astrophysics Data System (ADS)

Gamazo, Pablo; Schijven, Jack; Victoria, Matias; Alvareda, Elena; López Tort, Fernando; Ramos, Julián; Lizasoain, Andrés; Sapriza, Gonzalo; Castells, Matias; Colina, Rodney

2017-04-01

In Uruguay, as in many developed and developing countries, rotavirus and norovirus are major causes of diarrhea and others symptoms of acute gastroenteritis. In some areas of Uruguay, groundwater is the only source of water for human consumption. In the rural area of the Salto district, virus contamination has been detected in several groundwater wells. Because sewer coverage is low, the most probable sources of contamination are nearby septic systems. This work aims to evaluate the transport of rotavirus and norovirus from clinic samples in two sets of column experiments under saturated conditions: 6.7-cm columns with quartz sand (ionic strength 1mM, pH 7.0) and with sand from the Salto aquifer (Uruguay) (9,2% coarse sand, 47,8% medium sand, 40,5% fine sand, magnesium/calcium bicarbonate water, Ionic strength 15.1 mM, pH 7.2). Both viruses were seeded for 2 pore volumes onto the columns. Samples were collected at the column outlet and viruses were enumerated by Q-PRCR. Breakthrough curves were constructed and fitted to a two-site kinetic attachment/detachment model, including blocking using Hydrus-1D. In the quartz sand column, both rotavirus and norovirus were removed two orders in magnitude. In the Salto sand column, rotavirus was removed 2 log10 as well, but norovirus was removed 4 log10. The fitting of the breakthrough curves indicated that blocking played a role for rotavirus in the Salto sand column. These results are consistent with the field observation where only rotavirus was detected in the Salto aquifer, while similar concentrations in Salto sewer effluent were measured for both viruses. This work, besides reporting actual parameters values for human virus transport modelling, shows the significant differences in transport that human viruses can have in standardised and natural soil-water systems.

Rotarix in Japan: Expectations and Concerns.

PubMed

Nakagomi, Osamu; Nakagomi, Toyoko

2011-01-01

A live-attenuated, orally-administered, monovalent, human rotavirus vaccine, Rotarix® (GlaxoSmithKline Biologicals, Rixensart, Belgium), was licensed and launched in 2011 as the first rotavirus vaccine in Japan. The rotavirus causes a substantial disease burden with an estimated 790,000 outpatient visits, 27,000-78,000 hospitalizations, and approximately 10 deaths each year in Japan. Since a recent clinical trial showed that Rotarix was as efficacious in Japan as in other industrialized countries, it is expected that the annual number of rotavirus hospitalizations will be reduced to between 1000-3000, and that outpatient visits will be reduced to 200,000. The universal rotavirus immunization program with Rotarix was calculated to be at the threshold of being cost-effective, even from the healthcare perspective, and it was highly cost-effective from the societal perspective, assuming that Rotarix is co-administered with other childhood vaccines. While Rotarix contains only a single G1P[8] human rotavirus, the postlicensure studies in Brazil showed that Rotarix provided a 75%-85% protective efficacy against severe dehydrating diarrhea or hospitalizations due to fully-heterotypic G2P[4] strains. While postlicensure studies detected a small and finite risk of intussusception associated with the administration of Rotarix, the authors conclude that Rotarix is safe to administer to infants between 6-12 weeks of age for the first dose and by 24 weeks of age for the second dose. However, the authors strongly discourage the delayed administration of the first dose between 13-20 weeks of age, which is allowed without any warning. Given the high incidence of naturally-occurring intussusception in Japan (185 cases per 100,000 children/year among children less than 1 year of age), this should prevent pediatricians and parents from having ill-perceptions of Rotarix being associated with an increased number of temporally-associated intussusception, and fully appreciate the benefit of the rotavirus vaccine.

Cost effectiveness of a pentavalent rotavirus vaccine in Oman.

PubMed

Al Awaidy, Salah Thabit; Gebremeskel, Berhanu G; Al Obeidani, Idris; Al Baqlani, Said; Haddadin, Wisam; O'Brien, Megan A

2014-06-17

Rotavirus gastroenteritis (RGE) is the leading cause of diarrhea in young children in Oman, incurring substantial healthcare and economic burden. We propose to formally assess the potential cost effectiveness of implementing universal vaccination with a pentavalent rotavirus vaccine (RV5) on reducing the health care burden and costs associated with rotavirus gastroenteritis (RGE) in Oman A Markov model was used to compare two birth cohorts, including children who were administered the RV5 vaccination versus those who were not, in a hypothetical group of 65,500 children followed for their first 5 years of life in Oman. The efficacy of the vaccine in reducing RGE-related hospitalizations, emergency department (ED) and office visits, and days of parental work loss for children receiving the vaccine was based on the results of the Rotavirus Efficacy and Safety Trial (REST). The outcome of interest was cost per quality-adjusted life year (QALY) gained from health care system and societal perspectives. A universal RV5 vaccination program is projected to reduce, hospitalizations, ED visits, outpatient visits and parental work days lost due to rotavirus infections by 89%, 80%, 67% and 74%, respectively. In the absence of RV5 vaccination, RGE-related societal costs are projected to be 2,023,038 Omani Rial (OMR) (5,259,899 United States dollars [USD]), including 1,338,977 OMR (3,481,340 USD) in direct medical costs. However, with the introduction of RV5, direct medical costs are projected to be 216,646 OMR (563,280 USD). Costs per QALY saved would be 1,140 OMR (2,964 USD) from the health care payer perspective. An RV5 vaccination program would be considered cost saving, from the societal perspective. Universal RV5 vaccination in Oman is likely to significantly reduce the health care burden and costs associated with rotavirus gastroenteritis and may be cost-effective from the payer perspective and cost saving from the societal perspective.

Cost effectiveness of a pentavalent rotavirus vaccine in Oman

PubMed Central

2014-01-01

Background Rotavirus gastroenteritis (RGE) is the leading cause of diarrhea in young children in Oman, incurring substantial healthcare and economic burden. We propose to formally assess the potential cost effectiveness of implementing universal vaccination with a pentavalent rotavirus vaccine (RV5) on reducing the health care burden and costs associated with rotavirus gastroenteritis (RGE) in Oman Methods A Markov model was used to compare two birth cohorts, including children who were administered the RV5 vaccination versus those who were not, in a hypothetical group of 65,500 children followed for their first 5 years of life in Oman. The efficacy of the vaccine in reducing RGE-related hospitalizations, emergency department (ED) and office visits, and days of parental work loss for children receiving the vaccine was based on the results of the Rotavirus Efficacy and Safety Trial (REST). The outcome of interest was cost per quality-adjusted life year (QALY) gained from health care system and societal perspectives. Results A universal RV5 vaccination program is projected to reduce, hospitalizations, ED visits, outpatient visits and parental work days lost due to rotavirus infections by 89%, 80%, 67% and 74%, respectively. In the absence of RV5 vaccination, RGE-related societal costs are projected to be 2,023,038 Omani Rial (OMR) (5,259,899 United States dollars [USD]), including 1,338,977 OMR (3,481,340 USD) in direct medical costs. However, with the introduction of RV5, direct medical costs are projected to be 216,646 OMR (563,280 USD). Costs per QALY saved would be 1,140 OMR (2,964 USD) from the health care payer perspective. An RV5 vaccination program would be considered cost saving, from the societal perspective. Conclusions Universal RV5 vaccination in Oman is likely to significantly reduce the health care burden and costs associated with rotavirus gastroenteritis and may be cost-effective from the payer perspective and cost saving from the societal perspective. PMID:24941946

Efficacy and safety of a pentavalent live human-bovine reassortant rotavirus vaccine (RV5) in healthy Chinese infants: A randomized, double-blind, placebo-controlled trial.

PubMed

Mo, Zhaojun; Mo, Yi; Li, Mingqiang; Tao, Junhui; Yang, Xu; Kong, Jilian; Wei, Dingkai; Fu, Botao; Liao, Xueyan; Chu, Jianli; Qiu, Yuanzheng; Hille, Darcy A; Nelson, Micki; Kaplan, Susan S

2017-10-13

A randomized, double-blind, placebo-controlled multicenter trial was conducted in healthy Chinese infants to assess the efficacy and safety of a pentavalent live human-bovine reassortant rotavirus vaccine (RotaTeq™, RV5) against rotavirus gastroenteritis (RVGE). 4040 participants aged 6-12weeks were enrolled and randomly assigned to either 3 oral doses of RV5 (n=2020) or placebo (n=2020), administered ∼4weeks apart. The participants also received OPV and DTaP in a concomitant or staggered fashion. The primary objective was to evaluate vaccine efficacy (VE) against naturally-occurring RVGE at least 14days following the third dose. Key secondary objectives included: VE against naturally-occurring severe RVGE and VE against severe and any-severity RVGE caused by rotavirus serotypes contained in the vaccine, occurring at least 14days after the third dose. All adverse events (AEs) were collected for 30days following each dose. Serious AEs (SAEs) and intussusception cases were collected during the entire study. (ClinicalTrials.gov registry: NCT02062385). VE against RVGE of any-severity caused by any serotype was 69.3% (95% CI: 54.5, 79.7). The secondary efficacy analysis showed an efficacy of: 78.9% (95% CI: 59.1, 90.1) against severe RVGE caused by any serotype; 69.9% (95% CI: 55.2, 80.3) and 78.9% (95% CI: 59.1, 90.1) against any-severity and severe RVGE caused by serotypes contained in the vaccine, respectively. Within 30days following any vaccination, 53.5% (1079/2015) and 53.3% (1077/2019) of participants reported at least one AE, and 5.8% (116/2015) and 5.7% (116/2019) reported SAEs in the vaccine and placebo groups, respectively. No SAEs were considered vaccine-related in recipients of RV5. Two intussusception cases were reported in recipients of RV5 who recovered after receiving treatment. Neither was considered vaccine-related. In Chinese infants, RV5 was efficacious against any-severity and severe RVGE caused by any serotype and generally well-tolerated with respect to AEs. Copyright © 2017. Published by Elsevier Ltd.

Outbreak of G2P[4] rotavirus gastroenteritis in a retirement community, Brazil, 2015: An important public health risk?

PubMed

Luchs, Adriana; Madalosso, Geraldine; Cilli, Audrey; Morillo, Simone Guadagnucci; Martins, Sandra Regina; de Souza, Karen Aparecida Farias; Namiyama, Gislene Mitsue; Gonçalves, Cláudia Regina; Carmona, Rita de Cássia Compagnoli; Timenetsky, Maria do Carmo Sampaio Tavares

The present study described a group A rotavirus (RVA) outbreak in an age-care facility in Brazil, using epidemiologic and molecular diagnostic methods. A descriptive clinical, epidemiological and environmental investigation was conducted. Stool samples were collected and screened for RVA, Norovirus (NoV), Enteric Adenovirus 40/41 (AdV 40/41) and Astrovirus (AstV) using ELISA, RT-PCR, qRT-PCR, electron microscopy and sequencing methods. Outbreak occurred during 26th-29th October, 2015; 28 individuals affected (22 residents; 6 staff). The attack rate was 25.9% and 8.5% among residents (median-age: 85.5 years) and staff (median-age: 28 years), respectively. Female staff was identified as the index case. RVA G2P[4] genotype was detected in 87.5% (7/8). Genetic analysis demonstrated that the outbreak involved one single strain, suggesting a common-source infection. RVA should be considered during outbreaks investigations in residential facilities, and raise the question if the current licensed RVA vaccines for children could also be helpful for the elderly. Copyright © 2016 Elsevier Inc. All rights reserved.

Prevalence and genetic diversity of norovirus among patients with acute diarrhea in Guatemala.

PubMed

Estévez, Alejandra; Arvelo, Wences; Hall, Aron J; López, María R; López, Beatriz; Reyes, Lissette; Moir, Juan Carlos; Gregoricus, Nicole; Vinjé, Jan; Parashar, Umesh D; Lindblade, Kim A

2013-07-01

Noroviruses (NoVs) are a leading cause of acute gastroenteritis outbreaks and sporadic cases of diarrhea in industrialized countries. To study the prevalence and genetic diversity of NoVs in Guatemala, stool specimens were collected from hospitalized and ambulatory patients presenting with diarrhea (≥3 loose or liquid stools in a 24-hr period) who were enrolled in a prospective surveillance system in the Departments of Santa Rosa (October 2007 to August 2010) and Quetzaltenango (August 2009 to August 2010), Guatemala. Specimens were tested for rotavirus, enteric bacteria, and parasites by routine methods and for genogroups I and II NoV by real-time reverse transcription-PCR. A total of 2,403 stool specimens were collected from hospitalized (n = 528) and ambulatory patients (n = 1,875). Overall, 341 (14%) samples tested positive for NoVs including 114 (22%) hospitalized and 227 (12%) ambulatory patients. NoVs disease peaked during the winter (November-January) months. Among the 341 NoVs-positive patients, 32 (9%) were also positive for rotavirus, 32 (9%) for bacteria, and 9 (3%) for protozoa. Nucleotide sequences were obtained from 84 samples collected from hospitalized children aged <5 years of age, which could be grouped into nine GII and three GI genotypes with GII.4 (74%) and GI.8 (10%) being the most common. This is the first study on the prevalence of NoVs among hospitalized and ambulatory patients with diarrhea in Guatemala. The findings highlight the need to implement laboratory diagnostics for NoVs to improve appropriate clinical management of diarrheal diseases and guide vaccine development. Copyright © 2013 Wiley Periodicals, Inc.

Putative vaccine breakthrough event associated with heterotypic rotavirus infection in newborn calves, Turkey, 2015.

PubMed

Karayel, Ilke; Fehér, Enikő; Marton, Szilvia; Coskun, Nüvit; Bányai, Krisztián; Alkan, Feray

2017-03-01

Group A rotaviruses (RVA) are regarded as major enteric pathogens of large ruminants, including cattle. Rotavirus vaccines administered to pregnant cows are commonly used to provide passive immunity that protects newborn calves from the clinical disease. In this study we report the detection of RVA from calves with severe diarrhea in a herd regularly vaccinated to prevent enteric infections including RVA. Diarrheic disease was observed in newborn calves aged 4-15days, with high morbidity and mortality rates, but no diarrhea was seen in adult animals. Rotavirus antigen was detected by enzyme-immunoassay in the intestinal content or the fecal samples of all examined animals. Besides RVA, bovine coronavirus and bovine enteric calicivirus were detected in some samples. Selected RVA strains were characterized by whole genome sequencing. Two strains, RVA/Cow-wt/TUR/Amasya-1/2015/G8P[5] and RVA/Cow-wt/TUR/Amasya-2/2015/G8P[5] were genotyped as G8-P[5]-I2-R2-C2-M2-A3-N2-T6-E2-H3 and showed >99% nucleotide sequence identity among themselves. This genomic constellation is fairly common among bovine RVA strains; however, phylogenetic analysis of the G8 VP7 gene showed close genetic relationship to some European human RVA strains (up to 98.4% nt identity). Our findings is the first indication regarding the circulation of G8 RVA strains in Turkey. Given that the administered RVA vaccines contained type G6 and G10 VP7 antigens some concerns raised with regard to the level of heterotypic protection elicited by the vaccine strains against circulating bovine G8 RVA strains. Enhancement of surveillance of circulating RVA strains in calves across Turkey is needed to support ongoing vaccination programs. Copyright © 2016 Elsevier B.V. All rights reserved.

Impact of rotavirus vaccine introduction and post-introduction etiology of diarrhea requiring hospital admission in Haydom, Tanzania, a rural African setting.

PubMed

Platts-Mills, James A; Amour, Caroline; Gratz, Jean; Nshama, Rosemary; Walongo, Thomas; Mujaga, Buliga; Maro, Athanasia; McMurry, Timothy L; Liu, Jie; Mduma, Estomih; Houpt, Eric R

2017-05-29

No data are available on the etiology of diarrhea requiring hospitalization after rotavirus vaccine introduction in Africa. The monovalent rotavirus vaccine was introduced in Tanzania on January 1, 2013. We performed a vaccine impact and effectiveness study as well as a qPCR-based etiology study at a rural Tanzanian hospital. We obtained data on admissions among children under 5 years to Haydom Lutheran Hospital between January 1, 2010 and December 31, 2015, and estimated the impact of vaccine introduction on all-cause diarrhea admissions. We then performed a vaccine effectiveness study using the test-negative design. Finally, we tested diarrheal specimens during 2015 by qPCR for a broad range of enteropathogens and calculated pathogen-specific attributable fractions. Vaccine introduction was associated with a 44.9% (95% CI 17.6 - 97.4) reduction in diarrhea admissions in 2015, as well as delay of the rotavirus season. The effectiveness of two doses of vaccine was 74.8% (-8.2 - 94.1) using an enzyme immunoassay-based case definition and 85.1% (26.5 - 97.0) using a qPCR-based case definition. Among 146 children enrolled in 2015, rotavirus remained the leading etiology of diarrhea requiring hospitalization (AF 25.8%, 95% CI: 24.4 - 26.7), followed by heat-stabile enterotoxin-producing E. coli (18.4%, 12.9 - 21.9), Shigella/enteroinvasive E. coli (14.5%, 10.2 - 22.8), and Cryptosporidium (7.9%, 6.2 - 9.3). Despite the clear impact of vaccine introduction in this setting, rotavirus remained the leading etiology of diarrhea requiring hospitalization. Further efforts to maximize vaccine coverage and improve vaccine performance in these settings are warranted. © The Author 2017. Published by Oxford University Press for the Infectious Diseases Society of America.

Household catastrophic healthcare expenditure and impoverishment due to rotavirus gastroenteritis requiring hospitalization in Malaysia.

PubMed

Loganathan, Tharani; Lee, Way-Seah; Lee, Kok-Foo; Jit, Mark; Ng, Chiu-Wan

2015-01-01

While healthcare costs for rotavirus gastroenteritis requiring hospitalization may be burdensome on households in Malaysia, exploration on the distribution and catastrophic impact of these expenses on households are lacking. We assessed the economic burden, levels and distribution of catastrophic healthcare expenditure, the poverty impact on households and inequities related to healthcare payments for acute gastroenteritis requiring hospitalization in Malaysia. A two-year prospective, hospital-based study was conducted from 2008 to 2010 in an urban (Kuala Lumpur) and rural (Kuala Terengganu) setting in Malaysia. All children under the age of 5 years admitted for acute gastroenteritis were included. Patients were screened for rotavirus and information on healthcare expenditure was obtained. Of the 658 stool samples collected at both centers, 248 (38%) were positive for rotavirus. Direct and indirect costs incurred were significantly higher in Kuala Lumpur compared with Kuala Terengganu (US$222 Vs. US$45; p<0.001). The mean direct and indirect costs for rotavirus gastroenteritis consisted 20% of monthly household income in Kuala Lumpur, as compared with only 5% in Kuala Terengganu. Direct medical costs paid out-of-pocket caused 141 (33%) households in Kuala Lumpur to experience catastrophic expenditure and 11 (3%) households to incur poverty. However in Kuala Terengganu, only one household (0.5%) experienced catastrophic healthcare expenditure and none were impoverished. The lowest income quintile in Kuala Lumpur was more likely to experience catastrophic payments compared to the highest quintile (87% vs 8%). The concentration index for out-of-pocket healthcare payments was closer to zero at Kuala Lumpur (0.03) than at Kuala Terengganu (0.24). While urban households were wealthier, healthcare expenditure due to gastroenteritis had more catastrophic and poverty impact on the urban poor. Universal rotavirus vaccination would reduce both disease burden and health inequities in Malaysia.

Serological comparison of canine rotavirus with various simian and human rotaviruses by plaque reduction neutralization and hemagglutination inhibition tests.

PubMed Central

Hoshino, Y; Wyatt, R G; Greenberg, H B; Kalica, A R; Flores, J; Kapikian, A Z

1983-01-01

By the plaque reduction neutralization test, the CU-1 strain of canine rotavirus was similar, if not identical, to three strains (no. 14, no. 15, and P) of the tentatively designated third human rotavirus serotype. In addition, strain CU-1 demonstrated a one-way antigenic relationship with two other strains (M and B) of the third human rotavirus serotype. The CU-1 strain of canine rotavirus hemagglutinated human group O, rhesus monkey, dog, sheep, and guinea pig erythrocytes. A two-way antigenic relationship between canine (CU-1) and simian (MMU 18006 and SA11) rotaviruses demonstrated previously by the plaque reduction neutralization test was confirmed further with two additional isolates (A79-10 and LSU 79C-36) of canine rotavirus by the plaque reduction neutralization test and the hemagglutination inhibition test. The CU-1 strain of canine rotavirus, which is known to be distinct from two well-characterized human rotavirus serotypes (Wa and DS-1), was also found to be distinct from the St. Thomas no. 4 strain, which is a newly defined fourth human rotavirus serotype. Thus, this canine strain, which is related antigenically to one of four human rotavirus serotypes, is another example of an animal rotavirus which shares serotype specificity with a human rotavirus. Images PMID:6190752

New approaches in oral rotavirus vaccines.

PubMed

Kuate Defo, Zenas; Lee, Byong

2016-05-01

Rotavirus is the leading cause of severe dehydrating diarrhea worldwide, and affects primarily developing nations, in large part because of the inaccessibility of vaccines and high rates of mortality present therein. At present, there exist two oral rotaviral vaccines, Rotarix™ and RotaTeq™. These vaccines are generally effective in their actions: however, associated costs often stymie their effectiveness, and they continue to be associated with a slight risk of intussusception. While different programs are being implemented worldwide to enhance vaccine distribution and monitor vaccine administration for possible intussusception in light of recent WHO recommendation, another major problem persists: that of the reduced efficacy of the existing rotaviral vaccines in developing countries over time. The development of new oral rotavirus vaccine classes - live-attenuated vaccines, virus-like particles, lactic acid bacteria-containing vaccines, combination therapy with immunoglobulins, and biodegradable polymer-encapsulated vaccines - could potentially circumvent these problems.

Isolation, propagation, and characterization of a second equine rotavirus serotype.

PubMed Central

Hoshino, Y; Wyatt, R G; Greenberg, H B; Kalica, A R; Flores, J; Kapikian, A Z

1983-01-01

A rotavirus designated strain H-2 was isolated in primary African green monkey kidney cells from a foal with diarrhea. This cell culture-adapted strain was found to be similar, if not identical, to simian rotavirus (strains MMU18006 and SA-11) and canine rotavirus (strain CU-1) and, in addition, demonstrated a one-way antigenic relationship with five human rotavirus strains (P, B, no. 14, no. 15, and YO) of the third human rotavirus serotype by the plaque reduction neutralization test. This is the fifth example of an animal rotavirus which shares serotypic specificity with a human rotavirus. The H-2 strain is distinct from the H-1 strain (Y. Hoshino et al., J. Clin. Microbiol., in press) of equine rotavirus not only in serotypic specificity by neutralization but also in subgroup specificity, hemagglutinating activity, and RNA electrophoretic migration pattern, thus establishing the existence of a second equine rotavirus serotype. This H-2 isolate is also distinct by neutralization from three other human rotavirus serotypes, 1 (Wa), 2 (DS-1), and 4 (St. Thomas no. 4), as well as bovine (NCDV), and porcine (OSU) rotaviruses. Images PMID:6309657

Rotavirus vaccines

PubMed Central

Tate, Jacqueline E; Patel, Manish M; Cortese, Margaret M; Lopman, Benjamin; Fleming, Jessica; Lewis, Kristen; Jiang, Baoming; Gentsch, Jon; Steele, Duncan; Parashar, Umesh D

2011-01-01

Early rotavirus vaccine adopter countries in the Americas, Europe, and in Australia have documented substantial declines in rotavirus disease burden following the introduction of vaccination. However, the full public health impact of rotavirus vaccines has not been realized as they have not been introduced into routine immunization programs in countries of Africa and Asia with the highest rotavirus disease morbidity and mortality burden. In this article, we review the epidemiology of rotavirus disease, the development and current status of rotavirus vaccines including newly available vaccine impact data from early-introducer countries, and future priorities for implementation and monitoring of rotavirus vaccination programs in developing countries. PMID:22108032

Rotavirus vaccine - what you need to know

MedlinePlus

... is taken in its entirety from the CDC Rotavirus Vaccine Information Statement (VIS): www.cdc.gov/vaccines/hcp/ ... are also common in babies with rotavirus. Before rotavirus vaccine, rotavirus disease was a common and serious health ...

Characterization of in vivo anti-rotavirus activities of saponin extracts from Quillaja Saponaria Molina

PubMed Central

Tam, Ka Ian; Roner, Michael R.

2011-01-01

Rotavirus is the leading cause of severe diarrhea disease in newborns and young children worldwide with approximately 300,000 pre-adolescent deaths each year. Quillaja saponins are a natural aqueous extract obtained from the Chilean soapbark tree. The extract is approved for use in humans by the FDA for use in beverages as a food addictive. We have demonstrated that Quillaja extracts have strong antiviral activities in vitro against six different viruses. In this study, we evaluated the in vivo antiviral activity of these extracts against rhesus rotavirus (RRV) using a mouse model. We established that at a dosage of 0.015 mg/mouse of saponin extract, RRV induced diarrhea can be significantly reduced from 79% to 11% when mice are exposed to 500 plaque-forming-units (PFU) for each of five consecutive days. Additionally, while a reduction of RRV induced diarrhea depended both on the concentration of virus introduced and on the amount of Quillaja extract given to each mouse, the severity and interval of diarrhea under a variety of conditions tested, in all the treated mice were greatly reduced when compared to those that did not receive the Quillaja extracts. Mechanistically, there is strong evidence that the Quillaja extracts are able to “block” rotavirus infection by inhibiting virus-host attachment through disruption of cellular membrane proteins and/or virus receptors. We believe that Quillaja extracts have promise as antivirals to reduce rotavirus infection and the severity of the disease in humans. PMID:21549151

Infectious rotavirus enters cells by direct cell membrane penetration, not by endocytosis

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kaljot, K.T.; Shaw, R.D.; Greenberg, H.B.

1988-04-01

Rotaviruses are icosahedral viruses with a segmented, double-stranded RNA genome. They are the major cause of severe infantile infectious diarrhea. Rotavirus growth in tissue culture is markedly enhanced by pretreatment of virus with trypsin. Trypsin activation is associated with cleavage of the viral hemagglutinin (viral protein 3 (VP3); 88 kilodaltons) into two fragments (60 and 28 kilodaltons). The mechanism by which proteolytic cleavage leads to enhanced growth is unknown. To determine whether trypsin treatment affected rotavirus internalization, the authors studied the kinetics of entry of infectious rhesus rotavirus (RRV) into MA104 cells. Trypsin-activated RRV was internalized with a half-time ofmore » 3 to 5 min, while nonactivated virus disappeared from the cell surface with a half-time of 30 to 50 min. In contrast to trypsin-activated RRV, loss of nonactivated RRV from the cell surface did not result in the appearance of infection, as measured by plaque formation. Purified trypsin-activated RRV added to cell monolayers at pH 7.4 mediated {sup 51}Cr, ({sup 14}C)choline, and ({sup 3}H)inositol released from prelabeled MA104 cells. This release could be specifically blocked by neutralizing antibodies to VP3. These results suggest that MA104 cell infection follows the rapid entry of trypsin-activated RRV by direct cell membrane penetration. Cell membrane penetration of infectious RRV is initiated by trypsin cleavage of VP3. Neutralizing antibodies can inhibit this direct membrane penetration.« less

Scaling properties and symmetrical patterns in the epidemiology of rotavirus infection.

PubMed Central

José, Marco V; Bishop, Ruth F

2003-01-01

The rich epidemiological database of the incidence of rotavirus, as a cause of severe diarrhoea in young children, coupled with knowledge of the natural history of the infection, can make this virus a paradigm for studies of epidemic dynamics. The cyclic recurrence of childhood rotavirus epidemics in unvaccinated populations provides one of the best documented phenomena in population dynamics. This paper makes use of epidemiological data on rotavirus infection in young children admitted to hospital in Melbourne, Australia from 1977 to 2000. Several mathematical methods were used to characterize the overall dynamics of rotavirus infections as a whole and individually as serotypes G1, G2, G3, G4 and G9. These mathematical methods are as follows: seasonal autoregressive integrated moving-average (SARIMA) models, power spectral density (PSD), higher-order spectral analysis (HOSA) (bispectrum estimation and quadratic phase coupling (QPC)), detrended fluctuation analysis (DFA), wavelet analysis (WA) and a surrogate data analysis technique. Each of these techniques revealed different dynamic aspects of rotavirus epidemiology. In particular, we confirm the existence of an annual, biannual and a quinquennial period but additionally we found other embedded cycles (e.g. ca. 3 years). There seems to be an overall unique geometric and dynamic structure of the data despite the apparent changes in the dynamics of the last years. The inherent dynamics seems to be conserved regardless of the emergence of new serotypes, the re-emergence of old serotypes or the transient disappearance of a particular serotype. More importantly, the dynamics of all serotypes is multiple synchronized so that they behave as a single entity at the epidemic level. Overall, the whole dynamics follow a scale-free power-law fractal scaling behaviour. We found that there are three different scaling regions in the time-series, suggesting that processes influencing the epidemic dynamics of rotavirus over less than 12 months differ from those that operate between 1 and ca. 3 years, as well as those between 3 and ca. 5 years. To discard the possibility that the observed patterns could be due to artefacts, we applied a surrogate data analysis technique which enabled us to discern if only random components or linear features of the incidence of rotavirus contribute to its dynamics. The global dynamics of the epidemic is portrayed by wavelet-based incidence analysis. The resulting wavelet transform of the incidence of rotavirus crisply reveals a repeating pattern over time that looks similar on many scales (a property called self-similarity). Both the self-similar behaviour and the absence of a single characteristic scale of the power-law fractal-like scaling of the incidence of rotavirus infection imply that there is not a universal inherently more virulent serotype to which severe gastroenteritis can uniquely be ascribed. PMID:14561323

Efficacy of a Monovalent Human-Bovine (116E) Rotavirus Vaccine in Indian Infants: A Randomised Double Blind Placebo Controlled Trial

PubMed Central

Bhandari, Nita; Rongsen-Chandola, Temsunaro; Bavdekar, Ashish; John, Jacob; Antony, Kalpana; Taneja, Sunita; Goyal, Nidhi; Kawade, Anand; Kang, Gagandeep; Rathore, Sudeep Singh; Juvekar, Sanjay; Muliyil, Jayaprakash; Arya, Alok; Shaikh, Hanif; Abraham, Vinod; Vrati, Sudhanshu; Proschan, Michael; Kohberger, Robert; Thiry, Georges; Glass, Roger; Greenberg, Harry B; Curlin, George; Mohan, Krishna; Harshavardhan, GVJA; Prasad, Sai; Rao, TS; Boslego, John; Bhan, Maharaj Kishan

2015-01-01

Background Rotavirus is the most common cause of severe dehydrating gastroenteritis in developing countries. Safe, effective, and affordable rotavirus vaccines are needed for developing countries. Methods In a double-blind placebo controlled multicentre trial, 6799 infants aged 6 to 7 weeks were randomised to receive three doses of an oral human-bovine natural reassortant vaccine (116E) or placebo at ages 6, 10, and 14 weeks. Primary outcome was severe (≥11 on the Vesikari scale) rotavirus gastroenteritis. Efficacy outcomes and adverse events were ascertained through active surveillance. Findings At analyses, the median age was 17·2 months; over 96% subjects received all three doses of the vaccine/placebo and ~1% were lost to follow up. 4532 and 2267 subjects were randomly assigned to receive vaccine and placebo, respectively. The per protocol analyses included 4354 subjects in the vaccine and 2187 subjects in the placebo group. 71 events of severe rotavirus gastroenteritis were reported in 4752 person years among the vaccinees compared to 76 events in 2360 person years in the placebo recipients; vaccine efficacy against severe rotavirus gastroenteritis was 53·6% (95% CI 35·0–66·9; P<0·001) and 56·4% (95% CI 36·6–70·1; P <0·001) in the first year of life. The number of infants needed to be immunized to prevent one severe rotavirus gastroenteritis episode was 55 (95% CI 37–97). The incidence of severe rotavirus gastroenteritis/100 person years was 1·5 in vaccine and 3·2 in placebo group and an incidence rate ratio of 0·46 (95% CI 0·33–0·65). The absolute rate reduction for severe rotavirus gastroenteritis was 1·7 (95% CI 2·5–0·9). Efficacy against severe gastroenteritis of any aetiology was 18·6% (95% CI 1·9–32·3); it was 24·1% (95% CI 5·8–38·7) in the first year of life. The prevalence of immediate, solicited, and serious adverse events were similar in both groups. There were six cases of intussusception amongst 4532 vaccinees and two amongst 2267 placebo recipients (P=0·73). All intussusception cases occurred after the third dose. Among vaccine and placebo recipients, the minimum interval between dosing and intussusception was 112 and 36 days, respectively. Interpretation The monovalent human-bovine (116E) rotavirus vaccine is effective and well-tolerated in Indian infants. PMID:24629994

Rotavirus diarrhoea hospitalizations among children under 5 years of age in Nigeria, 2011-2016.

PubMed

Tagbo, B N; Mwenda, J M; Eke, C B; Edelu, B O; Chukwubuike, C; Armah, G; Mapaseka, S L; Isiaka, A; Namadi, L; Okafor, H U; Ozumba, U C; Nnani, R O; Okafor, V; Njoku, R; Odume, C; Benjamin-Pujah, C; Azubuike, C; Umezinne, N; Ogude, N; Osarogborun, V O; Okwesili, M U; Ezebilo, S K; Udemba, O; Yusuf, K; Mahmud, Z; Ticha, J M; Obidike, E O; Mphahlele, J M

2018-05-22

The high burden of rotavirus acute gastroenteritis (AGE) is well documented among children under 5 years of age, with the majority of mortality occurring in developing countries. Nigeria ranked second worldwide in the number of rotavirus deaths in 2013. As Nigeria plans to introduce rotavirus vaccine soon, a pre-vaccine documentation of rotavirus disease burden is necessary to determine vaccine impact. Routine rotavirus surveillance was conducted during 2011-2016 in 3 sentinel sites in Nigeria using the standard WHO protocol. Children under 5 years of age hospitalized for acute gastroenteritis were enrolled and demographic, clinical and outcome data were collected. A stool sample was subsequently obtained and tested for human rotavirus antigen using the Enzyme-linked immunosorbent assay (ELISA). 2694 children with acute gastroenteritis were enrolled during January 2011 to December 2016; of these, 1242 (46%) tested positive for rotavirus. Among the rotavirus positive cases, 66% and 94% were younger than 12 months and 24 months respectively. Marked peaks in rotavirus positivity were seen in January of each year. Vomiting, and use of oral and intravenous fluids occurred more often in rotavirus positive cases as compared to rotavirus negative cases. The high prevalence of rotavirus disease highlights the need for urgent introduction of rotavirus vaccine in Nigeria. Additionally, this study provides pre-vaccine introduction disease-burden data that will serve as a baseline for rotavirus vaccine impact-assessment once vaccine has been introduced in the national immunization program. Copyright © 2018 Elsevier Ltd. All rights reserved.

Improving rotavirus vaccine coverage: Can newer-generation and locally produced vaccines help?

PubMed Central

Kanungo, Suman; Anh, Dang Duc; Grais, Rebecca F.

2018-01-01

ABSTRACT There are two internationally available WHO-prequalified oral rotavirus vaccines (Rotarix and RotaTeq), two rotavirus vaccines licensed in India (Rotavac and Rotasiil), one in China (Lanzhou lamb rotavirus vaccine) and one in Vietnam (Rotavin-M1), and several candidates in development. Rotavirus vaccination has been rolled out in Latin American countries and is beginning to be deployed in sub-Saharan African countries but middle- and low-income Asian countries have lagged behind in rotavirus vaccine introduction. We provide a mini-review of the leading newer-generation rotavirus vaccines and compare them with Rotarix and RotaTeq. We discuss how the development and future availability of newer-generation rotavirus vaccines that address the programmatic needs of poorer countries may help scale-up rotavirus vaccination where it is needed. PMID:29135339

Reassortant group A rotavirus from straw-colored fruit bat (Eidolon helvum).

PubMed

Esona, Mathew D; Mijatovic-Rustempasic, Slavica; Conrardy, Christina; Tong, Suxiang; Kuzmin, Ivan V; Agwanda, Bernard; Breiman, Robert F; Banyai, Krisztian; Niezgoda, Michael; Rupprecht, Charles E; Gentsch, Jon R; Bowen, Michael D

2010-12-01

Bats are known reservoirs of viral zoonoses. We report genetic characterization of a bat rotavirus (Bat/KE4852/07) detected in the feces of a straw-colored fruit bat (Eidolon helvum). Six bat rotavirus genes (viral protein [VP] 2, VP6, VP7, nonstructural protein [NSP] 2, NSP3, and NSP5) shared ancestry with other mammalian rotaviruses but were distantly related. The VP4 gene was nearly identical to that of human P[6] rotavirus strains, and the NSP4 gene was closely related to those of previously described mammalian rotaviruses, including human strains. Analysis of partial sequence of the VP1 gene indicated that it was distinct from cognate genes of other rotaviruses. No sequences were obtained for the VP3 and NSP1 genes of the bat rotavirus. This rotavirus was designated G25-P[6]-I15-R8(provisional)-C8-Mx-Ax-N8-T11-E2-H10. Results suggest that several reassortment events have occurred between human, animal, and bat rotaviruses. Several additional rotavirus strains were detected in bats.

Reassortant Group A Rotavirus from Straw-colored Fruit Bat (Eidolon helvum)

PubMed Central

Esona, Mathew D.; Mijatovic-Rustempasic, Slavica; Conrardy, Christina; Tong, Suxiang; Kuzmin, Ivan V.; Agwanda, Bernard; Breiman, Robert F.; Banyai, Krisztian; Niezgoda, Michael; Rupprecht, Charles E.; Gentsch, Jon R.

2010-01-01

Bats are known reservoirs of viral zoonoses. We report genetic characterization of a bat rotavirus (Bat/KE4852/07) detected in the feces of a straw-colored fruit bat (Eidolon helvum). Six bat rotavirus genes (viral protein [VP] 2, VP6, VP7, nonstructural protein [NSP] 2, NSP3, and NSP5) shared ancestry with other mammalian rotaviruses but were distantly related. The VP4 gene was nearly identical to that of human P[6] rotavirus strains, and the NSP4 gene was closely related to those of previously described mammalian rotaviruses, including human strains. Analysis of partial sequence of the VP1 gene indicated that it was distinct from cognate genes of other rotaviruses. No sequences were obtained for the VP3 and NSP1 genes of the bat rotavirus. This rotavirus was designated G25-P[6]-I15-R8(provisional)-C8-Mx-Ax-N8-T11-E2-H10. Results suggest that several reassortment events have occurred between human, animal, and bat rotaviruses. Several additional rotavirus strains were detected in bats. PMID:21122212

Temporal Association of Rotavirus Vaccine Introduction and Reduction in All-Cause Childhood Diarrheal Hospitalizations in South Africa.

PubMed

Groome, Michelle J; Zell, Elizabeth R; Solomon, Fatima; Nzenze, Susan; Parashar, Umesh D; Izu, Alane; Madhi, Shabir A

2016-05-01

The public health impact of rotavirus vaccination in African settings with a high human immunodeficiency virus (HIV) infection prevalence is yet to be established. We evaluated trends in all-cause diarrheal hospitalizations in Soweto, Johannesburg, before and after the introduction of rotavirus vaccine into South Africa's national immunization program in August 2009. Hospitalizations in children <5 years of age with a diagnosis of diarrhea, defined byInternational Classification of Diseases, Tenth Revisioncodes A00-A05, A06.0-A06.3, A06.9, A07.0-A07.2, A07.9, and A08-A09, were identified at the Chris Hani Baragwanath Academic Hospital from 1 January 2006 to 31 December 2014. The median annual prevaccine (2006-2008) hospitalization incidence was compared to that of the vaccine era (2010-2014), and stratified by age group and HIV infection status. Incidence reductions (per 1000 population) were greatest in children aged <12 months: 54.4 in the prevaccine era vs 30.0, 23.6, 20.0, 18.8, and 18.9 in the postvaccine years 2010-2014, respectively (a 44.9%-65.4% reduction). Lower incidence reductions (39.8%-49.4%) were observed among children aged 12-24 months from the second year post-vaccine introduction onward. Reductions were observed in both HIV-infected and HIV-uninfected children. There was a change in the seasonal pattern of diarrheal hospitalizations post-vaccine introduction, with flattening of the autumn-winter peaks seen in the prevaccine years. An accelerated and sustained decline in all-cause diarrheal hospitalizations, temporally associated with rotavirus vaccine introduction, was observed in children <2 years of age. However, the impact of other interventions such as improved sanitation and changes in HIV management cannot be discounted. Published by Oxford University Press for the Infectious Diseases Society of America 2016. This work is written by (a) US Government employee(s) and is in the public domain in the US.

Efficacy and safety of an oral live attenuated human rotavirus vaccine against rotavirus gastroenteritis during the first 2 years of life in Latin American infants: a randomised, double-blind, placebo-controlled phase III study.

PubMed

Linhares, Alexandre C; Velázquez, F Raúl; Pérez-Schael, Irene; Sáez-Llorens, Xavier; Abate, Hector; Espinoza, Felix; López, Pío; Macías-Parra, Mercedes; Ortega-Barría, Eduardo; Rivera-Medina, Doris Maribel; Rivera, Luis; Pavía-Ruz, Noris; Nuñez, Ernesto; Damaso, Silvia; Ruiz-Palacios, Guillermo M; De Vos, Béatrice; O'Ryan, Miguel; Gillard, Paul; Bouckenooghe, Alain

2008-04-05

Peak incidence of rotavirus gastroenteritis is seen in infants between 6 and 24 months of age. We therefore aimed to assess the 2-year efficacy and safety of an oral live attenuated human rotavirus vaccine for prevention of severe gastroenteritis in infants. 15 183 healthy infants aged 6-13 weeks from ten Latin American countries randomly assigned in a 1 to 1 ratio to receive two oral doses of RIX4414 or placebo at about 2 and 4 months of age in a double-blind, placebo-controlled phase III study were followed up until about 2 years of age. Primary endpoint was vaccine efficacy from 2 weeks after dose two until 1 year of age. Treatment allocation was concealed from investigators and parents of participating infants. Efficacy follow-up for gastroenteritis episodes was undertaken from 2 weeks after dose two until about 2 years of age. Analysis was according to protocol. This study is registered with ClinicalTrials.gov, number NCT00140673 (eTrack444563-023). 897 infants were excluded from the according-to-protocol analysis. Fewer cases (p<0.0001) of severe rotavirus gastroenteritis were recorded for the combined 2-year period in the RIX4414 group (32 [0.4%] of 7205; 95% CI 0.3-0.6) than in the placebo group (161 [2.3%] of 7081; 1.9-2.6), resulting in a vaccine efficacy of 80.5% (71.3-87.1) to 82.1% (64.6-91.9) against wild-type G1, 77.5% (64.7-86.2) against pooled non-G1 strains, and 80.5% (67.9-88.8) against pooled non-G1 P[8] strains. Vaccine efficacy for hospital admission for rotavirus gastroenteritis was 83.0% (73.1-89.7) and for admission for diarrhoea of any cause was 39.3% (29.1-48.1). No cases of intussusception were reported during the second year of follow-up. Two doses of RIX4414 were effective against severe rotavirus gastroenteritis during the first 2 years of life in a Latin American setting. Inclusion of RIX4414 in routine paediatric immunisations should reduce the burden of rotavirus gastroenteritis worldwide.

Anticipating rotavirus vaccines--a pre-vaccine assessment of incidence and economic burden of rotavirus hospitalizations among children < 5 year of age in Libya, 2012-13.

PubMed

Alkoshi, Salem; Leshem, Eyal; Parashar, Umesh D; Dahlui, Maznah

2015-01-24

Libya introduced rotavirus vaccine in October 2013. We examined pre-vaccine incidence of rotavirus hospitalizations and associated economic burden among children < 5 years in Libya to provide baseline data for future vaccine impact evaluations. Prospective, hospital-based active surveillance for rotavirus was conducted at three public hospitals in two cities during August 2012 - April 2013. Clinical, demographic and estimated cost data were collected from children <5 hospitalized for diarrhea; stool specimens were tested for rotavirus with a commercial enzyme immunoassay. Annual rotavirus hospitalization incidence rate estimates included a conservative estimate based on the number of cases recorded during the nine months and an extrapolation to estimate 12 months incidence rate. National rotavirus disease and economic burden were estimated by extrapolating incidence and cost data to the national population of children aged < 5 years. A total of 410 children < 5 years of age with diarrhea were enrolled, of whom 239 (58%) tested positive rotavirus, yielding an incidence range of 418-557 rotavirus hospitalizations per 100,000 children < 5 years of age. Most (86%) rotavirus cases were below two years of age with a distinct seasonal peak in winter (December-March) months. The total cost of treatment for each rotavirus patient was estimated at US$ 679 (range: 200-5,423). By extrapolation, we estimated 2,948 rotavirus hospitalizations occur each year in Libyan children < 5 years of age, incurring total costs of US$ 2,001,662 (range: 1,931,726-2,094,005). Rotavirus incurs substantial morbidity and economic burden in Libya, highlighting the potential value of vaccination of Libyan children against rotavirus.

Uptake and timeliness of rotavirus vaccination in Norway: The first year post-introduction.

PubMed

Valcarcel Salamanca, Beatriz; Hagerup-Jenssen, Maria Elisabeth; Flem, Elmira

2016-09-07

To minimise vaccine-associated risk of intussusception following rotavirus vaccination, Norway adopted very strict age limits for initiating and completing the vaccine series at the time rotavirus vaccination was included in the national immunisation programme, October 2014. Although Norway has a high coverage for routine childhood vaccines, these stringent age limits could negatively affect rotavirus coverage. We documented the status and impact of rotavirus vaccination on other infant vaccines during the first year after its introduction. We used individual vaccination data from the national immunisation register to calculate coverage for rotavirus and other vaccines and examine adherence with the recommended schedules. We identified factors associated with completing the full rotavirus series by performing multiple logistic regression analyses. We also evaluated potential changes in uptake and timeliness of other routine vaccines after the introduction of rotavirus vaccine using the Kaplan-Meier method. The national coverage for rotavirus vaccine achieved a year after the introduction was 89% for one dose and 82% for two doses, respectively. Among fully rotavirus-vaccinated children, 98% received both doses within the upper age limit and 90% received both doses according to the recommended schedule. The child's age at the initiation of rotavirus series and being vaccinated with diphtheria, tetanus, pertussis, polio and Haemophilus influenzae type b (DTaP/IPV/Hib) and pneumococcal vaccines were the strongest predictors of completing the full rotavirus series. No major changes in uptake and timeliness of other paediatric vaccines were observed after introduction of rotavirus vaccine. Norway achieved a high national coverage and excellent adherence with the strict age limits for rotavirus vaccine administration during the first year of introduction, indicating robustness of the national immunisation programme. Rotavirus vaccination did not impact coverage or timeliness of other infant vaccines. Copyright © 2016. Published by Elsevier Ltd.

Genetic analysis of a human rotavirus that belongs to subgroup I but has an RNA pattern typical of subgroup II human rotaviruses.

PubMed Central

Nakagomi, O; Nakagomi, T; Hoshino, Y; Flores, J; Kapikian, A Z

1987-01-01

We have previously found (O. Nakagomi, T. Nakagomi, H. Oyamada, and T. Suto, J. Med. Virol. 17:29-34, 1985), during an epidemiological study in Japan, a novel human rotavirus that belongs to subgroup I but has a long RNA pattern typical of subgroup II human rotaviruses. From the stool specimen containing this virus, we successfully isolated in MA104 cells a rotavirus, designated AU-1, which possesses these novel characteristics. The possibility that strain AU-1 was a laboratory contaminant of an animal rotavirus previously adapted to tissue culture cells was ruled out, and the identity of the AU-1 strain was established. Genetic analysis by RNA-RNA hybridization revealed that the AU-1 strain is not a simple reassortant between subgroup I and II human rotaviruses but that it shares a high level of sequence homology only with the gene encoding VP7 (the major neutralization protein) of serotype 3 human rotaviruses. Weak homology of the genomic RNA segments was also observed between the AU-1 strain and animal rotavirus strains, including rhesus rotavirus strain RRV and bovine rotavirus strain NCDV. These results suggest that the AU-1 strain may be an animal rotavirus that infected a human. Images PMID:3038947

Isolation and characterization of an equine rotavirus.

PubMed Central

Hoshino, Y; Wyatt, R G; Greenberg, H B; Kalica, A R; Flores, J; Kapikian, A Z

1983-01-01

A rotavirus, designated as the H-1 strain, was isolated from a diarrheic foal in primary African green monkey kidney cells and MA104 cells. This cell culture-adapted strain hemagglutinated erythrocytes of human group O, rhesus monkeys, guinea pigs, and sheep. It was found to be similar, if not identical, to porcine rotaviruses (strains OSU, EE, and A-580) by plaque reduction neutralization and hemagglutination inhibition tests, and, in addition, it was found to belong to subgroup 1. This equine rotavirus has an RNA electrophoretic migration pattern which was distinct from those of the three strains of porcine rotavirus. The serological relationship established by plaque reduction neutralization and hemagglutination inhibition tests between the equine (H-1) and porcine (OSU, EE, and A-580) rotaviruses is an example of a rotavirus of the same serotype being isolated from different species. The H-1 strain was distinct from four human rotavirus serotypes (Wa, DS-1, P, and St. Thomas 4) as well as from bovine rotavirus NCDV, simian rotavirus MMU18006, and canine rotavirus CU-1 by plaque reduction neutralization tests. This equine isolate (H-1) was found to be related antigenically to canine CU-1 and bovine NCDV rotaviruses in a one-way fashion by hemagglutination inhibition tests. Images PMID:6313746

Effectiveness of Pentavalent Rotavirus Vaccine Under Conditions of Routine Use in Rwanda.

PubMed

Tate, Jacqueline E; Ngabo, Fidele; Donnen, Philippe; Gatera, Maurice; Uwimana, Jeannine; Rugambwa, Celse; Mwenda, Jason M; Parashar, Umesh D

2016-05-01

Rotavirus vaccine efficacy is lower in low-income countries than in high-income countries. Rwanda was one of the first low-income countries in sub-Saharan Africa to introduce rotavirus vaccine into its national immunization program. We sought to evaluate rotavirus vaccine effectiveness (VE) in this setting. VE was assessed using a case-control design. Cases and test-negative controls were children who presented with a diarrheal illness to 1 of 8 sentinel district hospitals and 10 associated health centers and had a stool specimen that tested positive (cases) or negative (controls) for rotavirus by enzyme immunoassay. Due to high vaccine coverage almost immediately after vaccine introduction, the analysis was restricted to children 7-18 weeks of age at time of rotavirus vaccine introduction. VE was calculated as (1 - odds ratio) × 100, where the odds ratio was the adjusted odds ratio for the rotavirus vaccination rate among case-patients compared with controls. Forty-eight rotavirus-positive and 152 rotavirus-negative children were enrolled. Rotavirus-positive children were significantly less likely to have received rotavirus vaccine (33/44 [73%] unvaccinated) compared with rotavirus-negative children (81/136 [59%] unvaccinated) (P= .002). A full 3-dose series was 75% (95% confidence interval [CI], 31%-91%) effective against rotavirus gastroenteritis requiring hospitalization or a health center visit and was 65% (95% CI, -80% to 93%) in children 6-11 months of age and 81% (95% CI, 25%-95%) in children ≥12 months of age. Rotavirus vaccine is effective in preventing rotavirus disease in Rwandan children who began their rotavirus vaccine series from 7 to 18 weeks of age. Protection from vaccination was sustained after the first year of life. Published by Oxford University Press for the Infectious Diseases Society of America 2016. This work is written by (a) US Government employee(s) and is in the public domain in the US.

An introduction to food and waterborne viruses: diseases, transmission, outbreaks, detection and control

USDA-ARS?s Scientific Manuscript database

Enteric viruses are the number one cause of foodborne illness throughout the world. In addition to foods, contaminated drinking water is another major cause of enteric viral illness. Among the enteric viruses are the noroviruses, hepatitis A and E viruses, enteric adenoviruses, rotavirus, and astro...

Geo(spatial) Health Investigation of Rotavirus in an Endemic Region: Hydroclimatic Influences and Epidemiology of Rotavirus in Bangladesh

NASA Astrophysics Data System (ADS)

Hasan, M. A.; Akanda, A. S.; Jutla, A.; Colwell, R. R.

2016-12-01

Rotavirus is the leading cause of severe dehydrating diarrhea among children under 5. Over 80% of the approximate half a million child deaths every year occur in South Asia and sub-Saharan Africa alone. Although less explored than cholera as a climate driven and influenced global health problem, recent studies have showed that the disease shown strong seasonality and spatio-temporal variability depending on regional hydroclimatic and local environmental conditions. Understanding the epidemiology of this disease, especially the spatio-temporal incidence patterns with respect to environmental factors is vitally important to allow for identification of "hotspots", preventative preparations, and vaccination strategies to improve wellbeing of the vulnerable populations. With climate change, spatio-temporal signatures and footprints of the disease are changing along with increasing burden. However, a robust understanding of the relationships between rotavirus epidemiology and hydroclimatic drivers is yet to be developed. In this study, we evaluate the seasonality and epidemiologic characteristics of rotavirous infection and its spatio-temporal incidence patterns with respect to regional hydroclimatic variables and their extremes in an endemic region in South Asia. Hospital-based surveillance data from different geographic locations allowed us to explore the detailed spatial and temporal characteristics of rotavirus propagation under the influence of climate variables in both coastal and inland areas. The rotavirus transmission patterns show two peaks in a year in the capital city of Dhaka, where winter season (highest in January) shows a high peak and the July-August monsoon season shows a smaller peak. Correlation with climate variables revealed that minimum temperature has strong influence on the winter season outbreak, while rainfall extremes show a strong positive association with the secondary monsoon peak. Spatial analysis also revealed that humidity and soil wetness may influence the timing as drier areas experience earlier outbreaks than wetter areas. Accurate understanding of rotavirus propagation with respect to hydroclimatic and environmental variability can be utilized to establish global surveillance and forecast imminent risk of diarrheal outbreaks in vulnerable regions.

Comparison of Rotavirus and Norovirus transport in standardised and natural soil-water systems

NASA Astrophysics Data System (ADS)

Gamazo, P. A.; Schijven, J. F.; Victoria, M.; Alvareda, E.; Lopez, F.; Ramos, J.; Lizasoain, A.; Sapriza-Azuri, G.; Castells, M.; Colina, R.

2016-12-01

Rotavirus and Norovirus are waterborne viruses that are major causes of diarrhea and others symptoms of acute gastroenteritis. An important pathway of these viruses is groundwater. In Uruguay, as in many developed and developing countries, there are areas where the only source of water for human consumption is groundwater. In the rural area of the Salto district, groundwater is commonly used without any treatment, as it is traditionally considered as a safe source. However, virus contamination have been detected in several wells in the area. The most probable source of contamination are nearby septic systems, since the sewer coverage is scarce. This work aims to evaluate and compare the virus transport processes for a standardised soil-water systems and for the Salto aquifer system. For this, the transport of Rotavirus and Norovirus from clinic samples was studied in two sets of column experiments: 6.7 cm columns with quartz sand under saturated conditions (ionic strength 1mM, pH 7.0) and with sand from the Salto aquifer (Uruguay) (9,2% coarse sand, 47,8% medium sand, 40,5% fine sand, magnesium/calcium bicarbonate water, Ionic strength 15.1 mM, pH 7.2). Both viruses were seeded for 2 pore volumes on the columns. Samples were collected at the column outlet and viruses were enumerated by Q-PRCR. Breakthrough curves were constructed and fitted to a two-site kinetic attachment/detachment model, including blocking using Hydrus-1D. In the quartz sand column, both Rotavirus and Norovirus were removed two orders in magnitude. In the Salto sand column, Rotavirus was removed 2 log10 as well, but Norovirus was removed 4 log10. The fitting of the breakthrough curves indicated that blocking played a role for Rotavirus in the Salto sand column. These results are consistent with field observation where only Rotavirus was detected in the Salto aquifer, while similar concentrations in Salto sewer effluent was measured for these two viruses. This work, besides reporting actual parameters values for human virus transport modelling, shows the significant differences in transport that human viruses can have in standardised and natural soil-water systems.

Report of the 7th African Rotavirus Symposium, Cape Town, South Africa, 8th November 2012.

PubMed

Seheri, L M; Mwenda, J M; Page, N

2014-11-12

The 7th African Rotavirus Symposium was held in Cape Town, South Africa, on the 8th November 2012 as a Satellite Symposium at the First International African Vaccinology Conference. Over 150 delegates participated in this symposium including scientists, clinicians, health officials, policymakers and vaccine manufacturers from across Africa. Key topics discussed included rotavirus surveillance, rotavirus vaccine introduction, post rotavirus vaccine impact analysis and intussusception data and surveillance in Africa. The symposium provided early rotavirus vaccine adopter countries in Africa (South Africa, Ghana and Botswana) an opportunity to share up-to-date information on vaccine introduction, and allowed colleagues to share experiences in establishing routine rotavirus surveillance (Tanzania, Niger and Rwanda). Overall, the symposium highlighted the high burden of rotavirus in Africa, and the need to continue to strengthen efforts in preventing rotavirus diarrhoea in Africa. Copyright © 2014. Published by Elsevier Ltd.. All rights reserved.

G1P[8] species A rotavirus over 27 years--pre- and post-vaccination eras--in Brazil: full genomic constellation analysis and no evidence for selection pressure by Rotarix® vaccine.

PubMed

da Silva, Marcelle Figueira Marques; Rose, Tatiana Lundgren; Gómez, Mariela Martínez; Carvalho-Costa, Filipe Anibal; Fialho, Alexandre Madi; de Assis, Rosane Maria Santos; de Andrade, Juliana da Silva Ribeiro; Volotão, Eduardo de Mello; Leite, José Paulo Gagliardi

2015-03-01

Epidemiological data on species A rotavirus (RVA) infections have demonstrated the genetic diversity of strains circulating worldwide. Many G and P genotype combinations have been described over the years, varying regionally and temporally, especially in developing countries. However, the most common G and P genotype combinations identified in RVA human strains worldwide are G1P[8], G2P[4], G3P[8], G4P[8] and G9P[8]. RVA genotype G1P[8] strains are responsible for more than 50% of child infections worldwide and component of the two vaccines (Rotarix® [RV1] and RotaTeq® [RV5]) licensed globally. For a better understanding of the evolutionary mechanisms of this genotype in Brazil, phylogenetic analyses based on the 11 RVA genome segments (genomic constellation) from 90 G1P[8] RVA strains collected in two eras - (i) pre-vaccination with RV1 (1996-February 2006); (ii) post-vaccination (March 2006-2013) - in different Brazilian states were performed. The results showed the Wa-like genomic constellation of the Brazilian G1P[8] strains with a I1-R1-C1-M1-A1-N1-T1-E1-H1 specificity, except for two strains (rj14055-07 and ba19030-10) that belong to a I1-R1-C1-M1-A1-N1-T3-E1-H1 genomic constellation, evidencing the occurrence of reassortment (Wa-like×AU-1-like) of the NSP3 gene. Reassortment events were also demonstrated between Brazilian G1P[8] strains and the RV1 vaccine strain in some genes in vaccinated and unvaccinated children. VP7 and VP8* antigenic site analysis showed that the amino acid substitutions observed in samples collected after the introduction of RV1 in Brazil were already detected in samples collected in the 1980s and 1990s, suggesting that mass Brazilian RV1 vaccination had no impact on the diversity observed inside antigenic sites for these two proteins. Copyright © 2015 Elsevier B.V. All rights reserved.

Perinatal Risk Factors Associated with Gastroenteritis Hospitalizations in Aboriginal and Non-Aboriginal Children in Western Australia (2000-2012): A Record Linkage Cohort Study.

PubMed

Fathima, Parveen; Snelling, Thomas Laurence; de Klerk, Nicholas; Lehmann, Deborah; Blyth, Christopher Charles; Waddington, Claire Shelley; Moore, Hannah Catherine

2018-03-31

Gastroenteritis is a leading cause of childhood morbidity worldwide. We aimed to assess the maternal and infant characteristics and population attributable fractions (PAFs) associated with childhood gastroenteritis-related hospitalizations. We conducted a whole-of-population retrospective birth cohort study of 367,476 children live-born in Western Australia (WA) 2000-2012. We identified hospital admissions up to age <15 years pertaining to these children, with a principal diagnosis code for infectious gastroenteritis. Cox regression was used to obtain the adjusted hazard ratios with 95% confidence intervals (CIs) and the PAFs associated with each risk factor in Aboriginal and non-Aboriginal children for their first gastroenteritis hospital admission. There were a total of 15,888 gastroenteritis-related hospital admissions (25.7% occurring among Aboriginal children). The overall gastroenteritis hospitalization rate for children aged <15 years was 4.6/1000 child-years for non-Aboriginal children and 21.5/1000 child-years for Aboriginal children. Male gender, maternal age <20 years, pre-term birth, low birth weight, residence in remote regions of WA and birth in the pre-rotavirus vaccine era were significant independent risk factors for gastroenteritis hospitalization in both Aboriginal and non-Aboriginal children. Additionally, birth by caesarean section and low socio-economic status were identified as being associated with gastroenteritis hospitalization in non-Aboriginal children. PAFs suggest that 39% of all gastroenteritis hospitalizations in non-Aboriginal children (38% in Aboriginal children) could be averted if all children receive the rotavirus vaccine. Given the beneficial effect of infant rotavirus vaccination in preventing all-cause gastroenteritis hospitalization, efforts should be taken to optimize rotavirus vaccine coverage in those at highest risk.

Vaccines for the prevention of diarrhea due to cholera, shigella, ETEC and rotavirus

PubMed Central

2013-01-01

Background Diarrhea is a leading cause of mortality in children under 5 years along with its long-term impact on growth and cognitive development. Despite advances in the understanding of diarrheal disorders and management strategies, globally nearly 750,000 children die annually as a consequence of diarrhea. Methods We conducted a systematic review of the efficacy and effectiveness studies. We used a standardized abstraction and grading format and performed meta-analyses for all outcomes. The estimated effect of cholera, shigella, Enterotoxigenic Escherichia coli (ETEC) and rotavirus vaccines was determined by applying the standard Child Health Epidemiology Reference Group (CHERG) rules. Results A total of 24 papers were selected and analyzed for all the four vaccines. Based on the evidence, we propose a 74% mortality reduction in rotavirus specific mortality, 52% reduction in cholera incidence due to their respective vaccines. We did not find sufficient evidence and a suitable outcome to project mortality reductions for cholera, ETEC and shigella in children under 5 years. Conclusion Vaccines for rotavirus and cholera have the potential to reduce diarrhea morbidity and mortality burden. But there is no substantial evidence of efficacy for ETEC and shigella vaccines, although several promising vaccine concepts are moving from the development and testing pipeline towards efficacy and Phase 3 trials. PMID:24564510

Budget impact and cost-utility analysis of universal infant rotavirus vaccination in Spain.

PubMed

Imaz, Iñaki; Rubio, Beltrán; Cornejo, Ana M; González-Enríquez, Jesús

2014-04-01

Rotavirus is not included in the Spanish mass infant vaccination schedule but has also not been economically evaluated for its inclusion. We analysed cost-utility of the universal infant rotavirus vaccination using RotaTeq® versus no vaccination in Spain. We also carried out a budget impact analysis and determined the effect on results of different variables introduced in the model. A deterministic Markov model was built considering loss of quality of life for children and their parents, and introducing direct and indirect costs updated to 2011. The introduction of the vaccination using RotaTeq® as a universal infant vaccination would increase the annual health care budget in 10.43 million euro and would result in a gain of an additional Quality Adjusted Life Year at a cost of 280,338€ from the healthcare system perspective and 210,167€ from the societal perspective. The model was stable to variable modifications. To sum up, according to our model and estimates, the introduction of a universal infant rotavirus vaccination with RotaTeq® in Spain would cause a large impact on the health care budget and would not be efficient unless significant variations in vaccine price, vaccine efficacy and/or utilities took place. Copyright © 2013 Elsevier Inc. All rights reserved.

Analysis by rotavirus gene 6 reverse transcriptase-polymerase chain reaction assay of rotavirus-positive gastroenteritis cases observed during the vaccination phase of the Rotavirus Efficacy and Safety Trial (REST)

PubMed Central

Matson, David O; Vesikari, Timo; Dennehy, Penelope; Dallas, Michael D; Goveia, Michelle G; Itzler, Robbin F; Ciarlet, Max

2014-01-01

During the vaccination phase of the Rotavirus Efficacy and Safety Trial (REST), the period between the administration of dose 1 through 13 days after the administration of dose 3, there were more wild-type rotavirus gastroenteritis (RVGE) cases among vaccine recipients compared with placebo recipients using the protocol-specified microbiological plaque assay in the clinical-efficacy cohort, a subset of subjects where vaccine efficacy against RVGE of any severity was assessed. In this study, a rotavirus genome segment 6-based reverse transcriptase–polymerase chain reaction assay was applied post hoc to clarify the accuracy of type categorization of all these RVGE cases in vaccine recipients during the vaccination phase of REST. The assay characterized 147 (90%) of 163 re-assayed RVGE cases or rotavirus-associated health care contacts as type-determinable: either wild-type or vaccine-type rotavirus strains. In the clinical-efficacy cohort (N = 5673), 19 (18.8%) of 101 samples from RVGE cases contained wild-type rotavirus, 70 (69.3%) vaccine virus, and 12 (11.9%) were indeterminable. In the large-scale cohort (N = 68,038), 10 (34.5%) of 29 samples from RVGE-related health care contacts contained wild-type rotavirus strains, 15 (51.7%) vaccine-type rotavirus strains, and 4 (13.8%) were indeterminable. Of the 33 samples from RVGE cases in placebo recipients, all were confirmed to contain wild-type rotaviruses. Altogether, this post-hoc re-evaluation showed that the majority (75%) of type-determinable RVGE cases or health care contacts that occurred during the vaccination phase of REST in vaccine recipients were associated with vaccine-type rotavirus strains rather than wild-type rotavirus strains. PMID:25424931

Uptake of oral rotavirus vaccine and timeliness of routine immunization in Brazil’s National Immunization Program

PubMed Central

Flannery, Brendan; Samad, Samia; de Moraes, José Cássio; Tate, Jacqueline E.; Danovaro-Holliday, M. Carolina; de Oliveira, Lúcia Helena; Rainey, Jeanette J.

2015-01-01

Introduction In March, 2006, oral rotavirus vaccine was added to Brazil’s infant immunization schedule with recommended upper age limits for initiating (by age 14 weeks) and completing (by age 24 weeks) the two-dose series to minimize age-specific risk of intussusception following rotavirus vaccination. Several years after introduction, estimated coverage with rotavirus vaccine (83%) was lower compared to coverage for other recommended childhood immunizations (≥94%). Methods We analyzed data from Brazil’s national immunization program on uptake of oral rotavirus vaccine by geographic region and compared administrative coverage estimates for first and second doses of oral rotavirus vaccine (Rota1 and Rota2) with first and second doses of diphtheria-tetanus-pertussis-Haemophilus influenzae type b vaccine (DTP-Hib1 and DTP-Hib2). For 27 Brazilian cities, we compared differences between estimated rotavirus and DTP-Hib coverage in 2010 with delayed receipt of DTP-Hib vaccine among a cohort of children surveyed before rotavirus introduction. Results In 2010, infant vaccination coverage was 99.0% for DTP-Hib1 versus 95.2% for Rota1 (3.8% difference), and 98.4% for DTP-Hib2 versus 83.0% for Rota2 (15.4% difference), with substantial regional variation. Differences between DTP-Hib and rotavirus vaccination coverage in Brazilian cities correlated with delay in DTP-Hib vaccination among children surveyed. Age restrictions for initiating and completing the rotavirus vaccination series likely contributed to lower coverage with rotavirus vaccine in Brazil. Conclusion To maximize benefits of rotavirus vaccination, strategies are needed to improve timeliness of routine immunizations; monitoring rotavirus vaccine uptake and intussusception risk is needed to guide further recommendations for rotavirus vaccination. PMID:23313652

Analysis by rotavirus gene 6 reverse transcriptase-polymerase chain reaction assay of rotavirus-positive gastroenteritis cases observed during the vaccination phase of the Rotavirus Efficacy and Safety Trial (REST).

PubMed

Matson, David O; Vesikari, Timo; Dennehy, Penelope; Dallas, Michael D; Goveia, Michelle G; Itzler, Robbin F; Ciarlet, Max

2014-01-01

During the vaccination phase of the Rotavirus Efficacy and Safety Trial (REST), the period between the administration of dose 1 through 13 days after the administration of dose 3, there were more wild-type rotavirus gastroenteritis (RVGE) cases among vaccine recipients compared with placebo recipients using the protocol-specified microbiological plaque assay in the clinical-efficacy cohort, a subset of subjects where vaccine efficacy against RVGE of any severity was assessed. In this study, a rotavirus genome segment 6-based reverse transcriptase-polymerase chain reaction assay was applied post hoc to clarify the accuracy of type categorization of all these RVGE cases in vaccine recipients during the vaccination phase of REST. The assay characterized 147 (90%) of 163 re-assayed RVGE cases or rotavirus-associated health care contacts as type-determinable: either wild-type or vaccine-type rotavirus strains. In the clinical-efficacy cohort (N = 5673), 19 (18.8%) of 101 samples from RVGE cases contained wild-type rotavirus, 70 (69.3%) vaccine virus, and 12 (11.9%) were indeterminable. In the large-scale cohort (N = 68,038), 10 (34.5%) of 29 samples from RVGE-related health care contacts contained wild-type rotavirus strains, 15 (51.7%) vaccine-type rotavirus strains, and 4 (13.8%) were indeterminable. Of the 33 samples from RVGE cases in placebo recipients, all were confirmed to contain wild-type rotaviruses. Altogether, this post-hoc re-evaluation showed that the majority (75%) of type-determinable RVGE cases or health care contacts that occurred during the vaccination phase of REST in vaccine recipients were associated with vaccine-type rotavirus strains rather than wild-type rotavirus strains.

The Vast and Varied Global Burden of Norovirus: Prospects for Prevention and Control

PubMed Central

Lopman, Benjamin A.; Steele, Duncan; Kirkwood, Carl D.; Parashar, Umesh D.

2016-01-01

Globally, norovirus is associated with approximately one-fifth of all diarrhea cases, with similar prevalence in both children and adults, and is estimated to cause over 200,000 deaths annually in developing countries. Norovirus is an important pathogen in a number of high-priority domains: it is the most common cause of diarrheal episodes globally, the principal cause of foodborne disease outbreaks in the United States, a key health care–acquired infection, a common cause of travel-associated diarrhea, and a bane for deployed military troops. Partly as a result of this ubiquity and burden across a range of different populations, identifying target groups and strategies for intervention has been challenging. And, on top of the breadth of this public health problem, there remain important gaps in scientific knowledge regarding norovirus, especially with respect to disease in low-income settings. Many pathogens can cause acute gastroenteritis. Historically, rotavirus was the most common cause of severe disease in young children globally. Now, vaccines are available for rotavirus and are universally recommended by the World Health Organization. In countries with effective rotavirus vaccination programs, disease due to that pathogen has decreased markedly, but norovirus persists and is now the most common cause of pediatric gastroenteritis requiring medical attention. However, the data supporting the precise role of norovirus in low- and middle-income settings are sparse. With vaccines in the pipeline, addressing these and other important knowledge gaps is increasingly pressing. We assembled an expert group to assess the evidence for the global burden of norovirus and to consider the prospects for norovirus vaccine development. The group assessed the evidence in the areas of burden of disease, epidemiology, diagnostics, disease attribution, acquired immunity, and innate susceptibility, and the group considered how to bring norovirus vaccines from their current state of development to a viable product that will benefit global health. PMID:27115709

The Vast and Varied Global Burden of Norovirus: Prospects for Prevention and Control.

PubMed

Lopman, Benjamin A; Steele, Duncan; Kirkwood, Carl D; Parashar, Umesh D

2016-04-01

Globally, norovirus is associated with approximately one-fifth of all diarrhea cases, with similar prevalence in both children and adults, and is estimated to cause over 200,000 deaths annually in developing countries. Norovirus is an important pathogen in a number of high-priority domains: it is the most common cause of diarrheal episodes globally, the principal cause of foodborne disease outbreaks in the United States, a key health care-acquired infection, a common cause of travel-associated diarrhea, and a bane for deployed military troops. Partly as a result of this ubiquity and burden across a range of different populations, identifying target groups and strategies for intervention has been challenging. And, on top of the breadth of this public health problem, there remain important gaps in scientific knowledge regarding norovirus, especially with respect to disease in low-income settings. Many pathogens can cause acute gastroenteritis. Historically, rotavirus was the most common cause of severe disease in young children globally. Now, vaccines are available for rotavirus and are universally recommended by the World Health Organization. In countries with effective rotavirus vaccination programs, disease due to that pathogen has decreased markedly, but norovirus persists and is now the most common cause of pediatric gastroenteritis requiring medical attention. However, the data supporting the precise role of norovirus in low- and middle-income settings are sparse. With vaccines in the pipeline, addressing these and other important knowledge gaps is increasingly pressing. We assembled an expert group to assess the evidence for the global burden of norovirus and to consider the prospects for norovirus vaccine development. The group assessed the evidence in the areas of burden of disease, epidemiology, diagnostics, disease attribution, acquired immunity, and innate susceptibility, and the group considered how to bring norovirus vaccines from their current state of development to a viable product that will benefit global health.

Epidemiology and genetic diversity of classic human astrovirus among hospitalized children with acute gastroenteritis in Uruguay.

PubMed

Lopez, Fernando; Lizasoain, Andrés; Victoria, Matías; Papalardo, Cecilia; Castro, Sebastian; Arreseigor, Edit; López, Patricia; Colina, Rodney

2017-10-01

Classic Human Astrovirus (Classic HAstV) are one of the most important causes of pediatric acute gastroenteritis (AGE), after rotaviruses and arguably caliciviruses. The aim of this study was to determine the molecular epidemiology of Classic HAstV from 175 clinical samples, being 153 stools and 22 vomits, collected from pediatric hospitalized patients with AGE in Salto city, Uruguay, from January 2011 to December 2012. Classic HAstV were detected and genotyped by using a qualitative Retro Transcription-Polimerase Chain Reaction (RT-PCR) directed to the Open Reading Frame-2 (ORF2) region C. Amplicons were sequenced and phylogenetic analyses were carried out in order to determine genotypes and lineages. Classic HAstV were detected in 18 out of 175 analyzed samples (10.3%) and 14 of them (78.0%) were successfully sequenced being 6 (42.8%) classified as HAstV-1 (1a lineage), 4 (28.6%) as HAstV-2 (2c lineage), and 4 (28.6%) as HAstV-3 (3c lineage). A higher detection of Classic HAstV infections was observed in autumn for both years of surveillance, and the majority of the positive cases were observed in 2011. The group of children between 2 and 5 years old presented the higher percentage of infections. To our knowledge, the present study represents the first report of astrovirus from acute gastroenteritis cases in Uruguay, evidencing its role as a relevant etiologic agent in severe cases of this disease. © 2017 Wiley Periodicals, Inc.

Reaching every child with rotavirus vaccine: Report from the 10th African rotavirus symposium held in Bamako, Mali.

PubMed

Sow, Samba O; Steele, A Duncan; Mwenda, Jason M; Armah, George E; Neuzil, Kathleen M

2017-10-09

The Center for Vaccine Development - Mali (CVD - Mali), the World Health Organization's regional office in Africa (WHO/AFRO), and the CVD at the University of Maryland School of Medicine hosted the 10th African Rotavirus Symposium in Bamako, Mali on 1-2 June 2016. The symposium is coordinated by WHO/AFRO, the Regional Rotavirus Reference Laboratories, and the African Rotavirus Network (ARN), with support from the Bill & Melinda Gates Foundation. The event brings together leading rotavirus researchers, scientists, and policy-makers from across Africa and the world. Over 150 participants, from 31 countries, including 27 in Africa, joined forces to address the theme "Reaching Every Child in Africa with Rotavirus Vaccines." This symposium, the first in francophone Africa, occurred at an unprecedented time when 33 African countries had introduced rotavirus vaccines into their national immunization programs. The symposium concluded with a Call to Action to introduce rotavirus vaccines in the 21 remaining African countries, to increase access in countries with existing vaccination programs, and to continue surveillance and research on rotavirus and other diarrheal diseases. Copyright © 2017.

Rotavirus Treatment

MedlinePlus

... Search Form Controls Cancel Submit Search The CDC Rotavirus Note: Javascript is disabled or is not supported ... message, please visit this page: About CDC.gov . Rotavirus Home About Rotavirus Symptoms Transmission Treatment Photos Vaccination ...

Rotavirus Symptoms

MedlinePlus

... Search Form Controls Cancel Submit Search The CDC Rotavirus Note: Javascript is disabled or is not supported ... message, please visit this page: About CDC.gov . Rotavirus Home About Rotavirus Symptoms Transmission Treatment Photos Vaccination ...

Candidate new rotavirus species in Schreiber's bats, Serbia.

PubMed

Bányai, Krisztián; Kemenesi, Gábor; Budinski, Ivana; Földes, Fanni; Zana, Brigitta; Marton, Szilvia; Varga-Kugler, Renáta; Oldal, Miklós; Kurucz, Kornélia; Jakab, Ferenc

2017-03-01

The genus Rotavirus comprises eight species designated A to H and one tentative species, Rotavirus I. In a virus metagenomic analysis of Schreiber's bats sampled in Serbia in 2014 we obtained sequences likely representing novel rotavirus species. Whole genome sequencing and phylogenetic analysis classified the representative strain into a tentative tenth rotavirus species, we provisionally called Rotavirus J. The novel virus shared a maximum of 50% amino acid sequence identity within the VP6 gene to currently known members of the genus. This study extends our understanding of the genetic diversity of rotaviruses in bats. Copyright © 2016 Elsevier B.V. All rights reserved.

Estimates of economic burden of providing inpatient care in childhood rotavirus gastroenteritis from Malaysia.

PubMed

Lee, Way Seah; Poo, Muhammad Izzuddin; Nagaraj, Shyamala

2007-12-01

To estimate the cost of an episode of inpatient care and the economic burden of hospitalisation for childhood rotavirus gastroenteritis (GE) in Malaysia. A 12-month prospective, hospital-based study on children less than 14 years of age with rotavirus GE, admitted to University of Malaya Medical Centre, Kuala Lumpur, was conducted in 2002. Data on human resource expenditure, costs of investigations, treatment and consumables were collected. Published estimates on rotavirus disease incidence in Malaysia were searched. Economic burden of hospital care for rotavirus GE in Malaysia was estimated by multiplying the cost of each episode of hospital admission for rotavirus GE with national rotavirus incidence in Malaysia. In 2002, the per capita health expenditure by Malaysian Government was US$71.47. Rotavirus was positive in 85 (22%) of the 393 patients with acute GE admitted during the study period. The median cost of providing inpatient care for an episode of rotavirus GE was US$211.91 (range US$68.50-880.60). The estimated average cases of children hospitalised for rotavirus GE in Malaysia (1999-2000) was 8571 annually. The financial burden of providing inpatient care for rotavirus GE in Malaysian children was estimated to be US$1.8 million (range US$0.6 million-7.5 million) annually. The cost of providing inpatient care for childhood rotavirus GE in Malaysia was estimated to be US$1.8 million annually. The financial burden of rotavirus disease would be higher if cost of outpatient visits, non-medical and societal costs are included.

Rotavirus - Global research density equalizing mapping and gender analysis.

PubMed

Köster, Corinna; Klingelhöfer, Doris; Groneberg, David A; Schwarzer, Mario

2016-01-02

Rotaviruses are the leading reason for dehydration and severe diarrheal disease and in infants and young children worldwide. An increasing number of related publications cause a crucial challenge to determine the relevant scientific output. Therefore, scientometric analyses are helpful to evaluate quantity as well as quality of the worldwide research activities on Rotavirus. Up to now, no in-depth global scientometric analysis relating to Rotavirus publications has been carried out. This study used scientometric tools and the method of density equalizing mapping to visualize the differences of the worldwide research effort referring to Rotavirus. The aim of the study was to compare scientific output geographically and over time by using an in-depth data analysis and New quality and quantity indices in science (NewQIS) tools. Furthermore, a gender analysis was part of the data interpretation. We retrieved all Rotavirus-related articles, which were published on "Rotavirus" during the time period from 1900 to 2013, from the Web of Science by a defined search term. These items were analyzed regarding quantitative and qualitative aspects, and visualized with the help of bibliometric methods and the technique of density equalizing mapping to show the differences of the worldwide research efforts. This work aimed to extend the current NewQIS platform. The 5906 Rotavirus associated articles were published in 138 countries from 1900 to 2013. The USA authored 2037 articles that equaled 34.5% of all published items followed by Japan with 576 articles and the United Kingdom - as the most productive representative of the European countries - with 495 articles. Furthermore, the USA established the most cooperations with other countries and was found to be in the center of an international collaborative network. We performed a gender analysis of authors per country (threshold was set at a publishing output of more than 100 articles by more than 50 authors whose names could be identified in more than 50% of cases) showed a domination of female scientists in Brazil, while in all other countries, male scientists predominate. Relating the number of publications to the population of a country (Q1) and compared to the GPD (Q2), we found that European and African countries as well as Australia and New Zealand - not the USA - were among the top ranked nations. Regarding rotavirus-related scientific output, the USA was the overall leading nation when qualitative and qualitative aspects were taken into account. In contrast to these classical scientometric variables, indices such as Q1 and Q2 enable comparability between countries with unequal conditions and scientific infrastructures helping to differentiate publishing quality and quantity in a more relevant way. Also, it was deduced that counties with a high rotavirus-associated child mortality, like the Democratic Republic of Congo, should be integrated into the collaborative efforts more intensively. Copyright © 2015 Elsevier Ltd. All rights reserved.

Silencing the alarms: innate immune antagonism by rotavirus NSP1 and VP3

PubMed Central

Morelli, Marco; Ogden, Kristen M.; Patton, John T.

2016-01-01

The innate immune response involves a broad array of pathogen sensors that stimulate the production of interferons (IFN) to induce an antiviral state. Rotavirus, a significant cause of childhood gastroenteritis and a member of the Reoviridae family of segmented, double-stranded RNA viruses, encodes at least two direct antagonists of host innate immunity: NSP1 and VP3. NSP1, a putative E3 ubiquitin ligase, mediates the degradation of cellular factors involved in both IFN induction and downstream signaling. VP3, the viral capping enzyme, utilizes a 2H-phosphodiesterase domain to prevent activation of the cellular oligoadenylate synthase (OAS)-RNase L pathway. Computational, molecular, and biochemical studies have provided key insights into the structural and mechanistic basis of innate immune antagonism by NSP1 and VP3 of group A rotaviruses (RVA). Future studies with non-RVA isolates will be essential to understand how other RV species evade host innate immune responses. PMID:25724417

Persistence of Giardia, Cryptosporidium, Rotavirus, and Adenovirus in treated sewage in São Paulo state, Brazil.

PubMed

Tonani, K A A; Padula, J A; Julião, F C; Fregonesi, B M; Alves, R I S; Sampaio, C F; Beda, C F; Hachich, E M; Segura-Muñoz, S I

2013-12-01

Abstract :  The persistence of Giardia, Cryptosporidium, Rotavirus, and Adenovirus in samples of raw and treated sewage collected monthly in 2010 at the Biological Wastewater Treatment Plant of Ribeirão Preto, SP, Brazil, was analyzed. The USEPA Method 1623 was used to detect and quantify Giardia and Cryptosporidium. An enzyme immunoassay was carried out to test Rotavirus and Adenovirus antigen optical density (Rotascreen® and Adenoscreen®). The results show a significant decrease in the concentrations of Giardia, Rotavirus and Adenovirus (P < 0.05) and a trend of decreasing Cryptosporidium densities, without statistical significance. Giardia concentrations ranged from 120 to 2,200 cysts/L in raw sewage and from 0.45 to 3.5 cysts/L in treated sewage. Cryptosporidium concentration ranged from undetectable to 28.9 oocysts/L in raw sewage and undetectable to 1.05 oocysts/L in treated sewage. Rotavirus presented absorbance values that ranged from 1.17 ± 0.81 in raw sewage to 0.46 ± 0.32 in treated sewage. Adenovirus, in turn, presented absorbance values of 0.64 ± 0.20 in raw sewage and of 0.45 ± 0.04 in treated sewage. There was no significant seasonal tendency observed in the distribution of protozoa (oo)cysts and in the viral antigen density in the monthly sewage samples during 2010 (P > 0.05). Even though these pathogenic agents decreased after treatment, the remaining loads observed in treated sewage can reach the watercourses receiving it. Giardia, Cryptosporidium, Rotavirus, and Adenovirus are pathogens with very low infectious doses, representing a public health risk especially for vulnerable groups, such as children living near these watercourses and homeless people using this water for various purposes. Studies addressing the environmental persistence of opportunistic pathogens in watercourses are hugely important in the public health sphere, especially in developing countries, where economic, social, cultural, and environmental factors still persist that are favorable to population's exposure to diarrhea-causing agents.

Evaluation of the Field Performance of ImmunoCard STAT!® Rapid Diagnostic Test for Rotavirus in Dadaab Refugee Camp and at the Kenya–Somalia Border

PubMed Central

Ope, Maurice; Nyoka, Raymond; Unshur, Ahmed; Oyier, Fredrick O.; Mowlid, Shafe A.; Owino, Brian; Ochieng, Steve B.; Okello, Charles I.; Montgomery, Joel M.; Wagacha, Burton; Galev, Aleksandar; Abdow, Abdikadir; Esona, Mathew D.; Tate, Jacqueline; Fitter, David; Cookson, Susan T.; Arunmozhi, Balajee; Marano, Nina

2017-01-01

Rotavirus commonly causes diarrhea in children, leading to hospitalization and even death. Rapid diagnostic tests are feasible alternatives for determining rotavirus outbreaks in refugee camps that have inadequate laboratory capacity. We evaluated the field performance of ImmunoCard STAT!® Rotavirus (ICS-RV) in Dadaab Refugee Camp and at the Kenya–Somalia border. From May to December 2014, we prospectively enrolled children aged < 5 years hospitalized with acute diarrhea, defined as ≥ 3 episodes of loose stool in 24 hours for < 7 days. Stool samples were collected and tested by trained surveillance clerks using ICS-RV per manufacturer's instructions. The field performance characteristics of ICS-RV were evaluated against the gold standard test, Premier™ Rotaclone® enzyme immunoassay. The operational characteristics were evaluated using World Health Organization (WHO) ASSURED criteria to determine whether ICS-RV is appropriate as a point-of-care test by administering a standard questionnaire and observing surveillance clerks performing the test. We enrolled 213 patients with a median age of 10 months (range = 1–48); 58.2% were male. A total of 71 (33.3%) and 60 (28.2%) patients tested positive for rotavirus infection by immunoassay and ICS-RV, respectively. The sensitivity, specificity, and positive and negative predictive values of ICS-RV compared with the immunoassay were 83.1% (95% confidence interval [CI] = 72.3–91.0), 99.3% (95% CI = 96.1–100), 98.3% (95% CI = 91.1–100), and 92.1% (95% CI = 86.6–95.5), respectively. The ICS-RV fulfilled the WHO ASSURED criteria for point-of-care testing. ICS-RV is a field-ready point-of-care test with good field performance and operational characteristics. It can be useful in determining rotavirus outbreaks in resource-limited settings. PMID:28719278

Evaluation of the Field Performance of ImmunoCard STAT!® Rapid Diagnostic Test for Rotavirus in Dadaab Refugee Camp and at the Kenya-Somalia Border.

PubMed

Ope, Maurice; Nyoka, Raymond; Unshur, Ahmed; Oyier, Fredrick O; Mowlid, Shafe A; Owino, Brian; Ochieng, Steve B; Okello, Charles I; Montgomery, Joel M; Wagacha, Burton; Galev, Aleksandar; Abdow, Abdikadir; Esona, Mathew D; Tate, Jacqueline; Fitter, David; Cookson, Susan T; Arunmozhi, Balajee; Marano, Nina

2017-06-01

AbstractRotavirus commonly causes diarrhea in children, leading to hospitalization and even death. Rapid diagnostic tests are feasible alternatives for determining rotavirus outbreaks in refugee camps that have inadequate laboratory capacity. We evaluated the field performance of ImmunoCard STAT! ® Rotavirus (ICS-RV) in Dadaab Refugee Camp and at the Kenya-Somalia border. From May to December 2014, we prospectively enrolled children aged < 5 years hospitalized with acute diarrhea, defined as ≥ 3 episodes of loose stool in 24 hours for < 7 days. Stool samples were collected and tested by trained surveillance clerks using ICS-RV per manufacturer's instructions. The field performance characteristics of ICS-RV were evaluated against the gold standard test, Premier ™ Rotaclone ® enzyme immunoassay. The operational characteristics were evaluated using World Health Organization (WHO) ASSURED criteria to determine whether ICS-RV is appropriate as a point-of-care test by administering a standard questionnaire and observing surveillance clerks performing the test. We enrolled 213 patients with a median age of 10 months (range = 1-48); 58.2% were male. A total of 71 (33.3%) and 60 (28.2%) patients tested positive for rotavirus infection by immunoassay and ICS-RV, respectively. The sensitivity, specificity, and positive and negative predictive values of ICS-RV compared with the immunoassay were 83.1% (95% confidence interval [CI] = 72.3-91.0), 99.3% (95% CI = 96.1-100), 98.3% (95% CI = 91.1-100), and 92.1% (95% CI = 86.6-95.5), respectively. The ICS-RV fulfilled the WHO ASSURED criteria for point-of-care testing. ICS-RV is a field-ready point-of-care test with good field performance and operational characteristics. It can be useful in determining rotavirus outbreaks in resource-limited settings.

Household Catastrophic Healthcare Expenditure and Impoverishment Due to Rotavirus Gastroenteritis Requiring Hospitalization in Malaysia

PubMed Central

2015-01-01

Background While healthcare costs for rotavirus gastroenteritis requiring hospitalization may be burdensome on households in Malaysia, exploration on the distribution and catastrophic impact of these expenses on households are lacking. Objectives We assessed the economic burden, levels and distribution of catastrophic healthcare expenditure, the poverty impact on households and inequities related to healthcare payments for acute gastroenteritis requiring hospitalization in Malaysia. Methods A two-year prospective, hospital-based study was conducted from 2008 to 2010 in an urban (Kuala Lumpur) and rural (Kuala Terengganu) setting in Malaysia. All children under the age of 5 years admitted for acute gastroenteritis were included. Patients were screened for rotavirus and information on healthcare expenditure was obtained. Results Of the 658 stool samples collected at both centers, 248 (38%) were positive for rotavirus. Direct and indirect costs incurred were significantly higher in Kuala Lumpur compared with Kuala Terengganu (US$222 Vs. US$45; p<0.001). The mean direct and indirect costs for rotavirus gastroenteritis consisted 20% of monthly household income in Kuala Lumpur, as compared with only 5% in Kuala Terengganu. Direct medical costs paid out-of-pocket caused 141 (33%) households in Kuala Lumpur to experience catastrophic expenditure and 11 (3%) households to incur poverty. However in Kuala Terengganu, only one household (0.5%) experienced catastrophic healthcare expenditure and none were impoverished. The lowest income quintile in Kuala Lumpur was more likely to experience catastrophic payments compared to the highest quintile (87% vs 8%). The concentration index for out-of-pocket healthcare payments was closer to zero at Kuala Lumpur (0.03) than at Kuala Terengganu (0.24). Conclusions While urban households were wealthier, healthcare expenditure due to gastroenteritis had more catastrophic and poverty impact on the urban poor. Universal rotavirus vaccination would reduce both disease burden and health inequities in Malaysia. PMID:25941805

Unexpected detection of porcine rotavirus C strains carrying human origin VP6 gene.

PubMed

Kattoor, Jobin Jose; Saurabh, Sharad; Malik, Yashpal Singh; Sircar, Shubhankar; Dhama, Kuldeep; Ghosh, Souvik; Bányai, Krisztián; Kobayashi, Nobumichi; Singh, Raj Kumar

2017-12-01

Rotavirus C (RVC), a known etiological agent of diarrheal outbreaks, mainly inflicts swine population globally with sporadic incidence in human, cattle, ferret, mink and dog. To demonstrate the presence of RVC in Indian swine population and characterization of its selected structural (VP6) and non-structural (NSP4 and NSP5) genes. A total of 108 diarrheic samples from different regions of India were used. Isolated RNA was loaded onto polyacrylamide gel to screen for the presence of RVs through the identification of specific electrophoretic genomic migration pattern. To characterize the RVC strains, VP6 gene and NSP4 and NSP5 genes were amplified, sequenced and analyzed. Based on VP6 gene specific diagnostic RT-PCR, the presence of RVC was confirmed in 12.0% (13/108) piglet fecal specimens. The nucleotide sequence analysis of VP6 gene, encoding inner capsid protein, from selected porcine RVC (PoRVC) strains revealed more than 93% homologies to human RVC strains (HuRVC) of Eurasian origin. These strains were distant from hitherto reported PoRVCs and clustered with HuRVCs, owning I2 genotype. However, the two non-structural genes, i.e. NSP4 and NSP5, of these strains were found to be of swine type, signifying a re-assortment event that has occurred in the Indian swine population. The findings indicate the presence of human-like RVC in Indian pigs and division of RVC clade with I2 genotype into further sub-clades. To the best of our knowledge, this appears to be the first report of RVC in Indian swine population. Incidence of human-like RVC VP6 gene in swine supports its subsequent zoonotic prospective.

Viral diarrhea in Japanese children: results from a one-year epidemiologic study.

PubMed

Phan, Tung Gia; Nguyen, Tuan Anh; Kuroiwa, Toshimasa; Kaneshi, Kunio; Ueda, Yuichi; Nakaya, Shigekazu; Nishimura, Shuichi; Nishimura, Tadashi; Yamamoto, Atsuko; Okitsu, Shoko; Ushijima, Hiroshi

2005-01-01

A total of 557 fecal specimens from infants and children with acute gastroenteritis in five places (Maizuru, Tokyo, Sapporo, Saga and Osaka) in Japan from July 2002 to June 2003 were tested for the presence of diarrheal viruses by RT-PCR, PRHA, RNA-PAGE and latex agglutination methods. Of these, 56.4% (314) were found positive for diarrheal viruses. Among them, group A rotavirus was the most prevalent (43.6%, 137 of 314) followed by norovirus (29.9%, 94 of 314), adenovirus (7.6%, 24 of 314), group C rotavirus (6.4%, 20 of 314), sapovirus (5.1%, 16 of 314) and astrovirus (1.6%, 5 of 314), respectively. A high rate (7.4%, 19 of 314) of viral mixed infections, including one triple infection (adenovirus, norovirus and astrovirus) was demonstrated. Norovirus infection that usually has a peak during November and January in Japan was detected year-round and highest in September in our study. Norovirus was subjected to molecular genetic analysis by sequencing. The results clearly indicated that norovirus group II was a dominant genogroup (94.3%, 100 of 106). It is noteworthy that noroviruses detected in this study were classified into 8 genotypes (GI/1, GI/4, GII/2, GII/3, GII/4, GII/5, GII/6 and GII/12). Of these, NVGII/4 was the predominant genotype, followed by NVGII/6, and these presented 75.6% (80 of 106) and 11.3% (12 of 106), respectively. Another interesting feature in our study was the sudden appearance and disappearance of SaitamaU16-like strains belonging to NVGII/6 in the short period (January 2003 to June 2003). Our findings confirmed the presence of many diarrheal viruses co-circulating among Japanese infants and children and showed the great genetic diversity among norovirus.

Detection of rotavirus before and after monovalent rotavirus vaccine introduction and vaccine effectiveness among children in mainland Tanzania.

PubMed

Jani, Bhavin; Hokororo, Adolfine; Mchomvu, Jackson; Cortese, Margaret M; Kamugisha, Christopher; Mujuni, Delphinius; Kallovya, Dotto; Parashar, Umesh D; Mwenda, Jason M; Lyimo, DaFrossa; Materu, Antonia; Omari, Kakuri Frank; Waziri, Mark; Laswai, Theresia; Juma, Hamisi; Mlay, Josephine; Dogani, Juliana; Stephen, Eugenia; Seugendo, Mwanisha; Nkumbi, Uyanjo; Lyakurwa, Anna; Matojo, Anivera; Bendera, Elice; Senyota, Jonathan; Msingwa, Veronica; Fungo, Yohana; Michael, Fausta; Mpamba, Amina; Chambo, Alfred; Cholobi, Happy; Lyamuya, Faraja; Chami, Inviollatha; Mchome, Esther; Mshana, Amina Mohamed; Mushi, Edward; Mariki, Uforo; Chard, Ronica; Tuju, Deborah; Ambokile, Nuswe; Lukwale, Fatuma; Kyessi, Furaha; Khamis, Asha; Michael, Innocent; Macha, Doreen; Saguti, Angelina

2018-04-11

Monovalent rotavirus vaccine (RV1) was introduced in Tanzania in January 2013 under the Reach Every Child initiative, to be given at ages 6 and 10 weeks. We used the sentinel hospital rotavirus surveillance system to examine the rotavirus detection rate before and after vaccine introduction and estimate vaccine effectiveness. Before vaccine introduction, rotavirus surveillance was established at two mainland hospitals; children admitted for acute diarrhea were eligible for enrollment and stools were tested for rotavirus antigen. We compared the rotavirus positivity rate in the pre-vaccine period (Tanga Hospital, 2009 and 2011; Bugando Medical Centre, 2012) to that from post-introduction years, 2014-2015. In 2013, surveillance was established at 9 additional hospitals. We examined rotavirus positivity among infants at these sites for 2014-2015. We obtained vaccine records and calculated vaccine effectiveness at 3 sites using case-test-negative control design. At Tanga Hospital, the rotavirus positivity rate among infants was 41% (102/251) pre-vaccine and 14% (28/197) in post-vaccine years (rate ratio: 0.35 [95% CI 0.22-0.54]). At Bugando, the positivity rate was 58% (83/143) pre-vaccine, and 18% (49/277) post-introduction (rate ratio 0.30 [95% CI 0.210.44]). Results were similar among children <5 years. At the new sites, the median site rotavirus positivity rate among infants was 26% in 2014 (range 19-44%) and 18% in 2015 (range 16-33%). The effectiveness of ≥1 RV1 dose against rotavirus hospitalization among children 5-23 months was 53% (95% CI: -14, 81), and 66% (95% CI: 9-87) against hospitalization with intravenous rehydration. Following introduction, peak rotavirus activity occurred later in the year and appeared more concentrated in time. Rotavirus surveillance data from Tanzania indicate that the rotavirus positivity rate among children hospitalized with diarrhea that were enrolled was substantially reduced after vaccine introduction. Low positivity rates among infants were detected at hospitals across the country. Overall, the data support that rotavirus vaccine has been successfully introduced and is effective in Tanzanian children. Copyright © 2018. Published by Elsevier Ltd.

Evaluation of the immunogenicity of a recombinant HSV-1 vector expressing human group C rotavirus VP6 protein.

PubMed

Rota, Rosana P; Palacios, Carlos A; Temprana, C Facundo; Argüelles, Marcelo H; Mandile, Marcelo G; Mattion, Nora; Laimbacher, Andrea S; Fraefel, Cornell; Castello, Alejandro A; Glikmann, Graciela

2018-06-01

Group C Rotavirus (RVC) has been associated globally with sporadic outbreaks of gastroenteritis in children and adults. RVC also infects animals, and interspecies transmission has been reported as well as its zoonotic potential. Considering its genetic diversity and the absence of effective vaccines, it is important and necessary to develop new generation vaccines against RVC for both humans and animals. The aim of the present study was to develop and characterize an HSV-1-based amplicon vector expressing a human RVC-VP6 protein and evaluate the humoral immune response induced after immunizing BALB/c mice. Local fecal samples positive for RVC were used for isolation and sequencing of the vp6 gene, which phylogenetically belongs to the I2 genotype. We show here that cells infected with the HSV[VP6C] amplicon vector efficiently express the VP6 protein, and induced specific anti-RVC antibodies in mice immunized with HSV[VP6C], in a prime-boost schedule. This work highlights that amplicon vectors are an attractive platform for the generation of safe genetic immunogens against RVC, without the addition of external adjuvants. Copyright © 2018 Elsevier B.V. All rights reserved.

Determinants of Rotavirus Transmission: A Lag Nonlinear Time Series Analysis.

PubMed

van Gaalen, Rolina D; van de Kassteele, Jan; Hahné, Susan J M; Bruijning-Verhagen, Patricia; Wallinga, Jacco

2017-07-01

Rotavirus is a common viral infection among young children. As in many countries, the infection dynamics of rotavirus in the Netherlands are characterized by an annual winter peak, which was notably low in 2014. Previous study suggested an association between weather factors and both rotavirus transmission and incidence. From epidemic theory, we know that the proportion of susceptible individuals can affect disease transmission. We investigated how these factors are associated with rotavirus transmission in the Netherlands, and their impact on rotavirus transmission in 2014. We used available data on birth rates and rotavirus laboratory reports to estimate rotavirus transmission and the proportion of individuals susceptible to primary infection. Weather data were directly available from a central meteorological station. We developed an approach for detecting determinants of seasonal rotavirus transmission by assessing nonlinear, delayed associations between each factor and rotavirus transmission. We explored relationships by applying a distributed lag nonlinear regression model with seasonal terms. We corrected for residual serial correlation using autoregressive moving average errors. We inferred the relationship between different factors and the effective reproduction number from the most parsimonious model with low residual autocorrelation. Higher proportions of susceptible individuals and lower temperatures were associated with increases in rotavirus transmission. For 2014, our findings suggest that relatively mild temperatures combined with the low proportion of susceptible individuals contributed to lower rotavirus transmission in the Netherlands. However, our model, which overestimated the magnitude of the peak, suggested that other factors were likely instrumental in reducing the incidence that year.

Multicenter prospective study on the burden of rotavirus gastroenteritis in children less than 3 years of age in Spain.

PubMed

Arístegui, J; Ferrer, J; Salamanca, I; Garrote, E; Partidas, A; San-Martin, M; San-Jose, B

2016-10-10

Rotavirus is acknowledged as an important cause of paediatric gastroenteritis worldwide. In Spain, comprehensive data on the burden of rotavirus disease was lacking. A prospective, multicenter, observational study was carried out, during the winter season, from October to April 2014 in selected areas of Spain (Catalonia, Basque Country, Andalusia) to estimate the frequency and characteristics of acute gastroenteritis (AGE) and rotavirus gastroenteritis (RVGE) in children ≤3 years of age seeking medical care in primary care and emergency department centres. Of the 1087 episodes of AGE registered, 33.89 % were RVGE positive. The estimated incidence of RVGE, was 40.3 (95 % CI 36.1-44.8) episodes per 10,000 child-months in children ≤ 3 years of age and the 5-month (December-April) seasonal RVGE incidence rate was 2.01 [1.81-2.24] per 100 children. No vaccination and attending a day care centre were the main risk factors for RV infection. RVGE infected children presented more frequently with fever (63.9 % vs. 45.1 %, p = 0.009), vomiting (61.2 % vs. 44.3 %, p = 0.015), suffered more dehydration, and were hospitalised and went to the emergency room more often (41.7 % vs. 15.7 %, p <0.001) than non-RVGE infected ones. Children were usually more tired (77.5 % vs. 54.2 %, p <0.001), tearful, (47.2 % vs. 34.8 %, p <0.001), and easily irritated (76.5 % vs. 59.8 %, p <0.001), and parents were more concerned (41.7 % vs. 15.7 %, p <0.001) and suffered more working rhythm disturbances (39.0 % vs. 22.9 %, p <0.001). The cost for families of RVGE cases was significantly higher than the cost of non-RVGE infected ones (47.3 vs 36.7 euros, p = 0.011). Vaccinated children suffered less clinical symptoms and no hospitalization. Therefore, vaccination decreases the psychosocial stressors caused by the disease in the family. Rotavirus infections are responsible for a substantial proportion of AGE cases in children ≤3 years of age in Spain attended at primary care visits. RVGE episodes are associated with greater clinical severity, greater alterations in the child´s behaviour, and higher parental distress. The outcomes of the present study recommend that routine rotavirus vaccination in infants ≤3 years of age could considerably reduce the serious burden of this potentially serious childhood disease.

Human Intestinal Enteroids: a New Model To Study Human Rotavirus Infection, Host Restriction, and Pathophysiology

PubMed Central

Saxena, Kapil; Blutt, Sarah E.; Ettayebi, Khalil; Zeng, Xi-Lei; Broughman, James R.; Crawford, Sue E.; Karandikar, Umesh C.; Sastri, Narayan P.; Conner, Margaret E.; Opekun, Antone R.; Graham, David Y.; Qureshi, Waqar; Sherman, Vadim; Foulke-Abel, Jennifer; In, Julie; Kovbasnjuk, Olga; Zachos, Nicholas C.; Donowitz, Mark

2015-01-01

ABSTRACT Human gastrointestinal tract research is limited by the paucity of in vitro intestinal cell models that recapitulate the cellular diversity and complex functions of human physiology and disease pathology. Human intestinal enteroid (HIE) cultures contain multiple intestinal epithelial cell types that comprise the intestinal epithelium (enterocytes and goblet, enteroendocrine, and Paneth cells) and are physiologically active based on responses to agonists. We evaluated these nontransformed, three-dimensional HIE cultures as models for pathogenic infections in the small intestine by examining whether HIEs from different regions of the small intestine from different patients are susceptible to human rotavirus (HRV) infection. Little is known about HRVs, as they generally replicate poorly in transformed cell lines, and host range restriction prevents their replication in many animal models, whereas many animal rotaviruses (ARVs) exhibit a broader host range and replicate in mice. Using HRVs, including the Rotarix RV1 vaccine strain, and ARVs, we evaluated host susceptibility, virus production, and cellular responses of HIEs. HRVs infect at higher rates and grow to higher titers than do ARVs. HRVs infect differentiated enterocytes and enteroendocrine cells, and viroplasms and lipid droplets are induced. Heterogeneity in replication was seen in HIEs from different patients. HRV infection and RV enterotoxin treatment of HIEs caused physiological lumenal expansion detected by time-lapse microscopy, recapitulating one of the hallmarks of rotavirus-induced diarrhea. These results demonstrate that HIEs are a novel pathophysiological model that will allow the study of HRV biology, including host restriction, cell type restriction, and virus-induced fluid secretion. IMPORTANCE Our research establishes HIEs as nontransformed cell culture models to understand human intestinal physiology and pathophysiology and the epithelial response, including host restriction of gastrointestinal infections such as HRV infection. HRVs remain a major worldwide cause of diarrhea-associated morbidity and mortality in children ≤5 years of age. Current in vitro models of rotavirus infection rely primarily on the use of animal rotaviruses because HRV growth is limited in most transformed cell lines and animal models. We demonstrate that HIEs are novel, cellularly diverse, and physiologically relevant epithelial cell cultures that recapitulate in vivo properties of HRV infection. HIEs will allow the study of HRV biology, including human host-pathogen and live, attenuated vaccine interactions; host and cell type restriction; virus-induced fluid secretion; cell-cell communication within the epithelium; and the epithelial response to infection in cultures from genetically diverse individuals. Finally, drug therapies to prevent/treat diarrheal disease can be tested in these physiologically active cultures. PMID:26446608

Reduced rotavirus vaccine effectiveness among children born during the rotavirus season: a pooled analysis of 5 case-control studies from the Americas.

PubMed

Premkumar, Prasanna S; Parashar, Umesh D; Gastanaduy, Paul A; McCracken, John P; de Oliveira, Lucia Helena; Payne, Daniel C; Patel, Manish M; Tate, Jacqueline E; Lopman, Ben A

2015-04-01

Using data from rotavirus vaccine effectiveness (VE) studies, we assessed whether rotavirus season modifies rotavirus VE in infants. In the first year of life, adjusted VE was 72% for children born during rotavirus season and 84% for children born in other months (P = .01). Seasonal factors may interfere with vaccine performance. © The Author 2014. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Global mortality associated with rotavirus disease among children in 2004.

PubMed

Parashar, Umesh D; Burton, Anthony; Lanata, Claudio; Boschi-Pinto, Cynthia; Shibuya, Kenji; Steele, Duncan; Birmingham, Maureen; Glass, Roger I

2009-11-01

As new rotavirus vaccines are being introduced in immunization programs, global and national estimates of disease burden, especially rotavirus-associated mortality, are needed to assess the potential health benefits of vaccination and to monitor vaccine impact. We identified 76 studies that were initiated after 1990, lasted at least 1 full year, and examined rotavirus among >100 children hospitalized with diarrhea. The studies were assigned to 5 groups (A-E) with use of World Health Organization classification of countries by child mortality and geography. For each group, the mean rotavirus detection rate was multiplied by diarrhea-related mortality figures from 2004 for countries in that group to yield estimates of rotavirus-associated mortality. Overall, rotavirus accounted for 527,000 deaths (95% confidence interval, 475,000-580,000 deaths) annually or 29% of all deaths due to diarrhea among children <5 years of age. Twenty-three percent of deaths due to rotavirus disease occurred in India, and 6 countries (India, Nigeria, Congo, Ethiopia, China, and Pakistan) accounted for more than one-half of deaths due to rotavirus disease. The high mortality associated with rotavirus disease underscores the need for targeted interventions, such as vaccines. To realize the full life-saving potential of vaccines, it will be vital to ensure that they reach children in countries with high mortality. These baseline figures will allow future assessment of vaccine impact on rotavirus-associated mortality.

Impact of rotavirus vaccines in low and middle-income countries.

PubMed

Sindhu, Kulandaipalayam Natarajan Chella; Babji, Sudhir; Ganesan, Santhosh Kumar

2017-10-01

Rotavirus vaccines are playing a pivotal role in improving lives of infants and young children in low and middle-income countries (LMICs). Many of these countries have adopted the vaccine into their routine immunization, whereas others are considering introduction. This article provides an update on the impact of rotavirus vaccines in LMICs on morbidity and mortality in children aged less than 5 years, and their cost-effectiveness. The WHO, in 2013, updated its recommendation to prioritize introduction of rotavirus vaccines in the routine immunization schedule, without age restrictions. Despite the decreased efficacy of the vaccines in LMICs, data from Sub-Saharan Africa have demonstrated a decrease in rotavirus-related morbidity, with some sites reporting an indirect protective effect on children age ineligible to receive the vaccine. Even with improvements in sanitation, nutritional status in children, and other health-related indices in LMICs, the use of rotavirus vaccines will play an important role in preventing rotavirus-related gastroenteritis. Economic models predict a reduction in economic burden because of rotavirus-related health costs, making vaccine introduction cost-effective in resource-constrained settings. Increasing evidence from impact studies shows the significant impact of rotavirus vaccination on hospitalizations and economic burden because of rotavirus gastroenteritis in LMICs. Universal rotavirus vaccination is recommended, and introductions should be monitored by robust surveillance systems to measure effectiveness and impact.

Influence of oral polio vaccines on performance of the monovalent and pentavalent rotavirus vaccines.

PubMed

Patel, Manish; Steele, A Duncan; Parashar, Umesh D

2012-04-27

In recent years, two live, oral rotavirus vaccines have been successfully tested in developing and industrialized countries, and both vaccines are now recommended by the World Health Organization for all children worldwide. Both immunogenicity and efficacy of these rotavirus vaccines has been lower in developing compared to industrialized settings. We reviewed the data on the effect of trivalent OPV on the immunogenicity and efficacy of two rotavirus vaccines currently recommended by the WHO. While rotavirus vaccines have not affected immune responses to OPV, in general, the immune responses (i.e., antibody levels) to rotavirus vaccination were lower when rotavirus vaccines were co-administered with OPV. Limited data suggests that the interference is greater after the first dose of OPV, presumably because the first dose is associated with greatest intestinal replication of vaccine polio virus strains, and this interference is largely overcome with subsequent rotavirus vaccine doses. Despite the lower immunogenicity, one large efficacy study in middle income Latin American countries showed no decrease in protective efficacy of rotavirus vaccine in infants receiving concurrent OPV. While these data are encouraging and support simultaneous administration of rotavirus vaccines and OPV, additional evidence should be gathered as rotavirus vaccines are used more widely in developing country settings, where OPV is routinely used, rather than inactivated polio vaccine. Published by Elsevier Ltd.

Projected health impact and cost-effectiveness of rotavirus vaccination among children <5 years of age in China.

PubMed

Liu, Na; Yen, Catherine; Fang, Zhao-yin; Tate, Jacqueline E; Jiang, Baoming; Parashar, Umesh D; Zeng, Guang; Duan, Zhao-jun

2012-11-06

Two rotavirus vaccines have been licensed globally since 2006. In China, only a lamb rotavirus vaccine is licensed and several new rotavirus vaccines are in development. Data regarding the projected health impact and cost-effectiveness of vaccination of children in China against rotavirus will assist policy makers in developing recommendations for vaccination. Using a Microsoft Excel model, we compared the national health and economic burden of rotavirus disease in China with and without a vaccination program. Model inputs included 2007 data on burden and cost of rotavirus outcomes (deaths, hospitalizations, outpatient visits), projected vaccine efficacy, coverage, and cost. Cost-effectiveness was measured in US dollars per disability-adjusted life-year (DALY) and US dollars per life saved. A 2-dose rotavirus vaccination program could annually avert 3013 (62%) deaths, 194,794 (59%) hospitalizations and 1,333,356 (51%) outpatient visits associated with rotavirus disease in China. The medical break-even price of the vaccine is $1.19 per dose. From a societal perspective, a vaccination program would be highly cost-effective in China at the vaccine price of $2.50 to $5 per dose, and be cost-effective at the price of $10 to $20 per dose. A national rotavirus vaccination program could be a cost-effective measure to effectively reduce deaths, hospitalizations, and outpatient visits due to rotavirus disease in China. Copyright © 2012 Elsevier Ltd. All rights reserved.

Impact of the introduction of rotavirus vaccine on the timeliness of other scheduled vaccines: the Australian experience.

PubMed

Hull, Brynley P; Menzies, Robert; Macartney, Kristine; McIntyre, Peter B

2013-04-08

Strict age limits for receipt of rotavirus vaccines and simultaneous use of vaccines requiring two (Rotarix(®)) and three (RotaTeq(®)) doses in Australia may impact on coverage and timeliness of other vaccines in the infant schedule. Using data from the Australian Childhood Immunisation Register (ACIR), coverage and timeliness of rotavirus vaccines and changes in timeliness of other infant vaccines following rotavirus vaccine introduction was examined, with particular emphasis on Indigenous infants in whom coverage is less optimal. Final dose rotavirus coverage reached 83% within 21 months of program commencement but remained 7% lower than other vaccines due in infancy. Coverage was 11-17% lower in Indigenous infants. Adherence to the first dose upper age limits for rotavirus vaccine was high with >97% of children vaccinated by the recommended age, but for subsequent rotavirus doses, receipt beyond the upper age limits was more common, especially in Indigenous children. Following rotavirus vaccine introduction, there were improvements in timeliness of receipt of all doses of DTPa-containing and 7-valent pneumococcal conjugate vaccines. High population coverage can be attained with rotavirus vaccines, even with adherence to strict upper age restrictions for vaccine dose administration. Rotavirus vaccine introduction appears to have impacted upon the timeliness of other concomitantly scheduled vaccines. These factors should be considered when rotavirus programs are introduced. Copyright © 2013 Elsevier Ltd. All rights reserved.

Evaluation of safety and immunogenicity of a live attenuated tetravalent (G1-G4) Bovine-Human Reassortant Rotavirus vaccine (BRV-TV) in healthy Indian adults and infants.

PubMed

Dhingra, M S; Kundu, R; Gupta, M; Kanungo, S; Ganguly, N; Singh, M P; Bhattacharya, M K; Ghosh, R; Kumar, R; Sur, D; Chadha, S M; Saluja, T

2014-08-11

Rotavirus infections, prevalent in human populations worldwide are mostly caused by Group A viruses. Live attenuated rotavirus vaccines are highly effective in preventing severe rotavirus gastroenteritis. However, the cost of these vaccines and local availability can be a barrier for widespread adoption in public health programs in developing countries where infants suffer a heavy burden of rotavirus related morbidity and mortality. A phase I/II study was carried out with the long term aim to produce a locally licensed vaccine which is equally safe and immunogenic as compared to available licensed vaccines. This study was conducted in two cohorts. In the first cohort, 20 healthy adults were administered a single dose of the rotavirus vaccine (highest antigen concentration planned for infants) or placebo and were followed up for 10 days for safety. Following demonstration of safety in adult volunteers, 100 healthy infants were recruited (cohort 2) and randomly divided into five equal study groups. They were administered three doses of either the investigational rotavirus vaccine (BRV-TV) at one of the three antigen concentrations or Rotateq or Placebo at 6-8, 10-12 and 14-16 weeks of age. All infants were followed up for safety till 28 days after the third dose. Immune response to the vaccine, in terms of seroresponse and geometric mean concentrations, was compared across the five study groups. Increase in anti-rotavirus serum IgA antibodies from baseline, demonstrated higher immune response for all the three antigen concentrations of BRV-TV vaccine and RotaTeq in comparison with the placebo. Sero-response rates for placebo, BRV-TV dose-levels 10(5.0) FFU, 10(5.8) FFU, 10(6.4) FFU, and Rotateq at 28 days post third dose were 11.1%, 27.8%, 41.2%, 83.3%, and 63.2% respectively using the four-fold or more criteria. The BRV-TV vaccine arm corresponding to the highest antigen concentration of 10(6.4) FFU had a higher sero-response rate compared to the active comparator arm (RotaTeq), 28 days post each vaccine dose. The safety profile was comparable across the treatment groups. Overall, the results showed that all three doses of BRV-TV vaccine were safe, well tolerated and displayed good immunogenicity (dose-response) in healthy Indian infants. Copyright © 2014. Published by Elsevier Ltd.

Annual changes in rotavirus hospitalization rates before and after rotavirus vaccine implementation in the United States.

PubMed

Shah, Minesh P; Dahl, Rebecca M; Parashar, Umesh D; Lopman, Benjamin A

2018-01-01

Hospitalizations for rotavirus and acute gastroenteritis (AGE) have declined in the US with rotavirus vaccination, though biennial peaks in incidence in children aged less than 5 years occur. This pattern may be explained by lower rotavirus vaccination coverage in US children (59% to 73% from 2010-2015), resulting in accumulation of susceptible children over two successive birth cohorts. Retrospective cohort analysis of claims data of commercially insured US children aged <5 years. Age-stratified hospitalization rates for rotavirus and for AGE from the 2002-2015 rotavirus seasons were examined. Median age and rotavirus vaccination coverage for biennial rotavirus seasons during pre-vaccine (2002-2005), early post-vaccine (2008-2011) and late post-vaccine (2012-2015) years. Age-stratified hospitalization rates decreased from pre-vaccine to early post-vaccine and then to late post-vaccine years. The clearest biennial pattern in hospitalization rates is the early post-vaccine period, with higher rates in 2009 and 2011 than in 2008 and 2010. The pattern diminishes in the late post-vaccine period. For rotavirus hospitalizations, the median age and the difference in age between biennial seasons was highest during the early post-vaccine period; these differences were not observed for AGE hospitalizations. There was no significant difference in vaccination coverage between biennial seasons. These observations provide conflicting evidence that incomplete vaccine coverage drove the biennial pattern in rotavirus hospitalizations that has emerged with rotavirus vaccination in the US. As this pattern is diminishing with higher vaccine coverage in recent years, further increases in vaccine coverage may reach a threshold that eliminates peak seasons in hospitalizations.

Serological analysis of the subgroup protein of rotavirus, using monoclonal antibodies.

PubMed Central

Greenberg, H; McAuliffe, V; Valdesuso, J; Wyatt, R; Flores, J; Kalica, A; Hoshino, Y; Singh, N

1983-01-01

Ten monoclones directed to the 42,000-dalton inner structural protein of rotavirus were analyzed. Eight monoclones reacted broadly with antigenic domains common to virtually all mammalian rotaviruses. Two monoclones had specificities similar or identical to previously characterized subgroup specificities. These subgroup monoclones were more efficient in detecting subgroup antigen than either hyperimmune or postinfection antisera. Using the subgroup monoclones, we determined that some animal as well as human rotavirus strains carry subgroup 2 specificity and that epizootic diarrhea of infant mice virus and turkey rotavirus are antigenically distinct from other mammalian rotavirus strains. Images PMID:6185436

Healthcare Costs of Rotavirus and Other Types of Gastroenteritis in Children in Norway.

PubMed

Shin, Minkyung; Salamanca, Beatriz Valcarcel; Kristiansen, Ivar S; Flem, Elmira

2016-04-01

Norway has initiated a publicly funded rotavirus immunization program for all age-eligible children in 2014. We aimed to estimate the healthcare costs of rotavirus gastroenteritis in children younger than 5 years old. We identified all gastroenteritis cases in children younger than 5 years old treated during 2009-2013 through the national claims database for primary care and the national hospital registry. We estimated direct medical costs of rotavirus-associated primary care consultations and hospital encounters (inpatient admission, outpatient visit and ambulatory care). We performed a range of one-way sensitivity analyses to explore uncertainty in the cost estimates. Before vaccine introduction, the mean healthcare cost of rotavirus gastroenteritis in children younger than 5 years old was €4,440,337 per year. Among rotavirus-associated costs, 92% were hospital costs and the remaining 8% were primary care costs. The mean annual cost of rotavirus-associated hospital encounters was €4,083,691, of which 95% were costs of inpatient hospital admissions. The average healthcare cost of medically attended gastroenteritis in children younger than 5 years old was approximately €8 million per year, of which rotavirus-related costs represented 56%. Healthcare costs of rotavirus gastroenteritis in Norway are substantial. The cost-effectiveness of ongoing rotavirus immunization program should be reassessed.

Rotavirus vaccine effectiveness in low-income settings: An evaluation of the test-negative design.

PubMed

Schwartz, Lauren M; Halloran, M Elizabeth; Rowhani-Rahbar, Ali; Neuzil, Kathleen M; Victor, John C

2017-01-03

The test-negative design (TND), an epidemiologic method currently used to measure rotavirus vaccine (RV) effectiveness, compares the vaccination status of rotavirus-positive cases and rotavirus-negative controls meeting a pre-defined case definition for acute gastroenteritis. Despite the use of this study design in low-income settings, the TND has not been evaluated to measure rotavirus vaccine effectiveness. This study builds upon prior methods to evaluate the use of the TND for influenza vaccine using a randomized controlled clinical trial database. Test-negative vaccine effectiveness (VE-TND) estimates were derived from three large randomized placebo-controlled trials (RCTs) of monovalent (RV1) and pentavalent (RV5) rotavirus vaccines in sub-Saharan Africa and Asia. Derived VE-TND estimates were compared to the original RCT vaccine efficacy estimates (VE-RCTs). The core assumption of the TND (i.e., rotavirus vaccine has no effect on rotavirus-negative diarrhea) was also assessed. TND vaccine effectiveness estimates were nearly equivalent to original RCT vaccine efficacy estimates. Neither RV had a substantial effect on rotavirus-negative diarrhea. This study supports the TND as an appropriate epidemiologic study design to measure rotavirus vaccine effectiveness in low-income settings. Copyright © 2016 The Author(s). Published by Elsevier Ltd.. All rights reserved.

Safety, Tolerability and Immunogenicity of Pentavalent Rotavirus Vaccine Manufactured by a Modified Process.

PubMed

Martinón-Torres, Federico; Greenberg, David; Varman, Meera; Killar, John A; Hille, Darcy; Strable, Erica L; Stek, Jon E; Kaplan, Susan S

2017-04-01

Rotavirus is the leading cause of severe diarrhea in infants and young children. The current formulation of pentavalent rotavirus vaccine (RV5) must be stored refrigerated at 2-8°C. A modified formulation of RV5 (RV5mp) has been developed with stability at 37°C for 7 days and an expiry extended to 36 months when stored at 2-8°C. This study (ClinicalTrials.gov identifier: NCT01600092; EudraCT number: 2012-001611-23) evaluated the safety, tolerability and immunogenicity of RV5mp versus the currently marketed RV5 in infants. To maintain blinding, both vaccine formulations were stored refrigerated at 2-8°C for the duration of the study. Immunogenicity endpoints were (1) serum neutralizing antibody titers to human rotavirus serotypes G1, G2, G3, G4 and P1A[8] and (2) proportion of subjects with a ≥3-fold rise from baseline for serum neutralizing antibody to human rotavirus serotypes G1, G2, G3, G4 and P1A[8] and serum antirotavirus immunoglobulin A. The RV5mp group (n = 505) and RV5 group (n = 509) had comparable safety profiles. There were no deaths and no vaccine-related serious adverse events in this study. With respect to immunogenicity, RV5mp was noninferior compared with RV5. Serum neutralizing antibody responses by country and breast-feeding status were generally consistent with the overall results. RV5mp enhances storage requirements while maintaining the immunogenicity and safety profile of the currently licensed RV5. A vaccine that is stable at room temperature may be more convenient for vaccinators, particularly in places where the cold chain is unreliable, and ultimately will permit more widespread use.

Trends in the incidence of acute watery diarrhoea in the Lao People's Democratic Republic, 2009–2013

PubMed Central

Houatthongkham, Souphatsone; Sithivong, Noikaseumsy; Jennings, Gregory; Phengxay, Manilay; Teepruksa, Phanthaneeya; Khamphaphongphane, Bouaphanh; Vongphrachanh, Phengta; Southalack, Kongmany; Luo, Dapeng

2016-01-01

Diarrhoeal disease is the second leading cause of death in children under age 5 worldwide, with rotavirus being the main etiology. In the Lao People's Democratic Republic, acute watery diarrhoea (AWD) was introduced as one of the national notifiable diseases in 2004. We retrospectively reviewed the aggregate (n = 117 277) and case-based (n = 67 755) AWD surveillance data from 2009 to 2013 reported weekly from 1115 health facilities nationwide. Rotavirus rapid test data from all eight sentinel sites in Vientiane Capital in 2013 were also collected for analysis. The incidence of AWD ranged between 215 and 476 cases per 100 000 population and increased from 2009 to 2012 when it levelled off. The most affected age group was children under 5 who were about seven to nine times more likely to have AWD than the rest of the population (P < 0.0001). In children under 5, 74.8% of the cases were aged 0–24 months and AWD was 1.28 times more common in males (P < 0.0001). Among the 230 stool specimens tested in children under 5 in 2013, 109 (47.4%) tested positive for rotavirus. The increased AWD incidence over the study period may reflect a true increase in AWD or an improved sensitivity of the system. We recommend new mothers breastfeed up to two years after birth, which is known to reduce AWD morbidity and mortality in young children. We also recommend conducting rotavirus disease burden and cost–effectiveness studies to explore the benefits of introduction of rotavirus vaccine. PMID:27818837

Efficacy of a monovalent human-bovine (116E) rotavirus vaccine in Indian infants: a randomised, double-blind, placebo-controlled trial.

PubMed

Bhandari, Nita; Rongsen-Chandola, Temsunaro; Bavdekar, Ashish; John, Jacob; Antony, Kalpana; Taneja, Sunita; Goyal, Nidhi; Kawade, Anand; Kang, Gagandeep; Rathore, Sudeep Singh; Juvekar, Sanjay; Muliyil, Jayaprakash; Arya, Alok; Shaikh, Hanif; Abraham, Vinod; Vrati, Sudhanshu; Proschan, Michael; Kohberger, Robert; Thiry, Georges; Glass, Roger; Greenberg, Harry B; Curlin, George; Mohan, Krishna; Harshavardhan, G V J A; Prasad, Sai; Rao, T S; Boslego, John; Bhan, Maharaj Kishan

2014-06-21

Rotavirus is the most common cause of severe dehydrating gastroenteritis in developing countries. Safe, effective, and affordable rotavirus vaccines are needed in these countries. We aimed to assess the efficacy and tolerability of a monovalent human-bovine rotavirus vaccine for severe rotavirus gastroenteritis in low-resource urban and rural settings in India. We did a randomised double-blind, placebo-controlled, multicentre trial at three sites in Delhi (urban), Pune (rural), and Vellore (urban and rural) between March 11, 2011, and Nov 5, 2012. Infants aged 6-7 weeks were randomly assigned (2:1), via a central interactive voice or web response system with a block size of 12, to receive either three doses of oral human-bovine natural reassortant vaccine (116E) or placebo at ages 6-7 weeks, 10 weeks, and 14 weeks. Infants' families, study investigators, paediatricians in referral hospitals, laboratory staff, and committee members were all masked to treatment allocation. The primary outcome was incidence of severe rotavirus gastroenteritis (≥11 on the Vesikari scale). Efficacy outcomes and adverse events were ascertained through active surveillance. Analysis was by intention to treat and per protocol. The trial is registered with Clinical Trial Registry-India (CTRI/2010/091/000102) and ClinicalTrials.gov (NCT01305109). 4532 infants were assigned to receive the 116E vaccine and 2267 to receive placebo, of whom 4354 (96%) and 2187 (96%) infants, respectively, were included in the primary per-protocol efficacy analysis. 71 events of severe rotavirus gastroenteritis were reported in 4752 person-years in infants in the vaccine group compared with 76 events in 2360 person-years in those in the placebo group; vaccine efficacy against severe rotavirus gastroenteritis was 53·6% (95% CI 35·0-66·9; p=0·0013) and 56·4% (36·6-70·1; p<0·0001) in the first year of life. The number of infants needed to be immunised to prevent one severe rotavirus gastroenteritis episode was 55 (95% CI 37-97). The incidence of severe rotavirus gastroenteritis per 100 person-years was 1·5 in the vaccine group and 3·2 in the placebo group, with an incidence rate ratio of 0·46 (95% CI 0·33-0·65). Prevalence of immediate, solicited, and serious adverse events was similar in both groups. One case of urticaria in the vaccine group and one each of acute gastroenteritis and suspected sepsis in the placebo group were regarded as related to the study product. We recorded six cases of intussusception in the vaccine group and two in the placebo group, all of which happened after the third dose. 25 (<1%) infants in the vaccine group and 17 (<1%) in the placebo group died; no death was regarded as related to the study product. Monovalent human-bovine (116E) rotavirus vaccine is effective and well tolerated in Indian infants. Department of Biotechnology and the Biotechnology Industry Research Assistance Council, Government of India; Bill & Melinda Gates Foundation to PATH, USA; Research Council of Norway; UK Department for International Development; National Institutes of Health, Bethesda, USA; and Bharat Biotech International, Hyderabad, India. Copyright © 2014 Elsevier Ltd. All rights reserved.

Global Seasonality of Rotavirus Disease

PubMed Central

Patel, Manish M.; Pitzer, Virginia; Alonso, Wladimir J.; Vera, David; Lopman, Ben; Tate, Jacqueline; Viboud, Cecile; Parashar, Umesh D.

2012-01-01

Background A substantial number of surveillance studies have documented rotavirus prevalence among children admitted for dehydrating diarrhea. We sought to establish global seasonal patterns of rotavirus disease before widespread vaccine introduction. Methods We reviewed studies of rotavirus detection in children with diarrhea published since 1995. We assessed potential relationships between seasonal prevalence and locality by plotting the average monthly proportion of diarrhea cases positive for rotavirus according to geography, country development, and latitude. We used linear regression to identify variables that were potentially associated with the seasonal intensity of rotavirus. Results Among a total of 99 studies representing all six geographical regions of the world, patterns of year-round disease were more evident in low- and low-middle income countries compared with upper-middle and high income countries where disease was more likely to be seasonal. The level of country development was a stronger predictor of strength of seasonality (P=0.001) than geographical location or climate. However, the observation of distinctly different seasonal patterns of rotavirus disease in some countries with similar geographical location, climate and level of development indicate that a single unifying explanation for variation in seasonality of rotavirus disease is unlikely. Conclusion While no unifying explanation emerged for varying rotavirus seasonality globally, the country income level was somewhat more predictive of the likelihood of having seasonal disease than other factors. Future evaluation of the effect of rotavirus vaccination on seasonal patterns of disease in different settings may help understand factors that drive the global seasonality of rotavirus disease. PMID:23190782

Transfer of Anti-Rotavirus Antibodies during Pregnancy and in Milk Following Maternal Vaccination with a Herpes Simplex Virus Type-1 Amplicon Vector.

PubMed

Meier, Anita F; Suter, Mark; Schraner, Elisabeth M; Humbel, Bruno M; Tobler, Kurt; Ackermann, Mathias; Laimbacher, Andrea S

2017-02-16

Rotaviruses (RVs) are important enteric pathogens of newborn humans and animals, causing diarrhea and in rare cases death, especially in very young individuals. Rotavirus vaccines presently used are modified live vaccines that lack complete biological safety. Previous work from our laboratory suggested that vaccines based on in situ produced, non-infectious rotavirus-like particles (RVLPs) are efficient while being entirely safe. However, using either vaccine, active mucosal immunization cannot induce protective immunity in newborns due to their immature immune system. We therefore hypothesized that offspring from vaccinated dams are passively immunized either by transfer of maternal antibodies during pregnancy or by taking up antibodies from milk. Using a codon optimized polycistronic gene expression cassette packaged into herpesvirus particles, the simultaneous expression of the RV capsid genes led to the intracellular formation of RVLPs in various cell lines. Vaccinated dams developed a strong RV specific IgG antibody response determined in sera and milk of both mother and pups. Moreover, sera of naïve pups nursed by vaccinated dams also had RV specific antibodies suggesting a lactogenic transfer of antibodies. Although full protection of pups was not achieved in this mouse model, our observations are important for the development of improved vaccines against RV in humans as well as in various animal species.

Transfer of Anti-Rotavirus Antibodies during Pregnancy and in Milk Following Maternal Vaccination with a Herpes Simplex Virus Type-1 Amplicon Vector

PubMed Central

Meier, Anita F.; Suter, Mark; Schraner, Elisabeth M.; Humbel, Bruno M.; Tobler, Kurt; Ackermann, Mathias; Laimbacher, Andrea S.

2017-01-01

Rotaviruses (RVs) are important enteric pathogens of newborn humans and animals, causing diarrhea and in rare cases death, especially in very young individuals. Rotavirus vaccines presently used are modified live vaccines that lack complete biological safety. Previous work from our laboratory suggested that vaccines based on in situ produced, non-infectious rotavirus-like particles (RVLPs) are efficient while being entirely safe. However, using either vaccine, active mucosal immunization cannot induce protective immunity in newborns due to their immature immune system. We therefore hypothesized that offspring from vaccinated dams are passively immunized either by transfer of maternal antibodies during pregnancy or by taking up antibodies from milk. Using a codon optimized polycistronic gene expression cassette packaged into herpesvirus particles, the simultaneous expression of the RV capsid genes led to the intracellular formation of RVLPs in various cell lines. Vaccinated dams developed a strong RV specific IgG antibody response determined in sera and milk of both mother and pups. Moreover, sera of naïve pups nursed by vaccinated dams also had RV specific antibodies suggesting a lactogenic transfer of antibodies. Although full protection of pups was not achieved in this mouse model, our observations are important for the development of improved vaccines against RV in humans as well as in various animal species. PMID:28212334

A critical review on a globally-licensed, live, orally-administrable, monovalent human rotavirus vaccine: Rotarix.

PubMed

Nakagomi, Toyoko; Nakagomi, Osamu

2009-08-01

Rotavirus is the major cause of severe gastroenteritis in children worldwide, and two, live, orally-administrable vaccines are licensed globally. They are Rotarix, a monovalent, human rotavirus-based vaccine (GlaxoSmithKline), and RotaTeq, a pentavalent, bovine-human reassortant vaccine (Merck). The RIX4414 strain, a G1P[8] virus, is contained in the Rotarix vaccine. It grows efficiently in the human intestine, as evidenced by vaccine virus shedding into faeces. Efficient multiplication of RIX4414 in the intestines may play a role in stimulating immune effectors other than neutralizing antibodies that may explain the protective immunity against fully heterotypic G2P[4] strains. The protective efficacy against severe rotavirus gastroenteritis afforded by Rotarix is consistently better against strains that share with RIX4414 both G and P serotypes (i.e., G1P[8]), or only P serotype (i.e., G3P[8], G4P[8] and G9P[8]). The Rotarix vaccine is safe regarding intussusception if its first dose is administered between 6 and 12 weeks of age and the last dose by 24 weeks of age with a minimum interval of 4 weeks between the two doses. The expansion by Advisory Committee on Immunization Practices, USA, of the age limit for the first dose to age <15 weeks, and the last dose by 8 months requires close monitoring.

Annual changes in rotavirus hospitalization rates before and after rotavirus vaccine implementation in the United States

PubMed Central

Dahl, Rebecca M.; Parashar, Umesh D.; Lopman, Benjamin A.

2018-01-01

Background Hospitalizations for rotavirus and acute gastroenteritis (AGE) have declined in the US with rotavirus vaccination, though biennial peaks in incidence in children aged less than 5 years occur. This pattern may be explained by lower rotavirus vaccination coverage in US children (59% to 73% from 2010–2015), resulting in accumulation of susceptible children over two successive birth cohorts. Methods Retrospective cohort analysis of claims data of commercially insured US children aged <5 years. Age-stratified hospitalization rates for rotavirus and for AGE from the 2002–2015 rotavirus seasons were examined. Median age and rotavirus vaccination coverage for biennial rotavirus seasons during pre-vaccine (2002–2005), early post-vaccine (2008–2011) and late post-vaccine (2012–2015) years. Results Age-stratified hospitalization rates decreased from pre-vaccine to early post-vaccine and then to late post-vaccine years. The clearest biennial pattern in hospitalization rates is the early post-vaccine period, with higher rates in 2009 and 2011 than in 2008 and 2010. The pattern diminishes in the late post-vaccine period. For rotavirus hospitalizations, the median age and the difference in age between biennial seasons was highest during the early post-vaccine period; these differences were not observed for AGE hospitalizations. There was no significant difference in vaccination coverage between biennial seasons. Conclusions These observations provide conflicting evidence that incomplete vaccine coverage drove the biennial pattern in rotavirus hospitalizations that has emerged with rotavirus vaccination in the US. As this pattern is diminishing with higher vaccine coverage in recent years, further increases in vaccine coverage may reach a threshold that eliminates peak seasons in hospitalizations. PMID:29444124

Estimated impact and cost-effectiveness of rotavirus vaccination in India: effects of geographic and economic disparities.

PubMed

Rheingans, Richard; Anderson, John D; Anderson, Benjamin; Chakraborty, Poulomy; Atherly, Deborah; Pindolia, Deepa

2014-08-11

India accounts for 23% of global rotavirus mortality in under-five children, with more than 100,000 deaths from rotavirus annually. Introduction of a vaccine in India is considered to be the most effective intervention for preventing rotavirus mortality. Recent research suggests that there is considerable variation in rotavirus mortality burden across regional, gender and socio-economic subpopulations within India. In addition, there is potential variability in who would likely receive rotavirus vaccine if introduced. We use available household data to estimate heterogeneity in rotavirus mortality risk, vaccination benefits, and cost-effectiveness across geographic and socio-economic groups within India. We account for heterogeneity by modeling estimated three-dose routine vaccinations as a proxy for a generalized rotavirus vaccine, and mortality for subpopulations of children aggregated by region and state, socio-economic status and sex, separately. Results are presented for six geographic regions and for Bihar, Uttar Pradesh, and Madhya Pradesh, three high mortality states accounting for 56% of national mortality estimates. Impact estimates accounting for disparities predict rotavirus vaccine introduction will prevent 35,000 deaths at an average cost of $118/DALY averted (7292 INR/DALY averted). Rotavirus vaccines are most cost-effective for the poor living in high mortality regions and states. Reductions in geographic and socio-economic disparities based on regional estimates could prevent an additional 9400 deaths annually, while reductions in socio-economic disparities in the three highest morality states alone could prevent an additional 10,600 deaths annually. Understanding the impact of heterogeneity can help improve strategies to maximize the benefits of rotavirus vaccination introduction, leading to fewer lives lost as a result of rotavirus disease. Copyright © 2014. Published by Elsevier Ltd.

Reduction in Diarrhea- and Rotavirus-related Healthcare Visits Among Children <5 Years of Age After National Rotavirus Vaccine Introduction in Zimbabwe.

PubMed

Mujuru, Hilda A; Yen, Catherine; Nathoo, Kusum J; Gonah, Nhamo A; Ticklay, Ismail; Mukaratirwa, Arnold; Berejena, Chipo; Tapfumanei, Ottias; Chindedza, Kenneth; Rupfutse, Maxwell; Weldegebriel, Goitom; Mwenda, Jason M; Burnett, Eleanor; Tate, Jacqueline E; Parashar, Umesh D; Manangazira, Portia

2017-10-01

In Zimbabwe, rotavirus accounted for 41%-56% of acute diarrhea hospitalizations before rotavirus vaccine introduction in 2014. We evaluated rotavirus vaccination impact on acute diarrhea- and rotavirus-related healthcare visits in children. We examined monthly and annual acute diarrhea and rotavirus test-positive hospitalizations and Accident and Emergency Department visits among children <60 months of age at 3 active surveillance hospitals during 2012-2016; we compared prevaccine introduction (2012-2013) with postvaccine introduction (2015 and 2016) data for 2 of the hospitals. We examined monthly acute diarrhea hospitalizations by year and age group for 2013-2016 from surveillance hospital registers and monthly acute diarrhea outpatient visits reported to the Ministry of Health and Child Care during 2012-2016. Active surveillance data showed winter seasonal peaks in diarrhea- and rotavirus-related visits among children <60 months of age during 2012-2014 that were substantially blunted in 2015 and 2016 after vaccine introduction; the percentage of rotavirus test-positive visits followed a similar seasonal pattern and decrease. Hospital register data showed similar pre-introduction seasonal variation and post-introduction declines in diarrhea hospitalizations among children 0-11 and 12-23 months of age. Monthly variation in outpatient diarrhea-related visits mirrored active surveillance data patterns. At 2 surveillance hospitals, the percentage of rotavirus-positive visits declined by 40% and 43% among children 0-11 months of age and by 21% and 33% among children 12-23 months of age in 2015 and 2016, respectively. Initial reductions in diarrheal illness among children <60 months of age, particularly among those 0-11 months of age, after vaccine introduction are encouraging. These early results provide evidence to support continued rotavirus vaccination and rotavirus surveillance in Zimbabwe.

Cost-effectiveness analysis of rotavirus vaccination in Argentina.

PubMed

Urueña, Analía; Pippo, Tomás; Betelu, María Sol; Virgilio, Federico; Hernández, Laura; Giglio, Norberto; Gentile, Ángela; Diosque, Máximo; Vizzotti, Carla

2015-05-07

Rotavirus is a leading cause of severe diarrhea in children under 5. In Argentina, the most affected regions are the Northeast and Northwest, where hospitalizations and deaths are more frequent. This study estimated the cost-effectiveness of adding either of the two licensed rotavirus vaccines to the routine immunization schedule. The integrated TRIVAC vaccine cost-effectiveness model from the Pan American Health Organization's ProVac Initiative (Version 2.0) was used to assess health benefits, costs savings, life-years gained (LYGs), DALYs averted, and cost/DALY averted of vaccinating 10 successive cohorts, from the health care system and societal perspectives. Two doses of monovalent (RV1) rotavirus vaccine and three doses of pentavalent (RV5) rotavirus vaccine were each compared to a scenario assuming no vaccination. The price/dose was US$ 7.50 and US$ 5.15 for RV1 and RV5, respectively. We ran both a national and sub-national analysis, discounting all costs and benefits 3% annually. Our base case results were compared to a range of alternative univariate and multivariate scenarios. The number of LYGs was 5962 and 6440 for RV1 and RV5, respectively. The cost/DALY averted when compared to no vaccination from the health care system and societal perspective was: US$ 3870 and US$ 1802 for RV1, and US$ 2414 and US$ 358 for RV5, respectively. Equivalent figures for the Northeast were US$ 1470 and US$ 636 for RV1, and US$ 913 and US$ 80 for RV5. Therefore, rotavirus vaccination was more cost-effective in the Northeast compared to the whole country; and, in the Northwest, health service's costs saved outweighed the cost of introducing the vaccine. Vaccination with either vaccine compared to no vaccination was highly cost-effective based on WHO guidelines and Argentina's 2011 per capita GDP of US$ 9090. Key variables influencing results were vaccine efficacy, annual loss of efficacy, relative coverage of deaths, vaccine price, and discount rate. Compared to no vaccination, routine vaccination against rotavirus in Argentina would be highly cost-effective with either vaccine. Health and economic benefits would be higher in the Northeast and Northwest regions, where the intervention would even be cost-saving. Copyright © 2015 Elsevier Ltd. All rights reserved.

Validity and reliability of the minimum basic data set in estimating nosocomial acute gastroenteritis caused by rotavirus.

PubMed

Redondo-González, Olga

2015-03-01

Rotavirus is the principal cause of nosocomial acute gastroenteritis (NAGE) under 5 years of age. The objectiveis to evaluate the validity and reliability of the minimum basic dataset (MBDS) in estimating the NAGE caused by rotavirus (NAGER) and to analyze any changes during the three years that the Rotarix® and Rotateq® vaccines were used in Spain. A descriptive, retrospectivestudy was carried out in the University Hospital of Guadalajara(UHG) (Spain) between 2003-2009 using the MBDS, positive microbiological results for rotavirus (PMRs), and medical histories.Three methods of estimation were used: 1) An ICD-9-CM code 008.61 in the secondary diagnosis fields (DIAG2) of MBDS; 2) method 1 and/or PMRs with a current or recent hospitalization; and 3) the reference method or method 2 contrasted with patient medical histories. The validity of methods 1 and 2 was determined -sensitivity, specificity, predictive values and likelihood ratios (LRs)-, along with their agreement with method 3 (Kappa coefficient). In addition, the incidence rate ratio between the NAGER rate in 2007-2009 (commercialization period of both vaccines) was calculated with respect to 2003-2005 (precommercialization period). Method 1 identified 65 records with a DIAG2 of 008.61. Method 2 found 62 probable cases, and the reference method, 49 true cases. The sensitivity of the MBDS was 67 %,the positive predictive value was 51 %, and both negative LR (LR-) and reliability were moderate (LR- 0.33, Kappa coefficient 0.58). During 2007-2009, the NARGE decreased by 5 cases per 103 hospitalizations and by 9 per 104 days of hospitalization. Method 2 overestimated both the decline in incidence by 2 per 103 hospitalizations and the decreased risk per day of stay by 10 %. The MBDS found no differences between the two three-year periods, but, like method 2, showed an excellent level of diagnostic evidence (LR+ 67). The MBDS taken together with microbiological results, is more exact, safer and more reliable than the MBDS alone in estimating NAGER; and more useful in ruling out it. Nevertheless, the MBDS alone may be used to estimate and compare such disease in contexts with different prevalences.

Identification of the two rotavirus genes determining neutralization specificities

DOE Office of Scientific and Technical Information (OSTI.GOV)

Offit, P.A.; Blavat, G.

1986-01-01

Bovine rotavirus NCDV and simian rotavirus SA-11 represent two distinct rotavirus serotypes. A genetic approach was used to determine which viral gene segments segregated with serotype-specific viral neutralization. There were 16 reassortant rotarviruses derived by coinfection of MA-104 cells in vitro with the SA-11 and NCDV strains. The parental origin of reassortant rotavirus double-stranded RNA segments was determined by gene segment mobility in polyacrylamide gels and by hybridization with radioactively labeled parental viral transcripts. The authors found that two rotavirus gene segments found previously to code for outer capsid proteins vp3 and vp7 cosegreated with virus neutralization specificities.

Immune Mediators of Rotavirus Antigenemia Clearance in Mice ▿

PubMed Central

Marcelin, Glendie; Miller, Amber D.; Blutt, Sarah E.; Conner, Margaret E.

2011-01-01

The immunological mediators that clear rotavirus antigenemia or viremia remain undefined. Immunodeficient mice and antibody transfer were used to test whether lymphocytes or rotavirus-specific serum antibodies are essential for resolving antigenemia. Clearance of antigenemia required lymphocytes, but neither T nor B lymphocytes were absolutely required. Transfer of convalescent-phase or nonneutralizing rotavirus-specific serum antibodies to the systemic compartment of severe-combined-immunodeficient (SCID) mice temporarily suppressed the onset or level of chronic rotavirus antigenemia. Our findings provide the first report demonstrating that clearance of rotavirus antigenemia and possibly viremia are mediated by multiple effector lymphocyte subsets and serum antibodies. PMID:21593155

Evaluating the first introduction of rotavirus vaccine in Thailand: Moving from evidence to policy.

PubMed

Tharmaphornpilas, Piyanit; Jiamsiri, Suchada; Boonchaiya, Somchit; Rochanathimoke, Onwipa; Thinyounyong, Wiravan; Tuntiwitayapun, Sumana; Guntapong, Ratigorn; Riewpaiboon, Arthorn; Rasdjarmrearnsook, Aim-On; Glass, Roger I

2017-02-01

We assessed the effectiveness and possible impact of introducing rotavirus vaccine into the routine immunization program. Two provinces were selected for an observational study, one where vaccine was introduced and another where vaccine was not available. In these areas, two sub-studies were linked. The prospective cohort study enrolled children 2month old and followed them to the age of 18months to detect all diarrhea episodes. The hospital surveillance study enrolled all children up to age 5 hospitalized with diarrhea whose fecal samples were tested for rotavirus. Rates of rotavirus hospitalizations in older children who had not been vaccinated in both settings provided data to determine whether immunization had an indirect herd effect. The key endpoints for the study were both vaccine effectiveness (VE) based upon hospitalized rotavirus diarrhea and herd protection. From the cohort study, the overall VE for hospitalized rotavirus diarrhea was 88% (95%CI 76-94). Data from hospital surveillance indicated that for 2 consecutive years, the seasonal peak of rotavirus admissions was no longer present in the vaccinated area. Herd protection was observed among older children born before the rotavirus vaccine program was introduced, who experienced a 40-69% reduction in admission for rotavirus. Rotavirus vaccine was highly effective in preventing diarrheal hospitalizations and in conferring herd protection among older children who had not been vaccinated. Copyright © 2016 Elsevier Ltd. All rights reserved.

A lattice-based model of rotavirus epidemics

NASA Astrophysics Data System (ADS)

Lara-Sagahón, A.; Govezensky, T.; Méndez-Sánchez, R. A.; José, M. V.

2006-01-01

The cyclic recurrence of childhood rotavirus epidemics in unvaccinated populations provides one of the best documented phenomena in population dynamics and can become a paradigm for epidemic studies. Herein we analyse the monthly incidence of rotavirus infection from the city of Melbourne, Australia during 1976-2003. We show that there is an inverse nonlinear relationship of the cumulative distribution of the number of cases per month in a log-log plot. It is also shown that the rate of transmission of rotavirus infection follows a symmetric distribution centered on zero. A wavelet phase analysis of rotavirus epidemics is also carried out. We test the hypothesis that rotavirus dynamics could be a realization of a forest-fire model with sparks and with immune trees. Some statistical properties of this model turn out to be similar to the above results of actual rotavirus data.

Detection and characterization of Human caliciviruses associated with sporadic acute diarrhea in adults in Djibouti (horn of Africa).

PubMed

Maslin, Jérôme; Nicand, Elisabeth; Ambert-Balay, Katia; Fouet, Christine; Kaplon, Jérôme; Haus, Rachel; Pothier, Pierre; Kohli, Evelyne

2008-03-01

Recent advances in molecular diagnostics have allowed us to recognize Human caliciviruses (HuCVs) as important agents of acute diarrhea in industrialized countries. Their prevalence and genetic diversity in developing countries remains unknown. We report on the characterization of HuCVs among adults presenting acute diarrheas in Djibouti; 108 stool samples collected were screened by EIA, RTPCR, or cell cultures for the group A Rotaviruses, Adenoviruses, Astroviruses, and HuCVs, which were further characterized by genotyping. Among stool samples screened for HuCVs, 25.3% were positive. The other enteric viruses were less prevalent. The 11 HuCV strains sequenced revealed a large diversity (3 sapoviruses and 8 noroviruses). GII strains noroviruses were predominant, five were newly described genotypes, and two were recombinant with a pol gene related to GGIIb strains with the particularity to associate a unique pol gene to different capsid genes. These results could help to the knowledge of HuCV infections in Tropical Africa.

Identification of co-infection by rotavirus and parvovirus in dogs with gastroenteritis in Mexico.

PubMed

Ortega, Ariadna Flores; Martínez-Castañeda, José Simón; Bautista-Gómez, Linda G; Muñoz, Raúl Fajardo; Hernández, Israel Quijano

This is the first report on circulating canine rotavirus in Mexico. Fifty samples from dogs with gastroenteritis were analyzed used polymerase chain reaction and reverse transcription polymerase chain reaction in order to identify parvovirus and rotavirus, respectively; 7% of dogs were infected with rotavirus exclusively, while 14% were co-infected with both rotavirus and parvovirus; clinical signs in co-infected dogs were more severe. Copyright © 2017 Sociedade Brasileira de Microbiologia. Published by Elsevier Editora Ltda. All rights reserved.

Diversity and Relationships of Cocirculating Modern Human Rotaviruses Revealed Using Large-Scale Comparative Genomics

PubMed Central

McKell, Allison O.; Rippinger, Christine M.; McAllen, John K.; Akopov, Asmik; Kirkness, Ewen F.; Payne, Daniel C.; Edwards, Kathryn M.; Chappell, James D.; Patton, John T.

2012-01-01

Group A rotaviruses (RVs) are 11-segmented, double-stranded RNA viruses and are primary causes of gastroenteritis in young children. Despite their medical relevance, the genetic diversity of modern human RVs is poorly understood, and the impact of vaccine use on circulating strains remains unknown. In this study, we report the complete genome sequence analysis of 58 RVs isolated from children with severe diarrhea and/or vomiting at Vanderbilt University Medical Center (VUMC) in Nashville, TN, during the years spanning community vaccine implementation (2005 to 2009). The RVs analyzed include 36 G1P[8], 18 G3P[8], and 4 G12P[8] Wa-like genogroup 1 strains with VP6-VP1-VP2-VP3-NSP1-NSP2-NSP3-NSP4-NSP5/6 genotype constellations of I1-R1-C1-M1-A1-N1-T1-E1-H1. By constructing phylogenetic trees, we identified 2 to 5 subgenotype alleles for each gene. The results show evidence of intragenogroup gene reassortment among the cocirculating strains. However, several isolates from different seasons maintained identical allele constellations, consistent with the notion that certain RV clades persisted in the community. By comparing the genes of VUMC RVs to those of other archival and contemporary RV strains for which sequences are available, we defined phylogenetic lineages and verified that the diversity of the strains analyzed in this study reflects that seen in other regions of the world. Importantly, the VP4 and VP7 proteins encoded by VUMC RVs and other contemporary strains show amino acid changes in or near neutralization domains, which might reflect antigenic drift of the virus. Thus, this large-scale, comparative genomic study of modern human RVs provides significant insight into how this pathogen evolves during its spread in the community. PMID:22696651

Epidemiology of rotavirus-associated hospital admissions in the province of Ferrara, Italy.

PubMed

Marsella, Maria; Raimondi, Licia; Bergamini, Mauro; Sprocati, Monica; Bigi, Ettore; De Sanctis, Vincenzo; Borgna-Pignatti, Caterina; Gabutti, Giovanni

2009-12-01

Hospital discharge forms with specific codes for rotavirus gastroenteritis in children 0 to 14 years of age were reviewed in the period 2003-2005 in the province of Ferrara. A total of 4,238 children were admitted to the pediatric departments; 151 patients were diagnosed with rotavirus gastroenteritis. The average annual rate of hospitalization for rotavirus gastroenteritis was 1.54/1,000 children <14 years of age and 2.9/1,000 children <5 years of age. Most hospitalizations (72%) involved children aged <60 months. The average length of hospital stay was about 5 days. Considering the Emilia Romagna regional reimbursement codes referable to rotavirus disease, the estimated costs of our 151 cases range from 214,033 euros to 341,832 euros. The results of this study contribute to the awareness of rotavirus epidemiology in Italy and underline the potential impact of rotavirus vaccination in our province.

[Prognosis of rotavirus diarrhea].

PubMed

Mota-Hernández, F; Gutiérrez-Camacho, C; Villa-Contreras, S; Calva-Mercado, J; Arias, C F; Padilla-Noriega, L; Guiscafré-Gallardo, H

2001-01-01

To compare the severity of rotavirus diarrhea (RV) and non-rotavirus diarrhea. Between October 1994 and March 1995, a cross-sectional study was performed in 520 infants with acute diarrhea, at seven primary care level centers in five states of Mexico. Diagnosis of RV was done through immunoenzymatic assay or electrophoresis. Central tendency measures were used for data analysis. Results were presented as means and standard deviations, or median and variation. RV was isolated from 264 children; most of them were males aged 6 months to 1 year. Differences in clinical manifestations were statistically significant between the rotavirus-positive group and the rotavirus-negative group, in the following variables: median number of stools/24 hours; frequency of vomiting; temperature > 38 degrees C; dehydration; and clinical severity scoring. These results showed a poorer prognosis and a higher severity of rotavirus diarrhea, as compared to non-rotavirus diarrhea in infants.

Acute gastroenteritis and enteric viruses in hospitalised children in southern Brazil: aetiology, seasonality and clinical outcomes

PubMed Central

Raboni, Sonia Maria; Damasio, Guilherme Augusto Costa; Ferreira, Carla EO; Pereira, Luciane A; Nogueira, Meri B; Vidal, Luine R; Cruz, Cristina R; Almeida, Sergio M

2014-01-01

Viral acute gastroenteritis (AG) is a significant cause of hospitalisation in children younger than five years. Group A rotavirus (RVA) is responsible for 30% of these cases. Following the introduction of RVA immunisation in Brazil in 2006, a decreased circulation of this virus has been observed. However, AG remains an important cause of hospitalisation of paediatric patients and only limited data are available regarding the role of other enteric viruses in these cases. We conducted a prospective study of paediatric patients hospitalised for AG. Stool samples were collected to investigate human adenovirus (HAdV), RVA, norovirus (NoV) and astrovirus (AstV). NoV typing was performed by nucleotide sequencing and phylogenetic analysis. From the 225 samples tested, 60 (26%) were positive for at least one viral agent. HAdV, NoV, RVA and AstV were detected in 16%, 8%, 6% and 0% of the samples, respectively. Mixed infections were found in nine patients: HAdV/RVA (5), HAdV/NoV (3) and HAdV/NoV/RVA (1). The frequency of fever and lymphocytosis was significantly higher in virus-infected patients. Phylogenetic analysis of NoV indicated that all of these viruses belonged to genotype GII.4. The significant frequency of these pathogens in patients with AG highlights the need to routinely implement laboratory investigations. PMID:25075782

Group A Rotavirus Associated with Encephalitis in Red Fox.

PubMed

Busi, Chiara; Martella, Vito; Papetti, Alice; Sabelli, Cristiano; Lelli, Davide; Alborali, G Loris; Gibelli, Lucia; Gelmetti, Daniela; Lavazza, Antonio; Cordioli, Paolo; Boniotti, M Beatrice

2017-09-01

In 2011, a group A rotavirus was isolated from the brain of a fox with encephalitis and neurologic signs, detected by rabies surveillance in Italy. Intracerebral inoculation of fox brain homogenates into mice was fatal. Genome sequencing revealed a heterologous rotavirus of avian origin, which could provide a model for investigating rotavirus neurovirulence.

Vaccine Policy Issues

DTIC Science & Technology

2005-05-19

evidence “favors rejection” of the idea that either the measles- mumps-rubella vaccine or thimerosal-containing vaccines cause autism (IOM...Immunization Safety Review: Vaccines and Autism , Washington, D.C., National Academies Press, 2004). 46ACIP’s rotavirus vaccine fact sheet is at [http...that the vaccines or preservatives or packaging might cause autism and other neurodevelopmental disorders. One focus has been on thimerosal, a mercury

Understanding hydro-climatic drivers of infectious diarrheal diseases in South Asia and their projected risks from regional climate models

NASA Astrophysics Data System (ADS)

Hasan, M. A.; Akanda, A. S.; Jutla, A.; Huq, A.; Colwell, R. R.

2017-12-01

Diarrheal diseases remain a major threat to global public health and are the second largest cause of death for children under the age of five. Cholera and Rotavirus diarrhea together comprise more than two-thirds of the diarrheal morbidity in South Asia. Recent studies have shown strong influences of hydrologic processes and climatic variabilities on the onset, intensity, and seasonality of the outbreaks of these diseases. However, our understanding of the propagation and manifestation of these diseases in a changing climate in vulnerable regions of the world are still limited. In this study, we build on our understanding of the role of the hydro-climatic drivers of diarrheal diseases in South Asia in recent decades to project the probable risks of the diseases in this century using the climate projection scenarios from dynamically downscaled climate models. To build the current model, we conducted a multivariate logistic regression assessment using 34 climate indices to examine the role of temperature and rainfall extremes over the seasonality of rotavirus and cholera over a South Asian country, Bangladesh. We utilize the availability of long and reliable time-series of cholera and rotavirus from Bangladesh and conducted a temporal and spatial analysis derived from both ground and satellite observations. For projecting the future risks of the diseases, we used five bias-corrected Regional Climate Model (RCM) results of the CMIP5 series under the RCP 4.5 scenario. Cholera risk shows a significantly higher rate of increase compared to Rotavirus in Bangladesh in the 21st century. As the disease is significantly influenced by extreme rainfall, majority projections showed a significant increase in flood-driven cholera risk. Most RCMs suggest a warmer winter in future years, suggesting reduced risk for Rotavirus. However, as the dryness of the climate is also highly correlated with rotavirus epidemics, the incremental risk of the disease due to drier winters would likely undermine the reduced risk due to temperature increase. Probabilistic risk assessments of these diarrheal diseases with respect to hydro-climatic variability will, not only improve the local policymaking processes, but also allow us to pinpoint the climate-health hotspots around the globe.

Cost-effectiveness of introducing a rotavirus vaccine in developing countries: The case of Mexico

PubMed Central

Valencia-Mendoza, Atanacio; Bertozzi, Stefano M; Gutierrez, Juan-Pablo; Itzler, Robbin

2008-01-01

Background In developing countries rotavirus is the leading cause of severe diarrhoea and diarrhoeal deaths in children under 5. Vaccination could greatly alleviate that burden, but in Mexico as in most low- and middle-income countries the decision to add rotavirus vaccine to the national immunisation program will depend heavily on its cost-effectiveness and affordability. The objective of this study was to assess the cost-effectiveness of including the pentavalent rotavirus vaccine in Mexico's national immunisation program. Methods A cost-effectiveness model was developed from the perspective of the health system, modelling the vaccination of a hypothetical birth cohort of 2 million children monitored from birth through 60 months of age. It compares the cost and disease burden of rotavirus in an unvaccinated cohort of children with one vaccinated as recommended at 2, 4, and 6 months. Results Including the pentavalent vaccine in the national immunisation program could prevent 71,464 medical visits (59%), 5,040 hospital admissions (66%), and 612 deaths from rotavirus gastroenteritis (70%). At US$10 per dose and a cost of administration of US$13.70 per 3-dose regimen, vaccination would cost US$122,058 per death prevented, US$4,383 per discounted life-year saved, at a total net cost of US$74.7 million dollars to the health care system. Key variables influencing the results were, in order of importance, case fatality, vaccine price, vaccine efficacy, serotype prevalence, and annual loss of efficacy. The results are also very sensitive to the discount rate assumed when calculated per life-year saved. Conclusion At prices below US $15 per dose, the cost per life-year saved is estimated to be lower than one GNP per capita and hence highly cost effective by the WHO Commission on Macroeconomics and Health criteria. The cost-effectiveness estimates are highly dependent upon the mortality in the absence of the vaccine, which suggests that the vaccine is likely to be significantly more cost-effective among poorer populations and among those with less access to prompt medical care – such that poverty reduction programs would be expected to reduce the future cost-effectiveness of the vaccine. PMID:18664280

Cost-effectiveness of introducing a rotavirus vaccine in developing countries: the case of Mexico.

PubMed

Valencia-Mendoza, Atanacio; Bertozzi, Stefano M; Gutierrez, Juan-Pablo; Itzler, Robbin

2008-07-29

In developing countries rotavirus is the leading cause of severe diarrhoea and diarrhoeal deaths in children under 5. Vaccination could greatly alleviate that burden, but in Mexico as in most low- and middle-income countries the decision to add rotavirus vaccine to the national immunisation program will depend heavily on its cost-effectiveness and affordability. The objective of this study was to assess the cost-effectiveness of including the pentavalent rotavirus vaccine in Mexico's national immunisation program. A cost-effectiveness model was developed from the perspective of the health system, modelling the vaccination of a hypothetical birth cohort of 2 million children monitored from birth through 60 months of age. It compares the cost and disease burden of rotavirus in an unvaccinated cohort of children with one vaccinated as recommended at 2, 4, and 6 months. Including the pentavalent vaccine in the national immunisation program could prevent 71,464 medical visits (59%), 5,040 hospital admissions (66%), and 612 deaths from rotavirus gastroenteritis (70%). At US$10 per dose and a cost of administration of US$13.70 per 3-dose regimen, vaccination would cost US$122,058 per death prevented, US$4,383 per discounted life-year saved, at a total net cost of US$74.7 million dollars to the health care system. Key variables influencing the results were, in order of importance, case fatality, vaccine price, vaccine efficacy, serotype prevalence, and annual loss of efficacy. The results are also very sensitive to the discount rate assumed when calculated per life-year saved. At prices below US $15 per dose, the cost per life-year saved is estimated to be lower than one GNP per capita and hence highly cost effective by the WHO Commission on Macroeconomics and Health criteria. The cost-effectiveness estimates are highly dependent upon the mortality in the absence of the vaccine, which suggests that the vaccine is likely to be significantly more cost-effective among poorer populations and among those with less access to prompt medical care - such that poverty reduction programs would be expected to reduce the future cost-effectiveness of the vaccine.

Survival and detection of rotaviruses on environmental surfaces in day care centers.

PubMed Central

Keswick, B H; Pickering, L K; DuPont, H L; Woodward, W E

1983-01-01

Previously, we demonstrated that children in day care centers commonly experience diarrhea due to rotavirus, giardia, and bacterial pathogens. Multiple agents frequently coexist, and the environment is heavily contaminated with enteric bacteria during outbreaks. A study of environmental surface contamination with rotavirus was performed during three non-outbreak periods. Of 25 samples collected from environmental surfaces and teachers hands at a day care center, 4 (16%) were positive for rotavirus antigen when a fluorescence assay was used. We also examined the survival of two animal viruses, rotavirus SA-11 and poliovirus type 1, and bacteriophage 12 on similar environmental surfaces in a laboratory. Poliovirus type 1 and bacteriophage f2 were more resistant to drying than rotavirus SA-11 and could be recovered after a 90-min exposure on a dry surface. Rotavirus SA-11 could be detected for 30 min. All three viruses survived longer when they were suspended in fecal material than when they were suspended in distilled water. These data suggest that several agents, including rotavirus, can remain viable on contaminated surfaces long enough to be transmitted to susceptible children. This finding helps explain why rotavirus shows a mode of spread like that of parasitic and bacterial agents within day care center settings. PMID:6314896

Report of the 5th European expert meeting on rotavirus vaccination (EEROVAC).

PubMed

de Hoog, Marieke L A; Vesikari, Timo; Giaquinto, Carlo; Huppertz, Hans-Iko; Martinon-Torres, Federico; Bruijning-Verhagen, Patricia

2018-04-03

The Fifth European Expert Meeting on Rotavirus Vaccination was convened in Utrecht, The Netherlands, in March 2017. The 2-day meeting included invited lectures as well as original oral and poster presentations and brought together experts from 21 countries. Summary findings of the meeting include: Rotavirus vaccination programmes in Europe have resulted in reductions of 60-90% in rotavirus outpatient visits and hospitalizations. Long term trends indicate this impact is sustained over the years. Herd effects, protecting unvaccinated children and neonates too young to be vaccinated have been observed in many European countries. Early evidence now also suggests that rotavirus vaccination may be instrumental in the prevention of celiac disease. Special attention should be given to preterm infants, who may age out of the vaccination window before hospital discharge and to HIV infected children who are at increased risk of severe rotavirus AGE. There is a small but increased risk of IS following rotavirus vaccination and parents should therefore be informed about possible signs and symptoms of IS. New insights in rotavirus genetic susceptibility and interactions with microbiome may open opportunities for interventions to improve protection by vaccination, in particular in LMIC. The development of several novel rotavirus vaccines discussed at the meeting is also promising in this respect.

Efficacy of pentavalent rotavirus vaccine in a high HIV prevalence population in Kenya.

PubMed

Feikin, Daniel R; Laserson, Kayla F; Ojwando, Joel; Nyambane, Geoffrey; Ssempijja, Victor; Audi, Allan; Nyakundi, Daveline; Oyieko, Janet; Dallas, Michael J; Ciarlet, Max; Neuzil, Kathleen M; Breiman, Robert F

2012-04-27

Rotavirus gastroenteritis (RVGE) is a leading cause of death in African children. The efficacy of pentavalent rotavirus vaccine (PRV) against severe RVGE evaluated in Ghana, Kenya, and Mali in a randomized, double-blind, placebo-controlled trial, showed a combined regional efficacy of 39.3% (95% confidence interval [CI]: 19.1,54.7) in nearly 2 years of follow-up. This report concentrates on the Kenya findings. Infants received 3 doses of PRV/placebo at approximately 6-, 10-, and 14-weeks of age. HIV testing was offered to all participants. Data on illness symptoms and signs were collected upon presentation to healthcare facilities, where stools were collected, and analyzed by rotavirus-specific enzyme-linked immunosorbent assay. The primary endpoint was severe RVGE (Vesikari score ≥ 11), occurring ≥ 14 days following the third dose. At monthly home visits, symptoms of illnesses during the past 2 weeks were solicited and limited physical exams were performed; dehydration was defined by WHO's Integrated Management of Childhood Illness. Vaccine efficacy (VE) against severe RVGE through nearly 2 years of follow-up among 1308 Kenyan children was 63.9% (95% CI: -5.9,89.8). Through the first year of life, VE against severe RVGE was 83.4% (95% CI: 25.5,98.2). From home visits, VE against all-cause gastroenteritis with severe dehydration was 34.4% (95% CI: 5.3,54.6) through the first year and 29.7% (95% CI: 2.5,49.3) through the entire follow-up period. The reduction in incidence of gastroenteritis with severe dehydration in the community during the first year of life (19.0 cases/100 person-years) was almost six times greater than the reduction in severe RVGE presenting to the clinic (3.3/100 person-years). Oral rehydration solution use was lower among PRV recipients (VE 23.1%, 95% CI: 8.8,35.1). An estimated 41% of gastroenteritis with severe dehydration in the first year reported at home was rotavirus-related. PRV significantly reduced severe RVGE in Kenya. The impact of PRV might be greatest in rural Africa in protecting the many children who develop severe gastroenteritis and cannot access health facilities. Copyright © 2012. Published by Elsevier Ltd.

Analysis by plaque reduction neutralization assay of intertypic rotaviruses suggests that gene reassortment occurs in vivo.

PubMed Central

Hoshino, Y; Sereno, M M; Midthun, K; Flores, J; Chanock, R M; Kapikian, A Z

1987-01-01

The SB-1A rotavirus recovered from a diarrheic piglet in the United States is a naturally occurring intertypic rotavirus. When studied by reciprocal neutralization tests, the SB-1A virus was similar, if not identical, to the porcine Gottfried virus (serotype 4) and the porcine OSU virus (serotype 5). Analysis of reassortant viruses prepared from the SB-1A virus and the serotype 2 human DS-1 virus revealed that the antigenic specificity of the outer capsid protein VP3 of SB-1A was shared with the OSU virus, while the antigenic specificity of another outer capsid protein, VP7, of SB-1A appeared to be shared with the Gottfried virus. This suggests that SB-1A is a naturally occurring reassortant rotavirus between OSU-like and Gottfried-like porcine rotaviruses. In addition, using a genetic approach, we found evidence that the fourth gene was responsible for the predominantly one-way cross-neutralizing reactivity between canine rotavirus strain CU-1 (serotype 3) and porcine rotavirus strains SB-1A (serotypes 4 and 5) and OSU (serotype 5). Assignment of hemagglutination function to the fourth genome segment of porcine rotaviruses SB-1A and OSU and canine rotavirus CU-1 confirmed a similar previous gene assignment established for certain rotaviruses. Analysis of single gene 4 substitution reassortants confirmed our previous finding that VP3 was as potent in stimulating neutralizing antibodies as VP7. The observations confirm the need for a binary system of rotavirus classification and nomenclature similar to that used for the influenza A viruses; in such a system the neutralization specificity of both VP3 and VP7 would be indicated. Images PMID:2434522

Impact of rotavirus vaccination on child mortality, morbidity, and rotavirus-related hospitalizations in Bolivia.

PubMed

Inchauste, Lucia; Patzi, Maritza; Halvorsen, Kjetil; Solano, Susana; Montesano, Raul; Iñiguez, Volga

2017-08-01

The public health impact of rotavirus vaccination in countries with high child mortality rates remains to be established. The RV1 rotavirus vaccine was introduced in Bolivia in August 2008. This study describes the trends in deaths, hospitalizations, and healthcare visits due to acute gastroenteritis (AGE) and in rotavirus-related hospitalizations, among children <5 years of age, during the pre- and post-vaccination periods. Data were obtained from the National Health Information System to calculate vaccine coverage and AGE-related health indicators. Trend reductions in the main health indicators were examined using the pre-vaccine period as baseline. The effect of vaccination on the epidemiology of rotavirus-related AGE was assessed using data from the active surveillance hospitals. Compared with the 2001-2008 pre-vaccine baseline, the mean number of rotavirus-related hospitalizations was reduced by 40.8% (95% confidence interval (CI) 21.7-66.4%) among children <5years of age in the post-vaccine period (2009-2013). Reductions were most pronounced in children <1year of age, eligible for vaccination. The mean proportions of AGE-related deaths, AGE-related hospitalizations, and AGE-related healthcare visits during 2009-2014 were reduced by 52.5% (95% CI 47.4-56.3), 30.2% (95% CI 23.5-36.1), and 12.9% (95% CI 12.0-13.2), respectively. The greatest effect in reduction of AGE-related deaths was found during the months with seasonal peaks of rotavirus disease. Over the post-vaccine period, changes in rotavirus epidemiology were observed, manifested by variations in seasonality and by a shift in the mean age of those with rotavirus infection. The significant decrease in main AGE-related health indicators in children <5years of age after the introduction of rotavirus vaccine provides evidence of a substantial public health impact of rotavirus vaccination in Bolivia, as a measure for protecting children against AGE. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

Estimating rotavirus gastroenteritis hospitalisations by using hospital episode statistics before and after the introduction of rotavirus vaccine in Australia.

PubMed

Jayasinghe, Sanjay; Macartney, Kristine

2013-01-30

Hospital discharge records and laboratory data have shown a substantial early impact from the rotavirus vaccination program that commenced in 2007 in Australia. However, these assessments are affected by the validity and reliability of hospital discharge coding and stool testing to measure the true incidence of hospitalised disease. The aim of this study was to assess the validity of these data sources for disease estimation, both before and after, vaccine introduction. All hospitalisations at a major paediatric centre in children aged <5 years from 2000 to 2009 containing acute gastroenteritis (AGE) ICD 10 AM diagnosis codes were linked to hospital laboratory stool testing data. The validity of the rotavirus-specific diagnosis code (A08.0) and the incidence of hospitalisations attributable to rotavirus by both direct estimation and with adjustments for non-testing and miscoding were calculated for pre- and post-vaccination periods. A laboratory record of stool testing was available for 36% of all AGE hospitalisations (n=4948) the rotavirus code had high specificity (98.4%; 95% CI, 97.5-99.1%) and positive predictive value (96.8%; 94.8-98.3%), and modest sensitivity (61.6%; 58-65.1%). Of all rotavirus test positive hospitalisations only a third had a rotavirus code. The estimated annual average number of rotavirus hospitalisations, following adjustment for non-testing and miscoding was 5- and 6-fold higher than identified, respectively, from testing and coding alone. Direct and adjusted estimates yielded similar percentage reductions in annual average rotavirus hospitalisations of over 65%. Due to the limited use of stool testing and poor sensitivity of the rotavirus-specific diagnosis code routine hospital discharge and laboratory data substantially underestimate the true incidence of rotavirus hospitalisations and absolute vaccine impact. However, this data can still be used to monitor vaccine impact as the effects of miscoding and under-testing appear to be comparable between pre and post vaccination periods. Copyright © 2012 Elsevier Ltd. All rights reserved.

Genetic relatedness among human rotavirus genes coding for VP7, a major neutralization protein, and its application to serotype identification.

PubMed Central

Midthun, K; Flores, J; Taniguchi, K; Urasawa, S; Kapikian, A Z; Chanock, R M

1987-01-01

Antigenic characterization of human rotaviruses by plaque reduction neutralization assay has revealed four distinct serotypes. The outer capsid protein VP7, coded for by gene 8 or 9, is a major neutralization protein; however, studies of rotaviruses derived from genetic reassortment between two strains have confirmed that another outer capsid protein, VP3, is in some cases equally important in neutralization. In this study, the genetic relatedness of the genes coding for VP7 of human rotaviruses belonging to serotypes 1 through 4 was examined by hybridization of their denatured double-stranded genomic RNAs to labeled single-stranded mRNA probes derived from human-animal rotavirus reassortants containing only the VP7 gene of their human rotavirus parent. A high degree of homology was demonstrated between the VP7 genes of strain D and other serotype 1 human rotaviruses, strain DS-1 and other serotype 2 human rotaviruses, strain P and other serotype 3 human rotaviruses, and strain ST3 and other serotype 4 human rotaviruses. Hybrid bands could not be demonstrated between the VP7 gene of D, DS-1, P, or ST3 and the corresponding gene of human rotaviruses belonging to a different serotype. RNA specimens extracted from the stools of 15 Venezuelan children hospitalized with rotavirus diarrhea were hybridized to each of the reassortant probes representing the four human serotypes. All five viruses with short RNA patterns showed homology with the DS-1 strain VP7 gene; two of these were previously adapted to tissue culture and shown to be serotype 2 strains by tissue culture neutralization. Of the remaining 10 viruses with long RNA patterns, 2 hybridized only to the D strain VP7 gene, 6 hybridized only to the P strain VP7 gene, and 2 hybridized only to the ST3 strain VP7 gene. Hybridization using single human rotavirus gene substitution reassortants as probes may provide an alternative method for identifying the VP7 serotype of field isolates that would circumvent the need for tissue culture adaptation. Images PMID:3038948

Identification of vaccine-derived rotavirus strains in children with acute gastroenteritis in Japan, 2012-2015.

PubMed

Kaneko, Mei; Takanashi, Sayaka; Thongprachum, Aksara; Hanaoka, Nozomu; Fujimoto, Tsuguto; Nagasawa, Koo; Kimura, Hirokazu; Okitsu, Shoko; Mizuguchi, Masashi; Ushijima, Hiroshi

2017-01-01

Two live attenuated oral rotavirus vaccines, Rotarix and RotaTeq, have been introduced as voluntary vaccination in Japan since 2011 and 2012, respectively. Effectiveness of the vaccines has been confirmed, whereas concerns such as shedding of the vaccine strains and gastroenteritis cases caused by vaccine strains are not well assessed. We aimed to identify the vaccine strains in children with acute gastroenteritis (AGE) to investigate the prevalence of AGE caused by vaccination or horizontal transmission of vaccine strains. A total of 1,824 stool samples were collected from children with AGE at six outpatient clinics in 2012-2015. Among all, 372 group A rotavirus (RVA) positive samples were screened for vaccine components by real-time RT-PCR which were designed to differentiate vaccine strains from rotavirus wild-type strains with high specificity. For samples possessing both vaccine and wild-type strains, analyses by next-generation sequencing (NGS) were conducted to characterize viruses existed in the intestine. As a result, Rotarix-derived strains were identified in 6 of 372 (1.6%) RVA positive samples whereas no RotaTeq strain was detected. Among six samples, four possessed Rotarix-derived strains while two possessed both Rotarix-derived strains and wild-type strains. In addition, other pathogens such as norovirus, enterovirus and E.coli were detected in four samples. The contribution of these vaccine strains to each patient's symptoms was unclear as all of the cases were vaccinated 2-14 days before sample collection. Proportion of average coverage for each segmented gene by NGS strongly suggested the concurrent infection of the vaccine-derived strain and the wild-type strain rather than reassortment of these two strains in one sample. This is the first study to report the prevalence of vaccine-derived strains in patients with RVA AGE in Japan as 1.6% without evidence of horizontal transmission. The results emphasized the importance of continuous monitoring on vaccine strains and their clinical impacts on children.

Identification of vaccine-derived rotavirus strains in children with acute gastroenteritis in Japan, 2012-2015

PubMed Central

Kaneko, Mei; Thongprachum, Aksara; Hanaoka, Nozomu; Fujimoto, Tsuguto; Nagasawa, Koo; Kimura, Hirokazu; Okitsu, Shoko; Mizuguchi, Masashi; Ushijima, Hiroshi

2017-01-01

Two live attenuated oral rotavirus vaccines, Rotarix and RotaTeq, have been introduced as voluntary vaccination in Japan since 2011 and 2012, respectively. Effectiveness of the vaccines has been confirmed, whereas concerns such as shedding of the vaccine strains and gastroenteritis cases caused by vaccine strains are not well assessed. We aimed to identify the vaccine strains in children with acute gastroenteritis (AGE) to investigate the prevalence of AGE caused by vaccination or horizontal transmission of vaccine strains. A total of 1,824 stool samples were collected from children with AGE at six outpatient clinics in 2012–2015. Among all, 372 group A rotavirus (RVA) positive samples were screened for vaccine components by real-time RT-PCR which were designed to differentiate vaccine strains from rotavirus wild-type strains with high specificity. For samples possessing both vaccine and wild-type strains, analyses by next-generation sequencing (NGS) were conducted to characterize viruses existed in the intestine. As a result, Rotarix-derived strains were identified in 6 of 372 (1.6%) RVA positive samples whereas no RotaTeq strain was detected. Among six samples, four possessed Rotarix-derived strains while two possessed both Rotarix-derived strains and wild-type strains. In addition, other pathogens such as norovirus, enterovirus and E.coli were detected in four samples. The contribution of these vaccine strains to each patient’s symptoms was unclear as all of the cases were vaccinated 2–14 days before sample collection. Proportion of average coverage for each segmented gene by NGS strongly suggested the concurrent infection of the vaccine-derived strain and the wild-type strain rather than reassortment of these two strains in one sample. This is the first study to report the prevalence of vaccine-derived strains in patients with RVA AGE in Japan as 1.6% without evidence of horizontal transmission. The results emphasized the importance of continuous monitoring on vaccine strains and their clinical impacts on children. PMID:28902863

Effect of pentavalent rotavirus vaccine introduction on hospital admissions for diarrhoea and rotavirus in children in Rwanda: a time-series analysis.

PubMed

Ngabo, Fidele; Tate, Jacqueline E; Gatera, Maurice; Rugambwa, Celse; Donnen, Philippe; Lepage, Philippe; Mwenda, Jason M; Binagwaho, Agnes; Parashar, Umesh D

2016-02-01

In May, 2012, Rwanda became the first low-income African country to introduce pentavalent rotavirus vaccine into its routine national immunisation programme. Although the potential health benefits of rotavirus vaccination are huge in low-income African countries that account for more than half the global deaths from rotavirus, concerns remain about the performance of oral rotavirus vaccines in these challenging settings. We conducted a time-series analysis to examine trends in admissions to hospital for non-bloody diarrhoea in children younger than 5 years in Rwanda between Jan 1, 2009, and Dec 31, 2014, using monthly discharge data from the Health Management Information System. Additionally, we reviewed the registries in the paediatric wards at six hospitals from 2009 to 2014 and abstracted the number of total admissions and admissions for diarrhoea in children younger than 5 years by admission month and age group. We studied trends in admissions specific to rotavirus at one hospital that had undertaken active rotavirus surveillance from 2011 to 2014. We assessed changes in rotavirus epidemiology by use of data from eight active surveillance hospitals. Compared with the 2009-11 prevaccine baseline, hospital admissions for non-bloody diarrhoea captured by the Health Management Information System fell by 17-29% from a pre-vaccine median of 4051 to 2881 in 2013 and 3371 in 2014, admissions for acute gastroenteritis captured in paediatric ward registries decreased by 48-49%, and admissions specific to rotavirus captured by active surveillance fell by 61-70%. The greatest effect was recorded in children age-eligible to be vaccinated, but we noted a decrease in the proportion of children with diarrhoea testing positive for rotavirus in almost every age group. The number of admissions to hospital for diarrhoea and rotavirus in Rwanda fell substantially after rotavirus vaccine implementation, including among older children age-ineligible for vaccination, suggesting indirect protection through reduced transmission of rotavirus. These data highlight the benefits of routine vaccination against rotavirus in low-income settings. Gavi, the Vaccine Alliance and the Government of Rwanda. Copyright © 2016. World Health Organization; licensee Elsevier. This is an Open Access article published without any waiver of WHO's privileges and immunities under international law, convention, or agreement. This Article should not be reproduced for use in association with the promotion of commercial products, services or any legal entity. There should be no suggestion that WHO endorses any specific organisation or products. The use of the WHO logo is not permitted. This notice should be preserved along with the Article's original URL.

Analysis of Host Range Restriction Determinants in the Rabbit Model: Comparison of Homologous and Heterologous Rotavirus Infections

PubMed Central

Ciarlet, Max; Estes, Mary K.; Barone, Christopher; Ramig, Robert F.; Conner, Margaret E.

1998-01-01

The main limitation of both the rabbit and mouse models of rotavirus infection is that human rotavirus (HRV) strains do not replicate efficiently in either animal. The identification of individual genes necessary for conferring replication competence in a heterologous host is important to an understanding of the host range restriction of rotavirus infections. We recently reported the identification of the P type of the spike protein VP4 of four lapine rotavirus strains as being P[14]. To determine whether VP4 is involved in host range restriction in rabbits, we evaluated infection in rotavirus antibody-free rabbits inoculated orally with two P[14] HRVs, PA169 (G6) and HAL1166 (G8), and with several other HRV strains and animal rotavirus strains of different P and G types. We also evaluated whether the parental rhesus rotavirus (RRV) (P5B[3], G3) and the derived RRV-HRV reassortant candidate vaccine strains RRV × D (G1), RRV × DS-1 (G2), and RRV × ST3 (G4) would productively infect rabbits. Based on virus shedding, limited replication was observed with the P[14] HRV strains and with the SA11 Cl3 (P[2], G3) and SA11 4F (P6[1], G3) animal rotavirus strains, compared to the homologous ALA strain (P[14], G3). However, even limited infection provided complete protection from rotavirus infection when rabbits were challenged orally 28 days postinoculation (DPI) with 103 50% infective doses of ALA rabbit rotavirus. Other HRVs did not productively infect rabbits and provided no significant protection from challenge, in spite of occasional seroconversion. Simian RRV replicated as efficiently as lapine ALA rotavirus in rabbits and provided complete protection from ALA challenge. Live attenuated RRV reassortant vaccine strains resulted in no, limited, or productive infection of rabbits, but all rabbits were completely protected from heterotypic ALA challenge. The altered replication efficiency of the reassortants in rabbits suggests a role for VP7 in host range restriction. Also, our results suggest that VP4 may be involved in, but is not exclusively responsible for, host range restriction in the rabbit model. The replication efficiency of rotavirus in rabbits also is not controlled by the product of gene 5 (NSP1) alone, since a reassortant rotavirus with ALA gene 5 and all other genes from SA11 was more severely replication restricted than either parental rotavirus strain. PMID:9499095

Effectiveness of monovalent human rotavirus vaccine against admission to hospital for acute rotavirus diarrhoea in South African children: a case-control study.

PubMed

Groome, Michelle J; Page, Nicola; Cortese, Margaret M; Moyes, Jocelyn; Zar, Heather J; Kapongo, Constant N; Mulligan, Christine; Diedericks, Ralph; Cohen, Cheryl; Fleming, Jessica A; Seheri, Mapaseka; Mphahlele, Jeffrey; Walaza, Sibongile; Kahn, Kathleen; Chhagan, Meera; Steele, A Duncan; Parashar, Umesh D; Zell, Elizabeth R; Madhi, Shabir A

2014-11-01

The effectiveness of the rotavirus vaccine under conditions of routine use in an African setting with a high prevalence of HIV infection needs to be established. We assessed the vaccine effectiveness of monovalent human rotavirus vaccine in preventing admission to hospital for acute rotavirus diarrhoea, after its introduction at age 6 and 14 weeks into South Africa's national immunisation programme. This case-control study was done at seven hospitals in South Africa between April 19, 2010, and Oct 31, 2012. The hospitals were located in a range of urban, peri-urban, and rural settings, with varying rates of population HIV infection. Cases were children aged from 18 weeks to 23 months who were age-eligible to have received at least one dose of the human rotavirus vaccine (ie, those born after June 14, 2009) admitted to hospital with laboratory-confirmed acute rotavirus diarrhoea, and the primary control group was children admitted to hospital with diarrhoea testing negative for rotavirus. A second control group comprised children admitted to a subset of three of the seven hospitals with respiratory illness. The primary endpoint was adjusted vaccine effectiveness (1 - adjusted odds ratio × 100%) in children aged from 18 weeks to 23 months and was calculated by unconditional logistic regression. This study is registered on the South African National Clinical Trial Register, number DOH-27-0512-3247. Of 540 rotavirus-positive cases, 278 children (52%) received two doses, 126 (23%) one dose, and 136 (25%) no doses of human rotavirus vaccine, compared with 1434 rotavirus-negative controls of whom 856 (60%) received two doses, 334 (23%) one dose, and 244 (17%) no doses. Adjusted vaccine effectiveness using rotavirus-negative controls was 57% (95% CI 40-68) for two doses and 40% (16-57) for one dose; estimates were similar when respiratory controls were used as the control group. Adjusted vaccine effectiveness for two doses was similar between age groups 18 weeks-11 months (54%, 95% CI 32-68) and 12-23 months (61%, 35-77), and was similar in HIV-exposed-uninfected (64%, 95% CI 34-80) and HIV-unexposed-uninfected children (54%, 31-69). Human rotavirus vaccine provided sustained protection against admission to hospital for acute rotavirus diarrhoea during the first and second years of life. This finding is encouraging and establishes the public health value of rotavirus vaccine in an African setting, especially as rotavirus vaccines are introduced into an increasing number of African countries. GAVI Alliance (with support from PATH). Copyright © 2014 Elsevier Ltd. All rights reserved.

Whole genomic analysis of bovine group A rotavirus strains A5-10 and A5-13 provides evidence for close evolutionary relationship with human rotaviruses.

PubMed

Komoto, Satoshi; Pongsuwanna, Yaowapa; Tacharoenmuang, Ratana; Guntapong, Ratigorn; Ide, Tomihiko; Higo-Moriguchi, Kyoko; Tsuji, Takao; Yoshikawa, Tetsushi; Taniguchi, Koki

2016-11-15

Bovine group A rotavirus (RVA) is an important cause of acute diarrhea in calves worldwide. In order to obtain precise information on the origin and evolutionary dynamics of bovine RVA strains, we determined and analyzed the complete nucleotide sequences of the whole genomes of six archival bovine RVA strains; four Thai strains (RVA/Cow-tc/THA/A5-10/1988/G8P[1], RVA/Cow-tc/THA/A5-13/1988/G8P[1], RVA/Cow-tc/THA/61A/1989/G10P[5], and RVA/Cow-tc/THA/A44/1989/G10P[11]), one American strain (RVA/Cow-tc/USA/B223/1983/G10P[11]), and one Japanese strain (RVA/Cow-tc/JPN/KK3/1983/G10P[11]). On whole genomic analysis, the 11 gene segments of strains A5-10, A5-13, 61A, A44, B223, and KK3 were found to be considerably genetically diverse, but to share a conserved non-G/P genotype constellation except for the NSP1 gene (I2-R2-C2-M2-(A3/11/13/14)-N2-T6-E2-H3), which is commonly found in RVA strains from artiodactyls such as cattle. Furthermore, phylogenetic analysis revealed that most genes of the six strains were genetically related to bovine and bovine-like strains. Of note is that the VP1, VP3, and NSP2 genes of strains A5-10 and A5-13 exhibited a closer relationship with the cognate genes of human DS-1-like strains than those of other RVA strains. Furthermore, the VP6 genes of strains A5-10 and A5-13 appeared to be equally related to both human DS-1-like and bovine strains. Thus, strains A5-10 and A5-13 were suggested to be derived from the same evolutionary origin as human DS-1-like strains, and were assumed to be examples of bovine RVA strains that provide direct evidence for a close evolutionary relationship between bovine and human DS-1-like strains. Our findings will provide important insights into the origin of bovine RVA strains, and into evolutionary links between bovine and human RVA strains. Copyright © 2016 Elsevier B.V. All rights reserved.

Whole genome analysis provides evidence for porcine-to-simian interspecies transmission of rotavirus-A.

PubMed

Navarro, Ryan; Aung, Meiji Soe; Cruz, Katalina; Ketzis, Jennifer; Gallagher, Christa Ann; Beierschmitt, Amy; Malik, Yashpal Singh; Kobayashi, Nobumichi; Ghosh, Souvik

2017-04-01

We report here whole genome analysis of a porcine rotavirus-A (RVA) strain RVA/Pig-wt/KNA/ET8B/2015/G5P[13] detected in a diarrheic piglet, and nearly whole genome (except for VP4 gene) analysis of a simian RVA strain RVA/Simian-wt/KNA/08979/2015/G5P[X] detected in a non-diarrheic African green monkey (AGM) on the island of St. Kitts, Caribbean region. Strain ET8B exhibited a G5-P[13]-I5-R1-C1-M1-A8-N1-T7-E1-H1 genotype constellation that was identical to those of Brazilian porcine RVA G5P[13] strains RVA/Pig-wt/BRA/ROTA01/2013/G5P[13] and RVA/Pig-wt/BRA/ROTA07/2013/G5P[13], the only porcine G5P[13] RVAs that have been analyzed for the whole genome so far. Phylogenetically, all the 11 gene segments of ET8B were closely related to those of porcine and porcine-like human RVAs within the respective genotypes. Although the porcine G5P[13] RVAs exhibited identical genotype constellations, ET8B did not appear to share common evolutionary pathways with the Brazilian porcine G5P[13] RVAs. Interestingly, the VP2, VP3, VP6, VP7, and NSP1-NSP5 genes of simian RVA strain 08979 were closely related to those of porcine and porcine-like human RVA strains, exhibiting 99%-100% nucleotide sequence identities to cognate genes of co-circulating porcine RVA strain ET8B. On the other hand, the VP1 of 08979 appeared to be genetically divergent from porcine and human RVAs within the R1 genotype, and its exact origin could not be ascertained. Taken together, these observations suggested that simian strain 08979 might have been derived from interspecies transmission events involving transmission of ET8B-like RVAs from pigs to AGMs. In St. Kitts, AGMs often stray from the wild into livestock farms. Therefore, it may be possible that the AGM acquired the infection from a pig farm on the island. To our knowledge, this is the first report on detection of porcine-like RVAs in monkeys. Also, the present study is the first to report whole genomic analysis of a porcine RVA strain from the Caribbean region. Copyright © 2016 Elsevier B.V. All rights reserved.

Viromic Analysis of Wastewater Input to a River Catchment Reveals a Diverse Assemblage of RNA Viruses

PubMed Central

Farkas, Kata; Harrison, Christian; Jones, David L.; McCarthy, Alan J.

2018-01-01

ABSTRACT Detection of viruses in the environment is heavily dependent on PCR-based approaches that require reference sequences for primer design. While this strategy can accurately detect known viruses, it will not find novel genotypes or emerging and invasive viral species. In this study, we investigated the use of viromics, i.e., high-throughput sequencing of the biosphere’s viral fraction, to detect human-/animal-pathogenic RNA viruses in the Conwy river catchment area in Wales, United Kingdom. Using a combination of filtering and nuclease treatment, we extracted the viral fraction from wastewater and estuarine river water and sediment, followed by high-throughput RNA sequencing (RNA-Seq) analysis on the Illumina HiSeq platform, for the discovery of RNA virus genomes. We found a higher richness of RNA viruses in wastewater samples than in river water and sediment, and we assembled a complete norovirus genotype GI.2 genome from wastewater effluent, which was not contemporaneously detected by conventional reverse transcription-quantitative PCR (qRT-PCR). The simultaneous presence of diverse rotavirus signatures in wastewater indicated the potential for zoonotic infections in the area and suggested runoff from pig farms as a possible origin of these viruses. Our results show that viromics can be an important tool in the discovery of pathogenic viruses in the environment and can be used to inform and optimize reference-based detection methods provided appropriate and rigorous controls are included. IMPORTANCE Enteric viruses cause gastrointestinal illness and are commonly transmitted through the fecal-oral route. When wastewater is released into river systems, these viruses can contaminate the environment. Our results show that we can use viromics to find the range of potentially pathogenic viruses that are present in the environment and identify prevalent genotypes. The ultimate goal is to trace the fate of these pathogenic viruses from origin to the point where they are a threat to human health, informing reference-based detection methods and water quality management. PMID:29795788

Viromic Analysis of Wastewater Input to a River Catchment Reveals a Diverse Assemblage of RNA Viruses.

PubMed

Adriaenssens, Evelien M; Farkas, Kata; Harrison, Christian; Jones, David L; Allison, Heather E; McCarthy, Alan J

2018-01-01

Detection of viruses in the environment is heavily dependent on PCR-based approaches that require reference sequences for primer design. While this strategy can accurately detect known viruses, it will not find novel genotypes or emerging and invasive viral species. In this study, we investigated the use of viromics, i.e., high-throughput sequencing of the biosphere's viral fraction, to detect human-/animal-pathogenic RNA viruses in the Conwy river catchment area in Wales, United Kingdom. Using a combination of filtering and nuclease treatment, we extracted the viral fraction from wastewater and estuarine river water and sediment, followed by high-throughput RNA sequencing (RNA-Seq) analysis on the Illumina HiSeq platform, for the discovery of RNA virus genomes. We found a higher richness of RNA viruses in wastewater samples than in river water and sediment, and we assembled a complete norovirus genotype GI.2 genome from wastewater effluent, which was not contemporaneously detected by conventional reverse transcription-quantitative PCR (qRT-PCR). The simultaneous presence of diverse rotavirus signatures in wastewater indicated the potential for zoonotic infections in the area and suggested runoff from pig farms as a possible origin of these viruses. Our results show that viromics can be an important tool in the discovery of pathogenic viruses in the environment and can be used to inform and optimize reference-based detection methods provided appropriate and rigorous controls are included. IMPORTANCE Enteric viruses cause gastrointestinal illness and are commonly transmitted through the fecal-oral route. When wastewater is released into river systems, these viruses can contaminate the environment. Our results show that we can use viromics to find the range of potentially pathogenic viruses that are present in the environment and identify prevalent genotypes. The ultimate goal is to trace the fate of these pathogenic viruses from origin to the point where they are a threat to human health, informing reference-based detection methods and water quality management.

World Reference Center for Arboviruses.

DTIC Science & Technology

1981-02-01

CTF isolates including clones of the Florio strain. Representatives of the genera Rotavirus , cytoplasmic polyhedrosis virus group, and plant reovirus...group were supplied as purified virus preparations; and the virus strains respectively included a human rotavirus isolated from a fecal sample, Bom x...strain - CTF), Rotavirus (human rotavirus - HR), cytoplasmic polyhedrosis group ( Bombyx mori cytoplasmic polyhedrosis -CPV), and plant reovirus group

Macular exanthema in a child with rotavirus gastroenteritis: a case report.

PubMed

Zulfikar Akelma, Ahmet; Nevzat Cizmeci, Mehmet; Mete, Emin; Dilara Malli, Dilsad; Erpolat, Seval; Mujgan Sonmez, Fatma

2014-04-01

Apart from gastroenteritis, rotavirus has been rarely implicated with some cutaneous disorders such as generalized maculo-papular exanthema, infantile acute hemorrhagic edema and Gianotti-Crosti syndrome. We report a 30-month old toddler boy who developed erythematous macular skin eruptions during the course of rotavirus gastroenteritis. To our knowledge, this is the first case in the literature reporting rotavirus-related macular erythematous lesions in a pediatric patient. We therefore would like to share our experience, to keep ro-tavirus infection in the differential diagnosis of children with gastroenteritis and erythematous eruption.

Effects of wastewater sludge and its detergents on the stability of rotavirus

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ward, R.L.; Ashley, C.S.

1980-06-01

Wastewater sludge reduced the heat required to inactivate rotavirus SA-11, and ionic detergents were identified as the sludge components responsible for this effect. A similar result was found previously with reovirus. The quantitative effects of individual ionic detergents on rotavirus and reovirus were very different, and rotavirus was found to be extremely sensitive to several of these detergents. However, neither virus was destabilized by nonionic detergents. On the contrary, rotavirus was stabilized by a nonionic detergent against the potent destabilizing effects of the ionic detergent sodium dodecyl sulfate. The destabilizing effects of both cationic and anionic detergents on rotavirus weremore » greatly altered by changes in the pH of the medium.« less

Rotavirus Vaccines: a story of success with challenges ahead

PubMed Central

O’Ryan, Miguel

2017-01-01

Approximately 40 years have passed since the discovery of the rotavirus and 10 years since the introduction and progressive dissemination of rotavirus vaccines worldwide. Currently, 92 countries have introduced rotavirus vaccines into national or subnational programs with evident impact in disease reduction. Two vaccines have been widely used, and four additional vaccines have been licensed and are being used in defined regions. In this context, one main issue that remains unsolved is the lower vaccine efficacy/effectiveness in low-income countries. An additional partially answered issue relates to rotavirus strain circulation in vaccinated populations. These issues are discussed in this review. The most imperative challenge ahead is to fulfill the WHO’s recommendation to introduce rotavirus vaccines in all countries. PMID:28928954

Group C rotavirus infection in patients with acute gastroenteritis in outbreaks in western India between 2006 and 2014.

PubMed

Joshi, M S; Jare, V M; Gopalkrishna, V

2017-01-01

Faecal specimens collected from outbreak (n = 253) and sporadic (n = 147) cases of acute gastroenteritis that occurred in western India between 2006 and 2014 were tested for group C rotavirus (GCR) using partial VP6 gene-based RT-PCR. All specimens were tested previously for the presence of other viral and bacterial aetiological agents by conventional methods. The rate of GCR detection was 8·6% and 0·7% in outbreak and sporadic cases, respectively. GCR infections prevailed in outbreaks reported from rural areas (10·9%) compared to urban areas (1·6%). Clinical severity score of the patients with GCR infection (n = 23) indicated severe disease in the majority (70%) of cases. The age distribution analysis indicated 52·1% of GCR infections in children aged <10 years. The male:female ratio in GCR-positive patients was 2·3:1. Of the 23 GCR-positive cases, 17 (73·9%) had a sole GCR infection and six had mixed infections with other viral and/or bacterial agents. Phylogenetic analysis of nucleotide sequences classified GCR strains of the study in to I2 genotype of the VP6 gene. This is the first study to show the occurrence of GCR in gastroenteritis outbreaks in India.

Detection of adenoviruses and rotaviruses in drinking water sources used in rural areas of Benin, West Africa.

PubMed

Verheyen, Jens; Timmen-Wego, Monika; Laudien, Rainer; Boussaad, Ibrahim; Sen, Sibel; Koc, Aynur; Uesbeck, Alexandra; Mazou, Farouk; Pfister, Herbert

2009-05-01

Diseases associated with viruses also found in environmental samples cause major health problems in developing countries. Little is known about the frequency and pattern of viral contamination of drinking water sources in these resource-poor settings. We established a method to analyze 10 liters of water from drinking water sources in a rural area of Benin for the presence of adenoviruses and rotaviruses. Overall, 541 samples from 287 drinking water sources were tested. A total of 12.9% of the sources were positive for adenoviruses and 2.1% of the sources were positive for rotaviruses at least once. Due to the temporary nature of viral contamination in drinking water sources, the probability of virus detection increased with the number of samples taken at one test site over time. No seasonal pattern for viral contaminations was found after samples obtained during the dry and wet seasons were compared. Overall, 3 of 15 surface water samples (20%) and 35 of 247 wells (14.2%) but also 2 of 25 pumps (8%) tested positive for adenoviruses or rotaviruses. The presence of latrines within a radius of 50 m in the vicinity of pumps or wells was identified as being a risk factor for virus detection. In summary, viral contamination was correlated with the presence of latrines in the vicinity of drinking water sources, indicating the importance of appropriate decision support systems in these socioeconomic prospering regions.

Characterization of a G1P[8] rotavirus causing an outbreak of gastroenteritis in the Northern Territory, Australia, in the vaccine era.

PubMed

Donato, Celeste M; Cowley, Daniel; Snelling, Thomas L; Akopov, Asmik; Kirkness, Ewen F; Kirkwood, Carl D

2014-07-01

In 2010, a large outbreak of rotavirus gastroenteritis occurred in the Alice Springs region of the Northern Territory, Australia. The outbreak occurred 43 months after the introduction of the G1P[8] rotavirus vaccine Rotarix(®). Forty-three infants were hospitalized during the outbreak and analysis of fecal samples from each infant revealed a G1P[8] rotavirus strain. The outbreak strain was adapted to cell culture and neutralization assays were performed using VP7 and VP4 neutralizing monoclonal antibodies. The outbreak strain exhibited a distinct neutralization resistance pattern compared to the Rotarix(®) vaccine strain. Whole genome sequencing of the 2010 outbreak virus strain demonstrated numerous amino acid differences compared to the Rotarix(®) vaccine strain in the characterized neutralization epitopes of the VP7 and VP4 proteins. Phylogenetic analysis of the outbreak strain revealed a close genetic relationship to global strains, in particular RVA/Human-wt/BEL/BE0098/2009/G1P[8] and RVA/Human-wt/BEL/BE00038/2008/G1P[8] for numerous genes. The 2010 outbreak strain was likely introduced from a globally circulating population of strains rather than evolving from an endemic Australian strain. The outbreak strain possessed antigenic differences in the VP7 and VP4 proteins compared to the Rotarix(®) vaccine strain. The outbreak was associated with moderate vaccine coverage and possibly low vaccine take in the population.