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Sample records for rotavirus vaccine live

  1. Reassortant rotaviruses as potential live rotavirus vaccine candidates.

    PubMed Central

    Midthun, K; Greenberg, H B; Hoshino, Y; Kapikian, A Z; Wyatt, R G; Chanock, R M

    1985-01-01

    A series of reassortants was isolated from coinfection of cell cultures with a wild-type animal rotavirus and a "noncultivatable" human rotavirus. Wild-type bovine rotavirus (UK strain) was reassorted with human rotavirus strains D, DS-1, and P; wild-type rhesus rotavirus was reassorted with human rotavirus strains D and DS-1. The D, DS-1, and P strains represent human rotavirus serotypes 1, 2, and 3, respectively. Monospecific antiserum (to bovine rotavirus, NCDV strain) or a set of monoclonal antibodies to the major outer capsid neutralization glycoprotein, VP7 (of the rhesus rotavirus), was used to select for reassortants with human rotavirus neutralization specificity. This selection technique yielded many reassortants which received only the gene segment coding for the major neutralization protein from the human rotavirus parent, whereas the remaining genes were derived from the animal rotavirus parent. Single human rotavirus gene substitution reassortants of this sort represent potential live vaccine strains. Images PMID:2983101

  2. Clinical trials of live oral rotavirus vaccines: the Finnish experience.

    PubMed

    Vesikari, T

    1993-01-01

    Live oral candidate rotavirus vaccines of bovine (RIT 4237) or rhesus (RRV-1) origin and reassortants of RRV-1 expressing human serotype 1 (DxRRV) or serotype 2 (DS1xRRV) VP7 protein were evaluated for clinical efficacy in young children in successive trials from 1983 to 1989. In each study, the vaccinations were given before a rotavirus epidemic season and the follow-up of vaccinees covered two rotavirus epidemic seasons lasting up to 2-3 years of age. Serotype 1 rotavirus was predominant in each season. Protection rates against all rotavirus-associated diarrhoea ranged from 0 to 67% but were higher, up to 100%, against more severe rotavirus disease. All tested vaccines also showed efficacy for diarrhoea not apparently associated with rotavirus; therefore the clinical benefit of the vaccinations was greater than could be deduced from efficacy rates for rotavirus-associated diarrhoea alone. Each of the candidate vaccines could significantly reduce severe diarrhoea in Finnish children in the first 2 to 3 years of life. For optimal efficacy, the vaccines should be administered in the autumn before the regular epidemic season of rotavirus.

  3. Rotavirus Vaccine

    MedlinePlus

    ... have had a type of bowel blockage called "intussusception" should not get rotavirus vaccine. Babies who are ... of rotavirus vaccine.Severe problems following rotavirus vaccine:Intussusception is a type of bowel blockage that is ...

  4. 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

    2016-01-01

    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

  5. Stability of live attenuated rotavirus vaccine with selected preservatives and primary containers.

    PubMed

    Lal, Manjari; Jarrahian, Courtney; Zhu, Changcheng; Hosken, Nancy A; McClurkan, Chris L; Koelle, David M; Saxon, Eugene; Roehrig, Andrew; Zehrung, Darin; Chen, Dexiang

    2016-05-11

    Rotavirus infection, which can be prevented by vaccination, is responsible for a high burden of acute gastroenteritis disease in children, especially in low-income countries. An appropriate formulation, packaging, and delivery device for oral rotavirus vaccine has the potential to reduce the manufacturing cost of the vaccine and the logistical impact associated with introduction of a new vaccine, simplify the vaccination procedure, and ensure that the vaccine is safely and accurately delivered to children. Single-dose prefilled presentations can be easy to use; however, they are typically more expensive, can be a bottleneck during production, and occupy a greater volume per dose vis-à-vis supply chain storage and medical waste disposal, which is a challenge in low-resource settings. Multi-dose presentations used thus far have other issues, including increased wastage of vaccine and the need for separate delivery devices. In this study, the goals were to evaluate both the technical feasibility of using preservatives to develop a liquid multi-dose formulation and the primary packaging alternatives for orally delivered, liquid rotavirus vaccines. The feasibility evaluation included evaluation of commonly used preservatives for compatibility with rotavirus vaccines and stability testing of rotavirus vaccine in various primary containers, including Lameplast's plastic tubes, BD's oral dispenser version of Uniject™ (Uniject DP), rommelag's blow-fill-seal containers, and MEDInstill's multi-dose vial and pouch. These presentations were compared to a standard glass vial. The results showed that none of the preservatives tested were compatible with a live attenuated rotavirus vaccine because they had a detrimental effect on the viability of the virus. In the presence of preservatives, vaccine virus titers declined to undetectable levels within 1 month. The vaccine formulation without preservatives maintained a stability profile over 12 months in all primary containers

  6. Effect of withholding breastfeeding on the immune response to a live oral rotavirus vaccine in North Indian infants.

    PubMed

    Rongsen-Chandola, Temsunaro; Strand, Tor A; Goyal, Nidhi; Flem, Elmira; Rathore, Sudeep Singh; Arya, Alok; Winje, Brita Askeland; Lazarus, Robin; Shanmugasundaram, Elango; Babji, Sudhir; Sommerfelt, Halvor; Vainio, Kirsti; Kang, Gagandeep; Bhandari, Nita

    2014-08-11

    Interference from transplacental and breast milk antibodies may impede the performance of oral live vaccines. The effect of breastfeeding on the immunogenicity of Rotarix, a two-dose oral monovalent rotavirus vaccine, was examined in a community-based trial in New Delhi, India. Four hundred mother-infant pairs were randomized into two equal groups. Infants were aged 6-7 weeks at enrollment. Mothers were encouraged to either breastfeed or to withhold breastfeeding during the 30 min prior to and after each vaccine dose was administered. We collected blood specimens from infants at enrollment and 4 weeks after the second vaccine dose. Blood and breast milk specimens were obtained from mothers at baseline and breast milk specimens were collected at the time of the second vaccine dose. Seroconversion was defined as infant serum anti-VP6 IgA antibody level of ≥20 IU/mL 4 weeks after the second vaccine dose and a ≥4-fold rise from baseline. There was no difference in the proportion who seroconverted between the two groups (26% vs 27%; p=0.92). The levels of infant serum IgA, maternal serum and breast milk IgA and IgG anti-rotavirus antibodies predicted the anti-rotavirus IgA level in infants at end-study and explained approximately 10% of the variability of the immune response (r(2)=0.10, p<0.001). In this population, the immune response to Rotarix was not enhanced by withholding breastfeeding around the time of vaccination. Maternal anti-rotavirus antibodies explained little of the variability in the immune response to the vaccine. Factors other than maternal anti-rotavirus antibodies probably explain why infants in low-and middle-income settings respond poorly to live oral rotavirus vaccines.

  7. [Impact of rotavirus vaccines in developing countries].

    PubMed

    Delacour, H

    2009-08-01

    Rotaviruses discovered in 1973 are the most common cause of severe diarrheal disease in infants and young children world-wide. Annually rotavirus infections are estimated to cause the deaths of more than 600,000 children under the age of 5 years with more than 90% of fatalities occurring in developing countries. In 2006 two live oral attenuated rotavirus vaccines were licensed: the monovalent human rotavirus vaccine (RotarixT) and the pentavalent bovine-human, reassortant vaccine (RotaTeqT). Both vaccines demonstrated excellent safety and protective effectiveness in large pre-licensing trials conducted in Europe, the United States and Latin America. Several countries in Latin and Central America have already decided to include rotavirus vaccines into their national immunization program. African and Asiatic countries have postponed their decisions pending the results of further studies.

  8. 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.

  9. Vaccine-Acquired Rotavirus in Infants with Severe Combined Immunodeficiency

    PubMed Central

    Patel, Niraj C.; Hertel, Paula M.; Estes, Mary K.; de la Morena, Maite; Petru, Ann M.; Noroski, Lenora M.; Revell, Paula A.; Celine Hanson, I.; Paul, Mary E.; Rosenblatt, Howard M.; Abramson, Stuart L.

    2014-01-01

    SUMMARY Live pentavalent human–bovine reassortant rotavirus vaccine is recommended in the United States for routine immunization of infants. We describe three infants, two with failure to thrive, who had dehydration and diarrhea within 1 month after their first or second rotavirus immunization and subsequently received a diagnosis of severe combined immunodeficiency. Rotavirus was detected, by means of reverse-transcriptase–polymerase-chain-reaction (RT-PCR) assay, in stool specimens obtained from all three infants, and gene-sequence analysis revealed the presence of vaccine rotavirus. These infections raise concerns regarding the safety of rotavirus vaccine in severely immunocompromised patients. PMID:20107217

  10. VP6: A candidate rotavirus vaccine.

    PubMed

    Ward, Richard L; McNeal, Monica M

    2010-09-01

    Several nonliving rotavirus vaccine candidates have been evaluated in animal models. Among them is the VP6 protein that comprises the intermediate layer of the rotavirus particle. This protein was expressed as a chimera with maltose binding protein (MBP::VP6) and was administered intranasally to mice. When later challenged with rotavirus, vaccinated mice were nearly 100% protected from fecal shedding of rotavirus, a result strictly dependent on coadministration of an effective adjuvant. Protection was stimulated by only 1 dose of MBP::VP6, remained fully intact for at least 1 year, was effective in all strains of mice tested, and could also be effectively delivered orally or intrarectally. When VP6 was derived from a human rotavirus, it stimulated protection comparable to that found when derived from the challenge murine EDIM strain. In contrast to live rotavirus vaccines, CD4(+) T cells were found to be the only lymphocytes required for protection. If VP6 elicits comparable protection in humans, it would represent a potential second-generation vaccine candidate.

  11. 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

    2016-11-11

    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.

  12. Why does the world need another rotavirus vaccine?

    PubMed Central

    Ward, Richard L; McNeal, Monica M; Steele, A Duncan

    2008-01-01

    A “Meeting on Upstream Rotavirus Vaccines and Emerging Vaccine Producers” was held at the World Health Organization in Geneva, Switzerland on March 28–30, 2006. The purpose was to discuss, evaluate, and weigh the importance of additional rotavirus vaccine candidates following the successful international licensure of rotavirus vaccines by two major pharmaceutical companies (GlaxoSmithKline and Merck) that had been in development for many years. Both licensed vaccines are composed of live rotaviruses that are delivered orally as have been all candidate rotavirus vaccines evaluated in humans. Each is built on the experience gained with previous candidates whose development had either been discontinued or, in the case of the previously licensed rhesus rotavirus reassortant vaccine (Rotashield), was withdrawn by its manufacturer after the discovery of a rare association with intussusception. Although which alternative candidate vaccines should be supported for development and where this should be done are controversial topics, there was general agreement expressed at the Geneva meeting that further development of alternative candidates is a high priority. This development will help insure that the most safe, effective and economic vaccines are available to children in Third World nations where the vast majority of the >600,000 deaths due to rotavirus occur each year. This review is intended to provide the history and present status of rotavirus vaccines as well as a perspective on the future development of candidate vaccines as a means of promulgating plans suggested at the Geneva meeting. PMID:18728720

  13. WHO informal consultation on quality, safety and efficacy specifications for live attenuated rotavirus vaccines Mexico City, Mexico, 8-9 February 2005.

    PubMed

    Wood, David

    2005-12-01

    Rotavirus vaccines are at an advanced stage of development but there are as yet no WHO recommendations on production and quality control to provide regulatory guidance. A meeting of experts was convened by WHO and PAHO/AMRO to review the scientific basis for production and quality control of rotavirus vaccines, and to discuss specific measures to assure the safety and efficacy of rotavirus vaccines. The meeting was attended by 25 experts from 14 countries, drawn from academia, public health, national regulatory authorities and vaccine producers. It was agreed that existing guidance for other live virus vaccines provides a very good basis for product characterization, especially for source materials and control of production. The basis for attenuation of current vaccines or vaccine candidates is not known but, at least for the vaccines based on the Jennerian approach of using animal (bovine) rotaviruses, is likely to be multigenic. The risk of intussusception in humans is influenced by genetic background and age. Recent analyzes of large vaccine safety trials found that certain strains of vaccine virus were not associated with intussusception, although in these trials the first dose of vaccine was not administered to children over 3 months of age. Since age is a risk factor for intussusception, this may suggest that early delivery of the first dose of vaccine is desirable. However, maternal antibodies may mitigate against early delivery of the first vaccine dose. Factors which could affect vaccine efficacy or safety include strain diversity, malnutrition, other enteric infections, parasitic infection or immune suppression. It was concluded that data from clinical trials conducted in one part of the world would not necessarily be predictive of vaccine efficacy in other places. It was agreed that in nonclinical evaluations there was a need to use oral dosing for toxicity studies and, because rotavirus is non-neurovirulent, that there was no need for an animal

  14. 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

  15. Rotavirus.

    PubMed

    Esona, Mathew D; Gautam, Rashi

    2015-06-01

    Group A rotavirus (RVA) is the major cause of acute gastroenteritis (AGE) in young children worldwide. Introduction of two live, attenuated rotavirus vaccines, Rotarix® and RotaTeq®, has dramatically reduced RVA-associated AGE and mortality. High-throughput, sensitive and specific techniques are required to rapidly diagnose and characterize rotavirus strains in stool samples for proper patient treatment and to monitor circulating vaccine and wild-type rotavirus strains. New molecular assays are rapidly developed that are more sensitive and specific than the conventional assays for detection, genotyping and full genome characterization of circulating rotavirus wild-type and vaccine (Rotarix® and RotaTeq®) strains causing AGE.

  16. New insights into rotavirus vaccines

    PubMed Central

    Mameli, Chiara; Fabiano, Valentina; Zuccotti, Gian Vincenzo

    2012-01-01

    Rotavirus vaccines have shown to be effective and well tolerated in clinical trials. However it’s crucial to point out that immunization occurs in “real-word” conditions different from ideal clinical trial settings. Thus, the impact of rotavirus vaccines in terms of effectiveness and safety needs to be evaluated in real-world conditions. Post-licensure data regarding vaccine impact, effectiveness and safety under routine use are now available and provide a “real-world view.” PMID:22699445

  17. Monitoring impact and effectiveness of rotavirus vaccination.

    PubMed

    Tate, Jacqueline E; Parashar, Umesh D

    2011-08-01

    Rotavirus infection is the most common cause of severe gastroenteritis in children <5 years of age globally. Since 2009, the WHO has recommended inclusion of rotavirus vaccine in the national immunization programs of all countries. Data regarding rotavirus vaccine impact and effectiveness under conditions of routine use are important for encouraging countries to implement vaccination programs. In the absence of a national rotavirus vaccination program in France, the IVANHOE study was initiated to determine the real-world impact and effectiveness of rotavirus vaccine following introduction in a limited geographic area. This study found a twofold reduction in rotavirus hospitalizations among children <2 years of age who were age-eligible to receive rotavirus vaccine and a 98% vaccine effectiveness, highlighting the health benefits of a vaccination program.

  18. Mice develop effective but delayed protective immune responses when immunized as neonates either intranasally with nonliving VP6/LT(R192G) or orally with live rhesus rotavirus vaccine candidates.

    PubMed

    VanCott, John L; Prada, Anne E; McNeal, Monica M; Stone, Susan C; Basu, Mitali; Huffer, Bert; Smiley, Kristi L; Shao, Mingyuan; Bean, Judy A; Clements, John D; Choi, Anthony H-C; Ward, Richard L

    2006-05-01

    Rotavirus vaccines are delivered early in life, when the immune system is immature. To determine the effects of immaturity on responses to candidate vaccines, neonatal (7 days old) and adult mice were immunized with single doses of either Escherichia coli-expressed rotavirus VP6 protein and the adjuvant LT(R192G) or live rhesus rotavirus (RRV), and protection against fecal rotavirus shedding following challenge with the murine rotavirus strain EDIM was determined. Neonatal mice immunized intranasally with VP6/LT(R192G) were unprotected at 10 days postimmunization (dpi) and had no detectable rotavirus B-cell (antibody) or CD4(+) CD8(+) T-cell (rotavirus-inducible, Th1 [gamma interferon and interleukin-2 {IL-2}]-, Th2 [IL-5 and IL-4]-, or ThIL-17 [IL-17]-producing spleen cells) responses. However, by 28 and 42 dpi, these mice were significantly (P >or= 0.003) protected and contained memory rotavirus-specific T cells but produced no rotavirus antibody. In contrast, adult mice were nearly fully protected by 10 dpi and contained both rotavirus immunoglobulin G and memory T cells. Neonates immunized orally with RRV were also less protected (P=0.01) than adult mice by 10 dpi and produced correspondingly less rotavirus antibody. Both groups contained few rotavirus-specific memory T cells. Protection levels by 28 dpi for neonates or adults were equal, as were rotavirus antibody levels. This report introduces a neonatal mouse model for active protection studies with rotavirus vaccines. It indicates that, with time, neonatal mice develop full protection after intranasal immunization with VP6/LT(R192G) or oral immunization with a live heterologous rotavirus and supports reports that protection depends on CD4(+) T cells or antibody, respectively.

  19. Mice Develop Effective but Delayed Protective Immune Responses When Immunized as Neonates either Intranasally with Nonliving VP6/LT(R192G) or Orally with Live Rhesus Rotavirus Vaccine Candidates

    PubMed Central

    VanCott, John L.; Prada, Anne E.; McNeal, Monica M.; Stone, Susan C.; Basu, Mitali; Huffer, Bert; Smiley, Kristi L.; Shao, Mingyuan; Bean, Judy A.; Clements, John D.; Choi, Anthony H.-C.; Ward, Richard L.

    2006-01-01

    Rotavirus vaccines are delivered early in life, when the immune system is immature. To determine the effects of immaturity on responses to candidate vaccines, neonatal (7 days old) and adult mice were immunized with single doses of either Escherichia coli-expressed rotavirus VP6 protein and the adjuvant LT(R192G) or live rhesus rotavirus (RRV), and protection against fecal rotavirus shedding following challenge with the murine rotavirus strain EDIM was determined. Neonatal mice immunized intranasally with VP6/LT(R192G) were unprotected at 10 days postimmunization (dpi) and had no detectable rotavirus B-cell (antibody) or CD4+ CD8+ T-cell (rotavirus-inducible, Th1 [gamma interferon and interleukin-2 {IL-2}]-, Th2 [IL-5 and IL-4]-, or ThIL-17 [IL-17]-producing spleen cells) responses. However, by 28 and 42 dpi, these mice were significantly (P ≥ 0.003) protected and contained memory rotavirus-specific T cells but produced no rotavirus antibody. In contrast, adult mice were nearly fully protected by 10 dpi and contained both rotavirus immunoglobulin G and memory T cells. Neonates immunized orally with RRV were also less protected (P = 0.01) than adult mice by 10 dpi and produced correspondingly less rotavirus antibody. Both groups contained few rotavirus-specific memory T cells. Protection levels by 28 dpi for neonates or adults were equal, as were rotavirus antibody levels. This report introduces a neonatal mouse model for active protection studies with rotavirus vaccines. It indicates that, with time, neonatal mice develop full protection after intranasal immunization with VP6/LT(R192G) or oral immunization with a live heterologous rotavirus and supports reports that protection depends on CD4+ T cells or antibody, respectively. PMID:16641286

  20. Prevaccination Rotavirus Serum IgG and IgA Are Associated With Lower Immunogenicity of Live, Oral Human Rotavirus Vaccine in South African Infants.

    PubMed

    Moon, Sung-Sil; Groome, Michelle J; Velasquez, Daniel E; Parashar, Umesh D; Jones, Stephanie; Koen, Antoinette; van Niekerk, Nadia; Jiang, Baoming; Madhi, Shabir A

    2016-01-15

    Live oral rotavirus (RV) vaccines have shown modest efficacy among children in African countries for reasons that are not completely understood. We examined the possible inhibitory effect of preexisting antirotavirus antibodies on immunogenicity of monovalent RV vaccine (RV1). Mother-infant pairs were enrolled at presentation for their routine immunization visit in Soweto, South Africa, when infants were aged 5-8 weeks. Infant serum samples were obtained before the first and second doses of RV1 and 1 month after the second dose. Maternal serum and breast milk samples were obtained prior to administration of each dose of RV1 to infants. RV-specific immunoglobulin G (IgG), IgA, and neutralizing activity in sera of infants and serum or breast milk samples of mothers were measured using enzyme-linked immunosorbent assays or a microneutralization test. Of the 107 serum pairs from infants who were seronegative for RV IgA at enrollment, we observed a strong positive association between IgG titers in pre-dose 1 sera of infants and mothers and significant negative associations between IgG titers in pre-dose 1 sera of infants and seroconversion to RV1 post-dose 1. Similarly, mothers whose infants' IgA seroconverted after RV1 had significantly lower pre-dose 1 IgG titers in sera than those whose infants did not seroconvert. High levels of preexisting serum IgG, including transplacentally acquired maternal IgG, appeared to have an inhibitory effect on the immunogenicity of RV1 among infants and may, in part, contribute to lower efficacy of RV vaccines in this and other low-income settings. Published by Oxford University Press for 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.

  1. Rotavirus Vaccine Cut Kids' Hospitalization, Medical Costs

    MedlinePlus

    ... fullstory_167720.html Rotavirus Vaccine Cut Kids' Hospitalization, Medical Costs Virus a common cause of diarrhea among ... a savings of more than $1 billion in medical costs, the researchers added. Rotavirus is a common ...

  2. Development of improved vaccine cell lines against rotavirus

    PubMed Central

    Wu, Weilin; Orr-Burks, Nichole; Karpilow, Jon; Tripp, Ralph A.

    2017-01-01

    Rotavirus is a major cause of severe gastroenteritis among very young children. In developing countries, rotavirus is the major cause of mortality in children under five years old, causing up to 20% of all childhood deaths in countries with high diarrheal disease burden, with more than 90% of these deaths occurring in Africa and Asia. Rotavirus vaccination mimics the first infection without causing illness, thus inducing strong and broad heterotypic immunity against prospective rotavirus infections. Two live vaccines are available, Rotarix and RotaTeq, but vaccination efforts are hampered by high production costs. Here, we present a dataset containing a genome-wide RNA interference (RNAi) screen that identified silencing events that enhanced rotavirus replication. Evaluated against several rotavirus vaccine strains, hits were validated in a Vero vaccine cell line as well as CRISPR/Cas9 generated cells permanently and stably lacking the genes that affect RV replication. Knockout cells were dramatically more permissive to RV replication and permitted an increase in rotavirus replication. These data show a means to improve manufacturing of rotavirus vaccine. PMID:28248921

  3. A reverse evidence of rotavirus vaccines impact.

    PubMed

    Martinón-Torres, Federico; Aramburo, Angela; Martinón-Torres, Nazareth; Cebey, Miriam; Seoane-Pillado, María Teresa; Redondo-Collazo, Lorenzo; Martinón-Sánchez, Jose Maria

    2013-06-01

    In 2010, and due to a quality problem identified in the vaccine manufacture, the rotavirus (RV) vaccination was withheld in Spain during 5 months. Our study aimed to evaluate the impact that this sudden cease had on rotavirus acute gastroenteritis (RAGE) hospitalizations. An increase in RAGE hospitalization was observed in parallel to the drop in vaccine coverage. Here, we report the first reverse evidence of rotavirus vaccine impact.

  4. A reverse evidence of rotavirus vaccines impact

    PubMed Central

    Martinón-Torres, Federico; Aramburo, Angela; Martinón-Torres, Nazareth; Cebey, Miriam; Seoane-Pillado, María Teresa; Redondo-Collazo, Lorenzo; Martinón-Sánchez, Jose Maria

    2013-01-01

    In 2010, and due to a quality problem identified in the vaccine manufacture, the rotavirus (RV) vaccination was withheld in Spain during 5 months. Our study aimed to evaluate the impact that this sudden cease had on rotavirus acute gastroenteritis (RAGE) hospitalizations. An increase in RAGE hospitalization was observed in parallel to the drop in vaccine coverage. Here, we report the first reverse evidence of rotavirus vaccine impact. PMID:23836258

  5. Rotavirus infections and vaccines: burden of illness and potential impact of vaccination.

    PubMed

    Grimwood, Keith; Lambert, Stephen B; Milne, Richard J

    2010-08-01

    Rotaviruses are the most common cause of severe gastroenteritis in children. By 5 years of age virtually every child worldwide will have experienced at least one rotavirus infection. This leads to an enormous disease burden, where every minute a child dies because of rotavirus infection and another four are hospitalized, at an annual societal cost in 2007 of $US2 billion. Most of the annual 527 000 deaths are in malnourished infants living in rural regions of low and middle income countries. In contrast, most measurable costs arise from medical expenses and lost parental wages in high income countries. Vaccines are the only public health prevention strategy likely to control rotavirus disease. They were developed to mimic the immunity following natural rotavirus infection that confers protection against severe gastroenteritis and consequently reduces the risk of primary healthcare utilization, hospitalization and death. The two currently licensed vaccines--one a single human strain rotavirus vaccine, the other a multiple strain human-bovine pentavalent reassortant rotavirus vaccine--are administered to infants in a two- or three-dose course, respectively, with the first dose given at 6-14 weeks of age. In various settings they are safe, immunogenic and efficacious against many different rotavirus genotypes. In high and middle income countries, rotavirus vaccines confer 85-100% protection against severe disease, while in low income regions of Africa and Asia, protection is less, at 46-77%. Despite this reduced efficacy in low income countries, the high burden of diarrheal disease in these regions means that proportionately more severe cases are prevented by vaccination than elsewhere. Post-licensure effectiveness studies show that rotavirus vaccines not only reduce rotavirus activity in infancy but they also decrease rates of rotavirus diarrhea in older and unimmunized children. A successful rotavirus vaccination program will rely upon sustained vaccine efficacy

  6. Potential safety issues and other factors that may affect the introduction and uptake of rotavirus vaccines.

    PubMed

    Aliabadi, N; Tate, J E; Parashar, U D

    2016-12-01

    Rotavirus vaccines have demonstrated significant impact in reducing the burden of morbidity and mortality from childhood diarrhoea in countries that have implemented routine vaccination to date. Despite this success, in many countries, rotavirus vaccine coverage remains lower than that of other routine childhood vaccines. Several issues may potentially affect vaccine uptake, namely safety concerns related to intussusception with consequent age restrictions on rotavirus vaccination, contamination with porcine circovirus, vaccine-derived reassortant strains and hospitalization in newborn nurseries at time of administration of live oral rotavirus vaccine. In addition to these safety concerns, other factors may also affect uptake, including lower vaccine efficacy in the developing world, potential emergence of strains escaping from vaccine protection resulting in lower overall impact of a vaccination programme and sustainable vaccine financing. Although further work is needed to address some of these concerns, global policy bodies have reaffirmed that the benefits of rotavirus vaccination outweigh the risks, and vaccine use is recommended globally.

  7. [Rotavirus vaccination in Europe in 2010].

    PubMed

    Grimprel, Emmanuel

    2010-11-01

    The important burden of rotavirus infections in infants largely justifies vaccine prevention. Two attenuated oral vaccines were licensed in Europe in 2006 and have proven effective against severe rotavirus gastroenteritis in infants, yet few countries have implemented vaccination. This hesitation may be related to a very low risk of intussusception in vaccinees, but is mainly due to national differences in cost-effectiveness.

  8. Public health impact and cost effectiveness of mass vaccination with live attenuated human rotavirus vaccine (RIX4414) in India: model based analysis

    PubMed Central

    Hawthorn, Rachael L; Watts, Brook; Singer, Mendel E

    2009-01-01

    Objectives To examine the public health impact of mass vaccination with live attenuated human rotavirus vaccine (RIX4414) in a birth cohort in India, and to estimate the cost effectiveness and affordability of such a programme. Design Decision analytical Markov model encompassing all direct medical costs. Infection risk and severity depended on age, number of previous infections, and vaccination history; probabilities of use of inpatient and outpatient health services depended on symptom severity. Data sources Published clinical, epidemiological, and economic data. When possible, parameter estimates were based on data specific for India. Population Simulated Indian birth cohort followed for five years. Main outcome measures Decrease in rotavirus gastroenteritis episodes (non-severe and severe), deaths, outpatient visits, and admission to hospital; incremental cost effectiveness ratio of vaccination expressed as net cost in 2007 rupees per life year saved. Results In the base case, vaccination prevented 28 943 (29.7%) symptomatic episodes, 6981 (38.2%) severe episodes, 164 deaths (41.0%), 7178 (33.3%) outpatient visits, and 812 (34.3%) admissions to hospital per 100 000 children. Vaccination cost 8023 rupees (about £100, €113, $165) per life year saved, less than India’s per capita gross domestic product, a common criterion for cost effectiveness. The net programme cost would be equivalent to 11.6% of the 2006-7 budget of the Indian Department of Health and Family Welfare. Model results were most sensitive to variations in access to outpatient care for those with severe symptoms. If this parameter was increased to its upper limit, the incremental cost effectiveness ratio for vaccination still fell between one and three times the per capita gross domestic product, meeting the World Health Organization’s criterion for “cost effective” interventions. Uncertainty analysis indicated a 94.7% probability that vaccination would be cost effective according to

  9. Effectiveness of a live oral human rotavirus vaccine after programmatic introduction in Bangladesh: A cluster-randomized trial

    PubMed Central

    Zaman, K.; Yunus, Mohammad; Hossain, Ilias; Azim, Tasnim; Rahman, Mustafizur; Lewis, Kristen D. C.; Feller, Andrea J.; Qadri, Firdausi; Halloran, M. Elizabeth; Cravioto, Alejandro

    2017-01-01

    Background Rotavirus vaccines are now globally recommended by the World Health Organization (WHO), but in early 2009 WHO’s Strategic Advisory Group of Experts on Immunization reviewed available data and concluded that there was no evidence for the efficacy or effectiveness of a two-dose schedule of the human rotavirus vaccine (HRV; Rotarix) given early at 6 and 10 wk of age. Additionally, the effectiveness of programmatic rotavirus vaccination, including possible indirect effects, has not been assessed in low-resource populations in Asia. Methods and findings In Bangladesh, we cluster-randomized (1:1) 142 villages of the Matlab Health and Demographic Surveillance System to include two doses of HRV with the standard infant vaccines at 6 and 10 wk of age or to provide standard infant vaccines without HRV. The study was initiated November 1, 2008, and surveillance was conducted concurrently at Matlab Diarrhoea Hospital and two community treatment centers to identify children less than 2 y of age presenting with acute rotavirus diarrhea (ARD) through March 31, 2011. Laboratory confirmation was made by enzyme immunoassay detection of rotavirus antigen in stool specimens. Overall effectiveness of the HRV vaccination program (primary objective) was measured by comparing the incidence rate of ARD among all children age-eligible for vaccination in villages where HRV was introduced to that among such children in villages where HRV was not introduced. Total effectiveness among vaccinees and indirect effectiveness were also evaluated. In all, 6,527 infants were age-eligible for vaccination in 71 HRV villages, and 5,791 in 71 non-HRV villages. In HRV villages, 4,808 (73.7%) infants received at least one dose of HRV. The incidence rate of ARD was 4.10 cases per 100 person-years in non-HRV villages compared to 2.8 per 100 person-years in HRV villages, indicating an overall effectiveness of 29.0% (95% CI, 11.3% to 43.1%). The total effectiveness of HRV against ARD among

  10. Economic Impact of a Rotavirus Vaccine in Brazil

    PubMed Central

    Constenla, Dagna O.; Linhares, Alexandre C.; Rheingans, Richard D.; Antil, Lynn R.; Waldman, Eliseu A.; da Silva, Luiz J.

    2008-01-01

    The study was done to evaluate the cost-effectiveness of a national rotavirus vaccination programme in Brazilian children from the healthcare system perspective. A hypothetical annual birth-cohort was followed for a five-year period. Published and national administrative data were incorporated into a model to quantify the consequences of vaccination versus no vaccination. Main outcome measures included the reduction in disease burden, lives saved, and disability-adjusted life-years (DALYs) averted. A rotavirus vaccination programme in Brazil would prevent an estimated 1,804 deaths associated with gastroenteritis due to rotavirus, 91,127 hospitalizations, and 550,198 outpatient visits. Vaccination is likely to reduce 76% of the overall healthcare burden of rotavirus-associated gastroenteritis in Brazil. At a vaccine price of US$ 7-8 per dose, the cost-effectiveness ratio would be US$ 643 per DALY averted. Rotavirus vaccination can reduce the burden of gastroenteritis due to rotavirus at a reasonable cost-effectiveness ratio. PMID:19069617

  11. Safety, immunogenicity, and protective efficacy of two doses of RIX4414 live attenuated human rotavirus vaccine in healthy infants.

    PubMed

    Araujo, Eliete C; Clemens, Sue Ann C; Oliveira, Consuelo S; Justino, Maria Cleonice A; Rubio, Pilar; Gabbay, Yvone B; da Silva, Veronilce B; Mascarenhas, Joana D P; Noronha, Vânia L; Clemens, Ralf; Gusmão, Rosa Helena P; Sanchez, Nervo; Monteiro, Talita Antônia F; Linhares, Alexandre C

    2007-01-01

    To determine the safety, immunogenicity and efficacy of two doses of rotavirus vaccine in healthy Brazilian infants. A randomized, multicenter, double-blind, placebo-controlled trial was conducted in Brazil, Mexico and Venezuela. Infants received two oral doses of vaccine or placebo at 2 and 4 months of age, concurrently with routine immunizations, except for oral poliomyelitis vaccine (OPV). This paper reports results from Belém, Brazil, where the number of subjects per group and the viral vaccine titers were: 194 (10(4.7) focus forming units - FFU), 196 (10(5.2) FFU), 194 (10(5.8) FFU) and 194 (placebo). Anti-rotavirus (anti-RV) antibody response was assessed in 307 subjects. Clinical severity of gastroenteritis episodes was measured using a 20-point scoring system with a score of >or= 11 defined as severe GE. The rates of solicited general symptoms were similar in vaccine and placebo recipients. At 2 months after the second dose, a serum IgA response to RV occurred in 54.7 to 74.4% of vaccinees. No interference was seen in the immunogenicity of routine vaccines. Vaccine efficacy against any rotavirus gastroenteritis (RVGE) was 63.5% (95%CI 20.8-84.4) for the highest concentration (10(5.8) FFU). Efficacy was 81.5% (95%CI 44.5-95.4) against severe RVGE. At its highest concentration (10(5.8) FFU), RIX4414 provided 79.8% (95%CI 26.4-96.3) protection against severe RVGE by G9 strain. RIX4414 was highly immunogenic with a low reactogenicity profile and did not interfere with seroresponse to diphtheria, tetanus, pertussis, hepatitis B and Hib antigens. Two doses of RIX4414 provided significant protection against severe GE caused by RV.

  12. Rotavirus: disease and vaccine update, 2007.

    PubMed

    Stebbins, Samuel

    2007-02-01

    Rotavirus infection is a ubiquitous illness, infecting the vast majority of children worldwide in the first 5 years of life. Rotavirus is one of the major causes of severe diarrhea in infants and young children throughout the developing and developed world. An estimated 500,000 deaths per year occur, with the burden of morbidity and mortality highest in the poorest nations. Two new oral, live, attenuated vaccines have recently shown efficacy and safety in clinical trials, and one of these, RotaTeq, was approved by the US Food and Drug Administration on February 3, 2006. RotaTeq is recommended for general use by the Centers for Disease Control and Prevention, American Academy of Family Practice, and American Academy of Pediatrics.

  13. Impact of rotavirus vaccination on hospitalizations for rotavirus diarrhea: the IVANHOE study.

    PubMed

    Gagneur, Arnaud; Nowak, Emmanuel; Lemaitre, Thomas; Segura, Jean-Francois; Delaperrière, Nadège; Abalea, Lydie; Poulhazan, Elise; Jossens, Anne; Auzanneau, Lucie; Tran, Adissa; Payan, Christopher; Jay, Nadine; de Parscau, Loic; Oger, Emmanuel

    2011-05-12

    The aim of the IVANHOE study was to determine the real-world impact of the rotavirus vaccine, controlling for epidemic-to-epidemic variation in disease burden. A population-based prospective cohort study was conducted in Brest City and 7 suburban districts (CUB area), North-western Brittany, France (210,000 inhabitants; 5500 births per year). The vaccination program started in May 2007 for a 2-year period for all infants born in the Brest birth zone through pediatricians, public outpatient clinics and general practitioners. To determine vaccine impact we monitored trends in hospitalizations for rotavirus-specific diarrhea using an active hospital-based surveillance system initiated 5 years before vaccine introduction. The number of hospitalizations for rotavirus-specific diarrhea during the 2008/2009 epidemic in infants less than 2 years of age whose parents lived within the CUB area was modelled as a function of (1) the number of hospitalizations in infants 2-5 years of age to control for epidemic-to-epidemic variation and (2) vaccine introduction. A total of 4684 infants received at least one dose. Of these, 2635 lived within the CUB area. Vaccine coverage for a complete schedule in the CUB area was 47.1%. Poisson modelling revealed a reduction by a factor of 2.04 (1.56-2.66) in the number of hospitalizations during the last epidemic season (2008/2009), the number of observed cases being equal to 30, against an expected number of 61. Relative risk reduction for hospitalizations for rotavirus diarrhea was 98% (95% CI: 83-100%). We observed a noticeable impact of vaccination on rotavirus diarrhea hospitalizations within 2 years of vaccine introduction integrating for the first time rotavirus epidemics variation. The trial is registered with ClinicalTrials.gov, number, NCT00740935. Copyright © 2011. Published by Elsevier Ltd.

  14. 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.

  15. Impact of Rotavirus Vaccine on Premature Infants

    PubMed Central

    Nowak, Emmanuel; Le Gal, Grégoire; Lemaitre, Thomas; Oger, Emmanuel; Poulhazan, Elise; Giroux, Jean-Dominique; Garenne, Armelle; Gagneur, Arnaud

    2014-01-01

    Infants born preterm are at a higher risk of complications and hospitalization in cases of rotavirus diarrhea than children born at term. We evaluated the impact of a rotavirus vaccination campaign (May 2007 to May 2010) on hospitalizations for rotavirus gastroenteritis in a population of children under 3 years old born prematurely (before 37 weeks of gestation) in the Brest University Hospital birth zone. Active surveillance from 2002 to 2006 and a prospective collection of hospitalizations for rotavirus diarrhea were initiated in the pediatric units of Brest University Hospital until May 2010. Numbers of hospitalizations for rotavirus diarrhea among the population of children born prematurely, before and after the start of the vaccination program, were compared using a Poisson regression model controlling for epidemic-to-epidemic variation. A total of 217 premature infants were vaccinated from 2007 to 2010. Vaccine coverage for a complete course of three doses was 41.9%. The vaccine safety in premature infants was similar to that in term infants. The vaccination program led to a division by a factor of 2.6 (95% confidence interval [CI], 1.3 to 5.2) in the number of hospitalizations for rotavirus diarrhea during the first two epidemic seasons following vaccine introduction and by a factor of 11 (95% CI, 3.5 to 34.8) during the third season. We observed significant effectiveness of the pentavalent rotavirus vaccine on the number of hospitalizations in a population of prematurely born infants younger than 3 years of age. A multicenter national study would provide better assessment of this impact. (This study [Impact of Systematic Infants Vaccination Against Rotavirus on Gastroenteritis Hospitalization: a Prospective Study in Brest District, France (IVANHOE)] has been registered at ClinicalTrials.gov under registration no. NCT00740935.) PMID:25080553

  16. Impact of rotavirus vaccine on premature infants.

    PubMed

    Roué, Jean-Michel; Nowak, Emmanuel; Le Gal, Grégoire; Lemaitre, Thomas; Oger, Emmanuel; Poulhazan, Elise; Giroux, Jean-Dominique; Garenne, Armelle; Gagneur, Arnaud

    2014-10-01

    Infants born preterm are at a higher risk of complications and hospitalization in cases of rotavirus diarrhea than children born at term. We evaluated the impact of a rotavirus vaccination campaign (May 2007 to May 2010) on hospitalizations for rotavirus gastroenteritis in a population of children under 3 years old born prematurely (before 37 weeks of gestation) in the Brest University Hospital birth zone. Active surveillance from 2002 to 2006 and a prospective collection of hospitalizations for rotavirus diarrhea were initiated in the pediatric units of Brest University Hospital until May 2010. Numbers of hospitalizations for rotavirus diarrhea among the population of children born prematurely, before and after the start of the vaccination program, were compared using a Poisson regression model controlling for epidemic-to-epidemic variation. A total of 217 premature infants were vaccinated from 2007 to 2010. Vaccine coverage for a complete course of three doses was 41.9%. The vaccine safety in premature infants was similar to that in term infants. The vaccination program led to a division by a factor of 2.6 (95% confidence interval [CI], 1.3 to 5.2) in the number of hospitalizations for rotavirus diarrhea during the first two epidemic seasons following vaccine introduction and by a factor of 11 (95% CI, 3.5 to 34.8) during the third season. We observed significant effectiveness of the pentavalent rotavirus vaccine on the number of hospitalizations in a population of prematurely born infants younger than 3 years of age. A multicenter national study would provide better assessment of this impact. (This study [Impact of Systematic Infants Vaccination Against Rotavirus on Gastroenteritis Hospitalization: a Prospective Study in Brest District, France (IVANHOE)] has been registered at ClinicalTrials.gov under registration no. NCT00740935.).

  17. Patterns of rotavirus vaccine uptake and use in privately-insured US infants, 2006-2010.

    PubMed

    Panozzo, Catherine A; Becker-Dreps, Sylvia; Pate, Virginia; Jonsson Funk, Michele; Stürmer, Til; Weber, David J; Brookhart, M Alan

    2013-01-01

    Rotavirus vaccines are highly effective at preventing gastroenteritis in young children and are now universally recommended for infants in the US. We studied patterns of use of rotavirus vaccines among US infants with commercial insurance. We identified a large cohort of infants in the MarketScan Research Databases, 2006-2010. The analysis was restricted to infants residing in states without state-funded rotavirus vaccination programs. We computed summary statistics and used multivariable regression to assess the association between patient-, provider-, and ecologic-level variables of rotavirus vaccine receipt and series completion. Approximately 69% of 594,117 eligible infants received at least one dose of rotavirus vaccine from 2006-2010. Most infants received the rotavirus vaccines at the recommended ages, but more infants completed the series for monovalent rotavirus vaccine than pentavalent rotavirus vaccine or a mix of the vaccines (87% versus 79% versus 73%, P<0.001). In multivariable analyses, the strongest predictors of rotavirus vaccine series initiation and completion were receipt of the diphtheria, tetanus and acellular pertussis vaccine (Initiation: RR = 7.91, 95% CI = 7.69-8.13; Completion: RR = 1.26, 95% CI = 1.23-1.29), visiting a pediatrician versus family physician (Initiation: RR = 1.51, 95% CI = 1.49-1.52; Completion: RR = 1.13, 95% CI = 1.11-1.14), and living in a large metropolitan versus smaller metropolitan, urban, or rural area. We observed rapid diffusion of the rotavirus vaccine in routine practice; however, approximately one-fifth of infants did not receive at least one dose of vaccine as recently as 2010. Interventions to increase rotavirus vaccine coverage should consider targeting family physicians and encouraging completion of the vaccine series.

  18. Effectiveness of Monovalent and Pentavalent Rotavirus Vaccine

    PubMed Central

    Immergluck, Lilly Cheng; Held, Melissa; Jain, Shabnam; Chan, Trisha; Grizas, Alexandra P.; Khizer, Saadia; Barrett, Carol; Quaye, Osbourne; Mijatovic-Rustempasic, Slavica; Gautam, Rashi; Bowen, Michael D.; Moore, Jessica; Tate, Jacqueline E.; Parashar, Umesh D.; Vázquez, Marietta

    2013-01-01

    OBJECTIVE: Previous US evaluations have not assessed monovalent rotavirus vaccine (RV1, a G1P[8] human rotavirus strain) effectiveness, because of its later introduction (2008). Using case-control methodology, we measured the vaccine effectiveness (VE) of the 2-dose RV1 and 3-dose pentavalent vaccine (RV5) series against rotavirus disease resulting in hospital emergency department or inpatient care. METHODS: Children were eligible for enrollment if they presented to 1 of 5 hospitals (3 in Georgia, 2 in Connecticut) with diarrhea of ≤10 days’ duration during January through June 2010 or 2011, and were born after RV1 introduction. Stools were collected; immunization records were obtained from providers and state electronic immunization information system (IIS). Case-subjects (children testing rotavirus antigen-positive) were compared with 2 control groups: children testing rotavirus negative and children selected from IIS. RESULTS: Overall, 165 rotavirus-case subjects and 428 rotavirus-negative controls were enrolled. Using the rotavirus-negative controls, RV1 VE was 91% (95% confidence interval [CI] 80 to 95) and RV5 VE was 92% (CI 75 to 97) among children aged ≥8 months. The RV1 VE against G2P[4] disease was high (94%, CI 78 to 98), as was that against G1P[8] disease (89%, CI 70 to 96). RV1 effectiveness was sustained among children aged 12 through 23 months (VE 91%; CI 75 to 96). VE point estimates using IIS controls were similar to those using rotavirus-negative controls. CONCLUSIONS: RV1 and RV5 were both highly effective against severe rotavirus disease. RV1 conferred sustained protection during the first 2 years of life and demonstrated high effectiveness against G2P[4] (heterotypic) disease. PMID:23776114

  19. Effect of breastfeeding on immunogenicity of oral live-attenuated human rotavirus vaccine: a randomized trial in HIV-uninfected infants in Soweto, South Africa.

    PubMed

    Groome, Michelle J; Moon, Sung-Sil; Velasquez, Daniel; Jones, Stephanie; Koen, Anthonet; van Niekerk, Nadia; Jiang, Baoming; Parashar, Umesh D; Madhi, Shabir A

    2014-04-01

    To investigate the effect of abstention from breastfeeding, for an hour before and after each vaccination, on the immune responses of infants to two doses of rotavirus vaccine. In Soweto, South Africa, mother-infant pairs who were uninfected with human immunodeficiency virus (HIV) were enrolled as they presented for the "6-week" immunizations of the infants. Each infant was randomly assigned to Group 1 - in which breastfeeding was deferred for at least 1 h before and after each dose of rotavirus vaccine - or Group 2 - in which unrestricted breastfeeding was encouraged. Enzyme-linked immunosorbent assays were used to evaluate the titres of rotavirus-specific IgA in samples of serum collected from each infant immediately before each vaccine dose and 1 month after the second dose. Among the infants, a fourfold or greater increase in titres of rotavirus-specific IgA following vaccination was considered indicative of seroconversion. The evaluable infants in Group 1 (n=98) were similar to those in Group 2 (n=106) in their baseline demographic characteristics and their pre-vaccination titres of anti-rotavirus IgA. After the second vaccine doses, geometric mean titres of anti-rotavirus IgA in the sera of Group-1 infants were similar to those in the sera of Group-2 infants (P=0.685) and the frequency of seroconversion in the Group-1 infants was similar to that in the Group-2 infants (P=0.485). Among HIV-uninfected South African infants, abstention from breastfeeding for at least 1 h before and after each vaccination dose had no significant effect on the infants' immune response to a rotavirus vaccine.

  20. 75 FR 48706 - Proposed Vaccine Information Materials for Rotavirus Vaccine

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-08-11

    ... HUMAN SERVICES Centers for Disease Control and Prevention Proposed Vaccine Information Materials for... Act (NCVIA) (42 U.S.C. 300aa-26), the CDC must develop vaccine information materials that all health.... CDC seeks written comment on proposed new vaccine information materials for rotavirus vaccine. DATES...

  1. 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

  2. Rotavirus and the Vaccine (Drops) to Prevent It

    MedlinePlus

    ... 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 vomiting. It affects mostly babies ...

  3. Rotavirus and the Vaccine (Drops) to Prevent It

    MedlinePlus

    ... Immunizations Rotavirus and the Vaccine (Drops) to Prevent It Language: English (US) Español (Spanish) Format: Select ... eating and drinking while they are sick. Is it serious? Rotavirus can be very harmful. Diarrhea, vomiting, ...

  4. 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.

  5. Vaccines: the pentavalent rotavirus vaccine: discovery to licensure and beyond.

    PubMed

    Heaton, Penny M; Ciarlet, Max

    2007-12-15

    Twenty-five years passed between the discovery of the parent strain (WC3) of the pentavalent human-bovine reassortant rotavirus vaccine (PRV) in 1981 and the licensure of PRV in 2006. This orally administered liquid vaccine, which is given as a 3-dose series, is indicated for the prevention of rotavirus gastroenteritis, caused by the G serotypes contained in the vaccine, in infants and children. PRV is recommended by the Advisory Committee on Immunization Practices and the American Academy of Pediatrics for administration to all infants in the United States. These recommendations are supported by the results of the phase III studies, which demonstrated that PRV is well tolerated and efficacious. PRV reduced rotavirus-related hospitalizations by 96% and was not associated with an increased incidence of serious adverse events, including intussusception. This report focuses on the safety and efficacy data from the late-phase studies of PRV and discusses plans for providing this vaccine to the developing world.

  6. Projected health benefits and costs of pneumococcal and rotavirus vaccination in Uganda.

    PubMed

    Tate, Jacqueline E; Kisakye, Annet; Mugyenyi, Prosper; Kizza, Diana; Odiit, Amos; Braka, Fiona

    2011-04-12

    We determined impact and cost-effectiveness of pneumococcal and rotavirus vaccination programs among children<5 years of age in Uganda from the public health system perspective. Disease-specific models compared the disease burden and cost with and without a vaccination program. If introduced, pneumococcal and rotavirus vaccine programs will save 10,796 and 5265 lives, respectively, prevent 94,071 Streptococcus pneumoniae and 94,729 rotavirus cases in children<5 years, and save 3886 and 996 million Ugandan shillings ($2.3 and $0.6 million US dollars), respectively, in direct medical costs annually. At the GAVI price ($0.15/dose), pneumococcal vaccine will be cost-saving and rotavirus vaccine highly cost-effective. Published by Elsevier Ltd.

  7. Gut microbiota in children vaccinated with rotavirus vaccine.

    PubMed

    García-López, Rodrigo; Pérez-Brocal, Vicente; Diez-Domingo, Javier; Moya, Andrés

    2012-12-01

    To assess the effect that the rotavirus vaccine RotaTeq may have on the gut microbiota, this study searched for differences in intestinal bacterial composition between vaccinated and unvaccinated children. Bacterial diversity in fecal samples was evaluated by pyrosequencing of the 16S rRNA gene and taxonomic analyses using bioinformatics tools. No evidence of such differences was observed.

  8. A dose-escalation safety and immunogenicity study of a new live attenuated human rotavirus vaccine (Rotavin-M1) in Vietnamese children.

    PubMed

    Dang, Duc Anh; Nguyen, Van Trang; Vu, Dinh Thiem; Nguyen, Thi Hien Anh; Nguyen, Duc Mao; Yuhuan, Wang; Baoming, Jiang; Nguyen, Dang Hien; Le, Thi Luan

    2012-04-27

    We tested a candidate live, oral, rotavirus vaccine (Rotavin-M1™) derived from an attenuated G1P [8] strain (KH0118-2003) isolated from a child in Vietnam. The vaccine was tested first for safety in 29 healthy adults. When deemed safe, it was further tested for safety and immunogenicity in 160 infants (4 groups) aged 6-12 weeks in a dose and schedule ranging study. The vaccine was administered in low titer (10(6.0)FFU/dose) on a 2-dose schedule given 2 months apart (Group 2L) and on a 3-dose schedule given 1 month apart (Group 3L) and in high titer (10(6.3)FFU/dose) in 2 doses 2 months apart (Group 2H) and in 3 doses 1 month apart (Group 3H). For comparison, 40 children (group Rotarix™) were given 2 doses of the lyophilized Rotarix™ vaccine (10(6.5)CCID(50)/dose) 1 month apart. All infants were followed for 30 days after each dose for clinical adverse events including diarrhea, vomiting, fever, abdominal pain, irritability and intussusception. Immunogenicity was assessed by IgA seroconversion and viral shedding was monitored for 7 days after administration of each dose. Two doses of Rotavin-M1 (10(6.3)FFU/dose) were well tolerated in adults. Among infants (average 8 weeks of age at enrollment), administration of Rotavin-M1 was safe and did not lead to an increased rate of fever, diarrhea, vomiting or irritability compared to Rotarix™, indicating that the candidate vaccine virus had been fully attenuated by serial passages. No elevation of levels of serum transaminase, blood urea, or blood cell counts were observed. The highest rotavirus IgA seroconversion rate (73%, 95%CI (58-88%)) was achieved in group 2H (2 doses--10(6.3)FFU/dose, 2 months apart). The 2 dose schedules performed slightly better than the 3 dose schedules and the higher titer doses performed slightly better than the lower titer doses. These rates of seroconversion were similar to that of the Rotarix™ group (58%, 95%CI (42-73%)). However more infants who received Rotarix™ (65%) shed virus

  9. Safety and Immunogenicity of Sequential Rotavirus Vaccine Schedules

    PubMed Central

    Libster, Romina; McNeal, Monica; Walter, Emmanuel B.; Shane, Andi L.; Winokur, Patricia; Cress, Gretchen; Berry, Andrea A.; Kotloff, Karen L.; Sarpong, Kwabena; Turley, Christine B.; Harrison, Christopher J.; Pahud, Barbara A.; Marbin, Jyothi; Dunn, John; El-Khorazaty, Jill; Barrett, Jill

    2016-01-01

    BACKGROUND AND OBJECTIVES: Although both licensed rotavirus vaccines are safe and effective, it is often not possible to complete the schedule by using the same vaccine formulation. The goal of this study was to investigate the noninferiority of the immune responses to the 2 licensed rotavirus vaccines when administered as a mixed schedule compared with administering a single vaccine formulation alone. METHODS: Randomized, multicenter, open-label study. Healthy infants (6–14 weeks of age) were randomized to receive rotavirus vaccines in 1 of 5 different schedules (2 using a single vaccine for all doses, and 3 using mixed schedules). The group receiving only the monovalent rotavirus vaccine received 2 doses of vaccine and the other 4 groups received 3 doses of vaccine. Serum for immunogenicity testing was obtained 1 month after the last vaccine dose and the proportion of seropositive children (rotavirus immunoglobulin A ≥20 U/mL) were compared in all the vaccine groups. RESULTS: Between March 2011 and September 2013, 1393 children were enrolled and randomized. Immune responses to all the sequential mixed vaccine schedules were shown to be noninferior when compared with the 2 single vaccine reference groups. The proportion of children seropositive to at least 1 vaccine antigen at 1 month after vaccination ranged from 77% to 96%, and was not significantly different among all the study groups. All schedules were well tolerated. CONCLUSIONS: Mixed schedules are safe and induced comparable immune responses when compared with the licensed rotavirus vaccines given alone. PMID:26823540

  10. Live attenuated tetravalent (G1-G4) bovine-human reassortant rotavirus vaccine (BRV-TV): Randomized, controlled phase III study in Indian infants.

    PubMed

    Saluja, Tarun; Palkar, Sonali; Misra, Puneet; Gupta, Madhu; Venugopal, Potula; Sood, Ashwani Kumar; Dhati, Ravi Mandyam; Shetty, Avinash; Dhaded, Sangappa Malappa; Agarkhedkar, Sharad; Choudhury, Amlan; Kumar, Ramesh; Balasubramanian, Sundaram; Babji, Sudhir; Adhikary, Lopa; Dupuy, Martin; Chadha, Sangeet Mohan; Desai, Forum; Kukian, Darshna; Patnaik, Badri Narayan; Dhingra, Mandeep Singh

    2017-06-16

    Rotavirus remains the leading cause of diarrhoea among children <5years. We assessed immunogenic non-inferiority of a tetravalent bovine-human reassortant rotavirus vaccine (BRV-TV) over the licensed human-bovine pentavalent rotavirus vaccine RV5. Phase III single-blind study (parents blinded) in healthy infants randomized (1:1) to receive three doses of BRV-TV or RV5 at 6-8, 10-12, and 14-16weeks of age. All concomitantly received a licensed diphtheria, tetanus, pertussis, hepatitis B, Haemophilus influenzae type b conjugate vaccine (DTwP-HepB-Hib) and oral polio vaccine (OPV). Immunogenic non-inferiority was evaluated in terms of the inter-group difference in anti-rotavirus serum IgA seroresponse (primary endpoint), and seroprotection/seroresponse rates to DTwP-HepB-Hib and OPV vaccines. Seroresponse was defined as a ≥4-fold increase in titers from baseline to D28 post-dose 3. Non-inferiority was declared if the difference between groups (based on the lower limit of the 95% confidence interval [CI]) was above -10%. Each subject was evaluated for solicited adverse events 7days and unsolicited & serious adverse events 28days following each dose of vaccination. Of 1195 infants screened, 1182 were randomized (590 to BRV-TV; 592 to RV5). Non-inferiority for rotavirus serum IgA seroresponse was not established: BRV-TV, 47.1% (95%CI: 42.8; 51.5) versus RV5, 61.2% (95%CI: 56.8; 65.5); difference between groups, -14.08% (95%CI: -20.4; -7.98). Serum IgA geometric mean concentrations at D28 post-dose 3 were 28.4 and 50.1U/ml in BRV-TV and RV5 groups, respectively. For all DTwP-HepB-Hib and OPV antigens, seroprotection/seroresponse was elicited in both groups and the -10% non-inferiority criterion between groups was met. There were 16 serious adverse events, 10 in BRV-TV group and 6 in RV5 group; none were classified as vaccine related. Both groups had similar vaccine safety profiles. BRV-TV was immunogenic but did not meet immunogenic non-inferiority criteria to RV5 when

  11. 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

  12. 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.

  13. 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

  14. 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.

  15. Rotavirus.

    PubMed Central

    Parashar, U. D.; Bresee, J. S.; Gentsch, J. R.; Glass, R. I.

    1998-01-01

    Rotavirus, the most common diarrheal pathogen in children worldwide, causes approximately one third of diarrhea-associated hospitalizations and 800,000 deaths per year. Because natural infection reduces the incidence and severity of subsequent episodes, rotavirus diarrhea might be controlled through vaccination. Serotypespecific immunity may play a role in protection from disease. Tetravalent rhesus-human reassortant rotavirus vaccine (RRV-TV) (which contains a rhesus rotavirus with serotype G3 specificity and reassortant rhesus-human rotaviruses with G1, G2, and G4 specificity) provides coverage against the four common serotypes of human rotavirus. In clinical trials in industrialized countries, RRV-TV conferred 49% to 68% protection against any rotavirus diarrhea and 61% to 100% protection against severe disease. This vaccine was licensed by the U.S. Food and Drug Administration on August 31, 1998, and should be cost-effective in reducing diarrheal diseases in industrialized countries. The vaccine's efficacy and cost-effectiveness in developing countries should be evaluated. PMID:9866732

  16. Oral Rotavirus Vaccines: How Well Will They Work Where They Are Needed Most?

    PubMed Central

    Patel, Manish; Shane, Andi L.; Parashar, Umesh D.; Jiang, Baoming; Gentsch, Jon R.; Glass, Roger I.

    2013-01-01

    Rotavirus vaccines hold promise to decrease the burden of severe diarrhea in the poorest countries, where 85% of deaths due to rotavirus occur. However, the potency of live oral vaccines is lower in these challenging settings than in middle- and upper-income countries. Many hypotheses have been suggested to explain these differences that could provide clues to improve the ultimate success of these novel vaccines. Although introduction today of even moderately effective vaccines will decrease the morbidity and mortality associated with rotavirus in low-income settings, research is urgently needed to understand why these differences in efficacy occur and what could be done to improve vaccine performance to maximize the life-saving benefits of vaccination. PMID:19817613

  17. Characterization of rotavirus genotypes before and after the introduction of a monovalent rotavirus vaccine in Colombia.

    PubMed

    Peláez-Carvajal, Dioselina; Cotes-Cantillo, Karol; Paternina-Caicedo, Angel; Gentsch, Jon; de la Hoz-Restrepo, Fernando; Patel, Manish

    2014-06-01

    Strain monitoring for emergence of novel strains after the introduction of rotavirus vaccine is an integral component of routine rotavirus immunization programs. Using a laboratory based strain surveillance system between 2008 and 2012, a wide variation in strain pattern in Colombia was founded both before and after the introduction of a monovalent rotavirus vaccine in 2009. G2P[4], a strain fully heterotypic to the vaccine was predominant before vaccine introduction in 2008 (47%) and after vaccine introduction in 2010 (54%), 2011 (86%), and 2012 (32%). The presence of this strain before the introduction of vaccine and decreasing prevalence during the most recent surveillance year suggests secular variation rather than vaccine pressure as a cause for this fluctuation. While strain monitoring can be valuable after vaccine introduction, these surveillance data alone without information on disease incidence or strain specific vaccine effectiveness can be prone to misinterpretation with regard to the role of vaccine pressure on emergence of new or persistent strains.

  18. Diarrheal Diseases Hospitalization in Yemen before and after Rotavirus Vaccination

    PubMed Central

    Al-Areqi, Lina; Mujally, Abulatif; Alkarshy, Fawzya; Nasser, Arwa; Jumaan, Aisha O.

    2016-01-01

    The study aims to assess the impact of rotavirus vaccine introduction on diarrheal diseases hospitalization and to identify the rotavirus genotypes most prevalent before and after vaccine introduction among children ≤ 5 years of age. Rotarix™ ® rotavirus vaccine is currently licensed for infants in Yemen and was introduced in 2012. The vaccination course consists of two doses. The first dose is administrated at 6 weeks of age and the second dose is completed by 10 weeks. Based on a longitudinal observational study, we assessed the impact of vaccination on rotavirus hospitalization before and after vaccination among children ≤ 5 years of age at the Yemeni-Swedish Hospital (YSH) in Taiz, Yemen. Prevaccination covered January 2009–July 2012 during which 2335 fecal samples were collected from children ≤ 5 years old. Postvaccination covered January 2013–December 2014 during which 1114 fecal samples were collected. Rotavirus was detected by Enzyme Linkage Immunosorbent Assay (ELISA). The incidence of rotavirus hospitalization decreased from 43.79% in 2009 to 10.54% in 2014. Hospitalization due to rotavirus diarrhea was reduced by 75.93%. Vaccine coverage increased from 23% in 2012 to 72% in 2014. Also, the results showed that the most predominant genotypes in prevaccination period were G2P[4] (55.0%), followed by G1P[8] (15.0%), while in postvaccination period G1P[8] (31%) was the predominant genotype, followed by G9P[8] (27.5%). In conclusion, rotavirus vaccination in Yemen resulted in sharp reduction in diarrheal hospitalization. A successful rotavirus vaccination program in Yemen will rely upon efficient vaccine delivery systems and sustained vaccine efficacy against diverse and evolving rotavirus strains. PMID:27437161

  19. Histo-blood group antigens as receptors for rotavirus, new understanding on rotavirus epidemiology and vaccine strategy

    PubMed Central

    Jiang, Xi; Liu, Yang; Tan, Ming

    2017-01-01

    The success of the two rotavirus (RV) vaccines (Rotarix and RotaTeq) in many countries endorses a live attenuated vaccine approach against RVs. However, the lower efficacies of both vaccines in many low- and middle-income countries indicate a need to improve the current RV vaccines. The recent discovery that RVs recognize histo-blood group antigens (HBGAs) as potential receptors has significantly advanced our understanding of RV diversity, evolution and epidemiology, providing important new insights into the performances of current RV vaccines in different populations and emphasizing a P-type-based vaccine approach. New understanding of RV diversity and evolution also raises a fundamental question about the ‘Jennerian' approach, which needs to be addressed for future development of live attenuated RV vaccines. Alternative approaches to develop safer and more cost-effective subunit vaccines against RVs are also discussed. PMID:28400594

  20. Production of two vaccinating recombinant rotavirus proteins in the milk of transgenic rabbits.

    PubMed

    Soler, Eric; Le Saux, Agnès; Guinut, Frédéric; Passet, Bruno; Cohen, Ruxandra; Merle, Christine; Charpilienne, Annie; Fourgeux, Cynthia; Sorel, Véronique; Piriou, Antoine; Schwartz-Cornil, Isabelle; Cohen, Jean; Houdebine, Louis-Marie

    2005-12-01

    Rotaviruses are the main cause of infantile viral gastroenteritis worldwide leading to approximately 500,000 deaths each year mostly in the developing world. For unknown reasons, live attenuated viruses used in classical vaccine strategies were shown to be responsible for intussusception (a bowel obstruction). New strategies allowing production of safe recombinant non-replicating rotavirus candidate vaccine are thus clearly needed. In this study we utilized transgenic rabbit milk as a source of rotavirus antigens. Individual transgenic rabbit lines were able to produce several hundreds of micrograms per ml of secreted recombinant VP2 and VP6 proteins in their milk. Viral proteins expressed in our model were immunogenic and were shown to induce a significant reduction in viral antigen shedding after challenge with virulent rotavirus in the adult mouse model. To our knowledge, this is the first report of transgenic mammal bioreactors allowing the rapid co-production of two recombinant viral proteins in milk to be used as a vaccine.

  1. Efficacy and safety of pentavalent rotavirus vaccine in Japan

    PubMed Central

    Iwata, Satoshi; Nakata, Shuji; Ukae, Susumu; Koizumi, Yoshitugu; Morita, Yasuyuki; Kuroki, Haruo; Tanaka, Yoshiyuki; Shizuya, Toshiyuki; Schödel, Florian; Brown, Michelle L; Lawrence, Jody

    2013-01-01

    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. PMID:23732903

  2. Relationship between Pentavalent Rotavirus Vaccine and Intussusception: A Retrospective Study at a Single Center in Korea.

    PubMed

    Kim, Kyu Yeun; Kim, Dong Soo

    2017-05-01

    Despite withdrawal of RotaShield® and the development of second generation live attenuated rotavirus vaccines, concerns remain regarding the relationship between rotavirus vaccine and intussusception. Nevertheless, since there is no study in Korea, we reviewed data from cases at Severance Children's Hospital to determine the association between rotavirus vaccine and intussusception. Patients coded as intussusception and following a prescription of RotaTeq® from 2007 to 2013 were reviewed. We calculated comparative incidence figures (CIFs) and 95% confidence intervals (CIs) to compare the risk of intussusception in Korea with the risk in the United States. Expected cases within the four-week post-vaccination window were calculated by applying rates of intussusception from data compiled by the Health Insurance Review and Assessment Service (for a five-year period) to numbers of vaccinations. In total, 10530 doses of pentavalent rotavirus vaccine were administered. A total of 65 intussusception cases were diagnosed, although only two cases occurred within four weeks after vaccination. This was compared to six cases within 999123 doses in United States from April 2008 to March 2013 (CIF, 31.63; CI, 31.33-31.93). When we adjusted incidence rate differences for both countries, the CIF decreased to 7.05 (CI, 6.72-7.40). When we compared our identified cases with the expected cases from our hospital, there was no increased intussusception occurring within four weeks of vaccination. We found no association between pentavalent rotavirus vaccine and intussusception. Therefore, rotavirus vaccination should be considered due to its benefits of preventing rotavirus-associated diseases.

  3. 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.

  4. Intussusception following rotavirus vaccination: an updated review of the available evidence.

    PubMed

    Rha, Brian; Tate, Jacqueline E; Weintraub, Eric; Haber, Penina; Yen, Catherine; Patel, Manish; Cortese, Margaret M; DeStefano, Frank; Parashar, Umesh D

    2014-11-01

    In 1999, the first rotavirus vaccine licensed in the USA was withdrawn 9 months after introduction due to an association with intussusception that was detected in post-licensure surveillance. This association prompted large clinical trials designed to ensure the safety of two current live oral rotavirus vaccines, RotaTeq and Rotarix, which have since been recommended for use worldwide. Following their introduction, post-licensure studies have focused not only on the effectiveness and impact of these vaccines, but also on continued surveillance for intussusception. Most recent evidence from several countries shows a small increased risk of intussusception following vaccination with Rotarix and RotaTeq within the context of their demonstrated benefits. This review summarizes the available data on the safety of rotavirus vaccines with regards to intussusception.

  5. Cost-effectiveness of rotavirus vaccination programs in Taiwan.

    PubMed

    Chang, Wan-Chi; Yen, Catherine; Chi, Cheng-Liang; Wu, Fang-Tzy; Huang, Yhu-Chering; Lin, Jen-Shiou; Huang, Fu-Chen; Tate, Jacqueline E; Wu, Ho-Sheng; Hsiung, Chao A

    2013-11-04

    In Taiwan, two rotavirus vaccines are available on the private market, but are not included in the National Immunization Program (NIP). To help assess whether to include rotavirus vaccines in the NIP, we examined the potential impact and cost-effectiveness of vaccination, from the health care system perspective alone. We used a Microsoft Excel-based model to assess rotavirus vaccination impact on rotavirus disease burden and the cost-effectiveness of 2-dose and 3-dose vaccination programs among a birth cohort of Taiwanese children followed for 5 years. Principal model inputs included data on rotavirus disease burden and related healthcare costs, vaccination cost and coverage rates, and vaccine efficacy. Principal model outputs included the number of health-related events and costs averted and incremental cost per disability-adjusted life year averted. A national rotavirus vaccination program, regardless of number of doses per course, would prevent 4 deaths, >10,500 hospitalizations, and >64,000 outpatient visits due to rotavirus infection among children <5 years annually, resulting in ~80%, 90%, and 70% declines in these outcomes, respectively, and a ~$7 million decline in annual medical costs. A national 2- or 3-dose vaccination program would be cost-saving up to $13.30/dose ($26.60/course) or $7.98/dose ($23.94/course), respectively; very cost-effective up to $24.08 per dose ($48.16/course) or $15.18/dose ($45.54/course), respectively; and cost-effective up to $45.65/dose ($91.30/course) or $29.59/dose ($88.77/course), respectively. A national rotavirus vaccination program could substantially reduce rotavirus disease burden among Taiwanese children and be potentially cost-effective, depending on the vaccine price. Copyright © 2013 Elsevier Ltd. All rights reserved.

  6. Monitoring of rotavirus vaccination in Morocco: establishing the baseline burden of rotavirus disease.

    PubMed

    Benhafid, Mohammed; Rguig, Ahmed; Trivedi, Tarak; Elqazoui, Maria; Teleb, Nadia; Mouane, Nezha; Maltouf, Abdelkarim Filali; Parashar, Umesh; Patel, Manish; Aouad, Rajae El

    2012-10-12

    Rotavirus is a leading cause of childhood morbidity and mortality worldwide. Clinical trials for two rotavirus vaccines recommended by the WHO for global use since 2009 have successfully demonstrated the safety and efficacy of these vaccines in a wide range of countries. To control the burden of severe and fatal diarrheal disease, the Ministry of Health of Morocco introduced the single strain rotavirus vaccine into their national immunization program in 2010. We employed a standard WHO case definition to identify children under 5 hospitalized with AGE at four hospitals from June 2006 to May 2010 to establish baseline burden of rotavirus disease before introduction of vaccine. Stool samples were collected and tested for rotavirus using a standard enzyme immunoassay. Overall, 40% (741 of 1841) of the children hospitalized with AGE tested positive for rotavirus, making it the single most common cause of severe gastroenteritis among children in Morocco. Applying this prevalence to the estimates of diarrheal hospitalizations and deaths in Morocco, we estimate that rotavirus annually causes 19,646 hospitalizations and 1604 deaths in children under 5 years of age. On the basis of these surveillance data, we estimate that 1 in 389 Moroccan children died and 1 in 32 was hospitalized due to rotavirus before their fifth birthday. A considerable proportion of these deaths and hospitalizations should be preventable through vaccination, and the 4 years of stable prevaccine surveillance in Morocco will be a tremendously useful platform for assessing potential changes in the epidemiology of rotavirus disease and measuring impact of the new rotavirus vaccine program in Morocco. Published by Elsevier Ltd.

  7. Effect of monovalent rotavirus vaccine on rotavirus disease burden and circulating rotavirus strains among children in Morocco.

    PubMed

    Benhafid, Mohammed; Elomari, Nezha; Azzouzi Idrissi, Meryem; Rguig, Ahmed; Gentsch, Jon R; Parashar, Umesh; Elaouad, Rajae

    2015-06-01

    Rotarix(TM) vaccine was introduced into the National Program of Immunization of Morocco in October 2010, reaching quickly 87% of the target population of children nationally. The incidence of rotavirus gastroenteritis and the prevalence of circulating rotavirus strains has been monitored in three sentinel hospitals since June 2006. The average percentage of rotavirus positive cases among all children under 5 years old hospitalized for gastroenteritis during the pre-vaccine period (2006-2010) was 44%. This percentage dropped to 29%, 15% and 24% in the 3 years post vaccine introduction (2011, 2012 and 2013), which is a decline of 34%, 66%, and 45%, respectively. Declines in prevalence were greatest among children 0-1 years of age (53%) and were most prominent during the winter and autumn rotavirus season. The prevalence of the G2P[4] and G9P[8] genotype sharply increased in the post vaccine period (2011-2013) compared to the previous seasons (2006-2010). Rotavirus vaccines have reduced greatly the number of children hospitalized due to rotavirus infection at the three sentinel hospitals; it is however unclear if the predominance of G2P[4] and G9P[8] genotypes is related to the vaccine introduction, or if this is attributable to normal genotype fluctuations. Continued surveillance will be pivotal to answer this question in the future. © 2015 Wiley Periodicals, Inc.

  8. Evaluation of pentavalent rotavirus vaccination in neonatal intensive care units.

    PubMed

    Thrall, Samuel; Doll, Margaret K; Nhan, Charles; Gonzales, Milagros; Perreault, Thérèse; Lamer, Philippe; Quach, Caroline

    2015-09-22

    Preterm infants are at highest risk for severe rotavirus gastroenteritis. While rotavirus vaccination is recommended for age-eligible, clinically stable preterm infants, controversy exists regarding vaccination of these infants during hospitalization. The objectives of this study were to examine tolerance of pentavalent rotavirus vaccination (RV5) among hospitalized infants and nosocomial rotavirus transmission in the neonatal intensive care units (NICU) at two urban hospitals. A retrospective, medical chart review of patients receiving RV5 vaccine was conducted to examine clinical histories of vaccine recipients. Average risk differences of gastrointestinal complications were estimated between the three days prior and up to four weeks following RV5 vaccination. A generalized linear regression model was used to examine the association between days since RV5 administration and daily feeding totals, using fixed effects to account for individual-level clustering. Rates of nosocomial rotavirus from active surveillance were compared between pre- and post-NICU-based vaccination periods. From July 1, 2011 to March 30, 2013, RV5 vaccination was initiated for 102 NICU patients. No changes in the average risk of gastrointestinal complications or daily feeding among participants overall were detected following RV5 administration. Rates of nosocomial rotavirus were similar during the periods before and after NICU-based vaccination. On average, RV5 appeared to be well tolerated among vaccine recipients, with no increase in nosocomial rotavirus transmission observed following NICU-based rotavirus vaccination. While the benefits of a RV5 NICU-based vaccination program for otherwise eligible preterm infants seem to outweigh the possible risk of vaccine virus transmission, further studies are needed. Copyright © 2015 Elsevier Ltd. All rights reserved.

  9. Effectiveness of rotavirus vaccines in preventing cases and hospitalizations due to rotavirus gastroenteritis in Navarre, Spain.

    PubMed

    Castilla, Jesús; Beristain, Xabier; Martínez-Artola, Víctor; Navascués, Ana; García Cenoz, Manuel; Alvarez, Nerea; Polo, Isabel; Mazón, Ana; Gil-Setas, Alberto; Barricarte, Aurelio

    2012-01-11

    Two rotavirus vaccines have been available since 2006. This study evaluates the effectiveness of these vaccines using a test-negative case-control design in Navarre, Spain. We included children 3-59 months of age who sought medical care for gastroenteritis and for whom stool samples were taken between January 2008 and June 2011. About 9% had received the pentavalent vaccine (RotaTeq) and another 8% received the monovalent vaccine (Rotarix). Cases were the 756 children with confirmed rotavirus and controls were the 6036 children who tested negative for rotavirus. Thirty-five percent of cases and 9% of controls had required hospitalization (p<0.0001). The adjusted effectiveness of complete vaccination was 78% (95% CI: 68-85%) in preventing rotavirus gastroenteritis and 83% (95% CI: 65-93%) in preventing hospitalization for rotavirus gastroenteritis. No differences between the two vaccines were detected (p=0.4523). Both vaccines were highly effective in preventing cases and hospital admissions in children due to rotavirus gastroenteritis.

  10. Rotavirus-associated hospitalization and emergency department costs and rotavirus vaccine program impact.

    PubMed

    Kilgore, April; Donauer, Stephanie; Edwards, Kathryn M; Weinberg, Geoffrey A; Payne, Daniel C; Szilagyi, Peter G; Rice, Marilyn; Cassedy, Amy; Ortega-Sanchez, Ismael R; Parashar, Umesh D; Staat, Mary Allen

    2013-08-28

    To determine the medical costs of laboratory-confirmed rotavirus hospitalizations and emergency department (ED) visits and estimate the economic impact of the rotavirus vaccine program. During 4 rotavirus seasons (2006-2009), children <3 years of age hospitalized or seen in the ED with laboratory-confirmed rotavirus were identified through active population-based rotavirus surveillance in three US counties. Medical costs were obtained from hospital and physician billing data, and factors associated with increased costs were examined. Annual national costs were estimated using rotavirus hospitalization and ED visit rates and medical costs for rotavirus hospitalizations and ED visits from our surveillance program for pre- (2006-2007) and post-vaccine (2008-2009) time periods. Pre-vaccine, for hospitalizations, the median medical cost per child was $3581, the rotavirus hospitalization rate was 22.1/10,000, with an estimated annual national cost of $91 million. Post-vaccine, the median medical cost was $4304, the hospitalization rate was 6.3/10,000 and the estimated annual national cost was $31 million. Increased costs were associated with study site, age <3 months, underlying medical conditions and an atypical acute gastroenteritis presentation. For ED visits, the pre-vaccine median medical cost per child was $574, the ED visit rate was 291/10,000 resulting in an estimated annual national cost of $192 million. Post-vaccine, the median medical cost was $794, the ED visit rate was 71/10,000 with an estimated annual national cost of $65 million. After implementation of rotavirus immunization, the total annual medical costs decreased from $283 million to $96 million, an annual reduction of $187 million. Copyright © 2013 Elsevier Ltd. All rights reserved.

  11. Removing the age restrictions for rotavirus vaccination: a benefit-risk modeling analysis.

    PubMed

    Patel, Manish M; Clark, Andrew D; Sanderson, Colin F B; Tate, Jacqueline; Parashar, Umesh D

    2012-01-01

    ,700-63,700) and cause an additional 294 (161-471) intussusception deaths, for an incremental benefit-risk ratio of 154 deaths averted for every death caused by vaccine. These extra deaths prevented under an unrestricted schedule reflect vaccination of an additional 21%-25% children, beyond the 63%-73% of the children who would be vaccinated under the restricted schedule. Importantly, these estimates err on the side of safety in that they assume high vaccine-associated risk of intussusception and do not account for potential herd immunity or non-fatal outcomes. Our analysis suggests that in low- and middle-income countries the additional lives saved by removing age restrictions for rotavirus vaccination would far outnumber the potential excess vaccine-associated intussusception deaths. Please see later in the article for the Editors' Summary.

  12. The effectiveness of rotavirus vaccine in preventing acute gastroenteritis during rotavirus seasons among Polish children

    PubMed Central

    Kieltyka, Agnieszka; Majewska, Renata; Augustyniak, Malgorzata

    2016-01-01

    Introduction Rotavirus is the main etiological cause of intestinal infections in children. Voluntary rotavirus vaccines were included in the Polish vaccination schedule in 2007. The aim of this study was to assess the effectiveness of a completed rotavirus vaccination course in preventing acute gastroenteritis in Polish infants during their first five years of life. Material and methods This was a retrospective cohort study conducted in Lesser Poland (Malopolska Province). The sample population included a group of 303 children who received the completed rotavirus vaccination course and 303 children not vaccinated against rotavirus. The date of the child's acute gastroenteritis diagnosis and his or her vaccination history were extracted from the physicians’ records. Each kind of diagnosed acute gastroenteritis during winter-spring rotavirus seasons was treated as the endpoint. The relative risk of having gastrointestinal infection was assessed using the hazard ratio from the Cox proportional hazards regression model. Results In the examined group, 96 (15.8%) children had winter-spring gastrointestinal infections. In the non-vaccinated children, the cumulative incidence of these infections in the first 5 years of life was 20.8%, whereas in the children vaccinated with Rotarix it was only 10.9%. Those who were vaccinated with Rotarix had a 44% reduction in the risk of a winter-spring acute gastroenteritis infection compared to those not vaccinated with Rotarix (p = 0.005). Birth weight less than 2500 g increased the risk of the infection twofold and also reached statistical significance (p = 0.044). Conclusions The results showed that Rotarix is effective in preventing acute gastroenteritis in Polish children during rotavirus seasons. PMID:27279856

  13. 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

  14. Construction and characterization of human rotavirus recombinant VP8* subunit parenteral vaccine candidates.

    PubMed

    Wen, Xiaobo; Cao, Dianjun; Jones, Ronald W; Li, Jianping; Szu, Shousun; Hoshino, Yasutaka

    2012-09-21

    Two currently licensed live oral rotavirus vaccines (Rotarix® and RotaTeq®) are highly efficacious against severe rotavirus diarrhea. However, the efficacy of such vaccines in selected low-income African and Asian countries is much lower than that in middle or high-income countries. Additionally, these two vaccines have recently been associated with rare case of intussusception in vaccinated infants. We developed a novel recombinant subunit parenteral rotavirus vaccine which may be more effective in low-income countries and also avert the potential problem of intussusception. Truncated recombinant VP8* (ΔVP8*) protein of human rotavirus strain Wa P[8], DS-1 P[4] or 1076 P[6] expressed in Escherichia coli was highly soluble and was generated in high yield. Guinea pigs hyperimmunized intramuscularly with each of the ΔVP8* proteins (i.e., P[8], P[4] or P[6]) developed high levels of homotypic as well as variable levels of heterotypic neutralizing antibodies. Moreover, the selected ΔVP8* proteins when administered to mice at a clinically relevant dosage, route and schedule, elicited high levels of serum anti-VP8* IgG and/or neutralizing antibodies. Our data indicated that the ΔVP8* proteins may be a plausible additional candidate as new parenteral rotavirus vaccines.

  15. Construction and Characterization of Human Rotavirus Recombinant VP8* Subunit Parenteral Vaccine Candidates

    PubMed Central

    Wen, Xiaobo; Cao, Dianjun; Jones, Ronald W.; Li, Jianping; Szu, Shousun; Hoshino, Yasutaka

    2012-01-01

    Two currently licensed live oral rotavirus vaccines (Rotarix® and RotaTeq®) are highly efficacious against severe rotavirus diarrhea. However, the efficacy of such vaccines in selected low-income African and Asian countries is much lower than that in middle or high-income countries. Additionally, these two vaccines have recently been associated with rare case of intussusception in vaccinated infants. We developed a novel recombinant subunit parenteral rotavirus vaccine which may be more effective in low-income countries and also avert the potential problem of intussusception. Truncated recombinant VP8* (ΔVP8*) protein of human rotavirus strain Wa P[8], DS-1 P[4] or 1076 P[6] expressed in E. coli was highly soluble and was generated in high yield. Guinea pigs hyperimmunized intramuscularly with each of the ΔVP8* proteins (i.e., (P[8], P[4] or P[6]) developed high levels of homotypic as well as variable levels of heterotypic neutralizing antibodies. Moreover, the selected ΔVP8* proteins when administered to mice at a clinically relevant dosage, route and schedule, elicited high levels of serum anti-VP8* IgG and/or neutralizing antibodies. Our data indicated that the ΔVP8* proteins may be a plausible additional candidate as new parenteral rotavirus vaccines. PMID:22885016

  16. [The role of the rotavirus vaccine in childhood vaccination schedules].

    PubMed

    Giménez Sánchez, F; Martinón Torres, F; Bernaola Iturbe, E; Baca Cots, M; de Juan Martín, F; Díez Delgado, J; Garcés Sánchez, M; Gómez Campderá, J A; Picazo, J; Pineda Solas, V

    2006-06-01

    Rotavirus is the leading cause of diarrhea in infants. In developed countries, this infection leads to considerable morbidity with a high number of hospitalizations and medical interventions in the winter season, giving rise to substantial medical and social costs. In developing countries, rotavirus is a major cause of mortality in infants due to dehydration, with an estimated 600.000 deaths or more per year worldwide. A vaccine that is easy administrated, safe and with high efficacy would be the ideal means to reduce the burden of this disease and its high economic and social cost and to decrease the number of deaths in low-income countries. Recently, the results of two well-designed clinical trials with a large number of subjects have been reported. Both studies, which used different vaccines, reported high efficacy in the prevention of severe gastroenteritis and hospitalizations caused by rotavirus. When these vaccines become available in Europe, a reduction in hospitalizations, medical consultations, and days of work lost can be expected.

  17. 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.

  18. [Potential cost effectiveness of a rotavirus vaccine in Chile].

    PubMed

    Constenla, Dagna; O'Ryan, Miguel; Navarrete, María S; Antil, Lynn; Rheingans, Richard D

    2006-06-01

    Cost effectiveness studies are essential to assess the real value of interventions with preventive or therapeutic objectives. To assess the theoretical cost-effectiveness of a vaccine against rotavirus in Chilean children of less than five years of age. An economic model was developed based on information on disease incidence, health care costs associated with treatment and the effectiveness and costs of vaccination. Net disease and vaccination costs were estimated from the health system perspective and were compared with life years and disability-adjusted life-years (DALYs) gained using a 3% discount rate. Local administrative and accounting hospital data and vaccine efficacy data were used to estimate healthcare costs and cost-effectiveness of vaccination. A rotavirus vaccination program would prevent 10 deaths due to rotavirus gastroenteritis, 6,245 related hospitalizations and 41,962 outpatient visits during the first five years of life, per vaccinated cohort. For every 1,000 children born, the healthcare service spends US$15,077 on treatment of gastroenteritis. From the healthcare perspective, vaccination would yield a cost-effectiveness ratio of US$11,261 per DALY when the price of the vaccine is US$24 per course. Rotavirus vaccine can effectively reduce the disease burden and healthcare costs of rotavirus gastroenteritis and can be a cost-effective investment compared to other options.

  19. Rotavirus vaccine: a cost effective control measure for India.

    PubMed

    Kumar, Arun; Goel, Manish K; Jain, Ram Bilas; Khanna, Pardeep; Vibha, Vibha

    2012-04-01

    Globally, rotavirus diarrhea results in 453,000 deaths in children younger than 5 y—37% of deaths attributable to diarrhea and 5% of all deaths in children younger than 5 y. India alone accounts for 22% (~100,000 deaths) of all deaths attributable to rotavirus infection. Two oral rotavirus vaccines are available: Rotarix, a monovalent P1A[8] G1 vaccine (GlaxoSmithKline), and RotaTeq, a pentavalent bovine-human reassortant vaccine (Merck). Rotarix is administered in a 2-dose schedule with the first and second doses of DTP (DTP1, DTP2). RotaTeq requires a 3-dose schedule with DTP1, DTP2 and DTP3 with an interval of 4–10 weeks between doses. The first dose of either vaccine should be administered to infants aged 6–15 weeks irrespective of the history of previous rotavirus infection, and the maximum age for administering the last dose of either vaccine should be 32 weeks. Although India would require funding from international health organizations/GAVI until new indigenous rotavirus vaccine candidates are developed at a cheaper price, introduction of vaccination into the national immunization program would be a cost-effective step toward control of the rotavirus diarrhea-related morbidity and mortality in India.

  20. Evidence of Vaccine-related Reassortment of Rotavirus, Brazil, 2008–2010

    PubMed Central

    Marques da Silva, Marcelle Figueira; Goméz, Mariela Martinéz; Resque, Hugo Reis; Ichihara, Maria Yury Travassos; Volotão, Eduardo de Mello; Leite, José Paulo Gagliardi

    2013-01-01

    Analysis of 27 rotavirus strains from vaccinated and unvaccinated children revealed reassortment events in 3 strains: a gene derived from a vaccine; a gene acquired from a circulating strain; and reassortment between circulating strains. Data suggest that the widespread use of this monovalent rotavirus vaccine may introduce vaccine genes into circulating human rotaviruses or vice versa. PMID:24188273

  1. Global economic evaluations of rotavirus vaccines: A systematic review.

    PubMed

    Kotirum, Surachai; Vutipongsatorn, Naaon; Kongpakwattana, Khachen; Hutubessy, Raymond; Chaiyakunapruk, Nathorn

    2017-06-08

    World Health Organization (WHO) recommends Rotavirus vaccines to prevent and control rotavirus infections. Economic evaluations (EE) have been considered to support decision making of national policy. Summarizing global experience of the economic value of rotavirus vaccines is crucial in order to encourage global WHO recommendations for vaccine uptake. Therefore, a systematic review of economic evaluations of rotavirus vaccine was conducted. We searched Medline, Embase, NHS EED, EconLit, CEA Registry, SciELO, LILACS, CABI-Global Health Database, Popline, World Bank - e-Library, and WHOLIS. Full economic evaluations studies, published from inception to November 2015, evaluating Rotavirus vaccines preventing Rotavirus infections were included. The methods, assumptions, results and conclusions of the included studies were extracted and appraised using WHO guide for standardization of EE of immunization programs. 104 relevant studies were included. The majority of studies were conducted in high-income countries. Cost-utility analysis was mostly reported in many studies using incremental cost-effectiveness ratio per DALY averted or QALY gained. Incremental cost per QALY gained was used in many studies from high-income countries. Mass routine vaccination against rotavirus provided the ICERs ranging from cost-saving to highly cost-effective in comparison to no vaccination among low-income countries. Among middle-income countries, vaccination offered the ICERs ranging from cost-saving to cost-effective. Due to low- or no subsidized price of rotavirus vaccines from external funders, being not cost-effective was reported in some high-income settings. Mass vaccination against rotavirus was generally found to be cost-effective, particularly in low- and middle-income settings according to the external subsidization of vaccine price. On the other hand, it may not be a cost-effective intervention at market price in some high-income settings. This systematic review provides

  2. Incidence of Rotavirus and Circulating Genotypes in Northeast Brazil during 7 Years of National Rotavirus Vaccination

    PubMed Central

    Gurgel, Ricardo Q.; Alvarez, Alberto De Juan; Rodrigues, Alda; Ribeiro, Robergson R.; Dolabella, Sílvio S.; Da Mota, Natanael L.; Santos, Victor S.; Iturriza-Gomara, Miren; Cunliffe, Nigel A.; Cuevas, Luis E.

    2014-01-01

    Background and Aims Rotavirus causes severe diarrhoea and Brazil introduced the Rotarix G1P[8] vaccine in 2006. We aimed to describe changes in rotavirus incidence and diarrhoea epidemiology before and after vaccine introduction. Methods Design: (i) hospital-based survey of children with diarrhoea (2006–2012); (ii) diarrhea-mortality and hospitalization surveillance (1999–2012). Setting (i) Aracaju and (ii) state and national level. Results 1841 children were enrolled and 231 (12.5%) had rotavirus. Rotavirus was less frequent from January-June than from July-December (9.4% versus 20.9%, p<0.01), but the seasonal variation was less defined after 2009. Very few rotavirus cases (8–3.9%) were detected in 2011, with an increase in 2012 (13–18.5%). In 2006, unvaccinated children were more likely to have rotavirus, but thereafter unvaccinated and vaccinated children had equally low incidence. Older children and those with rotavirus were more likely to have severe diarrhea episodes. The most frequent genotype from 2006 to 2010 was G2P[4]; except in 2009, when most cases were G1P[8]. Very few G2P[4] were detected from 2011 and 50% cases in 2012 were G8P[4]. Diarrhoea-hospitalizations decreased nationally from 89,934 (2003) to 53,705 (2012; 40.3% reduction) and in the state from 1729 to 748 (56.7% reduction). Diarrhoea-deaths decreased nationally from 4368 in 1999 to 697 in 2012 (84% reduction, p<0.001) and in the state from 132 to 18 (86% reduction). These changes were much larger after vaccine introduction. Conclusions The vaccine was associated with substantial reductions in rotavirus incidence and diarrhoea-hospitalizations and deaths. The G2P[4] genotype predominance disappeared over time and may be replaced by other heterotypic genotypes. PMID:25360784

  3. Effectiveness of the live attenuated rotavirus vaccine produced by a domestic manufacturer in China studied using a population-based case-control design.

    PubMed

    Zhen, Shan-Shan; Li, Yue; Wang, Song-Mei; Zhang, Xin-Jiang; Hao, Zhi-Yong; Chen, Ying; Wang, Dan; Zhang, Yan-Hong; Zhang, Zhi-Yong; Ma, Jing-Chen; Zhou, Peng; Zhang, Zhen; Jiang, Zhi-Wei; Zhao, Yu-Liang; Wang, Xuan-Yi

    2015-10-01

    A universal rotavirus (RV) immunization program is a potentially cost-effective measure for preventing RV infection in China. However, the efficacy of the only licensed RV vaccine (Lanzhou lamb rotavirus vaccine, LLR), which is made by a domestic manufacturer, has not been proven by a properly designed clinical trial. In October 2011 to March 2012, to measure the potential protection provided by LLR, a case-control study nested in a population-based active diarrhea surveillance study of children <5 years of age was conducted in rural Zhengding county. During the study period, 308 episodes of diarrhea were identified as being caused by RV infection, resulting in an incidence rate of 48.0/1000 people/year. The predominant RV serotype was G3 (61.5%), followed by G1 (15.2%), and G9 (6.5%). Overall, a protection of 35.0% (95% confidence interval (CI), 13.0%-52.0%) was identified, and higher protection was found among moderate RV gastroenteritis cases caused by the serotype G3 (52.0% 95% CI: 2.0%-76.1%). A concurrently conducted case-control study comparing non-RV viral diarrheal cases with non-diarrheal controls in the same population found that the RV vaccine offered no protection against non-RV diarrhea. Even under a less ideal immunization schedule, the oral LLR conferred a certain level of protection against RV gastroenteritis. However, further studies are needed to understand the full characteristics of the LLR, including its efficacy when administered following the optimal regimen, the potential risk of inducing intussusception, and the direct and indirect protective effects of LLR.

  4. Reduction in Rotavirus Disease and Sustained Predominance of G2P[4] Rotavirus Strain following Introduction of Rotavirus Vaccine in Recife, Brazil.

    PubMed

    Montenegro, Fernanda Maria Ulisses; Falbo, Ana Rodrigues; Germano, Eliane Mendes; Correia, Nancy Barros; Souza, Edvaldo da Silva; Nakagomi, Osamu; Nakagomi, Toyoko; Cuevas, Luis E; Cunliffe, Nigel A; Correia, Jailson B

    2015-06-01

    Rotavirus vaccination was introduced in Brazil in March 2006. We describe the distribution of rotavirus genotypes in children with acute gastroenteritis in a hospital in Recife, Brazil, during pre- and post-vaccination periods. There was a 43.8% reduction in the proportion of diarrhea episodes due to rotavirus. Nevertheless, we observed a sustained predominance of G2P[4] as the main genotype identified in the post-vaccination period.

  5. [Rotavirus infections].

    PubMed

    Stock, Ingo

    2011-01-01

    Rotaviruses are genetically highly variable, non-enveloped viruses with a double-stranded, segmented ribonucleic acid genome. They are a major cause of gastroenteritis worldwide. In children aged less than 5 years, they are the most frequent agent of severe acute diarrheal illnesses. In less developed countries, rotavirus diseases are one of the most frequent causes of death in infants and little children. Typically, symptomatic rotavirus diseases in infants (<5 years) and the elderly (>70 years) arise with sudden onset of watery diarrhoea with high risk of dehydration, accompanied by vomiting and, in several cases, unspecific respiratory symptoms such as cold and sore throat. In adults aged less than 70 years, illnesses due to rotavirus appear generally mild or as travel diarrhoea. Although rotavirus infections are considered to by systemic, extraintestinal manifestations such as rotavirus central nervous system diseases are relatively rare. Rotaviruses are transmitted primarily from person-to-person by the faecal-oral route. Treatment of rotavirus diarrhoea is usually symptomatic and comprises a sufficient fluid and electrolyte substitution. Although nitazoxanide and some other drugs show high efficacy against rotavirus in vitro and in vivo, there is currently no recommended specific antiviral therapy. For prophylaxis, special attention should be paid to adequate hygienic rules. Because of the high stability of rotaviruses to changing environmental conditions, disinfection should be performed applying disinfectants with proven activity against rotaviruses. In Germany, two efficient and secure live vaccines against rotaviruses have been approved. Their application, however, is not generally recommended.

  6. Catching-up with pentavalent vaccine: Exploring reasons behind lower rotavirus vaccine coverage in El Salvador.

    PubMed

    Suarez-Castaneda, Eduardo; Burnett, Eleanor; Elas, Miguel; Baltrons, Rafael; Pezzoli, Lorenzo; Flannery, Brendan; Kleinbaum, David; de Oliveira, Lucia Helena; Danovaro-Holliday, M Carolina

    2015-11-27

    Rotavirus vaccine was introduced in El Salvador in 2006 and is recommended to be given concomitantly with DTP-HepB-Haemophilus influenzae type b (pentavalent) vaccine at ages 2 months (upper age limit 15 weeks) and 4 months (upper age limit 8 months) of age. However, rotavirus vaccination coverage continues to lag behind that of pentavalent vaccine, even in years when national rotavirus vaccine stock-outs have not occurred. We analyzed factors associated with receipt of oral rotavirus vaccine among children who received at least 2 doses of pentavalent vaccine in a stratified cluster survey of children aged 24-59 months conducted in El Salvador in 2011. Vaccine doses included were documented on vaccination cards (94.4%) or in health facility records (5.6%). Logistic regression and survival analysis were used to assess factors associated with vaccination status and age at vaccination. Receipt of pentavalent vaccine by age 15 weeks was associated with rotavirus vaccination (OR: 5.1; 95% CI 2.7, 9.4), and receipt of the second pentavalent dose by age 32 weeks was associated with receipt of two rotavirus vaccine doses (OR: 5.0; 95% CI 2.1-12.3). Timely coverage with the first pentavalent vaccine dose was 88.2% in the 2007 cohort and 91.1% in the 2008 cohort (p=0.04). Children born in 2009, when a four-month national rotavirus vaccine stock-out occurred, had an older median age of receipt of rotavirus vaccine and were less likely to receive rotavirus on the same date as the same dose of pentavalent vaccine than children born in 2007 and 2008. Upper age limit recommendations for rotavirus vaccine administration contributed to suboptimal vaccination coverage. Survey data suggest that late rotavirus vaccination and co-administration with later doses of pentavalent vaccine among children born in 2009 helped increase rotavirus vaccine coverage following shortages. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

  7. Rotavirus Infection in the Auckland Region Following the Implementation of Universal Infant Rotavirus Vaccination: Impact on Hospitalisations and Laboratory Implications.

    PubMed

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

    2017-07-19

    In July 2014, New Zealand introduced universal infant vaccination with Rotateq (Merk & Co.) administered as three doses at 6 weeks, 3 and 5 months of age. We sought to assess the impact of rotavirus vaccination on gastroenteritis 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-December 2015), and year of vaccine introduction (2014). There was a 68% decline in rotavirus hospitalizations of children aged <5 years following vaccine introduction (from 258 per 100,000 to 83 per 100,000) and a 17% decline in all-cause gastroenteritis admissions (from 1815 per 100,000 to 1293 per 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 two prior years, and following 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 prior to vaccine introduction.

  8. Safety of second-generation rotavirus vaccines, intussusception.

    PubMed

    Vázquez, Marietta

    2014-02-01

    This article discusses new data available on the safety of the second-generation rotavirus vaccines both in the United States and internationally. Second-generation rotavirus vaccines are both highly effective against rotavirus disease. Recent data from passive and active surveillance systems in the United States indicate that RV1 and RV5 vaccines may possibly cause a small increase in the risk of intussusception; an estimated 1-3 US infants out of 100 000 might develop intussusception within 7 days of getting their first dose of rotavirus vaccine. Parents and health providers should be aware of the small risk of intussusception, the signs and symptoms of intussusception, and the need for prompt care. Taking into consideration available data on the benefits and risks, Centers for Disease Control and Prevention (CDC) continues to recommend that all US infants receive rotavirus vaccine based on the age and precaution/contraindication criteria. The benefits of RV5 and RV1 outweigh the small excess risk of intussusception. Safety monitoring will continue, both in the United States and internationally, to further quantitate the intussusception risk following each vaccine.

  9. 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

  10. Effectiveness of rotavirus vaccine in preventing severe gastroenteritis in young children according to socioeconomic status.

    PubMed

    Gosselin, Virginie; Généreux, Mélissa; Gagneur, Arnaud; Petit, Geneviève

    2016-10-02

    In 2011, the monovalent rotavirus vaccine was introduced into a universal immunization program in Quebec (Canada). This retrospective cohort study assessed vaccine effectiveness (VE) in preventing acute gastroenteritis (AGE) and rotavirus gastroenteritis (RVGE) hospitalizations among children <3 y living in the Quebec Eastern Townships region according to socioeconomic status (SES). Data were gathered from a tertiary hospital database paired with a regional immunization registry. Three cohorts of children were followed: (1) vaccinated children born in post-universal vaccination period (2011-2013, n = 5,033), (2) unvaccinated children born in post-universal vaccination period (n = 1,239), and (3) unvaccinated children born in pre-universal vaccination period (2008-2010, n = 6,436). In each cohort, AGE and RVGE hospitalizations were identified during equivalent follow-up periods to calculate VE globally and according to neighborhood-level SES. Using multivariable logistic regression, adjusted odds ratios (OR) were computed to obtain VE (1-OR). Adjusted VE of 2 doses was 62% (95% confidence interval [CI]: 37%-77%) and 94% (95%CI: 52%-99%) in preventing AGE and RVGE hospitalization, respectively. Stratified analyses according to SES showed that children living in neighborhoods with higher rates of low-income families had significantly lower VE against AGE hospitalizations compared to neighborhoods with lower rates of low-income families (30% vs. 78%, p = 0.027). Our results suggest that the rotavirus vaccine is highly effective in preventing severe gastroenteritis in young children, particularly among the most well-off. SES seems to influence rotavirus VE, even in a high-income country like Canada. Further studies are needed to determine factors related to lower rotavirus VE among socioeconomically disadvantaged groups.

  11. Effectiveness of rotavirus vaccine in preventing severe gastroenteritis in young children according to socioeconomic status

    PubMed Central

    Gosselin, Virginie; Généreux, Mélissa; Gagneur, Arnaud; Petit, Geneviève

    2016-01-01

    ABSTRACT In 2011, the monovalent rotavirus vaccine was introduced into a universal immunization program in Quebec (Canada). This retrospective cohort study assessed vaccine effectiveness (VE) in preventing acute gastroenteritis (AGE) and rotavirus gastroenteritis (RVGE) hospitalizations among children <3 y living in the Quebec Eastern Townships region according to socioeconomic status (SES). Data were gathered from a tertiary hospital database paired with a regional immunization registry. Three cohorts of children were followed: (1) vaccinated children born in post-universal vaccination period (2011–2013, n = 5,033), (2) unvaccinated children born in post-universal vaccination period (n = 1,239), and (3) unvaccinated children born in pre-universal vaccination period (2008–2010, n = 6,436). In each cohort, AGE and RVGE hospitalizations were identified during equivalent follow-up periods to calculate VE globally and according to neighborhood-level SES. Using multivariable logistic regression, adjusted odds ratios (OR) were computed to obtain VE (1-OR). Adjusted VE of 2 doses was 62% (95% confidence interval [CI]: 37%–77%) and 94% (95%CI: 52%–99%) in preventing AGE and RVGE hospitalization, respectively. Stratified analyses according to SES showed that children living in neighborhoods with higher rates of low-income families had significantly lower VE against AGE hospitalizations compared to neighborhoods with lower rates of low-income families (30% vs. 78%, p = 0.027). Our results suggest that the rotavirus vaccine is highly effective in preventing severe gastroenteritis in young children, particularly among the most well-off. SES seems to influence rotavirus VE, even in a high-income country like Canada. Further studies are needed to determine factors related to lower rotavirus VE among socioeconomically disadvantaged groups. PMID:27367155

  12. Influenza Vaccine, Live Intranasal

    MedlinePlus

    ... the recombinant influenza vaccine (RIV). The nasal spray flu vaccine (live attenuated influenza vaccine or LAIV) should NOT ... to your doctor or pharmacist about the best flu vaccine option for you or your family.

  13. Symptomatic infection and detection of vaccine and vaccine-reassortant rotavirus strains in 5 children: a case series.

    PubMed

    Boom, Julie A; Sahni, Leila C; Payne, Daniel C; Gautam, Rashi; Lyde, Freda; Mijatovic-Rustempasic, Slavica; Bowen, Michael D; Tate, Jacqueline E; Rench, Marcia A; Gentsch, Jon R; Parashar, Umesh D; Baker, Carol J

    2012-10-01

    Vaccine or vaccine-reassortant rotavirus strains were detected in fecal specimens from 5 of 106 (4.7%) immunocompetent children who required treatment for rotavirus gastroenteritis at a large pediatric hospital in Texas in 2009-2010. Four strains were related to pentavalent rotavirus vaccine, whereas one was related to monovalent rotavirus vaccine. The contribution of these strains to each patient's illness was unclear given that 2 patients had prominent respiratory symptoms and 2 were concurrently infected with another pathogen (group F adenovirus and norovirus). Continued monitoring is necessary to assess the role of vaccine strains and vaccine-reassortant strains in pediatric rotavirus infections.

  14. Symptomatic Infection and Detection of Vaccine and Vaccine-Reassortant Rotavirus Strains in 5 Children: A Case Series

    PubMed Central

    Boom, Julie A.; Sahni, Leila C.; Payne, Daniel C.; Gautam, Rashi; Lyde, Freda; Mijatovic-Rustempasic, Slavica; Bowen, Michael D.; Tate, Jacqueline E.; Rench, Marcia A.; Gentsch, Jon R.; Parashar, Umesh D.; Baker, Carol J.

    2015-01-01

    Vaccine or vaccine-reassortant rotavirus strains were detected in fecal specimens from 5 of 106 (4.7%) immunocompetent children who required treatment for rotavirus gastroenteritis at a large pediatric hospital in Texas in 2009–2010. Four strains were related to pentavalent rotavirus vaccine, whereas one was related to monovalent rotavirus vaccine. The contribution of these strains to each patient’s illness was unclear given that 2 patients had prominent respiratory symptoms and 2 were concurrently infected with another pathogen (group F adenovirus and norovirus). Continued monitoring is necessary to assess the role of vaccine strains and vaccine-reassortant strains in pediatric rotavirus infections. PMID:22872730

  15. [Vaccination against chickenpox, shingles and rotavirus-infection].

    PubMed

    Hartwig, Nico G; Rümke, Hans C; Visser, Henk K A

    2009-01-01

    The Dutch National Immunisation Programme (NIP) has been very successful over the past 50 years. In future, this programme shall not include all new vaccines. Such vaccines can, however, be individually administered. At present there are 3 vaccines available in the Netherlands that have not been included in the NIP to date: against varicella (chickenpox), herpes zoster (shingles) and rotavirus infections. These vaccines are safe and effective. Chickenpox is not always a harmless childhood disease. A chickenpox vaccine is now available as well as a combined vaccine against mumps, measles, rubella and chickenpox. Shingles (herpes zoster) is a common disease in the elderly people. For many patients it is a considerable burden with significant complications, mainly postherpetic neuralgia and herpes zoster ophthalmicus. Vaccination may be considered for people 60 years and older. Rotavirus is much more associated with severe symptoms of diarrhoea than other pathogens. More than 95% of children experience one or more episodes of rotavirus gastroenteritis before their 5th birthday. In the Netherlands about 3400 children are hospitalised each year for rehydration following rotavirus infection. The vaccine is given orally.

  16. 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

  17. Higher proportion of G2P[4] rotaviruses in vaccinated hospitalized cases compared with unvaccinated hospitalized cases, despite high vaccine effectiveness against heterotypic G2P[4] rotaviruses.

    PubMed

    Matthijnssens, J; Zeller, M; Heylen, E; De Coster, S; Vercauteren, J; Braeckman, T; Van Herck, K; Meyer, N; Pirçon, J-Y; Soriano-Gabarro, M; Azou, M; Capiau, H; De Koster, J; Maernoudt, A-S; Raes, M; Verdonck, L; Verghote, M; Vergison, A; Van Damme, P; Van Ranst, M

    2014-10-01

    The overall vaccine effectiveness of the monovalent rotavirus vaccine in an observational, prospective, multicentre, hospital-based case-control study in Belgium (RotaBel) was 90%. However, rotavirus genotype and co-infecting pathogens are important parameters to take into account when assessing vaccine effectiveness. In this study we specifically investigated the effect of rotavirus genotypes and co-infecting pathogens on vaccine effectiveness of the monovalent vaccine. In addition, we also investigated the effect of co-infecting pathogens on disease severity. From February 2008 to June 2010 stool samples of rotavirus gastroenteritis cases of a random sample of 39 Belgian hospitals were collected and subsequently genotyped. Fisher's exact tests were performed to investigate the relationships between rotavirus genotype, co-infecting pathogens and disease severity. The vaccine effectiveness of a full series of the monovalent rotavirus vaccine against hospitalized rotavirus gastroenteritis caused by G1P[8] rotavirus strains was 95% (95% CI 77.5-98.7). Against G2P[4], the vaccine effectiveness was 85% (95% CI: 63.7-93.8). G4P[8]- and G3P[8]-specific vaccine effectiveness was 90% (95% CI 19.2-98.7) and 87% (95% CI -5.2 to 98.4), respectively. A post-hoc analysis showed that the genotype distribution was significantly related to the vaccination status (p <0.001), whereby G2P[4] strains were proportionally more prevalent in vaccinated cases than in unvaccinated cases. No statistical associations were found between co-infection status and vaccination status, Vesikari severity score or rotavirus genotype. The high vaccine effectiveness against the individual genotypes implies robust protection of the monovalent rotavirus vaccine against hospitalized rotavirus gastroenteritis caused by the major human rotavirus genotypes. The prevalence of G2P[4] requires continued monitoring.

  18. Fulfilling the promise of rotavirus vaccines: how far have we come since licensure?

    PubMed

    Patel, Manish M; Glass, Roger; Desai, Rishi; Tate, Jacqueline E; Parashar, Umesh D

    2012-07-01

    Rotavirus is the most common cause of fatal and severe childhood diarrhoea worldwide. Two new rotavirus vaccines have shown efficacy against severe rotavirus disease in large clinical trials. Between 2006 and 2010, 27 countries introduced rotavirus vaccination into national immunisation programmes and, subsequently, the burden of severe rotavirus disease in these countries has decreased substantially in both vaccinated and unvaccinated children. Rotavirus vaccination has led to large, sustained declines in childhood deaths from diarrhoea in Brazil and Mexico, which supports estimates that rotavirus was the leading cause of diarrhoeal deaths in these countries. Studies after licensing have provided new insights into these vaccines, such as the duration of protection, relative effectiveness in poor populations, and strain evolution after vaccine introduction. The challenge for policy makers worldwide is to analyse the effect of vaccination in early adopter countries and to assess whether the benefits outweigh the costs and encourage wider dissemination of these vaccines. Copyright © 2012 Elsevier Ltd. All rights reserved.

  19. 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

  20. Dynamic Modeling of Cost-effectiveness of Rotavirus Vaccination, Kazakhstan

    PubMed Central

    Flem, Elmira; Latipov, Renat; Kuatbaeva, Ajnagul; Kristiansen, Ivar Sønbø

    2014-01-01

    The government of Kazakhstan, a middle-income country in Central Asia, is considering the introduction of rotavirus vaccination into its national immunization program. We performed a cost-effectiveness analysis of rotavirus vaccination spanning 20 years by using a synthesis of dynamic transmission models accounting for herd protection. We found that a vaccination program with 90% coverage would prevent ≈880 rotavirus deaths and save an average of 54,784 life-years for children <5 years of age. Indirect protection accounted for 40% and 60% reduction in severe and mild rotavirus gastroenteritis, respectively. Cost per life year gained was US $18,044 from a societal perspective and US $23,892 from a health care perspective. Comparing the 2 key parameters of cost-effectiveness, mortality rates and vaccine cost at vaccination program costs would be entirely offset. To further evaluate efficacy of a vaccine program, benefits of indirect protection conferred by vaccination warrant further study. PMID:24378188

  1. 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.

  2. Prevalence of rotavirus antibodies in breast milk and inhibitory effects to rotavirus vaccines

    PubMed Central

    Trang, Nguyen V; Braeckman, Tessa; Lernout, Tinne; Hau, Vu T B; Anh, Le T K; Luan, Le T; Van Damme, Pierre; Anh, Dang D

    2015-01-01

    Rotavirus (RV) is the most common cause of childhood diarrhea worldwide, and several vaccines have been successfully developed to reduce the burden of disease. However, lower vaccine immunogenicity and efficacy in developing countries might be related to the virus-neutralizing activity of breast milk. We examined possible differences in breast milk antibody levels (total IgA antibody, RV-specific antibodies, and RV-neutralizing antibodies) between healthy mothers living in a rural area (n = 145) and mothers living in an urban area (n = 147) of Vietnam. Total IgA concentration was significantly higher in samples from mothers in the rural region than in samples from mothers in the urban region, whereas urban mothers had significantly higher RV-specific IgA antibody titers than did rural mothers. Neutralizing antibodies against RV strain G1P[8] were undetected in nearly one-half of the breast milk samples (45–48%), whereas the majority of the remaining samples had low antibody titers (2–16). Despite these low titers, the breast milk still reduced vaccine strain titers (2 × 106 plaque forming units/mL) up to 80% or more, even at a milk-to-virus ratio of 1:8. An increase in neutralizing anti-G1P[8] antibody titers (P < 0.05) in rural infants over time suggests a continuous exposure to circulating RV. These results contribute to the understanding of the potential interference of breast milk with RV vaccine efficacy and immunogenicity in Vietnamese infants. PMID:25668672

  3. Prevalence of rotavirus antibodies in breast milk and inhibitory effects to rotavirus vaccines.

    PubMed

    Trang, Nguyen V; Braeckman, Tessa; Lernout, Tinne; Hau, Vu T B; Anh, Le T K; Luan, Le T; Van Damme, Pierre; Anh, Dang D

    2014-01-01

    Rotavirus (RV) is the most common cause of childhood diarrhea worldwide, and several vaccines have been successfully developed to reduce the burden of disease. However, lower vaccine immunogenicity and efficacy in developing countries might be related to the virus-neutralizing activity of breast milk. We examined possible differences in breast milk antibody levels (total IgA antibody, RV-specific antibodies, and RV-neutralizing antibodies) between healthy mothers living in a rural area (n=145) and mothers living in an urban area (n=147) of Vietnam. Total IgA concentration was significantly higher in samples from mothers in the rural region than in samples from mothers in the urban region, whereas urban mothers had significantly higher RV-specific IgA antibody titers than did rural mothers. Neutralizing antibodies against RV strain G1P[8] were undetected in nearly one-half of the breast milk samples (45-48%), whereas the majority of the remaining samples had low antibody titers (2-16). Despite these low titers, the breast milk still reduced vaccine strain titers (2×10(6) plaque forming units/mL) up to 80% or more, even at a milk-to-virus ratio of 1:8. An increase in neutralizing anti-G1P[8] antibody titers (P<0.05) in rural infants over time suggests a continuous exposure to circulating RV. These results contribute to the understanding of the potential interference of breast milk with RV vaccine efficacy and immunogenicity in Vietnamese infants.

  4. A randomized trial of rotavirus vaccine versus sucrose solution for vaccine injection pain.

    PubMed

    Taddio, Anna; Flanders, Daniel; Weinberg, Eitan; Lamba, Supriya; Vyas, Charmy; Ilersich, Andrew F; Ipp, Moshe; McNair, Carol

    2015-06-09

    Sucrose solutions are analgesic in infants. Oral rotavirus vaccine contains sucrose, however, it is not known if it possesses analgesic properties. The objective was to compare the analgesic effectiveness of rotavirus vaccine to sucrose solution when administered prior to injectable vaccines. Infants 2-4 months of age receiving oral rotavirus vaccine and two separate injectable vaccines on the same day were randomized to rotavirus vaccine (Rotarix) first followed by the injectable vaccines and sucrose (Tootsweet) afterwards, or vice versa. Pain was assessed by blinded raters using the Numerical Rating Scale (NRS, range 0-10) (parents, clinicians), or Modified Behavioural Pain Scale (MBPS, range 0-10) and cry duration (observers). Data were analyzed using t-tests or χ(2)-tests; Bonferroni correction was applied to correct for multiple comparisons, as appropriate. Altogether, 120 infants participated: 60 were randomized to rotavirus vaccine first. Groups did not differ in demographics, including; age (p=0.448) and sex (p=0.464). The mean pain score (standard deviation) for both vaccine injections did not differ between infants given rotavirus vaccine first versus sucrose solution first: observer MBPS, parent NRS and clinician NRS scores were 7.4 (1.6) vs. 7.7 (1.6), 4.9 (2.1) vs. 5.8 (2.1), and 4.2 (2.1) vs. 4.6 (2.2), respectively. Similarly, there was no difference between groups in cry duration. Rotavirus vaccine did not differ from sucrose solution in reducing injection-induced pain. Based on the findings, it is recommended that rotavirus vaccine be administered prior to injectable vaccines in infants aged 2 and 4 months. Copyright © 2015 Elsevier Ltd. All rights reserved.

  5. The first case of Kawasaki disease in a 20-month old baby following immunization with rotavirus vaccine and hepatitis A vaccine in China: A case report.

    PubMed

    Yin, Shi; Liubao, Peng; Chongqing, Tan; Xiaomin, Wan

    2015-01-01

    Kawasaki disease (KD) after rotavirus and hepatitis A vaccination has not previously been reported in a baby in China. Herein, we describe a 20-month-old child who developed Kawasaki disease after receiving her second dose of Lanzhou lamb rotavirus vaccine (LLR) and her first dose of freeze-dried live attenuated hepatitis A vaccine. The case report was conducted by collecting and analyzing the hospital in-patient medical records and reviewing both the domestic and foreign pertinent literature. These findings will be important to note this possible side effect and to further investigate the association between the above 2 vaccines and Kawasaki disease.

  6. The cost effectiveness of rotavirus vaccination in Iran

    PubMed Central

    Mousavi Jarrahi, Yasaman; Zahraei, Seyed Mohsen; Sadigh, Nader; Esmaeelpoor Langeroudy, Keyhan; Khodadost, Mahmoud; Ranjbaran, Mehdi; Sanjari Moghaddam, Ali; Besharat, Mehdi; Mosavi Jarrahi, Alireza

    2016-01-01

    ABSTRACT 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. PMID:26360331

  7. Decline in rotavirus hospitalizations and health care visits for childhood diarrhea following rotavirus vaccination in El Salvador.

    PubMed

    Yen, Catherine; Armero Guardado, Julio A; Alberto, Patricia; Rodriguez Araujo, David S; Mena, Carlos; Cuellar, Elizabeth; Nolasco, Jenny Brenda; De Oliveira, Lucia Helena; Pastor, Desiree; Tate, Jacqueline E; Parashar, Umesh D; Patel, Manish M

    2011-01-01

    A recent postlicensure study from El Salvador showed that the monovalent rotavirus vaccine conferred 76% protection against rotavirus hospitalizations. We further examined the impact of rotavirus vaccination on the national burden of childhood diarrhea to help assess the total public health benefits of vaccination. We compared all-cause diarrhea and rotavirus-specific hospitalization rates during prevaccine year 2006, with postvaccine years 2008 and 2009 in children < 5 years of age from 7 sentinel surveillance hospitals. We also compared annual rates of diarrhea-related healthcare events during prevaccine years 2005 and 2006 with postvaccine years 2008 and 2009 to examine the national burden of healthcare utilization for all-cause diarrhea. Among sentinel surveillance hospitals, rotavirus hospitalization rates among children < 5 years of age declined by 81% (95% confidence interval [CI]: 78%-84%) in 2008 when 2-dose rotavirus vaccine coverage was 50% among infants < 1 year; the decline was 69% (95% CI: 65%-73%) in 2009 when 2-dose vaccine coverage was 61% among infants < 1 year, compared with 2006. The greatest declines were observed in children ≤ 1 year of age, although sizeable reductions were also observed among children ≥ 2 years in 2008. National diarrhea-related healthcare visits during rotavirus season decreased by 48% (95% CI: 47%-48%) in 2008 and by 35% (95% CI: 34%-35%) in 2009 compared with the mean rate from the 2005 and 2006 rotavirus seasons. Rotavirus vaccination had a substantial public health impact on rotavirus disease and overall diarrhea events in El Salvador. Important age-related changes in diarrheal incidence emphasize the need for ongoing rotavirus surveillance after vaccine introduction.

  8. Hospitalised rotavirus gastroenteritis in New Zealand: The laboratory database is a valuable tool for assessing the impact of rotavirus vaccination.

    PubMed

    Kelly, Matthew J; Foley, David; Blackmore, Timothy K

    2017-08-16

    To assess the impact of the introduction of rotavirus vaccination in New Zealand at a regional and national level, underlining the utility of a passively collected laboratory dataset. Retrospective laboratory data for rotavirus testing from Wellington and Hutt Hospitals from 1 January 2010 to 31 December 2016, matched with hospital admissions data of children under 5years of age with gastroenteritis primary and secondary coded admissions. The second part of the study examined the national dataset of primary coded hospital gastroenteritis admissions from the same period. Rotavirus testing was performed in 1054 (64.1%) of the 1645 gastroenteritis admissions to Wellington and Hutt Hospitals. Four hundred and nine of these tests (38.8%) were positive. Children who were not given a primary code of gastroenteritis accounted for 5.7% of rotavirus admissions. The estimated annual rotavirus hospitalisation rate in the Hutt and Wellington regions for children under 5years during the pre-vaccination period was 427.1 per 100,000. In the post-vaccination period (2015-2016), there was a 94.6% reduction in confirmed rotavirus gastroenteritis hospitalisations with only 8 confirmed cases. The total number of gastroenteritis admissions declined by 51.4%. On a national scale, there was a decline of 34.4% in the average annual number of gastroenteritis admissions and the number of coded rotavirus admissions was 87.1% lower than the pre-vaccination average. The non-restrictive continuous approach to rotavirus testing has provided a detailed description of the epidemiology of rotavirus gastroenteritis hospitalisations in the Wellington and Hutt regions. Rotavirus vaccination introduced on the crest of a peak in rotavirus cases has lead to a marked reduction in the number of admissions with gastroenteritis in New Zealand in the two years following vaccine introduction. The national figures likely underestimate the impact of the vaccine. Copyright © 2017 Elsevier Ltd. All rights reserved.

  9. Demographic Variability, Vaccination, and the Spatiotemporal Dynamics of Rotavirus Epidemics

    PubMed Central

    Pitzer, Virginia E.; Viboud, Cécile; Simonsen, Lone; Steiner, Claudia; Panozzo, Catherine A.; Alonso, Wladimir J.; Miller, Mark A.; Glass, Roger I.; Glasser, John W.; Parashar, Umesh D.; Grenfell, Bryan T.

    2009-01-01

    Historically, annual rotavirus activity in the United States has started in the southwest in late fall and ended in the northeast 3 months later; this trend has diminished in recent years. Traveling waves of infection or local environmental drivers cannot account for these patterns. A transmission model calibrated against epidemiological data shows that spatiotemporal variation in birth rate can explain the timing of rotavirus epidemics. The recent large-scale introduction of rotavirus vaccination provides a natural experiment to further test the impact of susceptible recruitment on disease dynamics. The model predicts a pattern of reduced and lagged epidemics postvaccination, closely matching the observed dynamics. Armed with this validated model, we explore the relative importance of direct and indirect protection, a key issue in determining the worldwide benefits of vaccination. PMID:19608910

  10. 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

    2017-09-08

    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.

  11. Rotavirus Seasonal Distribution and Prevalence Before and After the Introduction of Rotavirus Vaccine in a Peri-Urban Community of Lima, Peru

    PubMed Central

    Chang, Millie R.; Velapatiño, Grace; Campos, Miguel; Chea-Woo, Elsa; Baiocchi, Nelly; Cleary, Thomas G.; Ochoa, Theresa J.

    2015-01-01

    We evaluated the monthly distribution of rotavirus diarrhea in a cohort of children 12–24 months of age followed as part of a diarrhea clinical trial in a peri-urban community of Lima. We observed a peak of rotavirus diarrhea in the winter months and a decrease in rotavirus prevalence after the introduction of the rotavirus vaccine in Peru. PMID:25778507

  12. Rotavirus shedding following administration of RV3-BB human neonatal rotavirus vaccine.

    PubMed

    Cowley, Daniel; Boniface, Karen; Bogdanovic-Sakran, Nada; Kirkwood, Carl D; Bines, Julie E

    2017-08-03

    The RV3-BB human neonatal rotavirus vaccine aims to provide protection from severe rotavirus disease from birth. A phase IIa safety and immunogenicity trial was undertaken in Dunedin, New Zealand between January 2012 and April 2014. Healthy, full-term (≥ 36 weeks gestation) babies, who were 0-5 d old were randomly assigned (1:1:1) to receive 3 doses of oral RV3-BB vaccine with the first dose given at 0-5 d after birth (neonatal schedule), or the first dose given at about 8 weeks after birth (infant schedule), or to receive placebo (placebo schedule). Vaccine take (serum immune response or stool shedding of vaccine virus after any dose) was detected after 3 doses of RV3-BB vaccine in >90% of participants when the first dose was administered in the neonatal and infant schedules. The aim of the current study was to characterize RV3-BB shedding and virus replication following administration of RV3-BB in a neonatal and infant vaccination schedule. Shedding was defined as detection of rotavirus by VP6 reverse transcription polymerase chain reaction (RT-PCR) in stool on days 3-7 after administration of RV3-BB. Shedding of rotavirus was highest following vaccination at 8 weeks of age in both neonatal and infant schedules (19/30 and 17/27, respectively). Rotavirus was detected in stool on days 3-7, after at least one dose of RV3-BB, in 70% (21/30) of neonate, 78% (21/27) of infant and 3% (1/32) placebo participants. In participants who shed RV3-BB, rotavirus was detectable in stool on day 1 following RV3-BB administration and remained positive until day 4-5 after administration. The distinct pattern of RV3-BB stool viral load demonstrated using a NSP3 quantitative qRT-PCR in participants who shed RV3-BB, suggests that detection of RV3-BB at day 3-7 was the result of replication rather than passage through the gastrointestinal tract.

  13. Skin Vaccination against Rotavirus Using Microneedles: Proof of Concept in Gnotobiotic Piglets

    PubMed Central

    Wang, Yuhuan; Vlasova, Anastasia; Velasquez, Daniel E.; Saif, Linda J.; Kandasamy, Sukumar; Kochba, Efrat; Levin, Yotam; Jiang, Baoming

    2016-01-01

    Live-attenuated oral rotavirus (RV) vaccines have lower efficacy in low income countries, and additionally are associated with a rare but severe adverse event, intussusception. We have been pursuing the development of an inactivated rotavirus vaccine (IRV) using the human rotavirus strain CDC-9 (G1P[8]) through parenteral immunization and previously demonstrated dose sparing and enhanced immunogenicity of intradermal (ID) unadjuvanted IRV using a coated microneedle patch in comparison with intramuscular (IM) administration in mice. The aim of this study was to evaluate the immune response and protection against RV infection and diarrhea conferred by the administration of the ID unadjuvanted IRV using the microneedle device MicronJet600® in neonatal gnotobiotic (Gn) piglets challenged with virulent Wa G1P[8] human RV. Three doses of 5 μg IRV when administered intradermally and 5 μg IRV formulated with aluminum hydroxide [Al(OH)3] when administered intramuscularly induced comparable rotavirus-specific antibody titers of IgA, IgG, IgG avidity index and neutralizing activity in sera of neonatal piglets. Both IRV vaccination regimens protected against RV antigen shedding in stools, and reduced the cumulative diarrhea scores in the piglets. This study demonstrated that the ID and IM administrations of IRV are immunogenic and protective against RV-induced diarrhea in neonatal piglets. Our findings highlight the potential value of an adjuvant sparing effect of the IRV ID delivery route. PMID:27824918

  14. Skin Vaccination against Rotavirus Using Microneedles: Proof of Concept in Gnotobiotic Piglets.

    PubMed

    Wang, Yuhuan; Vlasova, Anastasia; Velasquez, Daniel E; Saif, Linda J; Kandasamy, Sukumar; Kochba, Efrat; Levin, Yotam; Jiang, Baoming

    2016-01-01

    Live-attenuated oral rotavirus (RV) vaccines have lower efficacy in low income countries, and additionally are associated with a rare but severe adverse event, intussusception. We have been pursuing the development of an inactivated rotavirus vaccine (IRV) using the human rotavirus strain CDC-9 (G1P[8]) through parenteral immunization and previously demonstrated dose sparing and enhanced immunogenicity of intradermal (ID) unadjuvanted IRV using a coated microneedle patch in comparison with intramuscular (IM) administration in mice. The aim of this study was to evaluate the immune response and protection against RV infection and diarrhea conferred by the administration of the ID unadjuvanted IRV using the microneedle device MicronJet600® in neonatal gnotobiotic (Gn) piglets challenged with virulent Wa G1P[8] human RV. Three doses of 5 μg IRV when administered intradermally and 5 μg IRV formulated with aluminum hydroxide [Al(OH)3] when administered intramuscularly induced comparable rotavirus-specific antibody titers of IgA, IgG, IgG avidity index and neutralizing activity in sera of neonatal piglets. Both IRV vaccination regimens protected against RV antigen shedding in stools, and reduced the cumulative diarrhea scores in the piglets. This study demonstrated that the ID and IM administrations of IRV are immunogenic and protective against RV-induced diarrhea in neonatal piglets. Our findings highlight the potential value of an adjuvant sparing effect of the IRV ID delivery route.

  15. 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.

  16. Expanded Indian National Rotavirus Surveillance Network in the Context of Rotavirus Vaccine Introduction.

    PubMed

    Mehendale, Sanjay; Venkatasubramanian, S; Girish Kumar, C P; Kang, Gagandeep; Gupte, M D; Arora, Rashmi

    2016-07-08

    To extend a nation-wide rotavirus surveillance network in India, and to generate geographically representative data on rotaviral disease burden and prevalent strains. Hospital-based surveillance. A comprehensive multicenter, multi-state hospital based surveillance network was established in a phased manner involving 28 hospital sites across 17 states and two union territories in India. Cases of acute diarrhea among children below 5 years of age admitted in the participating hospitals. During the 28 month study period between September 2012 and December 2014, 11898 children were enrolled and stool samples from 10207 children admitted with acute diarrhea were tested; 39.6% were positive for rotavirus. Highest positivity was seen in Tanda (60.4%) and Bhubaneswar (60.4%) followed by Midnapore (59.5%). Rotavirus infection was seen more among children aged below 2 years with highest (46.7%) positivity in the age group of 12-23 months. Cooler months of September to February accounted for most of the rotavirus associated gastroenteritis, with highest prevalence seen during December to February (56.4%). 64% of rotaviru -infected children had severe to very severe disease. G1 P[8] was the predominant rotavirus strain (62.7%) during the surveillance period. The surveillance data highlights the high rotaviral disease burden in India. The network will continue to be a platform for monitoring the impact of the vaccine.

  17. Impact of rotavirus vaccination on coverage and timing of pentavalent vaccination – Experience from 2 Latin American countries

    PubMed Central

    Schweitzer, A.; Pessler, F.; Akmatov, M. K.

    2016-01-01

    ABSTRACT We examined the coverage and timing of rotavirus vaccination and the impact of rotavirus vaccine introduction on coverage and timing of the pentavalent vaccine. We used data from the Demographic and Health Surveys in Honduras (2011/2012) and Peru (2012). The samples were divided into 2 subcohorts: children born before and after the introduction of rotavirus vaccine. We compared coverage and timing of the pentavalent vaccine in the aforementioned subcohorts. Coverage with the first and second doses of rotavirus vaccination was 95% (95% confidence intervals: 93–97%) and 91% (89–95%) in Honduras and 79% (77–82%) and 72% (69–75%) in Peru, respectively. Coverage increased in both countries over the years. The proportion of children vaccinated according to age-appropriate vaccination schedules varied between 67% (second dose of rotavirus vaccinations in Peru) and 89% (first dose of rotavirus vaccination in Honduras). Coverage with the first and second doses of pentavalent vaccination remained constant over the years in Honduras, while in Peru there was a significant increase in coverage over the years (p for trend, <0.0001). In both countries, timing of pentavalent vaccination was better in post-rota-cohorts than in pre-rota-cohorts. Since its introduction, coverage of rotavirus vaccination has improved over time in both countries. An introduction of rotavirus vaccination in both countries appears to have improved the coverage and timing of other similarly scheduled vaccinations. PMID:26833132

  18. Early impact of rotavirus vaccination in a large paediatric hospital in the UK.

    PubMed

    Hungerford, D; Read, J M; Cooke, R P D; Vivancos, R; Iturriza-Gómara, M; Allen, D J; French, N; Cunliffe, N

    2016-06-01

    The impact of routine rotavirus vaccination on community-acquired (CA) and healthcare-associated (HA) rotavirus gastroenteritis (RVGE) at a large paediatric hospital, UK, was investigated over a 13-year period. A total of 1644 hospitalized children aged 0-15 years tested positive for rotavirus between July 2002 and June 2015. Interrupted time-series analysis demonstrated that, post vaccine introduction (July 2013 to June 2015), CA- and HA-RVGE hospitalizations were 83% [95% confidence interval (CI): 72-90%) and 83% (95% CI: 66-92%] lower than expected, respectively. Rotavirus vaccination has rapidly reduced the hospital rotavirus disease burden among both CA- and HA-RVGE cases.

  19. 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.

  20. Value of Post-Licensure Data on Benefits and Risks of Vaccination to Inform Vaccine Policy: The Example of Rotavirus Vaccines.

    PubMed

    Parashar, Umesh D; Cortese, Margaret M; Payne, Daniel C; Lopman, Benjamin; Yen, Catherine; Tate, Jacqueline E

    2015-12-01

    In 1999, the first rhesus-human reassortant rotavirus vaccine licensed in the U.S. was withdrawn within a year of its introduction after it was linked with intussusception at a rate of ~1 excess case per 10,000 vaccinated infants. While clinical trials of 60,000-70,000 infants of each of the two current live oral rotavirus vaccines, RotaTeq (RV5) and Rotarix (RV1), did not find an association with intussusception, post-licensure studies have documented a risk in several high and middle income countries, at a rate of ~1-6 excess cases per 100,000 vaccinated infants. However, considering this low risk against the large health benefits of vaccination that have been observed in many countries, including in countries with a documented vaccine-associated intussusception risk, policy makers and health organizations around the world continue to support the routine use of RV1 and RV5 in national infant immunization programs. Because the risk and benefit data from affluent settings may not be directly applicable to developing countries, further characterization of any associated intussusception risk following rotavirus vaccination as well as the health benefits of vaccination is desirable for low income settings.

  1. Value of post-licensure data on benefits and risks of vaccination to inform vaccine policy: The example of rotavirus vaccines.

    PubMed

    Parashar, Umesh D; Cortese, Margaret M; Payne, Daniel C; Lopman, Benjamin; Yen, Catherine; Tate, Jacqueline E

    2015-11-27

    In 1999, the first rhesus-human reassortant rotavirus vaccine licensed in the United States was withdrawn within a year of its introduction after it was linked with intussusception at a rate of ∼1 excess case per 10,000 vaccinated infants. While clinical trials of 60,000-70,000 infants of each of the two current live oral rotavirus vaccines, RotaTeq (RV5) and Rotarix (RV1), did not find an association with intussusception, post-licensure studies have documented a risk in several high and middle income countries, at a rate of ∼1-6 excess cases per 100,000 vaccinated infants. However, considering this low risk against the large health benefits of vaccination that have been observed in many countries, including in countries with a documented vaccine-associated intussusception risk, policy makers and health organizations around the world continue to support the routine use of RV1 and RV5 in national infant immunization programs. Because the risk and benefit data from affluent settings may not be directly applicable to developing countries, further characterization of any associated intussusception risk following rotavirus vaccination as well as the health benefits of vaccination is desirable for low income settings. Copyright © 2015 American Journal of Preventive Medicine. Published by Elsevier Ltd.. All rights reserved.

  2. Monovalent rotavirus vaccine provides protection against an emerging fully heterotypic G9P[4] rotavirus strain in Mexico.

    PubMed

    Yen, Catherine; Figueroa, Jesùs Reyna; Uribe, Edgar Sánchez; Carmen-Hernández, Luz Del; Tate, Jacqueline E; Parashar, Umesh D; Patel, Manish M; Richardson López-Collado, Vesta

    2011-09-01

    After the introduction of monovalent rotavirus vaccine (RV1) in Mexico in 2006-2007, diarrhea mortality and morbidity declined substantially among Mexican children under 5 years of age. In January 2010, surveillance identified the emergence of a novel G9P[4] rotavirus strain nationwide. We conducted a case-control study to assess the field effectiveness of RV1 against severe rotavirus gastroenteritis caused by this unusual strain and to determine whether the G9P[4] emergence was related to vaccine failure or failure to vaccinate. RV1 was 94% effective (95% confidence interval, 16%-100%) against G9P[4] rotavirus-related hospitalization, indicating that its emergence was likely unrelated to vaccine pressure.

  3. Variation in rotavirus vaccine coverage by provider location and subsequent disease burden.

    PubMed

    Sahni, Leila C; Tate, Jacqueline E; Payne, Daniel C; Parashar, Umesh D; Boom, Julie A

    2015-02-01

    Rotavirus vaccines were introduced in the United States in 2006. Full-series coverage is lower than for other vaccines, and disease continues to occur. We examined variation in vaccine coverage among provider locations and correlated coverage with the detection of rotavirus in children who sought treatment of severe acute gastroenteritis (AGE). Vaccine records of children enrolled in an AGE surveillance program were obtained and children were grouped by the location that administered each child's 2-month vaccines. Cases were children with laboratory-confirmed rotavirus AGE; controls were children with rotavirus-negative AGE or acute respiratory infection. Location-level coverage was calculated using ≥ 1 dose rotavirus vaccine coverage among controls and classified as low (<40%), medium (≥ 40% to <80%), or high (≥ 80%). Rotavirus detection rates among patients with AGE were calculated by vaccine coverage category. Of controls, 80.4% (n = 1123 of 1396) received ≥ 1 dose of rotavirus vaccine from 68 locations. Four (5.9%) locations, including a NICU, were low coverage, 22 (32.3%) were medium coverage, and 42 (61.8%) were high coverage. In low-coverage locations, 31.4% of patients with AGE were rotavirus-positive compared with 13.1% and 9.6% in medium- and high-coverage locations, respectively. Patients with AGE from low-coverage locations had 3.3 (95% confidence interval 2.4-4.4) times the detection rate of rotavirus than patients with AGE from high vaccine coverage locations. We observed the highest detection of rotavirus disease among locations with low rotavirus vaccine coverage, suggesting that ongoing disease transmission is related to failure to vaccinate. Educational efforts focusing on timely rotavirus vaccine administration to age-eligible infants are needed. Copyright © 2015 by the American Academy of Pediatrics.

  4. 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.

  5. 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.

  6. Live Virus Smallpox Vaccine

    MedlinePlus

    ... Submit What's this? Submit Button The Live Virus Smallpox Vaccine Language: English Español (Spanish) Recommend on Facebook ... the vaccinia virus. Who should NOT get the smallpox vaccine? People most likely to have side effects ...

  7. Intussusception following rotavirus vaccination in the Valencia Region, Spain

    PubMed Central

    Pérez-Vilar, Silvia; Díez-Domingo, Javier; Puig-Barberà, Joan; Gil-Prieto, Ruth; Romio, Silvana

    2015-01-01

    Studies have shown high intussusception rates in Spain. We performed a hospital-based retrospective observational study of the intussusception risk following rotavirus vaccinations among infants in Valencia, a region of Spain with an annual birth cohort of approximately 48,000 children, during 2007–2011, using a self-controlled case series design. We performed medical record review of all cases using Brighton Collaboration´s case definition and assessed the positive predictive value (PPV) of the intussusception diagnosis code. Among 151 hospitalized cases discharged as intussusception, we confirmed 136 as Brighton Collaboration's Levels 1 or 2, resulting in a PPV of 93% (95% CI: 87%–96%). Three confirmed cases occurred within days 1–7 following the first rotavirus vaccination. The incidence rate ratio was 9.0 (95% CI: 0.9–86.5) (crude) and 4.7 (95% CI:0.3–74.1)(age adjusted). In this first study in Europe, the intussusception risk point estimate was comparable to other studies, although results were not statistically significant, maybe due to limited power. The high PPV found will facilitate implementation of a larger study without requiring medical record review. Our finding of very few vaccinated cases despite a thorough 5-year investigation in a country that, according to previous studies, may have a large background rate of intussusception is reassuring and should contribute to deliberations about the need to include rotavirus vaccines in the official Spanish calendars. PMID:26083707

  8. Intussusception following rotavirus vaccination in the Valencia Region, Spain.

    PubMed

    Pérez-Vilar, Silvia; Díez-Domingo, Javier; Puig-Barberà, Joan; Gil-Prieto, Ruth; Romio, Silvana

    2015-01-01

    Studies have shown high intussusception rates in Spain. We performed a hospital-based retrospective observational study of the intussusception risk following rotavirus vaccinations among infants in Valencia, a region of Spain with an annual birth cohort of approximately 48,000 children, during 2007-2011, using a self-controlled case series design. We performed medical record review of all cases using Brighton Collaboration's case definition and assessed the positive predictive value (PPV) of the intussusception diagnosis code. Among 151 hospitalized cases discharged as intussusception, we confirmed 136 as Brighton Collaboration's Levels 1 or 2, resulting in a PPV of 93% (95% CI: 87%-96%). Three confirmed cases occurred within days 1-7 following the first rotavirus vaccination. The incidence rate ratio was 9.0 (95% CI: 0.9-86.5) (crude) and 4.7 (95% CI:0.3-74.1)(age adjusted). In this first study in Europe, the intussusception risk point estimate was comparable to other studies, although results were not statistically significant, maybe due to limited power. The high PPV found will facilitate implementation of a larger study without requiring medical record review. Our finding of very few vaccinated cases despite a thorough 5-year investigation in a country that, according to previous studies, may have a large background rate of intussusception is reassuring and should contribute to deliberations about the need to include rotavirus vaccines in the official Spanish calendars.

  9. Intussusception Rates Before and After the Introduction of Rotavirus Vaccine.

    PubMed

    Tate, Jacqueline E; Yen, Catherine; Steiner, Claudia A; Cortese, Margaret M; Parashar, Umesh D

    2016-09-01

    Recent US studies have identified a small increased risk of intussusception after rotavirus vaccination, mainly after the first dose. We examined trends in intussusception hospitalizations before (2000-2005) and after (2007-2013) rotavirus vaccine introduction to assess whether this observed temporal risk translates into more hospitalized cases at the population level. Intussusception hospitalizations in children <12 months of age were abstracted from the State Inpatient Database maintained by the Healthcare Cost and Utilization Project for 26 states that provided data from 2000 to 2013. Rates were calculated using bridged-race postcensal population estimates. Trends were analyzed by age groups (6-14 weeks, 15-24 weeks, and 25-34 weeks) based on the recommended ages for vaccine administration as well as 8-11 weeks when the majority of first doses are given. Rate ratios were calculated by using Poisson regression. No consistent change in intussusception hospitalization rates was observed among all children <12 months of age and among children 15 to 24 weeks and 25 to 34 weeks of age. The intussusception hospitalization rate for children aged 8 to 11 weeks was significantly elevated by 46% to 101% (range: 16.7-22.9 per 100 000) in all postvaccine years except 2011 and 2013 compared with the prevaccine baseline (11.7 per 100 000). The increase in the intussusception hospitalization rate in children 8 to 11 weeks when the majority of first doses of vaccine are given is consistent with recent US postlicensure studies. Given the magnitude of declines in rotavirus disease compared with this small increase in intussusception, the benefits of rotavirus vaccination outweigh the increase risk of intussusception. Copyright © 2016 by the American Academy of Pediatrics.

  10. Health Impact of Rotavirus Vaccination in Developing Countries: Progress and Way Forward.

    PubMed

    Parashar, Umesh D; Johnson, Hope; Steele, A Duncan; Tate, Jacqueline E

    2016-05-01

    Two rotavirus vaccines have been licensed in >100 countries worldwide since 2006. As of October 2105, these vaccines have been implemented in the national immunization programs of 79 countries, including 36 low-income countries that are eligible for support for vaccine purchase from Gavi, the Vaccine Alliance. Rotavirus vaccines were initially introduced in Australia and countries of the Americas and Europe after completion of successful clinical trials in these regions, and the impact of routine vaccination in reducing the health burden of severe childhood gastroenteritis in these regions has been well documented. Because of concerns around the performance of orally administered rotavirus vaccines in developing countries, vaccine implementation in these settings only began after additional clinical trials were completed and the World Health Organization issued a global recommendation for use of rotavirus vaccines in 2009. This supplementary issue of Clinical Infectious Diseases includes a collection of articles describing the impact and effectiveness of routine rotavirus vaccination in developing countries that were among the early adopters of rotavirus vaccine. The data highlight the benefits of vaccination and should provide valuable evidence to sustain vaccine use in these countries and encourage other countries to adopt routine rotavirus vaccination to reduce the health burden of severe childhood gastroenteritis.

  11. Diarrhea incidence and intestinal infections among rotavirus vaccinated infants from a poor area in Brazil: a spatial analysis

    PubMed Central

    2014-01-01

    Background Acute diarrhea is the second leading cause of mortality among children under 5 years of age in developing countries. The pathogen most strongly associated with diarrhea is rotavirus followed by enteric pathogens such as bacteria, helminthes and protozoan. Adequate sanitation and water supply contribute to decrease acute diarrhea incidence of most etiologic agents, although vaccination remains the most important intervention to control rotavirus acute diarrhea. This study aimed to describe environmental conditions and analyze spatially the acute diarrhea and intestinal infection among rotavirus vaccinated infants from Laranjeiras-Sergipe, Brazil. Methods Children were enrolled between 2 and 11 months of age and followed through 12 months. Demographic, socioeconomic and environmental data were obtained from a questionnaire, and immunization data were obtained from children vaccination card. Children stool samples were collected each month in order to run laboratory analyses. The household spatial localization was obtained by using a Global Positioning System (GPS). Spatial analysis was performed using the TerraView computer program and Kernel intensity estimation. Results A total of 1,113 stool samples were collected with 80 being diarrhea associated. Diarrhea incidence rate was 0.5 ± 1.0 episodes/child/year. The overall infection rates by Ascaris lumbricoides, Endolimax nana, Giardia lamblia and rotavirus were 5.1%, 3.0%, 0.9% and 2.6%, respectively. 3.8% of diarrhea-associated stool samples were positive for rotavirus and 11.3% were positive for helminths and protozoans. There were some changes on spatial distribution of intestinal infections and diarrhea episodes along the four trimesters evaluated. Conclusions The studied infants live equally in precarious conditions of sanitation which probably explain the significant rates of parasitic infections appearing in early life. The low acute diarrhea incidence in the studied rotavirus vaccinated

  12. Cost-Effectiveness of Rotavirus Vaccination in France-Accounting for Indirect Protection.

    PubMed

    Yamin, Dan; Atkins, Katherine E; Remy, Vanessa; Galvani, Alison P

    Vaccination against rotavirus has shown great potential for reducing the primary cause of severe childhood gastroenteritis. Previous economic evaluations of rotavirus vaccination in France have not modeled the potential impact of vaccines on disease burden via reduced transmission. To determine the cost-effectiveness of the introduction of pentavalent rotavirus vaccination into the French infant vaccination schedule. We developed an age-structured model of rotavirus transmission calibrated to 6 years of French gastroenteritis incidence and vaccine clinical trial data. We evaluated the cost-effectiveness of pentavalent rotavirus vaccination considering that 75% of infants would receive the three-dose vaccine course. Our model predicts that rotavirus vaccination will decrease rotavirus gastroenteritis incidence and associated clinical outcomes in vaccinated and unvaccinated individuals, delay the seasonal peak of infection, and increase the age of infection. From the societal perspective, our base-case scenario predicts that vaccination coverage would be cost-effective at €115 or €135 per vaccine course at €28,500 and €39,500/quality-adjusted life-year (QALY) gained, respectively, and suggests that almost 95% of the financial benefits will be recouped within the first 5 years following vaccination implementation. From the third-party payer perspective, incremental cost-effectiveness ratios ranged from €12,500 to €20,000/QALY, respectively. Our uncertainty analysis suggests that findings were sensitive to various assumptions including the number of hospitalizations, outpatient visits, and the extent of QALY losses per rotavirus episode. Introducing pentavalent rotavirus vaccination into the French infant vaccination schedule would significantly reduce the burden of rotavirus disease in children, and could be cost-effective under plausible conditions. Copyright © 2016 International Society for Pharmacoeconomics and Outcomes Research (ISPOR). Published by

  13. Potential intussusception risk versus health benefits from rotavirus vaccination in Latin America.

    PubMed

    Desai, Rishi; Parashar, Umesh D; Lopman, Benjamin; de Oliveira, Lucia Helena; Clark, Andrew D; Sanderson, Colin F B; Tate, Jacqueline E; Matus, Cuahtemoc Ruiz; Andrus, Jon K; Patel, Manish M

    2012-05-01

    With the recent postlicensure identification of an increased risk of intussusception with rotavirus vaccine, the 14 Latin American countries currently using rotavirus vaccine must now weigh the health benefits versus risks to assess whether to continue vaccination. To inform policy considerations, we estimated excess intussusception cases and mortality potentially caused by rotavirus vaccine for each of the 14 countries and compared these estimates to hospitalizations and deaths expected to be averted through vaccination. We used regional rotavirus disease burden and rotavirus vaccine efficacy data, global natural intussusception and regional rotavirus vaccine-related risk estimates, and country-specific diphtheria, tetanus, and pertussus vaccination coverage rates to estimate rotavirus vaccine coverage rates. We performed a probabilistic sensitivity analysis to account for uncertainty in these parameters. For an aggregate hypothetical birth cohort of 9.5 million infants in these 14 countries, rotavirus vaccine would annually prevent 144 746 (90% confidence interval [CI], 128 821-156 707) hospitalizations and 4124 deaths (90% CI, 3740-4239) due to rotavirus in their first 5 years of life but could cause an additional 172 hospitalizations (90% CI, 126-293) and 10 deaths (90% CI, 6-17) due to intussusception, yielding benefit-risk ratios for hospitalization and death of 841:1 (90% CI, 479:1 to 1142:1) and 395:1 (90% CI, 207:1 to 526:1), respectively. In an uncertainty analysis using 10 000 simulations of our probabilistic parameters, in comparing rotavirus disease averted to intussusception events caused, the hospitalization ratio was never below 100:1, and our death ratio fell below 100:1 only once. The health benefits of vaccination far outweigh the short-term risks and support continued rotavirus vaccination in Latin America.

  14. [Economic effectiveness of vaccination against rotavirus infection in the Russian Federation].

    PubMed

    Kostinov, M P; Zverev, V V

    2012-01-01

    Perform pharmacoeconomic analysis of the effectiveness of implementation of vaccination program against rotavirus infection in the Russian Federation. Cost-benefit analytical method was used for the evaluation of economic effectiveness of vaccination against rotavirus infection in the Russian Federation. The number of early vaccinated--1 800 000 individuals, the number of rotavirus enteritis cases in 0 - 5 age cohort--166 215, were determined. The effectiveness of vaccination against rotavirus gastroenteritis was adopted from ATP (according-to-protocol) clinical trial data and was 83.8% cases at a 95% vaccination level. The cost of a case of rotavirus infection according to calculations in the Russian Federation is 17 394 RUB (Russian rubles), and the cost of vaccination of 1 child--1000 RUB. The cost of realization of program of vaccination against rotavirus infection would be 1.7 billion RUB per year. The number of prevented cases of rotavirus infection per year in the cohort of children aged up to 5 years would be 148 114. Net benefit of vaccination of newborn children in the Russian Federation would be 866 million RUB. Implementation of program of vaccination against rotavirus infection in the Russian Federation would promote the decrease of morbidity and economical efficiency. The cost of vaccination program is 1.5 times less than the amount of expenses related to infection.

  15. Rotavirus vaccination of very low birth weight infants at discharge from the NICU.

    PubMed

    Stumpf, Katherine A; Thompson, Tami; Sánchez, Pablo J

    2013-09-01

    Preterm infants are at increased risk of severe rotavirus gastroenteritis. Although immunization with rotavirus vaccine is safe and effective, age restrictions limit the number of infants eligible for vaccination at discharge from the NICU. The objectives of this study were to assess the implementation of the rotavirus vaccine program in our NICU, recognize missed opportunities for vaccination, and document how often very low birth weight (VLBW; birth weight ≤1500 g) and extremely low birth weight (ELBW; birth weight <1000 g) infants were eligible to receive rotavirus vaccine at the time of NICU discharge. This study reports on a prospective, observational cohort of all VLBW infants who were discharged from the NICU at Parkland Memorial Hospital from May 2008 to April 2010. Medical records were reviewed and data collected regarding the number of infants who were eligible for and received rotavirus vaccination at discharge. A total of 63% (135 of 213) of VLBW infants did not receive rotavirus vaccine. The reasons for not providing vaccine included the following: <42 days of age at discharge (56 of 213; 26%), >84 or 104 days of age at discharge (48 of 213; 23%), or missed (35 of 213; 16%). The majority (75%) who were too old for vaccination at the time of discharge were ELBW. The current age restrictions for rotavirus immunization resulted in more than half of ELBW infants being ineligible for vaccination at the time of discharge from the NICU. Alternative strategies for rotavirus immunization in this population are needed.

  16. 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 Central

    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

    2017-01-01

    Introduction 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. Methods and analysis 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. Ethics and dissemination 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

  17. Rotavirus specific maternal antibodies and immune response to RV3-BB neonatal rotavirus vaccine in New Zealand.

    PubMed

    Chen, Mee-Yew; Kirkwood, Carl D; Bines, Julie; Cowley, Daniel; Pavlic, Daniel; Lee, Katherine J; Orsini, Francesca; Watts, Emma; Barnes, Graeme; Danchin, Margaret

    2017-05-04

    Maternal antibodies, acquired passively via placenta and/or breast milk, may contribute to the reduced efficacy of oral rotavirus vaccines observed in children in developing countries. This study aimed to investigate the effect of rotavirus specific maternal antibodies on the serum IgA response or stool excretion of vaccine virus after any dose of an oral rotavirus vaccine, RV3-BB, in parallel to a Phase IIa clinical trial conducted at Dunedin Hospital, New Zealand. At the time of the study rotavirus vaccines had not been introduced in New Zealand and the burden of rotavirus disease was evident. Rotavirus specific IgG and serum neutralizing antibody (SNA) levels in cord blood and IgA levels in colostrum and breast milk samples collected ∼4 weeks, ∼20 weeks and ∼28 weeks after birth were measured. Infants were randomized to receive the first dose of vaccine at 0-5 d (neonatal schedule) or 8 weeks (infant schedule). Breast feeding was with-held for 30 minutes before and after vaccine administration. The relationship between rotavirus specific IgG and SNA levels in cord blood and IgA in colostrum and breast milk at the time of first active dose of RV3-BB vaccine and level of IgA response and stool excretion after 3 doses of vaccine was assessed using linear and logistic regression. Forty infants received 3 doses of RV3-BB rotavirus vaccine and were included in the analysis of the neonatal and infant groups. Rotavirus specific IgA in colostrum (neonatal schedule group) and breast milk at 4 weeks (infant schedule group) was identified in 14/21 (67%) and 14/17 (82%) of infants respectively. There was little evidence of an association between IgA in colostrum or breast milk IgA at 4 weeks, or between cord IgG or SNA level, and IgA response or stool excretion after 3 doses of RV3-BB, or after one dose (neonatal schedule) (all p>0.05). The level of IgA in colostrum or breast milk and level of placental IgG and SNA did not impact on the serum IgA response or

  18. Pentavalent Rotavirus Vaccine in Infants With Surgical Gastrointestinal Disease

    PubMed Central

    McGrath, Eric J.; Thomas, Ron; Duggan, Christopher; Asmar, Basim I.

    2015-01-01

    Objectives Pentavalent rotavirus vaccine (RV5) has been shown to be well-tolerated and efficacious in preventing rotavirus gastroenteritis in healthy infants. Safety and immunogenicity of RV5 in infants with surgical gastrointestinal disease have not been studied. The aim of the present study was to evaluate the safety and immunogenicity of RV5 in infants with a history of congenital or acquired intestinal disease requiring resection compared with healthy infants. Methods Infants with intestinal resection were matched by gestational age and chronological age to healthy infants (controls). Dose 1 of RV5 was given at 10 to 12 weeks of chronological age. Doses 2 and 3 were given at intervals of 4 to 10 weeks, with all 3 doses given by 32 weeks. All infants were monitored for adverse events (AEs) by telephone calls, clinic visits, and parental written reports during the first 42 days after each dose and monthly thereafter by telephone for 12 months. Serum anti-rotavirus immunoglobulin A (IgA) titers were measured prevaccination and 2 weeks after dose 3. Results A total of 5 infants with surgical gastrointestinal disease and 3 control subjects were enrolled. All participants (100%) mounted a 3-fold increase in serum anti-rotavirus IgA geometric mean titer postvaccination. RV5 administration to surgical infants was well tolerated with a majority of AEs being attributed to the underlying medical condition. Conclusions Postvaccination serum anti-rotavirus IgA levels indicate that RV5 is immunogenic in infants with a history of bowel resection, despite varying lengths of residual bowel. RV5 was well tolerated with few vaccine-related AEs. PMID:24614127

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

    PubMed

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

    2016-04-02

    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.

  20. 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

  1. Does a monovalent inactivated human rotavirus vaccine induce heterotypic immunity? Evidence from animal studies.

    PubMed

    Jiang, Baoming; Wang, Yuhuan; Glass, Roger I

    2013-08-01

    There is substantial evidence for broad cross-reactive immunity and heterotypic protection among human rotavirus strains in children with natural infection or with monovalent Rotarix vaccination. In this commentary, we addressed this same topic by testing sera of guinea pigs and gnotobiotic piglets that were intramuscularly immunized with an inactivated human rotavirus vaccine and also demonstrated a broad cross-protective immunity among human rotavirus strains. Our findings from a single human strain in animal studies bode well for a low cost and efficacious inactivated vaccine to protect children against rotavirus disease throughout the world.

  2. Evaluating the safety of a rotavirus vaccine: the REST of the story

    PubMed Central

    Kuter, Barbara J; Dallas, Michael J; Heaton, Penny

    2008-01-01

    The Rotavirus Efficacy and Safety Trial (REST) was a blinded, placebo-controlled study of the live pentavalent human-bovine vaccine, RotaTeq® (Merck & Co. Inc., West Point, PA). REST was noteworthy because its primary objective was to evaluate the safety of RotaTeq® with regard to intussusception, a rare intestinal illness that occurs with a background incidence of approximately 50 cases per 100 000 infant years. The study involved approximately 70 000 infants at over 500 study sites in 11 countries. The study demonstrated that the risk of intussusception was similar in vaccine and placebo recipients and that the vaccine prevented rotavirus gastroenteritis, ameliorated the severity of disease in those who had any disease, and substantially reduced rotavirus-associated hospitalizations and other health care contacts. This report provides an in-depth review of the background, statistical and regulatory considerations, and execution of REST. We describe the rationale and methods used for sample size, continuous safety monitoring, group sequential design, and detailed study execution. The results of the study have been reported elsewhere. The design and conduct of this study may serve as a useful model for planning other future large-scale clinical trials, especially those evaluating uncommon adverse events. PMID:18375651

  3. Tandem truncated rotavirus VP8* subunit protein with T cell epitope as non-replicating parenteral vaccine is highly immunogenic

    PubMed Central

    Wen, Xiaobo; Cao, Dianjun; Jones, Ronald W; Hoshino, Yasutaka; Yuan, Lijuan

    2015-01-01

    The two currently available live oral rotavirus vaccines, Rotarix® and RotaTeq®, are highly efficacious in the developed countries. However, the efficacy of such vaccines in resource deprived countries in Africa and Southeast Asia is low. We reported previously that a bacterially-expressed rotavirus P2-P[8] ΔVP8* subunit vaccine candidate administered intramuscularly elicited high-titers of neutralizing antibodies in guinea pigs and mice and significantly shortened the duration of diarrhea in neonatal gnotobiotic pigs upon oral challenge with virulent human rotavirus Wa strain. To further improve its vaccine potential and provide wider coverage against rotavirus strains of global and regional epidemiologic importance, we constructed 2 tandem recombinant VP8* proteins, P2-P[8] ΔVP8*-P[8] ΔVP8* and P2-P[8] ΔVP8*-P[6] ΔVP8* based on Escherichia coli expression system. The two resulting recombinant tandem proteins were highly soluble and P2-P[8] ΔVP8*-P[8] ΔVP8* was generated with high yield. Moreover, guinea pigs immunized intramuscularly by 3 doses of the P2-P[8] ΔVP8*-P[8] ΔVP8* or P2-P[8] ΔVP8*-P[6] ΔVP8* vaccine with aluminum phosphate adjuvant developed high titers of homotypic and heterotypic neutralizing antibodies against human rotaviruses bearing G1-G4, G8, G9 and G12 with P[8], P[4] or P[6] combination. The results suggest that these 2 subunit vaccines in monovalent or bivalent formulation can provide antigenic coverage to almost all the rotavirus G (VP7) types and major P (VP4) types of global as well as regional epidemiologic importance. PMID:26091081

  4. Rotavirus epidemiology 5-6 years after universal rotavirus vaccination: persistent rotavirus activity in older children and elderly.

    PubMed

    Markkula, Jukka; Hemming-Harlo, Maria; Salminen, Marjo T; Savolainen-Kopra, Carita; Pirhonen, Jaana; Al-Hello, Haider; Vesikari, Timo

    2017-05-01

    Rotavirus (RV) vaccination using RotaTeq(®) vaccine exclusively was introduced into Finnish National Immunization Program (NIP) in 2009, and soon reached high (≥90%) coverage. Since mid-2013, all stool samples from laboratory diagnosed cases of RV gastroenteritis in the entire country have been typed. 364 RV positive stool samples collected from clinical laboratories over a 2-year period were G- and P-typed using RT-PCR, and the results were confirmed by sequencing. In addition, the genome segment encoding for VP6 was sequenced to distinguish between wild-type and vaccine origin (bovine) RVs. RV winter epidemic seasons 2013-2014 and 2014-2015 lasted until July each. The age distribution of RV cases showed two unusual clusters: one in children 6-16 years of age, too old to have been vaccinated in NIP, and the other in elderly over 70 years of age. In children, diverse genotypes were observed without any obvious predominance. The most common ones were G1P[8] (30.0%), G2P[4] (22.4%), G9P[8] (15.8%), G3P[8] (12.2%) and G4P[8] (11.2%). The genotype distribution was not different among vaccinated and unvaccinated children. Most cases in the elderly were associated with G2P[4]. Even at high vaccine coverage and high effectiveness of RV vaccine, RV activity continues to persist, particularly in unvaccinated older children. RV genotypes show greater diversity than before RV vaccinations. We conclude that RV disease can be controlled but not eliminated by vaccinations. Herd-protection in long-term follow-up may be less than at the start of RV vaccinations.

  5. Analysis of factors in response to rotavirus vaccination counselling in a private paediatric clinic.

    PubMed

    Kannan Kutty, P; Pathmanathan, G; Salleh, N M

    2010-06-01

    Rotavirus vaccine is available as an optional vaccine in Malaysia. The counselling of optional vaccines is considered an integral part of the health services offered in a private paediatric clinic. While ensuring that all babies are up-todate with their compulsory immunization, counselling of optional vaccines like the rotavirus vaccine could give parents the choice to make an informed decision on the acceptance of this vaccine. Over a period of two years, we counselled the parents regarding diarrhoea caused by rotavirus disease and the rotavirus vaccine. In this study, the factors that were significantly associated with the acceptance of the rotavirus vaccine were the gender of the baby, the mother's age, the mother's occupation, the mode of payment for the vaccine, the number of previous visits to the clinic by the parents, the number of counselling sessions given to the parents and the pre-counselling awareness or knowledge of rotavirus disease and rotavirus vaccine. It is hoped that these findings may assist busy clinicians in their continuous efforts to provide health education and vaccination counselling to the parents of their patients.

  6. Effectiveness of rotavirus vaccination in prevention of hospital admissions for rotavirus gastroenteritis among young children in Belgium: case-control study

    PubMed Central

    Braeckman, Tessa; Van Herck, Koen; Meyer, Nadia; Pirçon, Jean-Yves; Soriano-Gabarró, Montse; Heylen, Elisabeth; Zeller, Mark; Azou, Myriam; Capiau, Heidi; De Koster, Jan; Maernoudt, Anne-Sophie; Raes, Marc; Verdonck, Lutgard; Verghote, Marc; Vergison, Anne; Matthijnssens, Jelle; Van Ranst, Marc

    2012-01-01

    Objective To evaluate the effectiveness of rotavirus vaccination among young children in Belgium. Design Prospective case-control study. Setting Random sample of 39 Belgian hospitals, February 2008 to June 2010. Participants 215 children admitted to hospital with rotavirus gastroenteritis confirmed by polymerase chain reaction and 276 age and hospital matched controls. All children were of an eligible age to have received rotavirus vaccination (that is, born after 1 October 2006 and aged ≥14 weeks). Main outcome measure Vaccination status of children admitted to hospital with rotavirus gastroenteritis and matched controls. Results 99 children (48%) admitted with rotavirus gastroenteritis and 244 (91%) controls had received at least one dose of any rotavirus vaccine (P<0.001). The monovalent rotavirus vaccine accounted for 92% (n=594) of all rotavirus vaccine doses. With hospital admission as the outcome, the unadjusted effectiveness of two doses of the monovalent rotavirus vaccine was 90% (95% confidence interval 81% to 95%) overall, 91% (75% to 97%) in children aged 3-11 months, and 90% (76% to 96%) in those aged ≥12 months. The G2P[4] genotype accounted for 52% of cases confirmed by polymerase chain reaction with eligible matched controls. Vaccine effectiveness was 85% (64% to 94%) against G2P[4] and 95% (78% to 99%) against G1P[8]. In 25% of cases confirmed by polymerase chain reaction with eligible matched controls, there was reported co-infection with adenovirus, astrovirus and/or norovirus. Vaccine effectiveness against co-infected cases was 86% (52% to 96%). Effectiveness of at least one dose of any rotavirus vaccine (intention to vaccinate analysis) was 91% (82% to 95%). Conclusions Rotavirus vaccination is effective for the prevention of admission to hospital for rotavirus gastroenteritis among young children in Belgium, despite the high prevalence of G2P[4] and viral co-infection. PMID:22875947

  7. A universal infant rotavirus vaccine program in two delivery models: Effectiveness and adverse events following immunization.

    PubMed

    Sanford, Carolyn; Langley, Joanne M; Halperin, Scott A; Zelman, Mitchell; Mvrvp

    2015-01-01

    Rotavirus is the most common cause of diarrhea leading to hospitalization in young children. Rotavirus vaccines are available in Canada but have not been introduced in all provinces. In a controlled trial, 2 study sites (Prince Edward Island and the Capital District Health Authority (District 9, Nova Scotia) introduced universal rotavirus vaccine programs for infants at 2 and 4 months of age beginning 1 December 2010, using public health nurse or general practitioner-delivery models, respectively. A third site (Saint John, NB) served as the non-intervention control setting. Vaccine coverage, rotavirus hospitalizations, intussusception and all-cause diarrhea were monitored. A universal rotavirus vaccine program with >90% coverage was associated with reductions in rotavirus-associated hospitalizations (from a peak of 52.8 hospitalizations/100,000 population to 0 hospitalizations) in infants < 12 months and 1 to < 2 y of age 12 months after program implementation. No apparent reduction occurred in the site with vaccine coverage of < 40%, or in the non-intervention control site. No cases of intussusception were associated with vaccine receipt, and no increase in all-cause diarrhea was observed. A universal infant rotavirus vaccine program with high coverage was associated with reductions in rotavirus and no safety signals; no reduction was observed in settings with low vaccine coverage.

  8. Socio-economic modelling of rotavirus vaccination in Castilla y Leon, Spain.

    PubMed

    Pérez-Rubio, Alberto; Luquero, Francisco Javier; Eiros Bouza, Jose María; Castrodeza Sanz, Jose Javier; Bachiller Luque, Maria Rosario; de Lejarazu, Raúl Ortiz; Sánchez Porto, Antonio

    2011-09-01

    Rotavirus is one of the main causes of acute gastroenteritis in infants and young children. Furthermore, rotavirus is the leading cause of hospitalization and death from acute gastroenteritis among infants and young children worldwide. Although death due to rotavirus is rare in industrialized regions such as Spain, the rotavirus disease burden and its economic impact is severe. This study aims to assess systematic vaccination against rotavirus economically and socially in a Spanish region. Economic cost-effectiveness and cost-benefit assessment through a choice tree was designed. We estimated health provider costs, economic costs and quality-adjusted life years (QALYs) lost due to rotavirus infections. The study includes a fictitious cohort of 100,000 children from Castilla y Leon who were also administered the rotavirus vaccine together with diphtheria and tetanus toxoids and pertussis (DTP) . The study adopted a society and health care system perspective. A sensitivity analysis was developed to assess the uncertainty of some variables. According to the estimated incidence rate for children in Castilla y Leon, rotavirus immunization is projected to prevent 45% of cases with RotaTeq and 57% with Rotarix. The respective cost per QALY is about Euro 75,000 and 50,000 from the perspective of the health care system. Routine infant vaccination in Castilla y Leon using either rotavirus vaccine is not profitable from the payer's perspective and is not cost-effective under basic case assumptions unless the vaccine is available at a lower cost.

  9. Dual functions of Lactobacillus acidophilus NCFM™ at the intermediate dose in protection against rotavirus diarrhea in gnotobiotic pigs vaccinated with a human rotavirus vaccine

    PubMed Central

    Liu, Fangning; Wen, Ke; Li, Guohua; Yang, Xingdong; Kocher, Jacob; Bui, Tammy; Jones, Dorothy; Pelzer, Kevin; Clark-Deener, Sherrie; Yuan, Lijuan

    2014-01-01

    Objectives To examine dose effects of Lactobacillus acidophilus NCFM (LA) ™ strain on rotavirus-specific antibody and B cell responses in gnotobiotic pigs vaccinated with an oral attenuated human rotavirus (AttHRV). Methods Pigs were inoculated with AttHRV vaccine in conjunction with high dose LA (14 doses, total 2.2×109 colony forming units [CFU]), intermediate dose LA (9 doses, total 3.2×106 CFU), low dose LA (5 doses, total 2.1×106 CFU) or without LA feeding. Protection against rotavirus shedding and diarrhea was assessed upon challenge with a virulent HRV. Rotavirus-specific IgA and IgG antibodies in serum and rotavirus-specific IgA and IgG antibody-secreting cells (ASC) and memory B cells in ileum, spleen and blood of the pigs were measured and compared among treatment groups. Results The intermediate dose LA (MidLA), but not high or low dose LA, significantly reduced rotavirus diarrhea (MidLA only group) and significantly improved the protection conferred by AttHRV vaccine (MidLA+AttHRV group). Associated with the increased protection, MidLA significantly enhanced rotavirus-specific antibody, ASC and memory B cell responses to AttHRV vaccine. High or low dose LA did not enhance virus-specific antibody and ASC responses, hence did not improve the vaccine efficacy. Conclusions These findings highlight the importance of dose selection and indicate that certain specific lactobacilli strains at the appropriate dose have the dual function of reducing rotavirus diarrhea and enhancing the immunogenicity and protective efficacy of rotavirus vaccines. PMID:24126832

  10. Rotavirus specific plasma secretory immunoglobulin in children with acute gastroenteritis and children vaccinated with an attenuated human rotavirus vaccine

    PubMed Central

    Herrera, Daniel; Vásquez, Camilo; Corthésy, Blaise; Franco, Manuel A; Angel, Juana

    2013-01-01

    Rotavirus (RV)–specific secretory immunoglobulin (RV-SIg) has been previously detected in serum of naturally RV infected children and shown to reflect the intestinal Ig immune response. Total plasma SIgA and plasma RV-SIg were evaluated by ELISA in children with gastroenteritis due or not due to RV infection and in 50 children vaccinated with the attenuated RIX4414 human RV vaccine and 62 placebo recipients. RV-SIg was only detected in children with evidence of previous RV infection or with acute RV gastroenteritis. Vaccinees had higher RV-SIg titers than placebo recipients and RV-SIg titers increased after the second vaccine dose. RV-SIg measured after the second dose correlated with protection when vaccinees and placebo recipients were analyzed jointly. RV-SIg may serve as a valuable correlate of protection for RV vaccines. PMID:23839157

  11. 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.

  12. Rotavirus Vaccine: What You Need to Know

    MedlinePlus

    ... As with any medicine, there is a very remote chance of a vaccine causing a serious injury ... state health department. • Contact the Centers for Disease Control and Prevention (CDC): - Call 1-800-232-4636 ( ...

  13. Rotavirus vaccine - what you need to know

    MedlinePlus

    ... As with any medicine, there is a very remote chance of a vaccine causing a serious injury ... state health department . Contact the Centers for Disease Control and Prevention (CDC): Call 1-800-232-4636 ( ...

  14. Case-control study of the effectiveness of vaccination with pentavalent rotavirus vaccine in Nicaragua.

    PubMed

    Mast, T Christopher; Khawaja, Shazia; Espinoza, Félix; Paniagua, Margarita; Del Carmen, Leonel Palacio; Cardellino, Anna; Sánchez, Edmundo

    2011-11-01

    In 2006, Merck & Co., Inc., partnered with the Nicaraguan Ministry of Health to demonstrate the public health impact of routine universal vaccination by delivering more than 1.3 million doses of the oral, pentavalent rotavirus vaccine (RV5) in a 3-year period. A matched case-control study evaluated the effectiveness of RV5 in reducing the risk for severe wild-type rotavirus gastroenteritis (RGE) resulting in hospitalizations and emergency department visits among children who completed the recommended 3-dose regimen as part of the routine national vaccine program. Cases were identified from 6 hospitals from February 2007 to October 2009 and were age-matched with hospital controls and community controls. Vaccine effectiveness was calculated using conditional logistic regression. Three hundred RGE cases eligible for analysis were matched to 792 hospital and 851 community controls. Vaccine coverage of RV5 in the community reached 92%. Vaccine effectiveness during 2 years of follow-up against severe disease in children receiving 3 doses of RV5 was 87% (95% confidence interval [CI], 74-93) for community controls, 64% (95% CI, 44-78) for hospital controls, and 76% (95% CI, 63-84) when the groups were combined. For the combined groups, vaccine effectiveness was 85% (95% CI, 66-93) among children <12 months old at the time of RGE onset. The Merck-Nicaragua Rotavirus Vaccine Partnership promoted rapid and widespread uptake of a novel vaccine in a developing country. Vaccine effectiveness was greatest for children younger than 12 months of age who were at the highest risk for severe rotavirus disease.

  15. Post-licensure experience with rotavirus vaccination in high and middle income countries; 2006 to 2011.

    PubMed

    Lopman, Ben A; Payne, Daniel C; Tate, Jacqueline E; Patel, Manish M; Cortese, Margaret M; Parashar, Umesh D

    2012-08-01

    Rotavirus causes one-third to one-half of severe diarrheal disease in children under the age of five years worldwide. In 2006 two rotavirus vaccines became available and, in the intervening years, approximately thirty countries have introduced them into their immunization programs, primarily in high-income and middle-income settings. Major reductions in rotavirus hospitalizations have been observed in a number of these locations, and in select countries, there have been impacts on gastroenteritis mortality associated with rotavirus vaccine introduction. In addition to these direct health benefits, reduced gastroenteritis risk has been documented in unvaccinated groups, including older children and adults, suggesting indirect benefits (i.e. herd immunity). In this paper, we summarize what has been learned from programs studying post-licensure vaccine effectiveness, impact on health-care utilization and death, safety issues (namely, intussception and the detection of adventitious viruses) and the potential selective pressure of vaccination on the diversity of rotavirus genotypes.

  16. 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.

  17. Rotavirus vaccine strain transmission by vaccinated infants in the foster home.

    PubMed

    Miura, Hiroki; Kawamura, Yoshiki; Sugata, Ken; Koshiyama, Nozomi; Yoshikawa, Akiko; Komoto, Satoshi; Taniguchi, Koki; Ihira, Masaru; Yoshikawa, Tetsushi

    2017-01-01

    Previous studies have demonstrated the transmission of rotavirus vaccine strains from vaccinated children to nonvaccinated siblings. We sought to fully elucidate the safety of rotavirus (RV) vaccination in closed contact circumstance, such as the foster home for future assessment of the vaccine safety in an neonatal intensive care unit. Stool samples were collected from 4 RV vaccinated (160 samples) and 23 unvaccinated (766 samples) infants. RV viral RNA loads were measured using real-time reverse transcription polymerase chain reaction (RT-PCR). RV vaccine strain RNA was persistently detected in stool samples collected from the four vaccine recipients and one unvaccinated infant, but not in the stool samples collected from the 22 other unvaccinated infants. The unvaccinated infant who tested positive for the RV vaccine strain was vaccinated prior to enrollment in this study. The quantitative real-time RT-PCR data revealed a peak viral RNA load 1 week after vaccination followed by a gradual decrease. The current study suggests that RV vaccination may be safe in a close contact environment because there was limited transmission from RV vaccinated to unvaccinated infants. J. Med. Virol. 89:79-84, 2017. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  18. Rotavirus vaccines and health care utilization for diarrhea in the United States (2007-2011).

    PubMed

    Leshem, Eyal; Moritz, Rebecca E; Curns, Aaron T; Zhou, Fangjun; Tate, Jacqueline E; Lopman, Benjamin A; Parashar, Umesh D

    2014-07-01

    To examine reductions in diarrhea-associated health care utilization after rotavirus vaccine implementation and to assess direct and indirect effectiveness of vaccination. Retrospective cohort analysis of claims data of commercially insured US children aged <5 years. We examined annual pentavalent (RV5) and monovalent (RV1) rotavirus vaccine coverage. We compared rates of diarrhea-associated health care utilization in prevaccine (2001-2006) versus postvaccine introduction (2007-2011) years, compared rates of diarrhea-associated health care utilization in vaccinated versus unvaccinated children and compared rates in unvaccinated children in postvaccine versus prevaccine years. Among children aged <5 years, RV5 and RV1 rotavirus vaccine coverage rates reached 58% and 5%, respectively, by December 31, 2010. Compared with the average rate of rotavirus-coded hospitalizations in 2001-2006, rates were reduced by 75% in 2007-2008, 60% in 2008-2009, 94% in 2009-2010, and 80% in 2010-2011. Compared with unvaccinated children, in 2010-2011, the rate of rotavirus-coded hospitalizations was reduced by 92% among RV5 recipients and 96% among RV1 recipients. Rotavirus-coded hospitalization rate reductions among RV5 recipients versus unvaccinated children ranged from 87% among <1-year-olds to 81% among 4-year-olds. Compared with prevaccine rates in 2001-2006, rotavirus-coded hospitalization rates among unvaccinated children decreased by 50% in 2007-2008, 77% in 2009-2010, and 25% in 2010-2011. Implementation of rotavirus vaccines has substantially reduced diarrhea health care utilization in US children. Both rotavirus vaccines conferred high protection against rotavirus hospitalizations; RV5 conferred durable protection through the fourth year of life. Vaccination also conferred indirect benefits to unvaccinated children. Copyright © 2014 by the American Academy of Pediatrics.

  19. 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

  20. 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.

  1. [A cost-effectiveness analysis on universal infant rotavirus vaccination strategy in China].

    PubMed

    Sun, S L; Gao, Y Q; Yin, J; Zhuang, G H

    2016-02-01

    To evaluate the cost-effectiveness of current universal infant rotavirus vaccination strategy, in China. Through constructing decision tree-Markov model, we simulated rotavirus diarrhea associated cost and health outcome on those newborns in 2012 regarding different vaccination programs as: group with no vaccination, Rotavirus vaccination group and Rotateq vaccination group, respectively. We determined the optimal program, based on the comparison between incremental cost-effectiveness ratio (ICER) and China' s 2012 per capital gross domestic product (GDP). Compared with non-vaccination group, the Rotavirus vaccination and Rotateq vaccination groups had to pay 3 760 Yuan and 7 578 Yuan (both less than 2012 GDP per capital) to avert one disability adjusted life years (DALY) loss, respectively. RESULTS from sensitivity analysis indicated that both results were robust. Compared with Rotavirus vaccination program, the Rotateq vaccination program had to pay extra 81 068 Yuan (between 1 and 3 times GDP per capital) to avert one DALY loss. Data from the sensitivity analysis indicated that the result was not robust. From the perspective of health economics, both two-dose Rotarix vaccine and three-dose' s Rotateq vaccine programs were highly cost-effective, when compared to the non-vaccination program. It was appropriate to integrate rotavirus vaccine into the routine immunization program. Considering the large amount of extra cost that had to spend on Rotateq vaccination program, results from the sensitivity analysis showed that it was not robust. Rotateq vaccine required one more dose than the Rotarix vaccine, to be effective. However, it appeared more difficult to practice, suggesting that it was better to choose the Rotarix vaccine, at current stage.

  2. Understanding Reduced Rotavirus Vaccine Efficacy in Low Socio-Economic Settings

    PubMed Central

    Lopman, Benjamin A.; Pitzer, Virginia E.; Sarkar, Rajiv; Gladstone, Beryl; Patel, Manish; Glasser, John; Gambhir, Manoj; Atchison, Christina; Grenfell, Bryan T.; Edmunds, W. John; Kang, Gagandeep; Parashar, Umesh D.

    2012-01-01

    Introduction Rotavirus vaccine efficacy ranges from >90% in high socio-economic settings (SES) to 50% in low SES. With the imminent introduction of rotavirus vaccine in low SES countries, understanding reasons for reduced efficacy in these settings could identify strategies to improve vaccine performance. Methods We developed a mathematical model to predict rotavirus vaccine efficacy in high, middle and low SES based on data specific for each setting on incidence, protection conferred by natural infection and immune response to vaccination. We then examined factors affecting efficacy. Results Vaccination was predicted to prevent 93%, 86% and 51% of severe rotavirus gastroenteritis in high, middle and low SES, respectively. Also predicted was that vaccines are most effective against severe disease and efficacy declines with age in low but not high SES. Reduced immunogenicity of vaccination and reduced protection conferred by natural infection are the main factors that compromise efficacy in low SES. Discussion The continued risk of severe disease in non-primary natural infections in low SES is a key factor underpinning reduced efficacy of rotavirus vaccines. Predicted efficacy was remarkably consistent with observed clinical trial results from different SES, validating the model. The phenomenon of reduced vaccine efficacy can be predicted by intrinsic immunological and epidemiological factors of low SES populations. Modifying aspects of the vaccine (e.g. improving immunogenicity in low SES) and vaccination program (e.g. additional doses) may bring improvements. PMID:22879893

  3. Cost-effectiveness of rotavirus vaccination in the Netherlands; the results of a consensus model

    PubMed Central

    2011-01-01

    Background Each year rotavirus gastroenteritis results in thousands of paediatric hospitalisations and primary care visits in the Netherlands. While two vaccines against rotavirus are registered, routine immunisation of infants has not yet been implemented. Existing cost-effectiveness studies showed inconsistent results for these vaccines because of lack of consensus on the impact. We aimed to investigate which factors had a major impact on cost-effectiveness and were primarily responsible for the large differences in previously estimated cost-effectiveness ratios. Methods Based on updated data on health outcomes and cost estimates, we re-assessed the cost-effectiveness of routine paediatric rotavirus vaccination within the National Immunization Program for the Netherlands. Two consensus meetings were organised with national and international experts in the field to achieve consensus and resolve potential controversies. Results It was estimated that rotavirus vaccination in the Netherlands could avert 34,214 cases of rotavirus gastroenteritis in children aged less than 5 years. Notably, 2,779 hospitalisations were averted of which 315 were extensions of existing hospital stays due to nosocomial rotavirus infection. With a threshold varying from 20K€ - 50K€ per QALY and according to the base-case scenario, the full vaccination costs per child leading to cost-effectiveness was €57.76 -€77.71. Results were sensitive to the inclusion of potential vaccine induced herd protection, QALY losses and number of deaths associated with rotavirus gastroenteritis. Conclusions Our economic analysis indicates that inclusion of rotavirus vaccination in the Dutch National Immunization Program might be cost-effective depending on the cost of the vaccine and the impact of rotavirus gastroenteritis on children's quality of life. PMID:21663620

  4. Re–evaluation of the cost–effectiveness and effects of childhood rotavirus vaccination in Norway

    PubMed Central

    de Blasio, Birgitte Freiesleben; Salamanca, Beatriz Valcárcel; Flem, Elmira

    2017-01-01

    Background Rotavirus vaccination was included into the Norwegian childhood immunisation programme in 2014. Before implementation, rotavirus vaccination was found to be cost–effective from a societal perspective, but not from a healthcare perspective. Since introduction, new data on the incidence and economic effects of rotavirus disease have become available. We assessed early epidemiological effects of the rotavirus vaccination programme and re–evaluated its cost–effectiveness in Norway for the years 2015–2019. Methods Using a dynamic transmission model, we compared the epidemiological effects of the ongoing two–dose vaccination programme with Rotarix®, and a hypothetical 3–dose programme with RotaTeq® with no vaccination. A baseline cost of € 54 per fully vaccinated child was used. Cost–effectiveness was computed from a healthcare and societal perspective, using a decision analytical model. Data on healthcare use and costs, productivity losses and health utilities were based on published and own estimates. Uncertainty was accounted for in one–way, multi–way, and probabilistic sensitivity analyses. Results During 2015–2019, 114,658 home care cases, 34,571 primary care cases, 7,381 severe cases, and 2 deaths associated with rotavirus disease were avoided due to vaccination. Under baseline assumptions vaccination was cost–effective from a healthcare perspective with a cost per QALY of € 47,447 for Rotarix® and € 52,709 for RotaTeq®. The break–even price was € 70 for Rotarix® and € 67 for RotaTeq®. Vaccination was cost–saving from the societal perspective, and also from a healthcare perspective for vaccine prices below € 25 and € 22 per vaccinated child for Rotarix® and RotaTeq®, respectively. Conclusion Ongoing childhood rotavirus vaccination in Norway has reduced the rotavirus disease burden substantially, and is cost–effective compared with no vaccination. PMID:28817621

  5. Decline in cases of rotavirus gastroenteritis presenting to The Children's Hospital of Philadelphia after introduction of a pentavalent rotavirus vaccine.

    PubMed

    Clark, H Fred; Lawley, Diane; Mallette, Laura A; DiNubile, Mark J; Hodinka, Richard L

    2009-03-01

    A pentavalent rotavirus vaccine for infants became available in the United States in February 2006. By 2007, vaccination rates nationwide were estimated to be approximately 50%. We studied the effectiveness of the vaccine in a real-world setting outside of a clinical trial. All children presenting to The Children's Hospital of Philadelphia with acute gastroenteritis have been monitored for the presence of rotavirus antigen in the stool by enzyme-linked immunosorbent assay (ELISA [followed by genotyping if ELISA positive]) since the 1994-1995 epidemic season, presenting a unique opportunity to assess the impact of the recently introduced vaccine. The annual number of community-acquired cases over the preceding 13 years had approached or exceeded 100, with 271 cases in 2005 to 2006 and 167 cases in 2006 to 2007. In the 2007-2008 season, only 36 community-acquired cases were identified, representing an 87% reduction from the same period in 2005 to 2006. G3 was the predominant serotype, accounting for 15 community cases (42%). Our study is limited by its observational design using historical comparisons. Nonetheless, the abrupt decline in rotavirus gastroenteritis cases during the 2007-2008 season likely resulted from vaccination. Because protection rates appeared to have exceeded vaccination rates, herd immunity may have contributed to some degree to the effectiveness of the vaccine.

  6. 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.

  7. Potential intussusception risk versus benefits of rotavirus vaccination in the United States.

    PubMed

    Desai, Rishi; Cortese, Margaret M; Meltzer, Martin I; Shankar, Manjunath; Tate, Jacqueline E; Yen, Catherine; Patel, Manish M; Parashar, Umesh D

    2013-01-01

    International data show a low-level increased risk of intussusception associated with rotavirus vaccination. Although US data have not documented a risk, we assumed a risk similar to international settings and compared potential vaccine-associated intussusception cases with benefits of prevention of rotavirus gastroenteritis by a fully implemented US rotavirus vaccine program. To calculate excess intussusception cases, we used national data on vaccine coverage and baseline intussusception rates, and assumed a vaccine-associated intussusception relative risk of 5.3 (95% confidence interval [CI]: 3.0-9.3) in the first week after the first vaccine dose, the risk seen in international settings. We used postlicensure vaccine effectiveness data to calculate rotavirus disease burden averted. For a US birth cohort of 4.3 million infants, vaccine-associated intussusception could cause an excess 0.2 (range: 0.1-0.3) deaths, 45 (range: 21-86) hospitalizations and 13 (range: 6-25) cases managed in short-stay or emergency department settings. Vaccination would avert 14 (95% CI: 10-19) rotavirus-associated deaths, 53,444 (95% CI: 37,622-72,882) hospitalizations and 169,949 (95% CI: 118,161-238,630) emergency department visits. Summary benefit-risk ratios for death and hospitalization are 71:1 and 1093:1, respectively. The burden of severe rotavirus disease averted due to vaccination compared with the vaccine-associated intussusception events offers a side-by-side analysis of the benefits and potential risks. If an intussusception risk similar to that seen internationally exists in the United States, it is substantially exceeded by the benefits of rotavirus disease burden averted by vaccination.

  8. Parental preferences for rotavirus vaccination in young children: a discrete choice experiment.

    PubMed

    Veldwijk, Jorien; Lambooij, Mattijs S; Bruijning-Verhagen, Patricia C J; Smit, Henriette A; de Wit, G Ardine

    2014-10-29

    This study aimed to identify characteristics that affect parental decisions about rotavirus vaccination, to determine the relative importance of those characteristics and subsequently to estimate vaccination coverage for different implementation strategies. A Discrete choice experiment (DCE) questionnaire was sent to the parents of 1250 newborns aged 6 weeks (response rate 37.3%). Mixed-logit models were used to estimate the relative importance of the five included rotavirus vaccine and implementation characteristics; vaccine effectiveness, frequency of severe side effects, protection duration, the healthcare facility that administrates vaccination and out-of-pocket costs. Based on the utility functions of the mixed-logit model, the potential vaccination coverage was estimated for different vaccine scenarios and implementation strategies. All characteristics, except for healthcare facility that administrates vaccination, influenced parental willingness to vaccinate their newborn against rotavirus. Parents were willing to trade 20.2 percentage points vaccine effectiveness for the lowest frequency of severe side effects (i.e., 1 in 1,000,000) or 20.8 percentage points for a higher protection duration. Potential vaccination coverage ranged between 22.7 and 86.2%, depending on vaccine scenario (i.e., vaccine effectiveness and protection duration) and implementation strategy (i.e., out-of-pocket costs and healthcare facility that administrates vaccination). When deciding about vaccination against rotavirus, parents are mostly driven by the out-of-pocket costs, vaccine effectiveness, protection duration, and frequency of severe side effects. The highest vaccination coverage is expected for a vaccine with high effectiveness and protection duration that is implemented within the current National Immunization Program context. Implementation of the same rotavirus vaccine in the free market will result in lowest coverage. Copyright © 2014 Elsevier Ltd. All rights reserved.

  9. Economic costs of rotavirus gastroenteritis and cost-effectiveness of vaccination in developing countries.

    PubMed

    Rheingans, Richard D; Antil, Lynn; Dreibelbis, Robert; Podewils, Laura Jean; Bresee, Joseph S; Parashar, Umesh D

    2009-11-01

    Rotavirus is the leading cause of severe gastroenteritis in children worldwide. We evaluated the economic burden of rotavirus and the cost-effectiveness of vaccination from the health care perspective. Estimates were based on existing epidemiological data, cost estimates, vaccine coverage, and efficacy data, as well as hypothetical vaccine prices. Outcome measures included health care and societal costs of rotavirus and benefits and incremental cost-effectiveness ratio of vaccination. Sensitivity analyses evaluated the impact of estimate uncertainty. Treatment costs increased with income level, and health burden decreased; however, burden varied across regions. On the basis of current vaccination coverage and timing, rotavirus vaccination would annually prevent 228,000 deaths, 13.7 million hospital visits, and 8.7 million disability-adjusted life-years, saving $188 million in treatment costs and $243 million in societal costs. At $5 per dose, the incremental cost-effectiveness ratio in low-, lower-middle-, and upper-middle-income countries was $88, $291, and $329 per disability-adjusted life-year averted, respectively, and $3,015, $9,951 and $11,296 per life saved, respectively. Vaccination would prevent approximately 45% of deaths and approximately 58% of associated medical visits and costs. Vaccination is a cost-effective strategy to reduce the health and economic burden of rotavirus. The cost-effectiveness of vaccination depends mostly on vaccine price and reaching children at highest risk of mortality.

  10. Sustained low hospitalization rates after four years of rotavirus mass vaccination in Austria.

    PubMed

    Paulke-Korinek, Maria; Kollaritsch, Herwig; Aberle, Stephan W; Zwazl, Ines; Schmidle-Loss, Birgit; Vécsei, Andreas; Kundi, Michael

    2013-05-31

    This hospital based surveillance study evaluates the effects of the rotavirus mass vaccination program, which was initiated in Austria in August 2007. Since then, incidence rates of rotavirus hospitalizations in children <15 years of age have decreased by 70% and 64% in 2010 and 2011 compared to the pre-vaccination era (2001-2005). Incidence rates were highest in children <90 days of age, highlighting the importance of the early start of active rotavirus immunization. In children between 2 and 3.5 years in 2011, who were in the second and third year after vaccination in the universal mass vaccination program, incidence rates remained low suggesting sustained protection after vaccination up to three years. In the years 2010 and 2011, field effectiveness of the vaccines was between 79% and 96%, depending on the assumptions made for children without information on vaccination history. From genotyping an increase of the prevalence of G2P[4] in children with breakthrough infection (disease despite vaccination) can be suspected. The rate of severe adverse events was 1.3-1.5 per 10(-5) administered doses of rotavirus vaccines and no death, intussusception or Kawasaki disease was reported in 2010 and 2011 following rotavirus vaccination. Copyright © 2013 Elsevier Ltd. All rights reserved.

  11. 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

  12. 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

  13. Intussusception is associated with the detection of adenovirus C, enterovirus B and rotavirus in a rotavirus vaccinated population.

    PubMed

    Minney-Smith, Cara A; Levy, Avram; Hodge, Meredith; Jacoby, Peter; Williams, Simon H; Carcione, Dale; Roczo-Farkas, Susie; Kirkwood, Carl D; Smith, David W

    2014-12-01

    Intussusception, a condition where one segment of intestine invaginates into another, occurs predominantly in infants and young children. A number of potential causes have been identified including infectious agents and rotavirus vaccination. Following the introduction of rotavirus vaccination of infants in Western Australia, a laboratory surveillance programme testing notified intussusception cases for infectious agents was commenced. This led to a PCR-based study of the association between gastrointestinal viruses and intussusception. Conduct viral testing on stool samples from intussusception patients to determine viruses that may have an association with intussusception. A retrospective case-control study was conducted using stool samples collected from children with intussusception (n=74) and matched controls (n=289) between 2008 and 2011. Samples were tested for rotavirus, norovirus, adenovirus, enterovirus, rhinovirus, astrovirus, parechovirus and bocavirus. Adenovirus, enterovirus and rhinovirus species were determined by DNA sequencing. Human adenovirus C was detected in significantly more cases than controls with 31/74 (41.9%) cases testing positive compared to 39/289 (13.49%) controls (OR=4.38, p<0.001). A significant difference was seen in Enterovirus B detections with 11/74 (14.9%) cases testing positive compared to 21/289 (7.3%) controls (OR=2.24, p=0.04). Rotavirus was detected in 7/74 (9.46%) cases and 11/289 (3.81%) controls, which was also a significant difference (OR=2.88, p=0.045). Our results show that intussusception is associated with non-enteric adenovirus infections, and Enterovirus B infections. While a statistical association was seen with rotavirus and intussusception, we were not able to determine if this was related to vaccine strain or wild type rotavirus. Copyright © 2014 Elsevier B.V. All rights reserved.

  14. 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

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

    PubMed

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

    2015-12-21

    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.

  16. 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

  17. Effectiveness of pentavalent rotavirus vaccine in a large urban population in the United States.

    PubMed

    Boom, Julie A; Tate, Jacqueline E; Sahni, Leila C; Rench, Marcia A; Hull, Jennifer J; Gentsch, Jon R; Patel, Manish M; Baker, Carol J; Parashar, Umesh D

    2010-02-01

    The goal was to assess the effectiveness of complete (3-dose) or partial (1- or 2-dose) immunization with pentavalent rotavirus vaccine (RV5) against rotavirus acute gastroenteritis (AGE) in US clinical practice. A case-control evaluation was conducted in February through June 2008 at an emergency department in Houston, Texas. Case patients with rotavirus AGE (N = 90) were identified through testing for rotavirus in fecal specimens obtained from 205 children 15 days through 23 months of age presenting with AGE. Control groups included rotavirus-negative AGE patients (N = 115), concurrently enrolled patients with acute respiratory infection (ARI) (N = 228), and up to 10 age- and zip code-matched children sampled from the Houston-Harris County Immunization Registry (HHCIR) for each case patient >8 months of age. Immunization data were obtained from parent records, health care providers, and/or the HHCIR. Vaccine effectiveness was calculated as 1 minus odds of RV5 vaccination for case patients versus control patients, after adjustment for age at presentation and birth date. The vaccine effectiveness of a complete RV5 series was 89% (95% confidence interval [CI]: 70%-96%) and 85% (95% CI: 55%-95%) with rotavirus-negative AGE and ARI control patients, respectively. Immunization data were available for 44% of case patients (n = 40) from the HHCIR; the estimated 3-dose vaccine effectiveness with these HHCIR control patients was 82% (95% CI: 19%-96%). A complete RV5 series conferred 100% protection (95% CI: 71%-100%) against severe rotavirus disease requiring hospitalization and 96% protection (95% CI: 72%-99%) against disease requiring intravenous hydration. Vaccine effectiveness of 1 and 2 doses against hospitalization and emergency department visits was 69% (95% CI: 13%-89%) and 81% (95% CI: 13%-96%), respectively, using rotavirus-negative AGE and ARI control groups combined. In this setting, a complete series of RV5 was highly effective against severe rotavirus AGE

  18. Rapid Declines in Age Group-Specific Rotavirus Infection and Acute Gastroenteritis Among Vaccinated and Unvaccinated Individuals Within 1 Year of Rotavirus Vaccine Introduction in England and Wales.

    PubMed

    Atchison, Christina J; Stowe, Julia; Andrews, Nick; Collins, Sarah; Allen, David J; Nawaz, Sameena; Brown, David; Ramsay, Mary E; Ladhani, Shamez N

    2016-01-15

    The oral infant rotavirus vaccine, Rotarix, was introduced in England and Wales in July 2013. We estimated the impact on laboratory-confirmed rotavirus infections and hospitalizations for all-cause acute gastroenteritis (AGE) during the first year after introduction. We extracted data on laboratory-confirmed rotavirus infections (July 2000 through June 2015) and all-cause AGE-associated hospitalizations (July 2007 through June 2014) for all age groups using national databases (LabBase2 and HES). We determined the ratio of the rate during the 2013-2014 rotavirus season to the rate during the prevaccination era. In infants, there was a 77% decline (rate ratio [RR], 0.23; 95% confidence interval [CI], .16-.32) in laboratory-confirmed rotavirus infections and a 26% decline (RR, 0.74; 95% CI, .65-.84) in all-cause AGE-associated hospitalizations in 2013-2014, compared with the prevaccination era. Large reductions were also observed in older children, adults, and older adults. We estimated that 10 884 laboratory-confirmed infections and 50 427 all-cause AGE-associated hospital admissions were averted in 2013-2014. Similar reductions have been observed for laboratory-confirmed rotavirus infections during the 2014-2015 season. The rapid declines in rotavirus infection and AGE in vaccinated and unvaccinated age groups within 1 year of introducing an infant rotavirus vaccination program are far greater than expected and than previously reported by other countries. © The Author 2015. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail journals.permissions@oup.com.

  19. Health and economic impact of rotavirus vaccination in GAVI-eligible countries.

    PubMed

    Kim, Sun-Young; Sweet, Steve; Slichter, David; Goldie, Sue J

    2010-05-14

    Rotavirus infection is responsible for about 500,000 deaths annually, and the disease burden is disproportionately borne by children in low-income countries. Recently the World Health Organization (WHO) has released a global recommendation that all countries include infant rotavirus vaccination in their national immunization programs. Our objective was to provide information on the expected health, economic and financial consequences of rotavirus vaccines in the 72 GAVI support-eligible countries. We synthesized population-level data from various sources (primarily from global-level databases) for the 72 countries eligible for the support by the GAVI Alliance (GAVI-eligible countries) in order to estimate the health and economic impact associated with rotavirus vaccination programs. The primary outcome measure was incremental cost (in 2005 international dollars [I$]) per disability-adjusted life year (DALY) averted. We also projected the expected reduction in rotavirus disease burden and financial resources required associated with a variety of scale-up scenarios. Under the base-case assumptions (70% coverage), vaccinating one single birth cohort would prevent about 55% of rotavirus associated deaths in the 72 GAVI-eligible countries. Assuming I$25 per vaccinated child (approximately $5 per dose), the number of countries with the incremental cost per DALY averted less than I$200 was 47. Using the WHO's cost-effectiveness threshold based on per capita GDP, the vaccines were considered cost-effective in 68 of the 72 countries (approximately 94%). A 10-year routine rotavirus vaccination would prevent 0.9-2.8 million rotavirus associated deaths among children under age 5 in the poorest parts of the world, depending on vaccine scale-up scenarios. Over the same intervention period, rotavirus vaccination programs would also prevent 4.5-13.3 million estimated cases of hospitalization and 41-107 million cases of outpatient clinic visits in the same population. Our findings

  20. Effectiveness of rotavirus vaccination against childhood diarrhoea in El Salvador: case-control study

    PubMed Central

    de Palma, Orbelina; Cruz, Lilian; Ramos, Hector; de Baires, Amada; Villatoro, Nora; Pastor, Desiree; de Oliveira, Lucia Helena; Kerin, Tara; Bowen, Michael; Gentsch, Jon; Esposito, Douglas H; Parashar, Umesh; Tate, Jacqueline

    2010-01-01

    Objective To evaluate the effectiveness of a monovalent rotavirus vaccine against severe rotavirus disease and to assess its impact on diarrhoea in children aged less than 2 years after national introduction in El Salvador, a low-middle income country in Central America. Design Matched case-control study. Setting Seven hospitals in cities across El Salvador, January 2007 to June 2009. Participants 323 children aged less than 2 years admitted with laboratory confirmed rotavirus diarrhoea and 969 healthy controls matched for age and neighbourhood. Main outcome measure Effectiveness of rotavirus vaccination ((1–adjusted odds ratio of vaccination)×100) against rotavirus diarrhoea requiring hospital admission. Results Cases and controls were similar for breast feeding, premature birth, maternal education, and socioeconomic variables. G1P[8] strains were identified in 92% of rotavirus cases. Effectiveness of two doses of vaccination against diarrhoea requiring hospital admission was 76% (95% confidence interval 64% to 84%). Protection was significantly lower (P=0.046) among children aged 12 months or more (59%, 27% to 77%) compared with children aged 6-11 months (83%, 68% to 91%). One dose of vaccine was 51% (26% to 67%) effective. At the sentinel hospitals, all admissions for diarrhoea among children under 5 declined by 40% in 2008 and by 51% in 2009 from the prevaccine year 2006. Conclusions A monovalent rotavirus vaccine was highly effective against admissions for rotavirus diarrhoea in children aged less than 2 years in El Salvador and substantially reduced the number of such admissions in this low-middle income setting. The impact on disease epidemiology after vaccination, particularly among older children, warrants future attention. PMID:20551120

  1. Effectiveness of rotavirus vaccination against childhood diarrhoea in El Salvador: case-control study.

    PubMed

    de Palma, Orbelina; Cruz, Lilian; Ramos, Hector; de Baires, Amada; Villatoro, Nora; Pastor, Desiree; de Oliveira, Lucia Helena; Kerin, Tara; Bowen, Michael; Gentsch, Jon; Esposito, Douglas H; Parashar, Umesh; Tate, Jacqueline; Patel, Manish

    2010-06-15

    To evaluate the effectiveness of a monovalent rotavirus vaccine against severe rotavirus disease and to assess its impact on diarrhoea in children aged less than 2 years after national introduction in El Salvador, a low-middle income country in Central America. Matched case-control study. Seven hospitals in cities across El Salvador, January 2007 to June 2009. 323 children aged less than 2 years admitted with laboratory confirmed rotavirus diarrhoea and 969 healthy controls matched for age and neighbourhood. Effectiveness of rotavirus vaccination ((1-adjusted odds ratio of vaccination)x100) against rotavirus diarrhoea requiring hospital admission. Cases and controls were similar for breast feeding, premature birth, maternal education, and socioeconomic variables. G1P[8] strains were identified in 92% of rotavirus cases. Effectiveness of two doses of vaccination against diarrhoea requiring hospital admission was 76% (95% confidence interval 64% to 84%). Protection was significantly lower (P=0.046) among children aged 12 months or more (59%, 27% to 77%) compared with children aged 6-11 months (83%, 68% to 91%). One dose of vaccine was 51% (26% to 67%) effective. At the sentinel hospitals, all admissions for diarrhoea among children under 5 declined by 40% in 2008 and by 51% in 2009 from the prevaccine year 2006. A monovalent rotavirus vaccine was highly effective against admissions for rotavirus diarrhoea in children aged less than 2 years in El Salvador and substantially reduced the number of such admissions in this low-middle income setting. The impact on disease epidemiology after vaccination, particularly among older children, warrants future attention.

  2. [Immunization with monovalent oral vaccine against rotavirus in Mexico. Evaluation of the data of two years of the system of temporarily adverse event reports associated to vaccination (ETAV)].

    PubMed

    Reyna-Figueroa, Jesús; Vidal-Vázquez, Rosa Patricia; López-Collada, Vesta Louise Richardson

    2011-01-01

    The gastrointestinal manifestations are the adverse events mainly studied to the application of the vaccine against rotavirus. In order subsequent to consider the risk of associated events taken care of the vaccination against rotavirus in infants, we realized a retrospective study of 2 years, evaluating 7,691,757 distributed doses of oral vaccine, in 2008 and 2009. The risk considered of an event associated after the application of the oral vaccine against rotavirus is of 2.9 events by 1,000,000 distributed doses. The taken care of associated events were little common subsequent to the vaccination against rotavirus.

  3. Synthesizing evidences for policy translation: a public health discourse on rotavirus vaccine in India.

    PubMed

    Panda, Samiran; Das, Aritra; Samanta, Saheli

    2014-08-11

    The debate on the relevance of rotavirus vaccine to immunization program in India, where 27 million children are born every year, rages on. We synthesized the issues raised during these debates and reviewed the current literature to identify themes that could inform public health policy decision. The paradigm we used integrated disease burden data, host and environmental factors, vaccine efficacy, immunization program issues, and economic considerations. Our synthesis reveals that substantive country specific information on disease burden and economic impact of rotavirus illness in India is constrained by lack of public discussion and qualitative studies on mothers' perceptions of the vaccine in concern. The need to improve the performance of current immunization program against six major vaccine preventable diseases (tuberculosis, diphtheria, tetanus, pertussis, polio, and measles) is often cited as a priority over introduction of rotavirus vaccine. Health in India being a state subject, we emphasize that the states which are in a position to reap the benefit of rotavirus vaccine, due to their good immunization program performance, should not be restrained from doing so. Meanwhile, the poorly performing states should step up their vaccination program and increase immunization coverage. Scientific, ethical and societal concerns captured through multiple sources indicate that the introduction of rotavirus vaccine would be a good investment for India.

  4. 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.

  5. Cost-effectiveness of childhood rotavirus vaccination in Germany.

    PubMed

    Aidelsburger, Pamela; Grabein, Kristin; Böhm, Katharina; Dietl, Markus; Wasem, Jürgen; Koch, Judith; Ultsch, Bernhard; Weidemann, Felix; Wichmann, Ole

    2014-04-07

    Rotavirus (RV) causes a highly contagious gastroenteritis especially in children under five years of age. Since 2006 two RV-vaccines are available in Europe (Rotarix(®) and RotaTeq(®)). To support informed decision-making within the German Standing Committee on Vaccination (STIKO) the cost-effectiveness of these two vaccines was evaluated for the German healthcare setting. A Markov model was developed to evaluate the cost-effectiveness from the statutory health insurance (SHI) and from the societal perspective. RV-cases prevented, RV-associated hospitalizations avoided, and quality-adjusted life years (QALY) gained were considered as health outcomes. RV-incidences were calculated based on data from the national mandatory disease reporting system. RV-vaccine efficacy was determined as pooled estimates based on data from randomized controlled trials. Vaccine list prices and price catalogues were used for cost-assessment. Effects and costs were discounted with an annual discount rate of 3%. The base-case analysis (SHI-perspective) resulted in an incremental cost-effectiveness and cost-utility ratio for Rotarix(®) of € 184 per RV-case prevented, € 2457 per RV-associated hospitalization avoided, and € 116,973 per QALY gained. For RotaTeq(®), the results were € 234 per RV-case prevented, € 2622 per RV-associated hospitalization avoided, and € 142,732 per QALY gained. Variation of various parameters in sensitivity analyses showed effects on the ICERs without changing the overall trend of base-case results. When applying base-case results to the 2012 birthcohort in Germany with 80% vaccination coverage, an estimated 206,000-242,000 RV-cases and 18,000 RV-associated hospitalizations can be prevented in this birthcohort over five years for an incremental cost of 44.5-48.2 million €. Our analyses demonstrate that routine RV-vaccination could prevent a substantial number of RV-cases and hospitalizations in the German healthcare system, but the saved treatment

  6. Sustained protection from pentavalent rotavirus vaccination during the second year of life at a large, urban United States pediatric hospital.

    PubMed

    Boom, Julie A; Tate, Jacqueline E; Sahni, Leila C; Rench, Marcia A; Quaye, Osbourne; Mijatovic-Rustempasic, Slavica; Patel, Manish M; Baker, Carol J; Parashar, Umesh D

    2010-12-01

    Fecal specimens from children presenting to Texas Children's Hospital with acute gastroenteritis were tested for the presence of rotavirus. Children were grouped according to vaccination status, and pentavalent rotavirus vaccine effectiveness was calculated. Pentavalent rotavirus vaccine effectiveness against severe rotavirus gastroenteritis was sustained during the first 2 years of the vaccination program. Overall 3-dose effectiveness was 83% to 86%; it was 92% to 93% among children 6 to 11 months of age and 78% to 84% among children ≥12 months of age.

  7. 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.

  8. Detection of rotavirus antigenemia in routinely obtained serum specimens to augment surveillance and vaccine effectiveness evaluations.

    PubMed

    Patel, Manish; Rench, Marcia A; Boom, Julie A; Tate, Jacqueline E; Sahni, Leila C; Hull, Jennifer A; Gentsch, Jon R; Parashar, Umesh D; Baker, Carol J

    2010-09-01

    : Antigenemia is common among children with rotavirus disease. Because obtaining stool specimens is cumbersome, we evaluated whether detection of antigenemia in sera obtained during routine clinical practice could augment rotavirus surveillance to assess the effect of vaccination. : We determined the sensitivity, specificity, and positive and negative predictive values of serum/plasma rotavirus antigen detection using fecal antigen positivity as the gold standard. Fecal specimens obtained by active surveillance and residual serum/plasma specimens obtained during routine clinical testing from children 15 days to 23 months of age presenting with acute gastroenteritis (AGE) to a children's hospital in Houston were tested for rotavirus using a commercially available enzyme immunoassay. Using case-control methods, we compared vaccine effectiveness (VE) using cases identified through serum/plasma testing versus stool testing. : Of the 205 AGE patients with fecal specimens, 71 (35%) had a serum/plasma sample available. Among these 71 children, antigenemia was detected in 22 of 29 with rotavirus-positive fecal specimens (sensitivity = 75%; 95% confidence interval [CI] = 60%-91%) versus 2 of 42 children with rotavirus-negative fecal specimens (specificity = 95%; 95% CI = 89%-100%). The positive and negative predictive values of rotavirus antigenemia were 92% (95% CI = 81%-100%) and 85% (95% CI = 75%-95%), respectively. Thirty-four of 195 children with AGE without fecal specimens had serum/plasma available; 10 (29%) had rotavirus antigenemia. Three-dose VE using cases identified through serum/plasma testing was similar (VE = 84%; 95% CI = 25%-96%) to that using cases identified though fecal testing (VE = 85%; 95% CI = 55%-95%). : Detection of antigenemia in routinely collected serum/plasma could augment identification of rotavirus disease for postlicensure evaluation of impact and effectiveness of rotavirus vaccination.

  9. Genotypes of rotavirus strains circulating in Amman, Jordan, in 2006/07 and their significance for the potential effectiveness of future rotavirus vaccination.

    PubMed

    Salem, Khitam; Bdour, Salwa; Zeller, Mark; Van Ranst, Marc; Matthijnssens, Jelle

    2011-09-01

    The prevalence, seasonality and genotypes of rotavirus circulating in Jordan were determined to provide data useful for the implementation of a rotavirus vaccine in the national childhood vaccination program. During 2006/07, rotavirus was detected in 35% of hospitalized children, and 88% of the cases occurred in children aged between 6 and 23 months. Rotavirus infection persisted throughout the year and peaked in winter. Seven genotypes were identified by RT-PCR and sequencing: G1P[8], G9P[8], G2P[4], G1P[4], G3P[8], G4P[8] and G9P[6], which represented 69%, 8.8%, 2.4%, 2.0%, 1.2%, 0.4% and 0.4% of the rotavirus strains, respectively. Thirteen percent and 2.8% of the total strains were partially typed or untypeable, respectively. Eighty-eight percent and 12% of the rotavirus strains possessed a long and short electropherotype, respectively. As more than 90% of the rotavirus strains circulating in Jordan possessed the G1 or P[8]-genotype, it is concluded that the implementation of the rotavirus vaccine in the framework of the national childhood vaccination program of Jordan would most likely be very effective. Continuous monitoring of the currently circulating genotypes in Jordan should be encouraged.

  10. Association of Maternal Immunity with Rotavirus Vaccine Immunogenicity in Zambian Infants

    PubMed Central

    Chilengi, Roma; Simuyandi, Michelo; Beach, Lauren; Mwila, Katayi; Becker-Dreps, Sylvia; Emperador, Devy M.; Velasquez, Daniel E.; Bosomprah, Samuel; Jiang, Baoming

    2016-01-01

    Introduction Live attenuated oral vaccines against rotavirus (RV) have been shown to be less efficacious in children from developing countries. Reasons for this disparity are not fully understood. We assessed the role of maternal factors including breast milk RV-specific IgA, transplacentally acquired infant serum RV-specific IgG and maternal HIV status in seroconversion among Zambian infants routinely immunized with Rotarix™ (RV1). Methods 420 mother-child pairs were recruited at infant age 6–12 weeks in Lusaka. Clinical information and samples were collected at baseline and at one month following the second dose of RV1. Determination of breast milk RV-specific IgA and serum RV-specific IgA and IgG was done using standardized ELISA. Seroconversion was defined as a ≥ 4 fold rise in serum IgA titre from baseline to one-month post RV1 dose 2, while seropositivity of IgA was defined as serum titre ≥ 40 and antibody variables were modelled on log-base 2. Logistic regression was used to identify predictors of the odds of seroconversion. Results Baseline infant seropositivity was 25.5% (91/357). The seroconversion frequency was 60.2% (130/216). Infants who were IgA seropositive at baseline were less likely to seroconvert compared to their seronegative counterparts (P = 0.04). There was no evidence of an association between maternal HIV status and seroconversion (P = 0.25). Higher titres of breast milk rotavirus-specific IgA were associated with a lower frequency of seroconverson (Nonparametric test for trend Z = -2.84; P<0.01): a two-fold increase in breast milk RV-specific IgA titres was associated with a 22% lower odds of seroconversion (OR = 0.80; 95% CI = 0.68–0.94; P = 0.01). There was seasonal variation in baseline breast milk rotavirus-specific IgA titres, with significantly higher GMTs during the cold dry months (P = 0.01). Conclusion Low immunogenicity of RV1 vaccine could be explained in part by exposure to high antibody titres in breast milk and

  11. 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

  12. Public finance of rotavirus vaccination in India and Ethiopia: an extended cost-effectiveness analysis.

    PubMed

    Verguet, Stéphane; Murphy, Shane; Anderson, Benjamin; Johansson, Kjell Arne; Glass, Roger; Rheingans, Richard

    2013-10-01

    An estimated 4% of global child deaths (approximately 300,000 deaths) were attributed to rotavirus in 2010. About a third of these deaths occurred in India and Ethiopia. Public finance of rotavirus vaccination in these two countries could substantially decrease child mortality and also reduce rotavirus-related hospitalizations, prevent health-related impoverishment and bring significant cost savings to households. We use a methodology of 'extended cost-effectiveness analysis' (ECEA) to evaluate a hypothetical publicly financed program for rotavirus vaccination in India and Ethiopia. We measure program impact along four dimensions: 1) rotavirus deaths averted; 2) household expenditures averted; 3) financial risk protection afforded; 4) distributional consequences across the wealth strata of the country populations. In India and Ethiopia, the program would lead to a substantial decrease in rotavirus deaths, mainly among the poorer; it would reduce household expenditures across all income groups and it would effectively provide financial risk protection, mostly concentrated among the poorest. Potential indirect benefits of vaccination (herd immunity) would increase program benefits among all income groups, whereas potentially decreased vaccine efficacy among poorer households would reduce the equity benefits of the program. Our approach incorporates financial risk protection and distributional consequences into the systematic economic evaluation of vaccine policy, illustrated here with the case study of public finance for rotavirus vaccination. This enables selection of vaccine packages based on the quantitative inclusion of information on equity and on how much financial risk protection is being bought per dollar expenditure on vaccine policy, in addition to how much health is being bought. Copyright © 2013 Elsevier Ltd. All rights reserved.

  13. Sustained Effectiveness of Monovalent and Pentavalent Rotavirus Vaccines in Children.

    PubMed

    Immergluck, Lilly Cheng; Parker, Trisha Chan; Jain, Shabnam; Laghaie, Elham; Spandorfer, Philip; Jerris, Robert C; Bowen, Michael D; Parashar, Umesh D; Cortese, Margaret M

    2016-05-01

    Using case-control methodology, we measured the vaccine effectiveness (VE) of the 2-dose monovalent rotavirus vaccine (RV1) and 3-dose pentavalent rotavirus vaccine (RV5) series given in infancy against rotavirus disease resulting in hospital emergency department or inpatient care. Children were eligible for enrollment if they presented to any 1 of 3 hospitals in Atlanta, Georgia with diarrhea ≤10 days duration during January-June 2013 and were born after RV1 introduction. Stool samples were tested for rotavirus by enzyme immunoassay and immunization records were obtained from providers and the state electronic immunization information system. Case-subjects (children testing rotavirus antigen-positive) were compared with children testing rotavirus antigen-negative. Overall, 98 rotavirus-case subjects and 175 rotavirus-negative controls were enrolled. Genotype G12P[8] predominated (n = 87, 89%). The VE of 2 RV1 doses was 84% (95% CI 38, 96) among children aged 8-23 months and 82% (95% CI 41, 95) among children aged ≥24 months. For the same age groups, the VE of 3 RV5 doses was 80% (95% CI 27, 95) and 87% (95% CI 22, 98), respectively. Under routine use, the RV1 and RV5 series were both effective against moderate-to-severe rotavirus disease during a G12P[8] season, and both vaccines demonstrated sustained protection beyond the first 2 years of life. Copyright © 2016 Elsevier Inc. All rights reserved.

  14. Passive immunity in calf diarrhea: vaccination with K99 antigen of enterotoxigenic Escherichia coli and rotavirus.

    PubMed Central

    Snodgrass, D R; Nagy, L K; Sherwood, D; Campbell, I

    1982-01-01

    Twenty-four pregnant cows were vaccinated intramuscularly with K99 extract from enterotoxigenic Escherichia coli and inactivated rotavirus as follows: six cows were injected with 2 ml of oil-adjuvanted vaccine; six cows were injected with 0.5 ml of oil-adjuvanted vaccine; six cows were injected with 4 ml of aluminum hydroxide-adjuvanted vaccine twice with a four-week interval; and six cows were unvaccinated as controls. Calves born to these cows were challenged with enterotoxigenic E. coli at 6 to 18 h after birth. Serum and milk antibodies to K99 and rotavirus in cows vaccinated with either dose of oil vaccine were significantly increased until at least 28 days after calving. In cows vaccinated with alhydrogel vaccine, there was a significant K99 antibody increase in serum and in colostrum but not in milk and a significant rotavirus antibody increase only in colostrum. Five of six calves born to unvaccinated cows developed enterotoxic colibacillosis after challenge, and all excreted the challenge strain of enterotoxigenic E. coli. None of the 18 calves in the three vaccinated groups developed clinical colibacillosis, and fecal excretion of the challenge organism was reduced. A combined enterotoxigenic E. coli-rotavirus vaccine may prove useful in preventing some outbreaks of calf diarrhea. PMID:6288567

  15. Overcoming perceptions of financial barriers to rotavirus vaccine introduction in Asia

    PubMed Central

    Nelson, E Anthony S; de Quadros, Ciro A; Santosham, Mathuram; Parashar, Umesh D; Steele, A Duncan

    2013-01-01

    Despite a WHO recommendation in 2009, reaffirmed in 2013, that all countries should consider introducing rotavirus vaccines into their National Immunization Programs, as of June 2013 only 45 have done so. One major consideration appears to have been the costs of the vaccine to countries. Of concern, is that Asian countries have been slow to introduce rotavirus vaccines despite having robust data that could inform the decision-making process. Although decisions on new vaccine introduction are very complex and vary by country and region, economic evaluations are often pivotal once vaccine efficacy and safety has been established, and disease burden documented and communicated. Unfortunately, with private sector list prices of vaccines often used in economic evaluations, rather than a potential public health sector pricing structure, policy-makers may defer decisions on rotavirus vaccine introduction based on the belief that “the vaccine price is too high,” even though this might be based on erroneous data. The Pan American Health Organization’s Revolving Fund provides one example of how vaccine price can be made more competitive and transparent through a regional tendering process. Other mechanisms, such as tiered pricing and UNICEF procurement, also exist that could help Asian and other countries move forward more quickly with rotavirus vaccine introduction. PMID:23955246

  16. Overcoming perceptions of financial barriers to rotavirus vaccine introduction in Asia.

    PubMed

    Nelson, E Anthony S; de Quadros, Ciro A; Santosham, Mathuram; Parashar, Umesh D; Steele, Duncan

    2013-11-01

    Despite a WHO recommendation in 2009, reaffirmed in 2013, that all countries should consider introducing rotavirus vaccines into their National Immunization Programs, as of June 2013 only 45 have done so. One major consideration appears to have been the costs of the vaccine to countries. Of concern, is that Asian countries have been slow to introduce rotavirus vaccines despite having robust data that could inform the decision-making process. Although decisions on new vaccine introduction are very complex and vary by country and region, economic evaluations are often pivotal once vaccine efficacy and safety has been established, and disease burden documented and communicated. Unfortunately, with private sector list prices of vaccines often used in economic evaluations, rather than a potential public health sector pricing structure, policy-makers may defer decisions on rotavirus vaccine introduction based on the belief that "the vaccine price is too high," even though this might be based on erroneous data. The Pan American Health Organization's Revolving Fund provides one example of how vaccine price can be made more competitive and transparent through a regional tendering process. Other mechanisms, such as tiered pricing and UNICEF procurement, also exist that could help Asian and other countries move forward more quickly with rotavirus vaccine introduction.

  17. 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

  18. 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.

  19. 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.

  20. Universal Mass Vaccination Against Rotavirus: Indirect Effects on Rotavirus Infections in Neonates and Unvaccinated Young Infants Not Eligible for Vaccination.

    PubMed

    Prelog, Martina; Gorth, Peter; Zwazl, Ines; Kleines, Michael; Streng, Andrea; Zlamy, Manuela; Heinz-Erian, Peter; Wiedermann, Ursula

    2016-08-15

    Rotavirus (RV)-associated infections account for high numbers of hospitalizations in neonates and young infants. Universal mass vaccination (UMV) has been shown to prevent the burden of disease in vaccinated children. The present study investigated the long-term effects of UMV on RV-associated hospitalizations in children with particular focus on neonates and young infants (≤42 days old) not eligible for vaccination. Ten years of Austrian surveillance data were compared, including 10 960 laboratory-confirmed RV cases before (prevaccination period [PreVP]) and after (postvaccination period [PostVP]) introduction of UMV. A postvaccination decrease in hospitalized community-acquired RV infections by 89.3% was seen in all age groups, including unvaccinated neonates and young infants. Of the latter, 27.6% had a nosocomial RV infection in PreVP, and 19.3% in PostVP. Overall, the proportion of nosocomial RV infections increased from 5.5% in PreVP to 13.0% in PostVP. Breakthrough infections, usually after incomplete RV vaccination, could be identified in 6.2% of patients. Unvaccinated neonates and infants ≤42 days old may indirectly benefit from UMV by reduction of RV infections. Breakthrough infections underline the importance of early and complete protection by the vaccine. In older patients, heightened awareness of nosocomial RV infections is warranted. Identification of RV reservoirs is also needed. © 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.

  1. European Society for Paediatric Infectious Diseases consensus recommendations for rotavirus vaccination in Europe: update 2014.

    PubMed

    Vesikari, Timo; Van Damme, Pierre; Giaquinto, Carlo; Dagan, Ron; Guarino, Alfredo; Szajewska, Hania; Usonis, Vytautas

    2015-06-01

    The first evidence-based recommendations for rotavirus (RV) vaccination in Europe were prepared at the time of licensure of 2 live oral RV vaccines (Rotarix, GlaxoSmithKline Biologicals, and RotaTeq, Sanofi Pasteur MSD) in 2006 and published in 2008. Since then several countries in Europe and more globally have adopted universal RV vaccination of all healthy infants as part of their national immunization programs (NIPs). The experience from these NIPs has produced a wealth of post-introduction effectiveness data that, together with the evidence from prelicensure efficacy trials presented in the 2008 Recommendations, support the case of RV vaccination in Europe. The prelicensure safety trials of Rotarix and RotaTeq, each in populations of more than 60,000 infants, did not reveal risk of intussusception (IS), but postvaccination surveillance in several countries, particularly Australia and Mexico, has established that the risk of IS for both vaccines after the first dose might be between 1:50,000 and 1:80,000. Although it may be argued that the risk is acceptable vis-à-vis the great benefits of RV vaccination, this argument alone may not suffice, and every effort should be made to reduce the risk of IS. Considerable evidence, including postvaccination surveillance data from Germany, suggests that the risk of IS can be reduced by early administration of the first dose of oral RV vaccine. The previous European Society for Paediatric Infectious Diseases/European Society for Paediatric Gastroenterology, Hepatology and Nutrition recommendations held that the first dose of oral RV vaccine should be given between 6 and 12 weeks of age; this recommendation is sustained but with an emphasis toward the lower range of the recommended age, that is, preferably between 6 and 8 weeks of age. At the time of the earlier recommendations, experience of RV vaccination in premature infants and other special target groups was limited. It is now recommended with greater confidence than

  2. [Post-licensure passive safety surveillance of rotavirus vaccines: reporting sensitivity for intussusception].

    PubMed

    Pérez-Vilar, S; Díez-Domingo, J; Gomar-Fayos, J; Pastor-Villalba, E; Sastre-Cantón, M; Puig-Barberà, J

    2014-08-01

    The aims of this study were to describe the reports of suspected adverse events due to rotavirus vaccines, and assess the reporting sensitivity for intussusception. Descriptive study performed using the reports of suspected adverse events following rotavirus vaccination in infants aged less than 10 months, as registered in the Pharmacovigilance Centre of the Valencian Community during 2007-2011. The reporting rate for intussusception was compared to the intussusception rate in vaccinated infants obtained using the hospital discharge database (CMBD), and the regional vaccine registry. The adverse event reporting rate was 20 per 100,000 administered doses, with the majority (74%) of the reports being classified as non-serious. Fever, vomiting, and diarrhea were the adverse events reported more frequently. Two intussusception cases, which occurred within the first seven days post-vaccination, were reported as temporarily associated to vaccination. The reporting sensitivity for intussusception at the Pharmacovigilance Centre in the 1-7 day interval following rotavirus vaccination was 50%. Our results suggest that rotavirus vaccines have, in general, a good safety profile. Intussusception reporting to the Pharmacovigilance Centre shows sensitivity similar to other passive surveillance systems. The intussusception risk should be further investigated using well-designed epidemiological studies, and evaluated in comparison with the well-known benefits provided by these vaccines. Copyright © 2013 Asociación Española de Pediatría. Published by Elsevier Espana. All rights reserved.

  3. Epidemiology of intussusception in New Zealand pre-rotavirus vaccination.

    PubMed

    Rosie, Bronwyn; Dalziel, Stuart; Wilson, Elizabeth; Best, Emma J

    2016-09-23

    To describe the epidemiology of intussusception in New Zealand children aged 0-36 months prior to the introduction of routine rotavirus vaccination. ICD-10 coding data from the New Zealand National Minimum Data Set (NMDS) was used to identify all cases of intussusception in children aged 0-36 months between January 1998 and December 2013. These data were linked with birth data from the New Zealand census. Population incidence rates of intussusception were calculated, and demographic characteristics described. Over the 16-year study period, there were 794 cases of intussusception. The majority (56%) occurred in the first year of life (age adjusted incidence rate 56.1/100,000 child-years, 95% confidence interval (CI) 41.7-71.2). Intussusception occurred more frequently in males (36.4/100,000 (95% CI 24.6-48.2) versus 19.5/100,000 (95% CI 10.8-28.1, p<0.001)). There was no difference in intussusception incidence between ethnic groups, although cases occurred at a younger age in Māori and Pacific infants compared to Asian and other ethnicities (Pacific median 7.5 months (interquartile range 5.9-11.6), Māori 7.8 months (IQR 5.5-12.3), European 9.2 months (IQR 5.8-15.8), Other Ethnicity 10.2 months (IQR 8.2-12.3), Asian 10.5 months (IQR 7.0-17.1 )). There was a weak seasonal trend with incidence troughs in January and July, and corresponding peaks in March and September. There was wide variation in presentation rates across District Health Board (DHB) regions, with a national average of 18.0/100,000 child-years (95% CI 9.7-26.3). Most patients were admitted on a single occasion to a single hospital for treatment (81%). This study updates background incidence rates of intussusception prior to the introduction of a national rotavirus vaccination programme in July 2014. It identifies a trend of earlier intussusception in Māori and Pacific infants; the relationship between earlier intussusception and the risk of vaccine-associated events is unknown.

  4. Maintaining Vaccine Delivery Following the Introduction of the Rotavirus and Pneumococcal Vaccines in Thailand

    PubMed Central

    Lee, Bruce Y.; Assi, Tina-Marie; Rookkapan, Korngamon; Wateska, Angela R.; Rajgopal, Jayant; Sornsrivichai, Vorasith; Chen, Sheng-I; Brown, Shawn T.; Welling, Joel; Norman, Bryan A.; Connor, Diana L.; Bailey, Rachel R.; Jana, Anirban; Van Panhuis, Willem G.; Burke, Donald S.

    2011-01-01

    Although the substantial burdens of rotavirus and pneumococcal disease have motivated many countries to consider introducing the rotavirus vaccine (RV) and heptavalent pneumococcal conjugate vaccine (PCV-7) to their National Immunization Programs (EPIs), these new vaccines could affect the countries' vaccine supply chains (i.e., the series of steps required to get a vaccine from their manufacturers to patients). We developed detailed computational models of the Trang Province, Thailand, vaccine supply chain to simulate introducing various RV and PCV-7 vaccine presentations and their combinations. Our results showed that the volumes of these new vaccines in addition to current routine vaccines could meet and even exceed (1) the refrigerator space at the provincial district and sub-district levels and (2) the transport cold space at district and sub-district levels preventing other vaccines from being available to patients who arrive to be immunized. Besides the smallest RV presentation (17.1 cm3/dose), all other vaccine introduction scenarios required added storage capacity at the provincial level (range: 20 L–1151 L per month) for the three largest formulations, and district level (range: 1 L–124 L per month) across all introduction scenarios. Similarly, with the exception of the two smallest RV presentation (17.1 cm3/dose), added transport capacity was required at both district and sub-district levels. Added transport capacity required across introduction scenarios from the provincial to district levels ranged from 1 L–187 L, and district to sub-district levels ranged from 1 L–13 L per shipment. Finally, only the smallest RV vaccine presentation (17.1 cm3/dose) had no appreciable effect on vaccine availability at sub-districts. All other RV and PCV-7 vaccines were too large for the current supply chain to handle without modifications such as increasing storage or transport capacity. Introducing these new vaccines to Thailand could have dynamic effects on

  5. 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

  6. [Rotavirus Vaccine. Statement of the Consultive Committee of Immunizations on behalf of The Chilean Infectious Diseases Society. March 2006].

    PubMed

    Muñoz M, Alma; Abarca V, Katia; Luchsinger F, Vivian; Valenzuela B, M Teresa; Jiménez de la J, Jorge

    2006-06-01

    The article briefly reviews the epidemiology of rotavirus infection and the scientific information of the rotavirus vaccines: Rotashield, withdrawn from the market due to its association with intussusception, Rotateq currently in an advanced phase of development, and Rotarix, recently licensed in Chile. Considering the available information, the Consultive Committee of Immunizations of the Chilean Society of Infectious Diseases, summarizes its conclusions and makes recommendations for infants vaccination against rotavirus in our country.

  7. Implementation of a universal rotavirus vaccination program: comparison of two delivery systems.

    PubMed

    Zelman, Mitchell; Sanford, Carolyn; Neatby, Anne; Halperin, Beth A; MacDougall, Donna; Rowswell, Corinne; Langley, Joanne M; Halperin, Scott A

    2014-09-02

    Rotavirus vaccine is recommended for all infants in Canada. To evaluate the logistics of implementing a universal rotavirus vaccination program, we compared the effectiveness of program implementation in jurisdictions with either a physician-administered or public health nurse-administered program. All infants born between October 1, 2010 and September 30, 2012 in Prince Edward Island and Nova Scotia's Capital District Health Authority were eligible for the vaccination program. A universal rotavirus vaccination program was implemented and delivered in public health clinics in Prince Edward Island and in physicians' offices in Nova Scotia. Engagement of vaccinators in delivery of the universal vaccination program was more successful in Prince Edward Island than in Nova Scotia. Vaccine coverage rates rose rapidly in Prince Edward Island, exceeding 90% for both doses within 3 months and remaining at those levels over the two-year program. In contrast, coverage rates in Nova Scotia rose more slowly and never exceeded 40% during the two years. Access to coverage data was more timely and accurate in Prince Edward Island than Nova Scotia. A universal rotavirus vaccination program delivered through public health clinics achieved more rapid and higher levels of coverage than a program administered through physicians' offices. NCT01273077.

  8. A qualitative assessment of factors influencing acceptance of a new rotavirus vaccine among health care providers and consumers

    SciTech Connect

    Manish M Patel, Alan P Janssen, Richard Tardif, Mark Herring, Umesh Parashar

    2007-10-18

    In 2006, a new rotavirus vaccine (RotaTeq) was licensed in the US and recommended for routine immunization of all US infants. Because a previously licensed vaccine (Rotashield) was withdrawn from the US for safety concerns, identifying barriers to uptake of RotaTeq will help develop strategies to broaden vaccine coverage. Our qualitative assessment provides complementary data to recent quantitative surveys and suggests that physicians and parents are likely to adopt the newly licensed rotavirus vaccine. Increasing parental awareness of the rotavirus disease burden and providing physicians with timely post-marketing surveillance data will be integral to a successful vaccination program.

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

    PubMed

    Alkoshi, Salem; Maimaiti, Namaitijiang; Dahlui, Maznah

    2014-01-01

    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. 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. 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. The model shows that rotavirus vaccination could be economically a very attractive intervention in Libya.

  10. 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

  11. 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

  12. 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.

  13. 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.

  14. Rotavirus genotype distribution during the pre-vaccine period in Bolivia: 2007–2008

    PubMed Central

    Rivera, Rosario; Forney, Kristen; Castro, Maria René; Rebolledo, Paulina A.; Mamani, Nataniel; Patzi, Maritza; Halkyer, Percy; Leon, Juan S.; Iñiguez, Volga

    2013-01-01

    Summary Objectives Rotavirus is the most important etiology of severe diarrhea in Bolivia. The monovalent attenuated human oral rotavirus vaccine Rotarix® was introduced in Bolivia in 2008. We describe the molecular epidemiology of circulating rotavirus strains before vaccine introduction. Methods Two thousand one hundred thirty-five diarrheal samples were collected from hospitals in four Bolivian cities during 2007–2008. Forty-three percent (445 of 1030 rotavirus-positive samples) were analyzed for G and P genotypes. Among those, 331 were electropherotyped by polyacrylamide gel electrophoresis. Disease severity was quantified using a modified Vesikari scale. Results Among the 445 samples, five genotypes were found to be prevalent: G9P[8] (33%), G1P[6] (17%), G2P[4] (13%), G9P[6] (12%), and G1P[8] (4%). Co-infections with two or more strains accounted for 14% of samples. The most prevalent strain, G9, showed greater electropherotype diversity compared to other serogroups. Strain G1P[6] generally infected younger children and peaked later in the year than other strains. No particular genotype was associated with a higher severity score, though there was a significant difference in the duration of diarrhea between genotypes. Conclusions During the 2-year pre-vaccine period, substantial diversity of rotavirus co-circulating strains was observed. These data constitute a baseline against which changes in circulating strains post-vaccine introduction can be monitored. PMID:23688547

  15. Rotavirus genotype distribution during the pre-vaccine period in Bolivia: 2007-2008.

    PubMed

    Rivera, Rosario; Forney, Kristen; Castro, Maria René; Rebolledo, Paulina A; Mamani, Nataniel; Patzi, Maritza; Halkyer, Percy; Leon, Juan S; Iñiguez, Volga

    2013-09-01

    Rotavirus is the most important etiology of severe diarrhea in Bolivia. The monovalent attenuated human oral rotavirus vaccine Rotarix(®) was introduced in Bolivia in 2008. We describe the molecular epidemiology of circulating rotavirus strains before vaccine introduction. Two thousand one hundred thirty-five diarrheal samples were collected from hospitals in four Bolivian cities during 2007-2008. Forty-three percent (445 of 1030 rotavirus-positive samples) were analyzed for G and P genotypes. Among those, 331 were electropherotyped by polyacrylamide gel electrophoresis. Disease severity was quantified using a modified Vesikari scale. Among the 445 samples, five genotypes were found to be prevalent: G9P[8] (33%), G1P[6] (17%), G2P[4] (13%), G9P[6] (12%), and G1P[8] (4%). Co-infections with two or more strains accounted for 14% of samples. The most prevalent strain, G9, showed greater electropherotype diversity compared to other serogroups. Strain G1P[6] generally infected younger children and peaked later in the year than other strains. No particular genotype was associated with a higher severity score, though there was a significant difference in the duration of diarrhea between genotypes. During the 2-year pre-vaccine period, substantial diversity of rotavirus co-circulating strains was observed. These data constitute a baseline against which changes in circulating strains post-vaccine introduction can be monitored. Copyright © 2013 International Society for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.

  16. Effectiveness of vaccination with the pentavalent rotavirus vaccine in Nicaragua as determined using the screening method.

    PubMed

    Cardellino, Anna; Khawaja, Shazia; Sánchez Cruz, Edmundo; Mast, T Christopher

    2013-07-01

    The screening method is a surveillance tool to evaluate vaccine effectiveness (VE) using coverage data on cases and available administrative estimates of vaccine coverage in the population. The aim of this analysis was to evaluate the utility and limitations of using the screening methodology to estimate VE, particularly in a developing world country with a high coverage rate, and to compare it with the VE estimates from 2 case-control studies. Using data from 2008, the screening method employed in this study estimated that VE for 3 doses of RV5 among children<12 mo of age to prevent wild-type severe disease, resulting in hospitalization or emergency department visits, was 92% (95% confidence interval [CI]: 78-100%). Additional sensitivity analysis demonstrated that the point estimates of VE against severe disease ranged from 72% (95% CI: 62-83%) to 92% (95% CI: 78-100%); this range of VE estimates, although wide, is relatively consistent with results reported from 2 case-control studies in Nicaragua for the same time period. When the infrastructure is in place to collect reasonably robust case data, the use of the screening method to estimate VE is possible in the developing world setting. Cases of severe wild-type rotavirus gastroenteritis were obtained through an observational, hospital-based, prospective, surveillance program to assess rotavirus acute gastroenteritis. The proportion of cases vaccinated was estimated using the child's vaccination card or health record. The proportion of the population vaccinated was estimated using administrative population-based vaccination coverage estimates provided by the Nicaraguan Ministry of Health.

  17. Investigation of a regulatory agency enquiry into potential porcine circovirus type 1 contamination of the human rotavirus vaccine, Rotarix™

    PubMed Central

    Dubin, Gary; Toussaint, Jean-François; Cassart, Jean-Pol; Howe, Barbara; Boyce, Donna; Friedland, Leonard; Abu-Elyazeed, Remon; Poncelet, Sylviane; Han, Htay Htay; Debrus, Serge

    2013-01-01

    In January 2010, porcine circovirus type 1 (PCV1) DNA was unexpectedly detected in the oral live-attenuated human rotavirus vaccine, Rotarix™ (GlaxoSmithKline [GSK] Vaccines) by an academic research team investigating a novel, highly sensitive analysis not routinely used for adventitious agent screening. GSK rapidly initiated an investigation to confirm the source, nature and amount of PCV1 in the vaccine manufacturing process and to assess potential clinical implications of this finding. The investigation also considered the manufacturer’s inactivated poliovirus (IPV)-containing vaccines, since poliovirus vaccine strains are propagated using the same cell line as the rotavirus vaccine strain. Results confirmed the presence of PCV1 DNA and low levels of PCV1 viral particles at all stages of the Rotarix™ manufacturing process. PCV type 2 DNA was not detected at any stage. When tested in human cell lines, productive PCV1 infection was not observed. There was no immunological or clinical evidence of PCV1 infection in infants who had received Rotarix™ in clinical trials. PCV1 DNA was not detected in the IPV-containing vaccine manufacturing process beyond the purification stage. Retrospective testing confirmed the presence of PCV1 DNA in Rotarix™ since the initial stages of its development and in vaccine lots used in clinical studies conducted pre- and post-licensure. The acceptable safety profile observed in clinical trials of Rotarix™ therefore reflects exposure to PCV1 DNA. The investigation into the presence of PCV1 in Rotarix™ could serve as a model for risk assessment in the event of new technologies identifying adventitious agents in the manufacturing of other vaccines and biological products. PMID:24056737

  18. Potential epidemiological and economical impact of two rotavirus vaccines in Colombia.

    PubMed

    De la Hoz, Fernando; Alvis, Nelson; Narváez, Javier; Cediel, Natalia; Gamboa, Oscar; Velandia, Martha

    2010-05-14

    A complete economic study was carried out to assess the economical impact of two rotavirus vaccine in Colombia. A Markov decision model was built to assess the health outcomes from birth to 24 months of age for three hypothetical cohorts: one unvaccinated, one vaccinated with 2 doses of Rotarix and the third, with 3 doses of Rotateq. Without vaccination, the annual number of medical visits by diarrhea in children under 2 years would be 1,293,159 cases, with 105,378 medical visits and 470 deaths (IC95% 295-560) related to rotavirus. Without vaccination, rotavirus disease would cost around USD$8 millions including direct and indirect costs. Assuming a cost per dose of USD$7.5, average cost-effectiveness ratio would be USD$663/DALY with Rotarix and USD$1391 with Rotateq. When price per dose falls below USD$7 both vaccines yield a similar average cost-effectiveness ratio (USD$1063/DALY). Incremental cost-effectiveness ratio of Rotateq versus Rotarix was USD$7787/DALY. Cost-effectiveness ratio was influenced mainly by vaccine cost and cost per case hospitalized. Other programmatic aspects such as number of doses to be applied, likelihood of completing vaccination schedule with shorter versus longer schedules, and storage space within the chain cold should be considered to make decisions on which vaccine should be introduced. In conclusion, vaccinating against rotavirus in Colombia with either vaccine would be very cost effective. If cost per vaccinated children falls below USD$3 per dose vaccination would be cost saving.

  19. Molecular Epidemiological Traits of Group A Rotaviruses in Japanese Children During Transitional Period of Rotavirus Vaccine Implementation, 2011 - 2014.

    PubMed

    Takanashi, Sayaka; Thongprachum, Aksara; Okitsu, Shoko; Nishimura, Shuichi; Kobayashi, Masaaki; Kikuta, Hideaki; Yamamoto, Atsuko; Sugita, Kumiko; Baba, Tsuneyoshi; Hayakawa, Satoshi; Mizuguchi, Masashi; Ushijima, Hiroshi

    2017-05-01

    Group A rotavirus (RVA) vaccines have been introduced in Japan since 2011. To investigate the molecular epidemiological traits of RVA during the transitional period of rotavirus vaccine implementation in Japan, this study was undertaken by following up three-decade long surveillance conducted in the same regions. RVA were screened and genotyped by RT-PCR from diarrheal samples collected from non-hospitalized patients in six localities (Hokkaido, Tokyo, Shizuoka, Osaka, Kyoto, and Saga) during 2011 - 2014. Selected samples were sequenced to elucidate the evolutionary trend. Among 1858 specimens, the detection rate of RVA declined to 4.0% in 2013 - 2014 from 17.9% in 2011 - 2012 and 22.1% in 2012 - 2013. G1P[8] was the most predominant genotype in the first two years accounting for more than half, and G9P[8] showed the highest detection rate as 35.0% in the last year. Interestingly, the proportional rate of G2 strains in the studied period increased from 0% to 25%. VP6 genotyping revealed that DS-1 like reassortant G1P[8] strains were detected all over Japan and their prevalence fluctuated greatly from 35.0% to 89.5%. Sequence analysis of VP6 showed that strains in the current strains were closely related but distinct from the original reference strains, namely Wa and DS-1. The detection rates of RVA, their GP combinations, prevalence of reassortant strains varied greatly after the introduction of rotavirus vaccines in Japan. Continuous monitoring is warranted to refine future vaccine strategy.

  20. Incidence of rotavirus gastroenteritis by age in African, Asian and European children: Relevance for timing of rotavirus vaccination

    PubMed Central

    Steele, A. Duncan; Madhi, Shabir A.; Cunliffe, Nigel A.; Vesikari, Timo; Phua, Kong Boo; Lim, Fong Seng; Nelson, E. Anthony S.; Lau, Yu-Lung; Huang, Li-Min; Karkada, Naveen; Debrus, Serge; Han, Htay Htay; Benninghoff, Bernd

    2016-01-01

    ABSTRACT Variability in rotavirus gastroenteritis (RVGE) epidemiology can influence the optimal vaccination schedule. We evaluated regional trends in the age of RVGE episodes in low- to middle- versus high-income countries in three continents. We undertook a post-hoc analysis based on efficacy trials of a human rotavirus vaccine (HRV; Rotarix™, GSK Vaccines), in which 1348, 1641, and 5250 healthy infants received a placebo in Europe (NCT00140686), Africa (NCT00241644), and Asia (NCT00197210, NCT00329745). Incidence of any/severe RVGE by age at onset was evaluated by active surveillance over the first two years of life. Severity of RVGE episodes was assessed using the Vesikari-scale. The incidence of any RVGE in Africa was higher than in Europe during the first year of life (≤2.78% vs. ≤2.03% per month), but much lower during the second one (≤0.86% versus ≤2.00% per month). The incidence of severe RVGE in Africa was slightly lower than in Europe during the first year of life. Nevertheless, temporal profiles for the incidence of severe RVGE in Africa and Europe during the first (≤1.00% and ≤1.23% per month) and second (≤0.53% and ≤1.13% per month) years of life were similar to those of any RVGE. Any/severe RVGE incidences peaked at younger ages in Africa vs. Europe. In high-income Asian regions, severe RVGE incidence (≤0.31% per month) remained low during the study. The burden of any RVGE was higher earlier in life in children from low- to middle- compared with high-income countries. Differing rotavirus vaccine schedules are likely warranted to maximize protection in different settings. PMID:27260009

  1. Incidence of rotavirus gastroenteritis by age in African, Asian and European children: Relevance for timing of rotavirus vaccination.

    PubMed

    Steele, A Duncan; Madhi, Shabir A; Cunliffe, Nigel A; Vesikari, Timo; Phua, Kong Boo; Lim, Fong Seng; Nelson, E Anthony S; Lau, Yu-Lung; Huang, Li-Min; Karkada, Naveen; Debrus, Serge; Han, Htay Htay; Benninghoff, Bernd

    2016-09-01

    Variability in rotavirus gastroenteritis (RVGE) epidemiology can influence the optimal vaccination schedule. We evaluated regional trends in the age of RVGE episodes in low- to middle- versus high-income countries in three continents. We undertook a post-hoc analysis based on efficacy trials of a human rotavirus vaccine (HRV; Rotarix™, GSK Vaccines), in which 1348, 1641, and 5250 healthy infants received a placebo in Europe (NCT00140686), Africa (NCT00241644), and Asia (NCT00197210, NCT00329745). Incidence of any/severe RVGE by age at onset was evaluated by active surveillance over the first two years of life. Severity of RVGE episodes was assessed using the Vesikari-scale. The incidence of any RVGE in Africa was higher than in Europe during the first year of life (≤2.78% vs. ≤2.03% per month), but much lower during the second one (≤0.86% versus ≤2.00% per month). The incidence of severe RVGE in Africa was slightly lower than in Europe during the first year of life. Nevertheless, temporal profiles for the incidence of severe RVGE in Africa and Europe during the first (≤1.00% and ≤1.23% per month) and second (≤0.53% and ≤1.13% per month) years of life were similar to those of any RVGE. Any/severe RVGE incidences peaked at younger ages in Africa vs. Europe. In high-income Asian regions, severe RVGE incidence (≤0.31% per month) remained low during the study. The burden of any RVGE was higher earlier in life in children from low- to middle- compared with high-income countries. Differing rotavirus vaccine schedules are likely warranted to maximize protection in different settings.

  2. Acute diarrhoea in a community cohort of children who received an oral rotavirus vaccine in Northeast Brazil.

    PubMed

    Vieira, Sarah Cristina Fontes; Gurgel, Ricardo Queiroz; Kirby, Andrew; Barreto, Isis Pinheiro; Souza, Liane Desiderio de; Oliveira, Oderlan Carvalho; Correia, Jailson de Barros; Dove, Winifred; Cunliffe, Nigel A; Cuevas, Luis E

    2011-05-01

    Rotavirus is an important cause of childhood diarrhoea. A monovalent rotavirus vaccine (Rotarix®) was introduced into the Immunization Program of Brazil in 2006. In this study, we describe the incidence and burden of disease of rotavirus diarrhoea in two cohorts of children (vaccinated and unvaccinated). We followed two groups of 250 children under one year old, who were enrolled in December 2006 from a low-income residential area in Northeast Brazil. The children were monitored every two weeks for two years. Stool samples from children with diarrhoea were examined for the presence of rotavirus. Rotaviruses were genotyped using real time-polymerase chain reaction. The mean numbers of all-cause diarrhoea episodes/child (adjusted for age) in the first year were 0.87 and 0.84, in vaccinated and unvaccinated children, respectively. During the second year, the number of episodes/child decreased to 0.52 and 0.42. Only 16 (4.9%) of 330 stool samples were rotavirus-positive (10 vaccinated and 6 unvaccinated children) and only P[4]G2 rotaviruses were identified. All-cause diarrhoea episodes were more severe in unvaccinated children in the first year of age (p < 0.05), while vaccinated children had more severe episodes 18 months after vaccination. Rotavirus diarrhoea incidence was very low in both groups.

  3. Effectiveness of monovalent rotavirus vaccine in Bolivia: case-control study.

    PubMed

    Patel, Manish M; Patzi, Maritza; Pastor, Desiree; Nina, Aleida; Roca, Yelin; Alvarez, Leovigildo; Iniguez, Volga; Rivera, Rosario; Tam, Ka Ian; Quaye, Osbourne; Bowen, Michael; Parashar, Umesh; De Oliveira, Lucia Helena

    2013-06-19

    To evaluate the effectiveness of two doses of a monovalent rotavirus vaccine (RV1) against hospital admission for rotavirus in Bolivia. Case-control study. Six hospitals in Bolivia, between March 2010 and June 2011. 400 hospital admissions for rotavirus, 1200 non-diarrhea hospital controls, and 718 rotavirus negative hospital controls. Odds of antecedent vaccination between case patients and controls; effectiveness of vaccination ((1-adjusted odds ratio)×100), adjusted for age and other confounders; and stratified effectiveness by dose, disease severity, age group, and serotype. In comparison with non-diarrhea controls, case patients were more likely to be male and attend day care but less likely to have chronic underlying illness, higher level maternal education, and telephones and computers in their home. Rotavirus negative controls were somewhat more similar to case patients but also were more likely to be male and attend day care and less likely to have higher level maternal education and computers in their homes. The adjusted effectiveness of RV1 against hospital admission for rotavirus was 69% (95% confidence interval 54% to 79%) with rotavirus negative controls and 77% (65% to 84%) with non-diarrhea controls. The effectiveness of one dose of RV1 was 36% and 56%, respectively. With both control groups, protection was sustained through two years of life, with similar efficacy against hospital admission among children under 1 year (64% and 77%) and over 1 year of age (72% and 76%). RV1 provided significant protection against diverse serotypes, partially and fully heterotypic to the G1P[8] vaccine. Effectiveness using the two control groups was 80% and 85% against G9P[8], 74% and 93%% against G3P[8], 59% and 69% against G2P[4], and 80% and 87% against G9P[6] strains. The monovalent rotavirus vaccine conferred high protection against hospital admission for diarrhea due to rotavirus in Bolivian children. Protection was sustained through two years of life against

  4. Effectiveness of monovalent rotavirus vaccine in Bolivia: case-control study

    PubMed Central

    Patzi, Maritza; Pastor, Desiree; Nina, Aleida; Roca, Yelin; Alvarez, Leovigildo; Iniguez, Volga; Rivera, Rosario; Tam, Ka Ian; Quaye, Osbourne; Bowen, Michael; Parashar, Umesh; De Oliveira, Lucia Helena

    2013-01-01

    Objective To evaluate the effectiveness of two doses of a monovalent rotavirus vaccine (RV1) against hospital admission for rotavirus in Bolivia. Design Case-control study. Setting Six hospitals in Bolivia, between March 2010 and June 2011. Participants 400 hospital admissions for rotavirus, 1200 non-diarrhea hospital controls, and 718 rotavirus negative hospital controls. Main outcome measures Odds of antecedent vaccination between case patients and controls; effectiveness of vaccination ((1–adjusted odds ratio)×100), adjusted for age and other confounders; and stratified effectiveness by dose, disease severity, age group, and serotype. Results In comparison with non-diarrhea controls, case patients were more likely to be male and attend day care but less likely to have chronic underlying illness, higher level maternal education, and telephones and computers in their home. Rotavirus negative controls were somewhat more similar to case patients but also were more likely to be male and attend day care and less likely to have higher level maternal education and computers in their homes. The adjusted effectiveness of RV1 against hospital admission for rotavirus was 69% (95% confidence interval 54% to 79%) with rotavirus negative controls and 77% (65% to 84%) with non-diarrhea controls. The effectiveness of one dose of RV1 was 36% and 56%, respectively. With both control groups, protection was sustained through two years of life, with similar efficacy against hospital admission among children under 1 year (64% and 77%) and over 1 year of age (72% and 76%). RV1 provided significant protection against diverse serotypes, partially and fully heterotypic to the G1P[8] vaccine. Effectiveness using the two control groups was 80% and 85% against G9P[8], 74% and 93%% against G3P[8], 59% and 69% against G2P[4], and 80% and 87% against G9P[6] strains. Conclusion The monovalent rotavirus vaccine conferred high protection against hospital admission for diarrhea due to rotavirus

  5. Rotavirus Vaccination Coverage among Children Aged 2-59 Months: A Report from Guangzhou, China

    PubMed Central

    He, Qing; Wang, Ming; Xu, Jianxiong; Zhang, Chunhuan; Wang, Hui; Zhu, Wei; Fu, Chuanxi

    2013-01-01

    Objective We aimed to estimate the Lanzhou lamb rotavirus (LLR) vaccination coverage (VC) and timeliness among children aged 2 to 59 months in Guangzhou, China. Methods An electronic system-based VC survey was conducted using stratified cluster random sampling. Results We reported an overall Lanzhou lamb rotavirus vaccine coverage of 25.3% among children aged 2-59 months (2-8 months, 2.6%) in Guangzhou, China. Conclusion Great efforts should be taken to increase LLR VC in eligible children in Guangzhou, China. PMID:23840828

  6. Efficacy, Immunogenicity, and Safety of Two Doses of a Tetravalent Rotavirus Vaccine RRV-TV in Ghana With the First Dose Administered During the Neonatal Period

    PubMed Central

    Armah, George E.; Kapikian, Albert Z.; Vesikari, Timo; Cunliffe, Nigel; Jacobson, Robert M.; Burlington, D. Bruce; Ruiz, Leonard P.

    2013-01-01

    Background. Oral rhesus/rhesus-human reassortant rotavirus tetravalent vaccine (RRV-TV) was licensed in 1998 but withdrawn in 1999 due to a rare association with intussusception, which occurred disproportionately in infants receiving their first dose at ≥90 days of age. This study examined RRV-TV for the prevention of rotavirus gastroenteritis (RV-GE) in Ghana, West Africa, with infants receiving the first dose during the neonatal period and the second before 60 days of age. Methods. In a double-blinded, randomized, placebo-controlled trial in Navrongo, Ghana, we recruited neonates to receive 2 doses of RRV-TV or placebo and followed them to age 12 months. Results. In the intention-to-treat population of 998 infants, we measured a vaccine efficacy of 63.1% against RV-GE of any severity associated with any of the 4 serotypes represented in the vaccine and 60.7% against RV-GE associated with any rotavirus serotype. Conclusions. RRV-TV in a 2-dose schedule with the first dose during the neonatal period is efficacious in preventing RV-GE in rural Ghana. Neonatal dosing results in early protection and may be the optimum schedule to avoid or significantly reduce intussusception, now reported to be associated in international settings with the 2 most widely marketed, licensed, live virus, oral rotavirus vaccines. PMID:23599316

  7. A multi-center, qualitative assessment of pediatrician and maternal perspectives on rotavirus vaccines and the detection of Porcine circovirus.

    PubMed

    Payne, Daniel C; Humiston, Sharon; Opel, Douglas; Kennedy, Allison; Wikswo, Mary; Downing, Kimberly; Klein, Eileen J; Kobayashi, Ana; Locke, David; Albertin, Christina; Chesley, Claudia; Staat, Mary A

    2011-09-26

    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. 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. 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. 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

  8. Summary of effectiveness and impact of rotavirus vaccination with the oral pentavalent rotavirus vaccine: a systematic review of the experience in industrialized countries.

    PubMed

    Giaquinto, Carlo; Dominiak-Felden, Geraldine; Van Damme, Pierre; Myint, Tin Tin Htar; Maldonado, Yvonne A; Spoulou, Vana; Mast, T Christopher; Staat, Mary Allen

    2011-07-01

    The pentavalent rotavirus (RV) vaccine RotaTeq™ has been available in industrialized countries since 2006. Several studies have been conducted to evaluate the benefit of RV vaccination under routine conditions of use. A systematic review of all publicly available data from RotaTeq™ vaccine-effectiveness and vaccination-impact studies in the USA, Europe and Australia between 2006 and February 2010 was undertaken. Depending on the population studied, effectiveness of up to 100% (95% confidence interval 85-100%) associated with decreased hospitalizations for RV gastroenteritis (RVGE) was seen. Vaccination-impact studies demonstrated that the burden of RVGE has been reduced significantly since the introduction of RV vaccination. Evidence included reductions in healthcare utilization due to RVGE (hospitalizations and emergency-department visits reduced by up to 90%), reductions in the magnitude and duration of the RV season as assessed by laboratory testing for RV, and the possible induction of herd immunity.

  9. Predictors of Uptake and Timeliness of Newly Introduced Pneumococcal and Rotavirus Vaccines, and of Measles Vaccine in Rural Malawi: A Population Cohort Study.

    PubMed

    Mvula, Hazzie; Heinsbroek, Ellen; Chihana, Menard; Crampin, Amelia C; Kabuluzi, Storn; Chirwa, Geoffrey; Mwansambo, Charles; Costello, Anthony; Cunliffe, Nigel A; Heyderman, Robert S; French, Neil; Bar-Zeev, Naor

    2016-01-01

    Malawi introduced pneumococcal conjugate vaccine (PCV13) and monovalent rotavirus vaccine (RV1) in 2011 and 2012 respectively, and is planning the introduction of a second-dose measles vaccine (MV). We assessed predictors of availability, uptake and timeliness of these vaccines in a rural Malawian setting. Commencing on the first date of PCV13 eligibility we conducted a prospective population-based birth cohort study of 2,616 children under demographic surveillance in Karonga District, northern Malawi who were eligible for PCV13, or from the date of RV1 introduction both PCV13 and RV1. Potential predictors of vaccine uptake and timeliness for PCV13, RV1 and MV were analysed respectively using robust Poisson and Cox regression. Vaccine coverage was high for all vaccines, ranging from 86.9% for RV1 dose 2 to 95.4% for PCV13 dose 1. Median time delay for PCV13 dose 1 was 17 days (IQR 7-36), 19 days (IQR 8-36) for RV1 dose 1 and 20 days (IQR 3-46) for MV. Infants born to lower educated or farming mothers and those living further away from the road or clinic were at greater risk of being not fully vaccinated and being vaccinated late. Delays in vaccination were also associated with non-facility birth. Vaccine stock-outs resulted in both a delay in vaccine timeliness and in a decrease in completion of schedule. Despite high vaccination coverage in this setting, delays in vaccination were common. We identified programmatic and socio-demographic risk factors for uptake and timeliness of vaccination. Understanding who remains most vulnerable to be unvaccinated allows for focussed delivery thereby increasing population coverage and maximising the equitable benefits of universal vaccination programmes.

  10. Rotavirus vaccines contribute towards universal health coverage in a mixed public-private healthcare system.

    PubMed

    Loganathan, Tharani; Jit, Mark; Hutubessy, Raymond; Ng, Chiu-Wan; Lee, Way-Seah; Verguet, Stéphane

    2016-11-01

    To evaluate rotavirus vaccination in Malaysia from the household's perspective. The extended cost-effectiveness analysis (ECEA) framework quantifies the broader value of universal vaccination starting with non-health benefits such as financial risk protection and equity. These dimensions better enable decision-makers to evaluate policy on the public finance of health programmes. The incidence, health service utilisation and household expenditure related to rotavirus gastroenteritis according to national income quintiles were obtained from local data sources. Multiple birth cohorts were distributed into income quintiles and followed from birth over the first five years of life in a multicohort, static model. We found that the rich pay more out of pocket (OOP) than the poor, as the rich use more expensive private care. OOP payments among the poorest although small are high as a proportion of household income. Rotavirus vaccination results in substantial reduction in rotavirus episodes and expenditure and provides financial risk protection to all income groups. Poverty reduction benefits are concentrated amongst the poorest two income quintiles. We propose that universal vaccination complements health financing reforms in strengthening Universal Health Coverage (UHC). ECEA provides an important tool to understand the implications of vaccination for UHC, beyond traditional considerations of economic efficiency. © 2016 John Wiley & Sons Ltd.

  11. 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.

  12. Direct and Indirect Effects of Rotavirus Vaccination: Comparing Predictions from Transmission Dynamic Models

    PubMed Central

    Pitzer, Virginia E.; Atchison, Christina J.; Harris, John P.; Shim, Eunha; Galvani, Alison P.; Edmunds, W. John; Viboud, Cécile; Patel, Manish M.; Grenfell, Bryan T.; Parashar, Umesh D.; Lopman, Ben A.

    2012-01-01

    Early observations from countries that have introduced rotavirus vaccination suggest that there may be indirect protection for unvaccinated individuals, but it is unclear whether these benefits will extend to the long term. Transmission dynamic models have attempted to quantify the indirect protection that might be expected from rotavirus vaccination in developed countries, but results have varied. To better understand the magnitude and sources of variability in model projections, we undertook a comparative analysis of transmission dynamic models for rotavirus. We fit five models to reported rotavirus gastroenteritis (RVGE) data from England and Wales, and evaluated outcomes for short- and long-term vaccination effects. All of our models reproduced the important features of rotavirus epidemics in England and Wales. Models predicted that during the initial year after vaccine introduction, incidence of severe RVGE would be reduced 1.8–2.9 times more than expected from the direct effects of the vaccine alone (28–50% at 90% coverage), but over a 5-year period following vaccine introduction severe RVGE would be reduced only by 1.1–1.7 times more than expected from the direct effects (54–90% at 90% coverage). Projections for the long-term reduction of severe RVGE ranged from a 55% reduction at full coverage to elimination with at least 80% coverage. Our models predicted short-term reductions in the incidence of RVGE that exceeded estimates of the direct effects, consistent with observations from the United States and other countries. Some of the models predicted that the short-term indirect benefits may be offset by a partial shifting of the burden of RVGE to older unvaccinated individuals. Nonetheless, even when such a shift occurs, the overall reduction in severe RVGE is considerable. Discrepancies among model predictions reflect uncertainties about age variation in the risk and reporting of RVGE, and the duration of natural and vaccine-induced immunity

  13. The composition of demand for newly launched vaccines: results from the pneumococcal and rotavirus vaccine introductions in Ethiopia and Malawi

    PubMed Central

    Kidane, Teklay; Chirwa, Geoffrey; Tesfaye, Neghist; Prescott, Marta R; Scotney, Soleine T; Valle, Moussa; Abebe, Sintayehu; Tambuli, Adija; Malewezi, Bridget; Mohammed, Tahir; Kobayashi, Emily; Wootton, Emily; Wong, Renee; Dosani, Rahima; Subramaniam, Hamsa; Joseph, Jessica; Yavuz, Elif; Apple, Aliza; Le Tallec, Yann; Kang’ethe, Alice

    2016-01-01

    Understanding post-launch demand for new vaccines can help countries maximize the benefits of immunization programmes. In particular, low- and middle-income countries (LMICs) should ensure adequate resource planning with regards to stock consumption and service delivery for new vaccines, whereas global suppliers must produce enough vaccines to meet demand. If a country underestimates the number of children seeking vaccination, a stock-out of commodities will create missed opportunities for saving lives. We describe the post-launch demand for the first dose of pneumococcal conjugate vaccine (PCV1) in Ethiopia and Malawi and the first dose of rotavirus vaccine (Rota1) in Malawi, with focus on the new birth cohort and the ‘backlog cohort’, comprised of older children who are still eligible for vaccination at the time of launch. PCV1 and Rota1 uptake were compared with the demand for the first dose of pentavalent vaccine (Penta1), a routine immunization that targets the same age group and immunization schedule. In the first year, the total demand for PCV1 was 37% greater than that of Penta1 in Ethiopia and 59% greater in Malawi. In the first 6 months, the demand of Rota1 was only 5.9% greater than Penta1 demand in Malawi. Over the first three post-introduction months, 70.7% of PCV1 demand in Ethiopia and 71.5% of demand in Malawi came from children in the backlog cohort, whereas only 28.0% of Rota1 demand in Malawi was from the backlog cohort. The composition of demand was impacted by time elapsed since vaccine introduction and age restrictions. Evidence suggests that countries’ plans should account for the impact of backlog demand, especially in the first 3 months post-introduction. LMICs should request for higher stock volumes when compared with routine needs, plan social mobilization activities to reach the backlog cohort and allocate human resources and cold chain capacity to accommodate high demand following vaccine introduction. PMID:26856361

  14. The composition of demand for newly launched vaccines: results from the pneumococcal and rotavirus vaccine introductions in Ethiopia and Malawi.

    PubMed

    Williams, B Adam; Kidane, Teklay; Chirwa, Geoffrey; Tesfaye, Neghist; Prescott, Marta R; Scotney, Soleine T; Valle, Moussa; Abebe, Sintayehu; Tambuli, Adija; Malewezi, Bridget; Mohammed, Tahir; Kobayashi, Emily; Wootton, Emily; Wong, Renee; Dosani, Rahima; Subramaniam, Hamsa; Joseph, Jessica; Yavuz, Elif; Apple, Aliza; Le Tallec, Yann; Kang'ethe, Alice

    2016-06-01

    Understanding post-launch demand for new vaccines can help countries maximize the benefits of immunization programmes. In particular, low- and middle-income countries (LMICs) should ensure adequate resource planning with regards to stock consumption and service delivery for new vaccines, whereas global suppliers must produce enough vaccines to meet demand. If a country underestimates the number of children seeking vaccination, a stock-out of commodities will create missed opportunities for saving lives. We describe the post-launch demand for the first dose of pneumococcal conjugate vaccine (PCV1) in Ethiopia and Malawi and the first dose of rotavirus vaccine (Rota1) in Malawi, with focus on the new birth cohort and the 'backlog cohort', comprised of older children who are still eligible for vaccination at the time of launch. PCV1 and Rota1 uptake were compared with the demand for the first dose of pentavalent vaccine (Penta1), a routine immunization that targets the same age group and immunization schedule. In the first year, the total demand for PCV1 was 37% greater than that of Penta1 in Ethiopia and 59% greater in Malawi. In the first 6 months, the demand of Rota1 was only 5.9% greater than Penta1 demand in Malawi. Over the first three post-introduction months, 70.7% of PCV1 demand in Ethiopia and 71.5% of demand in Malawi came from children in the backlog cohort, whereas only 28.0% of Rota1 demand in Malawi was from the backlog cohort. The composition of demand was impacted by time elapsed since vaccine introduction and age restrictions. Evidence suggests that countries' plans should account for the impact of backlog demand, especially in the first 3 months post-introduction. LMICs should request for higher stock volumes when compared with routine needs, plan social mobilization activities to reach the backlog cohort and allocate human resources and cold chain capacity to accommodate high demand following vaccine introduction. © The Author 2016. Published by

  15. Rotavirus vaccination and infection induce VP6-specific IgA responses.

    PubMed

    Lappalainen, Suvi; Blazevic, Vesna; Malm, Maria; Vesikari, Timo

    2017-02-01

    Rotavirus (RV) is the leading cause of severe gastroenteritis (GE) in young children, but RVGE has drastically been reduced with the introduction of live oral RV vaccines into childhood immunization program in many countries. Serum IgA antibody is a marker of clinical protection against severe RVGE after RV infection and vaccination. This study investigated VP6-specificity of anti-RV IgA antibody levels in Finnish children aged 6-23 months before and after introduction of RotaTeq® into national immunization program. Although RV inner capsid protein VP6 is considered as antigenic target in clinical and seroepidemiological studies, at present VP6 protein is not commonly employed as a primary ELISA-antigen. Thus, sera from 20 unvaccinated and 19 vaccinated children were examined in ELISA with recombinant VP6 (rVP6) protein, and the VP6-specific responses were compared to responses observed with human RV Wa and bovine RV WC3 cell culture antigens. Moreover, fecal antibodies were tested with rVP6 and Wa cell culture antigen. Equal levels of serum anti-RV IgA antibodies were detected by the three antigens. Fecal IgA titers against rVP6 and Wa antigen showed a correlation with the corresponding serum levels. The results suggest that the IgA response measured by virus-capture ELISA is mainly directed to VP6 protein, supporting the usage of rVP6 in detection of anti-RV IgA antibodies. Natural RV infections and vaccinations induced similar levels of serum VP6-specific IgA antibodies. Serum IgA antibodies after RotaTeq® vaccination showed sustained levels up to two years of age in line with long term protection. J. Med. Virol. 89:239-245, 2017. © 2016 Wiley Periodicals, Inc.

  16. Presence of rotavirus and free-living amoebae in the water supplies of Karachi, Pakistan

    PubMed Central

    Yousuf, Farzana Abubakar; Siddiqui, Ruqaiyyah; Khan, Naveed Ahmed

    2017-01-01

    ABSTRACT Rotavirus and pathogenic free-living amoebae are causative agents of important health problems, especially for developing countries like Pakistan where the population has limited access to clean water supplies. Here, we evaluated the prevalence of rotavirus and free-living amoebae (Acanthamoeba spp., Balamuthia mandrillaris, Naegleria fowleri) in drinking water supplies of Karachi, Pakistan. Six water filtration plants that supply drinking water to the population of Karachi were investigated. Additionally, drinking water samples from households were analyzed for the presence of rotavirus and free-living amoebae. Rotavirus was present in 35% of the water samples collected from water filtration plants; however, domestic tap water samples had a prevalence of only 5%. Out of 20 water samples from filtration plants, 13 (65%) were positive for Acanthamoeba spp., and one (5%) was positive for B. mandrillaris. Out of 20 drinking water samples collected from different areas of Karachi, 35% were positive for Acanthamoeba spp. Rotavirus was detected in 5% of the drinking water samples tested. Overall, these findings showed for the first time the presence of rotavirus, in addition to pathogenic free-living amoebae in drinking water supplies of Karachi that could be an important public health risk for the affected population. PMID:28591260

  17. Presence of rotavirus and free-living amoebae in the water supplies of Karachi, Pakistan.

    PubMed

    Yousuf, Farzana Abubakar; Siddiqui, Ruqaiyyah; Khan, Naveed Ahmed

    2017-06-01

    Rotavirus and pathogenic free-living amoebae are causative agents of important health problems, especially for developing countries like Pakistan where the population has limited access to clean water supplies. Here, we evaluated the prevalence of rotavirus and free-living amoebae (Acanthamoeba spp., Balamuthia mandrillaris, Naegleria fowleri) in drinking water supplies of Karachi, Pakistan. Six water filtration plants that supply drinking water to the population of Karachi were investigated. Additionally, drinking water samples from households were analyzed for the presence of rotavirus and free-living amoebae. Rotavirus was present in 35% of the water samples collected from water filtration plants; however, domestic tap water samples had a prevalence of only 5%. Out of 20 water samples from filtration plants, 13 (65%) were positive for Acanthamoeba spp., and one (5%) was positive for B. mandrillaris. Out of 20 drinking water samples collected from different areas of Karachi, 35% were positive for Acanthamoeba spp. Rotavirus was detected in 5% of the drinking water samples tested. Overall, these findings showed for the first time the presence of rotavirus, in addition to pathogenic free-living amoebae in drinking water supplies of Karachi that could be an important public health risk for the affected population.

  18. Analysis of rotavirus genotypes in Korea during 2013: an increase in the G2P[4] genotype after the introduction of rotavirus vaccines.

    PubMed

    Kim, Jae-Seok; Kim, Hyun Soo; Hyun, Jungwon; Kim, Han-Sung; Song, Wonkeun; Lee, Kyu Man; Shin, Seon-Hee

    2014-11-12

    Group A rotavirus is the leading cause of acute gastroenteritis in children worldwide. We investigated G and P genotypes of group A rotavirus strains isolated from patients during 2013 and investigated which genotypes were identified from vaccinated patients. From January to December 2013, 2235 fecal specimens were tested for rotavirus antigen, of which 374 specimens (16.7%) showed positive results. Strains from 288 rotavirus-positive specimens were genotyped using PCR and sequencing, and individual patients' corresponding vaccine histories were investigated through the Korean Center for Disease Control website. G2 (22.6%) and P[4] (24.0%) were the most frequently identified G and P genotypes, respectively; accordingly, G2P[4] (19.8%) was the most prevalent G/P genotype observed in this period. G4P[6] (10.1%) was the second most prevalent G/P genotype and was mostly detected in neonates. Other genotypes, G1P[8], G9P[8], G1P[6], and G3P[6], were also detected. Of 288 rotavirus-positive specimens, 48 specimens were obtained from previously vaccinated patients. G2P[4] was also the genotype most frequently isolated from vaccinated patients. VP7 epitope analysis of G1P[8] and G2P[4] strains showed at least one amino acid differences in comparison with Rotarix and RotaTeq vaccine strains. The genotypic distribution of rotavirus strains in Korea has been shown temporal and geographical differences. This study showed that G2P[4] was the genotype most frequently isolated from both vaccinated and unvaccinated patients in Korea during 2013. However, it is unclear whether the change of predominant genotype is due to the effect of vaccination or due to natural variation. Copyright © 2014 Elsevier Ltd. All rights reserved.

  19. Human rotavirus vaccine (Rotarix): focus on effectiveness and impact 6 years after first introduction in Africa.

    PubMed

    O'Ryan, Miguel; Giaquinto, Carlo; Benninghoff, Bernd

    2015-01-01

    A decade after licensure of the human rotavirus vaccine (HRV), a wealth of evidence supports a reduction of rotavirus (RV) gastroenteritis-associated mortality and hospitalizations following HRV inclusion in national immunization programs. Nevertheless, the majority of real-world data has been generated in high- or middle-income settings. Clinical efficacy trials previously indicated RV vaccine performance may be lower in less-developed countries compared with wealthier counterparts. Using recently published data from Africa, we examine the effectiveness and impact of HRV in resource-deprived areas, exploring whether vaccine performance differs by socioeconomic setting and the potential underlying factors. HRV vaccine effectiveness in early adopting African countries has proven to be similar or even superior to the efficacy results observed in pre-licensure studies.

  20. 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.

  1. 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

  2. A cost comparison of introducing and delivering pneumococcal, rotavirus and human papillomavirus vaccines in Rwanda.

    PubMed

    Ngabo, Fidèle; Levin, Ann; Wang, Susan A; Gatera, Maurice; Rugambwa, Celse; Kayonga, Celestin; Donnen, Philippe; Lepage, Philippe; Hutubessy, Raymond

    2015-12-16

    Detailed cost evaluations of delivery of new vaccines such as pneumococcal conjugate, human papillomavirus (HPV), and rotavirus vaccines in low and middle-income countries are scarce. This paper differs from others by comparing the costs of introducing multiple vaccines in a single country and then assessing the financial and economic impact at the time and implications for the future. The objective of the analysis was to understand the introduction and delivery cost per dose or per child of the three new vaccines in Rwanda to inform domestic and external financial resource mobilization. Start-up, recurrent, and capital costs from a government perspective were collected in 2012. Since pneumococcal conjugate and HPV vaccines had already been introduced, cost data for those vaccines were collected retrospectively while prospective (projected) costing was done for rotavirus vaccine. The financial unit cost per fully immunized child (or girl for HPV vaccine) of delivering 3 doses of each vaccine (without costs related to vaccine procurement) was $0.37 for rotavirus (RotaTeq(®)) vaccine, $0.54 for pneumococcal (Prevnar(®)) vaccine in pre-filled syringes, and $10.23 for HPV (Gardasil (®)) vaccine. The financial delivery costs of Prevnar(®) and RotaTeq(®) were similar since both were delivered using existing health system infrastructure to deliver infant vaccines at health centers. The total financial cost of delivering Gardasil(®) was higher than those of the two infant vaccines due to greater resource requirements associated with creating a new vaccine delivery system in for a new target population of 12-year-old girls who have not previously been served by the existing routine infant immunization program. The analysis indicates that service delivery strategies have an important influence on costs of introducing new vaccines and costs per girl reached with HPV vaccine are higher than the other two vaccines because of its delivery strategy. Documented information

  3. Cost-Effectiveness of a new Rotavirus Vaccination Program in Pakistan: a Decision Tree Model

    PubMed Central

    Patel, Hiten D.; Roberts, Eric T.; Constenla, Dagna O.

    2013-01-01

    Background Rotavirus gastroenteritis places a significant health and economic burden on Pakistan. To determine the public health impact of a national rotavirus vaccination program, we performed a cost-effectiveness study from the perspective of the health care system. Methods A decision tree model was developed to assess the cost-effectiveness of a national vaccination program in Pakistan. Disease and cost burden with the program were compared to the current state. Disease parameters, vaccine-related costs, and medical treatment costs were based on published epidemiological and economic data, which were specific to Pakistan when possible. An annual birth cohort of children was followed for 5 years to model the public health impact of vaccination on health-related events and costs. The cost-effectiveness was assessed and quantified in cost (2012 US$) per disability-adjusted life-year (DALY) averted and cost per death averted. Sensitivity analyses were performed to assess the robustness of the incremental cost-effectiveness ratios (ICERs). Results The base case results showed vaccination prevented 1.2 million cases of rotavirus gastroenteritis, 93,000 outpatient visits, 43,000 hospitalizations, and 6,700 deaths by 5 years of age for an annual birth cohort scaled from 6% current coverage to DPT3 levels (85%). The medical cost savings would be US$1.4 million from hospitalizations and US$200,000 from outpatient visit costs. The vaccination program would cost US$35 million at a vaccine price of US$5.00. The ICER was US$149.50 per DALY averted or US$4,972 per death averted. Sensitivity analyses showed changes in case-fatality ratio, vaccine efficacy, and vaccine cost exerted the greatest influence on the ICER. Conclusions Across a range of sensitivity analyses, a national rotavirus vaccination program was predicted to decrease health and economic burden due to rotavirus gastroenteritis in Pakistan by ~40%. Vaccination was highly cost-effective in this context. As

  4. 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

  5. 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

  6. Factors associated with rotavirus diarrhoea in children living in a socially diverse urban centre in Brazil.

    PubMed

    Strina, Agostino; Rodrigues, Laura C; Cairncross, Sandy; Ferrer, Suzana R; Fialho, Alexandre Madi; Leite, Jose Paulo G; Ribeiro, Hugo C; Barreto, Mauricio L

    2012-07-01

    A case-control study, aimed at identifying factors associated with rotavirus diarrhoea cases presenting to health facilities, was conducted in children from low-income and middle-low-income families in Brazil. Cases were 390 children with diarrhoea and rotavirus in stools; controls were 1674 children without diarrhoea presenting to the same facilities. Data were collected by questionnaire and observations during home visits. Explanatory variables were grouped according to a conceptual model of causation. The ORs by non-conditional logistic regression and population-attributable fractions were calculated. Socioeconomic factors contributed a third of cases, followed by contact with diarrhoea cases and by not being breast fed. In cases aged <1 year, not being breast fed was the main determinant, followed by socioeconomic factors, and crowding and contact outside the home; in older children, socioeconomic factors followed by contact inside and outside the home were the main determinants. Environmental and sanitation variables were not associated with diarrhoea in the final model, and socioeconomic factors were only partly mediated by proximal variables. Transmission of rotavirus appears to be mostly by person-to-person contact, and shows marked social differentials not explained by the biological factors studied. The rotavirus vaccine is unlikely to protect against the full range of circulating genotypes of rotavirus, and understanding rotavirus epidemiology remains essential to the development of control policies. Copyright © 2012 Royal Society of Tropical Medicine and Hygiene. Published by Elsevier Ltd. All rights reserved.

  7. 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

  8. Knowledge, attitudes, beliefs, and behaviors of parents and healthcare providers before and after implementation of a universal rotavirus vaccination program.

    PubMed

    MacDougall, Donna M; Halperin, Beth A; Langley, Joanne M; MacKinnon-Cameron, Donna; Li, Li; Halperin, Scott A

    2016-01-27

    In Canada, rotavirus vaccine is recommended for all infants, but not all provinces/territories have publicly funded programs. We compared public and healthcare provider (HCP) knowledge, attitudes, beliefs, and behaviors in a province with a public health nurse-delivered, publicly funded rotavirus vaccination program to a province with a publicly funded, physician-delivered program. A third province with no vaccination program acted as a control. Information about knowledge, attitudes, beliefs, and behaviors of parents whose children were eligible for the universal program and healthcare providers responsible for administering the vaccine were collected through the use of two validated surveys distributed in public health clinics, physicians' offices, and via e-mail. Early and postvaccine-program survey results were compared. A total of 722 early implementation and 709 postimplementation parent surveys and 180 early and 141 postimplementation HCP surveys were analyzed. HCP and public attitudes toward rotavirus vaccination were generally positive and didn't change over time. More parents postprogram were aware of the NACI recommendation and the vaccination program and reported that their healthcare provider discussed rotavirus infection and vaccine with them. Prior to the program across all sites, more physicians than nurses were aware of the national recommendation regarding rotavirus vaccine. In the postprogram survey, however, more nurses were aware of the national recommendation and their provincial universal rotavirus vaccination program. Nurses had higher knowledge scores than physicians in the postprogram survey (p<0.001). Parents of young infants were also more knowledgeable about rotavirus and rotavirus vaccine in the two areas where universal programs were in place (p<0.001). Implementation of a universal rotavirus vaccination program was associated with an increase in knowledge and more positive attitudes toward rotavirus vaccine amongst parents of

  9. Genome-Wide Evolutionary Analyses of G1P[8] Strains Isolated Before and After Rotavirus Vaccine Introduction.

    PubMed

    Zeller, Mark; Donato, Celeste; Trovão, Nídia Sequeira; Cowley, Daniel; Heylen, Elisabeth; Donker, Nicole C; McAllen, John K; Akopov, Asmik; Kirkness, Ewen F; Lemey, Philippe; Van Ranst, Marc; Matthijnssens, Jelle; Kirkwood, Carl D

    2015-08-08

    Rotaviruses are the most important etiological agent of acute gastroenteritis in young children worldwide. Among the first countries to introduce rotavirus vaccines into their national immunization programs were Belgium (November 2006) and Australia (July 2007). Surveillance programs in Belgium (since 1999) and Australia (since 1989) offer the opportunity to perform a detailed comparison of rotavirus strains circulating pre- and postvaccine introduction. G1P[8] rotaviruses are the most prominent genotype in humans, and a total of 157 G1P[8] rotaviruses isolated between 1999 and 2011 were selected from Belgium and Australia and their complete genomes were sequenced. Phylogenetic analysis showed evidence of frequent reassortment among Belgian and Australian G1P[8] rotaviruses. Although many different phylogenetic subclusters were present before and after vaccine introduction, some unique clusters were only identified after vaccine introduction, which could be due to natural fluctuation or the first signs of vaccine-driven evolution. The times to the most recent common ancestors for the Belgian and Australian G1P[8] rotaviruses ranged from 1846 to 1955 depending on the gene segment, with VP7 and NSP4 resulting in the most recent estimates. We found no evidence that rotavirus population size was affected after vaccine introduction and only six amino acid sites in VP2, VP3, VP7, and NSP1 were identified to be under positive selective pressure. Continued surveillance of G1P[8] strains is needed to determine long-term effects of vaccine introductions, particularly now rotavirus vaccines are implemented in the national immunization programs of an increasing number of countries worldwide.

  10. National Vaccine Injury Compensation Program: Addition of Intussusception as Injury for Rotavirus Vaccines to the Vaccine Injury Table. Final rule.

    PubMed

    2015-06-23

    On July 24, 2013, the Secretary of Health and Human Services (the Secretary) published in the Federal Register a Notice of Proposed Rulemaking (NPRM) proposing changes to the regulations governing the National Vaccine Injury Compensation Program (VICP). Specifically, the Secretary proposed revisions to the Vaccine Injury Table (Table). The basis for this change is consistent with the Secretary's findings that intussusceptions can reasonably be determined in some circumstances to be caused by rotavirus vaccines. The Secretary is now making this amendment to the Table and to the Qualifications and Aids to Interpretation (QAI), described below under Background Information, as proposed in the NPRM. These regulations will apply only to petitions for compensation under the VICP filed after this final rule becomes effective.

  11. Live attenuated vaccines against pertussis.

    PubMed

    Locht, Camille; Mielcarek, Nathalie

    2014-09-01

    The intensive use of pertussis vaccines has dramatically reduced the incidence of whooping cough during the 20th century. However, recent outbreaks in countries with high vaccination coverage illustrate the shortcomings of current vaccination regimens, and immunity induced by the most recent, acellular vaccines wanes much faster than anticipated. As an alternative, live attenuated vaccine candidates have recently been developed in order to mimic natural infection, which induces long-lasting immunity. One of them has successfully completed a Phase I trial in humans and is now undergoing further product and clinical developments. This article describes the development of such vaccines, discusses their advantages over existing vaccines and their interesting bystander properties as powerful anti-inflammatory agents, which widens their potential use far beyond that for protection against whooping cough.

  12. Community Diarrhea Incidence Before and After Rotavirus Vaccine Introduction in Nicaragua

    PubMed Central

    Becker-Dreps, Sylvia; Meléndez, Marlon; Liu, Lan; Enrique Zambrana, Luis; Paniagua, Margarita; Weber, David J.; Hudgens, Michael G.; Cáceres, Mercedes; Källeståll, Carina; Morgan, Douglas R.; Espinoza, Félix; Peña, Rodolfo

    2013-01-01

    We estimated the incidence of watery diarrhea in the community before and after introduction of the pentavalent rotavirus vaccine in León, Nicaragua. A random sample of households was selected before and after rotavirus vaccine introduction. All children < 5 years of age in selected households were eligible for inclusion. Children were followed every 2 weeks for watery diarrhea episodes. The incidence rate was estimated as numbers of episodes per 100 child-years of exposure time. A mixed effects Poisson regression model was fit to compare incidence rates in the pre-vaccine and vaccine periods. The pre-vaccine cohort (N = 726) experienced 36 episodes per 100 child-years, and the vaccine cohort (N = 826) experienced 25 episodes per 100 child-years. The adjusted incidence rate ratio was 0.60 (95% confidence interval [CI] 0.40, 0.91) during the vaccine period versus the pre-vaccine period, indicating a lower incidence of watery diarrhea in the community during the vaccine period. PMID:23817336

  13. Knowledge and attitudes towards rotavirus diarrhea and the vaccine amongst healthcare providers in Yogyakarta Indonesia.

    PubMed

    Seale, Holly; Sitaresmi, Mei Neni; Atthobari, Jarir; Heywood, Anita E; Kaur, Rajneesh; MacIntyre, Raina C; Soenarto, Yati; Padmawati, Retna Siwi

    2015-11-30

    Rotavirus has been identified as the most common pathogen associated with severe diarrhoea. Two effective vaccines against the pathogen have been licensed. However, many countries including Indonesia have yet to introduce the vaccine into their national immunisation programs. This study aimed to examine the attitudes of healthcare providers (HCPs) and other health stakeholders towards the pathogen and the vaccine. Semi-structured in-depth interviews were undertaken in two districts of Yogyakarta Province, Indonesia with nurses, midwives, primary care providers, pediatricians and other health stakeholders. Thematic analysis was undertaken. Fourteen interviews were conducted between August and October 2013. We identified that while participants do not consider diarrhea to be an important problem in Indonesia, they do acknowledge that it can be serious if not properly treated. While the majority had some level of knowledge about rotavirus, not all participants knew that a vaccine was available. There were mixed feelings towards the need for the vaccine. Some felt that the vaccine is not ranked as a priority as it is not listed on the national program. However, others agreed there is a rationale for its use in Indonesia. The cost of the vaccine (when sold in the private sector) was perceived to be the primary barrier impacting on its use. The high cost and the low priority given to this vaccine by the public health authorities are the biggest obstacles impacting on the acceptance of this vaccine in Indonesia. HCPs need to be reminded of the burden of disease associated with rotavirus. In addition, reminding providers about the costs associated with treating severe cases versus the costs associated with prevention may assist with improving the acceptance of HCPs towards the vaccine. Promotion campaigns need to target the range of HCPs involved in the provision of care to infants and pregnant women.

  14. Vaccine-Derived NSP2 Segment in Rotaviruses from Vaccinated Children with Gastroenteritis in Nicaragua

    PubMed Central

    Bucardo, Filemón; Rippinger, Christine M.; Svensson, Lennart; Patton, John T.

    2012-01-01

    Rotavirus (RV) vaccination programs have been established in several countries using the human-attenuated G1P[8] monovalent vaccine Rotarix™ (GlaxoSmithKline) and/or the human-bovine reassortant G1, G2, G3, G4, P[8] pentavalent vaccine RotaTeq™ (Merck). The efficacy of both vaccines is high (~90%) in developed countries, but can be remarkably lower in developing countries. For example, a vaccine efficacy against severe diarrhea of only 58% was observed in a 2007–2009 Nicaraguan study using RotaTeq. To gain insight into the significant level of vaccine failure in this country, we sequenced the genomes of RVs recovered from vaccinated Nicaraguan children with gastroenteritis. The results revealed that all had genotype specificities typical for human RVs (11 G1P[8], 1 G3P[8]) and that the sequences and antigenic epitopes of the outer capsid proteins (VP4 and VP7) of these viruses were similar to those reported for RVs isolated elsewhere in the world. As expected, nine of the G1P[8] viruses and the single G3P[8] virus had genome constellations typical of human G1P[8] and G3P[8] RVs: G1/3-P[8]-I1-R1-C1-M1-A1-N1-T1-E1-H1. However, two of the G1P[8] viruses had atypical constellations, G1-P[8]-I1-R1-C1-M1-A1-N2-T1-E1-H1, due to the presence of a genotype-2 NSP2 (N2) gene. The sequence of the N2 NSP2 gene was identical to the bovine N2 NSP2 gene of RotaTeq, indicating that the two atypical viruses originated via reassortment of human G1P[8] RVs with RotaTeq viruses. Together, our data suggest that the high level of vaccine failure in Nicaraguan is probably not due to antigenic drift of commonly circulating virus strains nor the emergence of new antigenetically distinct virus strains. Furthermore, our data suggests that the widespread use of the RotaTeq vaccine has led to the introduction of vaccine genes into circulating human RVs. PMID:22487061

  15. Cost-effectiveness analysis of the introduction of rotavirus vaccine in Iran.

    PubMed

    Javanbakht, Mehdi; Moradi-Lakeh, Maziar; Yaghoubi, Mohsen; Esteghamati, Abdoulreza; Mansour Ghanaie, Roxana; Mahmoudi, Sussan; Shamshiri, Ahmad-Reza; Zahraei, Seyed Mohsen; Baxter, Louise; Shakerian, Sareh; Chaudhri, Irtaza; Fleming, Jessica A; Munier, Aline; Baradaran, Hamid R

    2015-05-07

    Although the mortality from diarrheal diseases has been decreasing dramatically in Iran, it still represents an important proportion of disease burden in children <5 years old. Rotavirus vaccines are among the most effective strategies against diarrheal diseases in specific epidemiological conditions. This study aimed to evaluate the cost-effectiveness of the introduction of rotavirus vaccine (3 doses of pentavalent RotaTeq (RV5)) in Iran, from the viewpoints of Iran's health system and society. The TRIVAC decision support model was used to calculate total incremental costs, life years (LYs) gained, and disability-adjusted life years (DALYs) averted due to the vaccination program. Necessary input data were collected from the most valid accessible sources as well as a systematic review and meta-analysis on epidemiological studies. We used WHO guidelines to estimate vaccination cost. An annual discount rate of 3% was considered for both health gain and costs. A deterministic sensitivity analysis was performed for testing the robustness of the models results. Our results indicated that total DALYs potentially lost due to rotavirus diarrhea within 10 years would be 138,161, of which 76,591 could be prevented by rotavirus vaccine. The total vaccination cost for 10 cohorts was estimated to be US$ 499.91 million. Also, US$ 470.61 million would be saved because of preventing outpatient visits and inpatient admissions (cost-saving from the society perspective). We estimated a cost per DALY averted of US$ 2868 for RV5 vaccination, which corresponds to a highly cost-effective strategy from the government perspective. In the sensitivity analysis, all scenarios tested were still cost-saving or highly cost-effective from the society perspective, except in the least favorable scenario and low vaccine efficacy and disease incidence scenario. Based on the findings, introduction of rotavirus vaccine is a highly cost-effective strategy from the government perspective. Introducing the

  16. The establishment of the infant intestinal microbiome is not affected by rotavirus vaccination

    PubMed Central

    Ang, Li; Arboleya, Silvia; Lihua, Guo; Chuihui, Yuan; Nan, Qin; Suarez, Marta; Solís, Gonzalo; de los Reyes-Gavilán, Clara G.; Gueimonde, Miguel

    2014-01-01

    The microbial colonization of the intestine during the first months of life constitutes the most important process for the microbiota-induced host-homeostasis. Alterations in this process may entail a high-risk for disease in later life. However, the potential factors affecting this process in the infant are not well known. Moreover, the potential impact of orally administered vaccines upon the establishing microbiome remains unknown. Here we assessed the intestinal microbiome establishment process and evaluated the impact of rotavirus vaccination upon this process. Metagenomic, PCR-DGGE and faecal short chain fatty acids analyses were performed on faecal samples obtained from three infants before and after the administration of each dose of vaccine. We found a high inter-individual variability in the early life gut microbiota at microbial composition level, but a large similarity between the infants' microbiomes at functional level. Rotavirus vaccination did not show any major effects upon the infant gut microbiota. Thus, the individual microbiome establishment and development process seems to occur in a defined manner during the first stages of life and rotavirus vaccination appears to be inconsequential for this process. PMID:25491920

  17. The Impact of Socio-Economic Determinants on the Vaccination Rates with Rotavirus and Human Papiloma Virus Vaccine

    PubMed Central

    GRDADOLNIK, Urška; SOČAN, Maja

    2016-01-01

    Background Socio-economic inequalities may have an impact on the uptake of selfpaid vaccines. The aim of the study was to identify the effect of some socio economic determinants on vaccination rates with self-paid human papilloma virus (HPV) and rotavirus (RV) vaccines. Methods Vaccination coverage data, available in electronic database cepljenje.net (administered by the National Institute of Public Health), were collected at administrative unit level. The socio-economic determinants (the average gross pay in euros, the unemployment rate, the educational and households structure, the population density, the number of inhabitants, the number of children aged from 0 to 4, the number of women aged from 15 to 30) were extracted from Statistical Office of the Republic of Slovenia web page. The strength of the correlation between socioeconomic variables and self-paid HPV and RV vaccination rates was determined. Results Rotavirus vaccination rates show a slight negative correlation with the number of residents per administrative unit (ρ=−0.29, p=0.04), and no correlation with other socio-economic variables. Likewise, no correlation has been found between HPV vaccination rates and the selected socio-economic variables. Conclusion Ecological study did not reveal any correlations between socio economic variables and vaccination rates with RV and HPV self-paid vaccines on administrative unit level. PMID:27647088

  18. The Impact of Socio-Economic Determinants on the Vaccination Rates with Rotavirus and Human Papiloma Virus Vaccine.

    PubMed

    Grdadolnik, Urška; Sočan, Maja

    2016-03-01

    Socio-economic inequalities may have an impact on the uptake of selfpaid vaccines. The aim of the study was to identify the effect of some socio economic determinants on vaccination rates with self-paid human papilloma virus (HPV) and rotavirus (RV) vaccines. Vaccination coverage data, available in electronic database cepljenje.net (administered by the National Institute of Public Health), were collected at administrative unit level. The socio-economic determinants (the average gross pay in euros, the unemployment rate, the educational and households structure, the population density, the number of inhabitants, the number of children aged from 0 to 4, the number of women aged from 15 to 30) were extracted from Statistical Office of the Republic of Slovenia web page. The strength of the correlation between socioeconomic variables and self-paid HPV and RV vaccination rates was determined. Rotavirus vaccination rates show a slight negative correlation with the number of residents per administrative unit (ρ=-0.29, p=0.04), and no correlation with other socio-economic variables. Likewise, no correlation has been found between HPV vaccination rates and the selected socio-economic variables. Ecological study did not reveal any correlations between socio economic variables and vaccination rates with RV and HPV self-paid vaccines on administrative unit level.

  19. Developing live vaccines against plague.

    PubMed

    Sun, Wei; Roland, Kenneth L; Curtiss, Roy

    2011-09-14

    Three great plague pandemics caused by the gram-negative bacterium Yersinia pestis have killed nearly 200 million people and it has been linked to biowarfare in the past. Plague is endemic in many parts of the world. In addition, the risk of plague as a bioweapon has prompted increased research to develop plague vaccines against this disease. Injectable subunit vaccines are being developed in the United States and United Kingdom.  However, the live attenuated Y. pestis-EV NIIEG strain has been used as a vaccine for more than 70 years in the former Soviet Union and in some parts of Asia and provides a high degree of efficacy against plague.  This vaccine has not gained general acceptance because of safety concerns.  In recent years, modern molecular biological techniques have been applied to Y. pestis to construct strains with specific defined mutations designed to create safe, immunogenic vaccines with potential for use in humans and as bait vaccines to reduce the load of Y. pestis in the environment.  In addition, a number of live, vectored vaccines have been reported using attenuated viral vectors or attenuated Salmonella strains to deliver plague antigens. Here we summarize the progress of live attenuated vaccines against plagu.

  20. Therapeutics and Immunoprophylaxis against Noroviruses and Rotaviruses.

    PubMed

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

    2017-09-12

    Noroviruses and rotaviruses are important viral etiologies of severe gastroenteritis. Noroviruses are the primary cause of non-bacterial 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. Technological advances coupled with 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. Herein, we focus on the developments in the field 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). Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  1. Serologic response to porcine circovirus type 1 (PCV1) in infants vaccinated with the human rotavirus vaccine, Rotarix™: A retrospective laboratory analysis

    PubMed Central

    Han, Htay Htay; Karkada, Naveen; Jayadeva, Girish; Dubin, Gary

    2017-01-01

    ABSTRACT In 2010, porcine circovirus type 1 (PCV1) material was unexpectedly detected in the oral live-attenuated human rotavirus (RV) vaccine, Rotarix™ (GSK Vaccines, Belgium). An initial study (NCT01511133) found no immunologic response against PCV1 in 40 vaccinated infants. As a follow-up, the current study (NCT02153333), searched for evidence of post-vaccination serologic response to PCV1 in a larger number of archived serum samples. Unlike the previous study, serum anti-PCV1 antibodies were assessed with an adapted Immuno Peroxidase Monolayer Assay (IPMA) using a Vero-adapted PCV1 strain. Samples from 596 infants who participated in clinical trials of the human RV vaccine were randomly selected and analyzed. The observed anti-PCV1 antibody seropositivity rate 1–2 months post-dose 2 was approximately 1% [90% Confidence Interval (CI): 0.3–2.6] (3/299 samples) in infants who received the human RV vaccine and 0.3% [90% CI: 0.0–1.6] (1/297 samples) in those who received placebo; the difference between the groups was −0.66 [90% CI: −2.16–0.60]. One subject in the vaccinated group was also seropositive before vaccination. Notably, the seropositivity rate observed in vaccinated subjects was below that observed during assay qualification in samples from unvaccinated subjects outside of this study (2.5%; 5/200 samples). No serious adverse events had been reported in any of the 4 subjects providing anti-PCV1 positive samples during the 31-day post-vaccination follow-up period in the original studies. In conclusion, the presence of PCV1 in the human RV vaccine is considered to be a manufacturing quality issue and does not appear to pose a safety risk to vaccinated infants. PMID:27657348

  2. Serologic response to porcine circovirus type 1 (PCV1) in infants vaccinated with the human rotavirus vaccine, Rotarix™: A retrospective laboratory analysis.

    PubMed

    Han, Htay Htay; Karkada, Naveen; Jayadeva, Girish; Dubin, Gary

    2017-01-02

    In 2010, porcine circovirus type 1 (PCV1) material was unexpectedly detected in the oral live-attenuated human rotavirus (RV) vaccine, Rotarix™ (GSK Vaccines, Belgium). An initial study (NCT01511133) found no immunologic response against PCV1 in 40 vaccinated infants. As a follow-up, the current study (NCT02153333), searched for evidence of post-vaccination serologic response to PCV1 in a larger number of archived serum samples. Unlike the previous study, serum anti-PCV1 antibodies were assessed with an adapted Immuno Peroxidase Monolayer Assay (IPMA) using a Vero-adapted PCV1 strain. Samples from 596 infants who participated in clinical trials of the human RV vaccine were randomly selected and analyzed. The observed anti-PCV1 antibody seropositivity rate 1-2 months post-dose 2 was approximately 1% [90% Confidence Interval (CI): 0.3-2.6] (3/299 samples) in infants who received the human RV vaccine and 0.3% [90% CI: 0.0-1.6] (1/297 samples) in those who received placebo; the difference between the groups was -0.66 [90% CI: -2.16-0.60]. One subject in the vaccinated group was also seropositive before vaccination. Notably, the seropositivity rate observed in vaccinated subjects was below that observed during assay qualification in samples from unvaccinated subjects outside of this study (2.5%; 5/200 samples). No serious adverse events had been reported in any of the 4 subjects providing anti-PCV1 positive samples during the 31-day post-vaccination follow-up period in the original studies. In conclusion, the presence of PCV1 in the human RV vaccine is considered to be a manufacturing quality issue and does not appear to pose a safety risk to vaccinated infants.

  3. 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

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

    2016-10-02

    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.

  4. 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

  5. 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.

  6. Understanding internalization of rotavirus VP6 nanotubes by cells: towards a recombinant vaccine.

    PubMed

    Rodríguez, Mabel; Wood, Christopher; Sanchez-López, Rosana; Castro-Acosta, Ricardo M; Ramírez, Octavio T; Palomares, Laura A

    2014-05-01

    Rotavirus VP6 nanotubes are an attractive option for a recombinant vaccine against rotavirus disease. Protection against rotavirus infection and an adjuvant effect have been observed upon immunization with VP6 nanotubes. However, little information exists on how VP6 nanotubes interact with cells and trigger an immune response. In this work, the interaction between VP6 nanotubes and different cell lines was characterized. VP6 nanotubes were not cytotoxic to any of the animal or human cell lines tested. Uptake of nanotubes into cells was cell-line-dependent, as only THP1 and J774 macrophage cells internalized them. Moreover, the size and spatial arrangement of VP6 assembled into nanotubes allowed their uptake by macrophages, as double-layered rotavirus-like particles also displaying VP6 in their surface were not taken up. The internalization of VP6 nanotubes was inhibited by methyl-β-cyclodextrin, but not by genistein, indicating that nanotube entry is specific, depends on the presence of cholesterol in the plasma membrane, and does not require the activity of tyrosine kinases. The information generated here expands our understanding of the interaction of protein nanotubes with cells, which is useful for the application of VP6 nanotubes as a vaccine.

  7. Immunogenicity of a plant-derived edible rotavirus subunit vaccine transformed over fifty generations.

    PubMed

    Li, Jin-Tao; Fei, Lei; Mou, Zhi-Rong; Wei, Jing; Tang, Yan; He, Hai-Yang; Wang, Li; Wu, Yu-Zhang

    Major efforts have been put forth for the development of effective rotavirus vaccines including transgenic plant vaccines. Previous studies have reported that rotavirus VP7 maintains its neutralizing immunity when it is transformed into the potato genome. The present study was aimed at investigating the hereditary stability of VP7-transformed potatoes over fifty generations. The VP7 gene was stably transcribed and expressed in potato cells as detected by RT-PCR and Western blotting. Humeral and mucosal responses were successfully induced in BALB/c mice fed with the fiftieth generation transformed potato tubers. There were no significant differences in serum IgG and fecal IgA between the mice fed with the first and fiftieth generation potatoes (P>0.05). Profiles of cytokines such as IFN-gamma, IL-2, IL-4, IL-5 and TGF-beta in immunized mice showed a naive T-cells bias to Th1 and Th3 polarization. Moreover, specific CTL responses were also detected in C57BL/6 mice fed with transformed potatoes. This research represents a significant step towards the development of rotavirus vaccines derived from a transgenic plant that can be obtained by long-term and large-scale vegetative reproduction. To our knowledge, this is the first finding regarding vaccines derived from plants that can be propagated for many generations.

  8. Post-rotavirus vaccine intussusception in identical twins: A case report.

    PubMed

    La Rosa, F; Scuderi, M G; Taranto, V; La Rosa, V; Spinello, C M; La Camera, G; Astuto, M

    2016-09-01

    The intussusception is one of the most frequent causes of occlusive syndrome in infants and in children. (1) The mesenteric lymphadenopathy, wich is very rare post rotavirus vaccination, can cause intussusception, (2-5) especially in genetically predisposed individuals. (6) There is an association between intussusception and some classes of genotype. (7-9) Two infants aged 3 months, vaccinated against rotavirus. After about a week, one of the 2 identical infants presented inconsolable crying, vomiting, loose stools mixed with blood, and was diagnosed with bowel obstruction with intussusception. He was operated in urgency. After a few hours, his brother presented vomiting, and was admitted to our Hospital for suspected intussusception. The controls carried out have confirmed the presence of intussusception that was treated early, before the onset of severe symptoms. The incidence of post rotavirus vaccine intussusception is very low. The determining factor hypothetically might be linked to the presence of a genotype that exposes infants to a greater risk of developing mesenteric lymphadenitis and intussusception. In our case, the diagnosis of intussusception occurred in a twin, which allowed us to recognize early symptoms which accused the brother and schedule the surgery with less urgency. Our experience may want to sensitize families and pediatricians to report cases of intussusception given a theoretical familiar association. The study of the genotype could be decisive for or not to exclude the presence of a risk of invagination, thus avoiding vaccination.

  9. 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.

  10. Inclusion of a universal tetanus toxoid CD4(+) T cell epitope P2 significantly enhanced the immunogenicity of recombinant rotavirus ΔVP8* subunit parenteral vaccines.

    PubMed

    Wen, Xiaobo; Wen, Ke; Cao, Dianjun; Li, Guohua; Jones, Ronald W; Li, Jianping; Szu, Shousun; Hoshino, Yasutaka; Yuan, Lijuan

    2014-07-31

    Currently available live oral rotavirus vaccines, Rotarix(®) and RotaTeq(®), are highly efficacious in developed countries. However, the immunogenicity and efficacy of such vaccines in some developing countries are low. We reported previously that bacterially-expressed rotavirus ΔVP8* subunit vaccine candidates with P[8], P[4] or P[6] specificity elicited high-titer virus neutralizing antibodies in animals immunized intramuscularly. Of note was the finding that antibodies induced with the P[8]ΔVP8* vaccine neutralized both homotypic P[8] and heterotypic P[4] rotavirus strains to high titer. To further improve its vaccine potential, a tetanus toxoid universal CD4(+) T cell epitope P2 was introduced into P[8] or P[6]ΔVP8* construct. The resulting recombinant fusion proteins expressed in Escherichia coli were of high solubility and were produced with high yield. Two doses (10 or 20 μg/dose) of the P2-P[8]ΔVP8* vaccine or P2-P[6]ΔVP8* vaccine with aluminum phosphate adjuvant elicited significantly higher geometric mean homologous neutralizing antibody titers than the vaccines without P2 in intramuscularly immunized guinea pigs. Interestingly, high levels of neutralizing antibody responses induced in guinea pigs with 3 doses of the P2-P[8]ΔVP8* vaccine persisted for at least 6 months. Furthermore, in the gnotobiotic piglet challenge study, three intramuscular doses (50 μg/dose) of the P2-P[8]ΔVP8* vaccine with aluminum phosphate adjuvant significantly delayed the onset of diarrhea and significantly reduced the duration of diarrhea and the cumulative diarrhea score after oral challenge with virulent human rotavirus Wa (G1P[8]) strain. The P2-P[8]ΔVP8* vaccine induced serum virus neutralizing antibody and VP4-specific IgG antibody production prechallenge, and primed the pigs for higher antibody and intestinal and systemic virus-specific IFN-γ producing CD4(+) T cell responses postchallenge. These two subunit vaccines could be used at a minimum singly or

  11. Inclusion of a universal tetanus toxoid CD4+ T cell epitope P2 significantly enhanced the immunogenicity of recombinant rotavirus ΔVP8* subunit parenteral vaccines

    PubMed Central

    Wen, Xiaobo; Wen, Ke; Cao, Dianjun; Li, Guohua; Jones, Ronald W.; Li, Jianping; Szu, Shousun; Hoshino, Yasutaka; Yuan, Lijuan

    2014-01-01

    Currently available live oral rotavirus vaccines, Rotarix® and RotaTeq®, are highly efficacious in developed countries. However, the immunogenicity and efficacy of such vaccines in some developing countries are low. We reported previously that bacterially-expressed rotavirus ΔVP8* subunit vaccine candidates with P[8], P[4] or P[6] specificity elicited high-titer virus neutralizing antibodies in animals immunized intramuscularly. Of note was the finding that antibodies induced with the P[8]ΔVP8* vaccine neutralized both homotypic P[8] and heterotypic P[4] rotavirus strains to high titer. To further improve its vaccine potential, a tetanus toxoid universal CD4+ T cell epitope P2 was introduced into P[8] or P[6]ΔVP8* construct. The resulting recombinant fusion proteins expressed in Escherichia coli were of high solubility and were produced with high yield. Two doses (10 or 20μg/dose) of the P2-P[8]ΔVP8* vaccine or P2-P[6]ΔVP8* vaccine with aluminum phosphate adjuvant elicited significantly higher geometric mean homologous neutralizing antibody titers than the vaccines without P2 in intramuscularly immunized guinea pigs. Interestingly, high levels of neutralizing antibody responses induced in guinea pigs with 3 doses of the P2-P[8]ΔVP8* vaccine persisted for at least 6 months. Furthermore, in the gnotobiotic piglet challenge study, three intramuscular doses (50μg/dose) of the P2-P[8]ΔVP8* vaccine with aluminum phosphate adjuvant significantly delayed the onset of diarrhea and significantly reduced the duration of diarrhea and the cumulative diarrhea score after oral challenge with virulent human rotavirus Wa (G1P[8]) strain. The P2-P[8]ΔVP8* vaccine induced serum virus neutralizing antibody and VP4-specific IgG antibody production prechallenge, and primed the pigs for higher antibody and intestinal and systemic virus-specific IFN-γ producing CD4+ T cell responses postchallenge. These two subunit vaccines could be used at a minimum singly or preferably in

  12. Use of Patients With Diarrhea Who Test Negative for Rotavirus as Controls to Estimate Rotavirus Vaccine Effectiveness Through Case-Control Studies.

    PubMed

    Tate, Jacqueline E; Patel, Manish M; Cortese, Margaret M; Payne, Daniel C; Lopman, Benjamin A; Yen, Catherine; Parashar, Umesh D

    2016-05-01

    Case-control studies are often performed to estimate postlicensure vaccine effectiveness (VE), but the enrollment of controls can be challenging, time-consuming, and costly. We evaluated whether children enrolled in the same hospital-based diarrheal surveillance used to identify rotavirus cases but who test negative for rotavirus (test-negative controls) can be considered a suitable alternative to nondiarrheal hospital or community-based control groups (traditional controls). We compared calculated VE estimates as a function of varying values of true VE, attack rates of rotavirus and nonrotavirus diarrhea in the population, and sensitivity and specificity of the rotavirus enzyme immunoasssay. We also searched the literature to identify rotavirus VE studies that used traditional and test-negative control groups and compared VE estimates obtained using the different control groups. Assuming a 1% attack rate for severe rotavirus diarrhea, a 3% attack rate for severe nonrotavirus diarrhea in the population, a test sensitivity of 96%, and a specificity of 100%, the calculated VE estimates using both the traditional and test-negative control groups closely approximated the true VE for all values from 30% to 100%. As true VE decreased, the traditional case-control approach slightly overestimated the true VE and the test-negative case-control approach slightly underestimated this estimate, but the absolute difference was only ±0.2 percentage points. Field VE estimates from 10 evaluations that used both traditional and test-negative control groups were similar regardless of control group used. The use of rotavirus test-negative controls offers an efficient and cost-effective approach to estimating rotavirus VE through case-control studies. 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.

  13. Rotavirus Vaccination and the Risk of Celiac Disease or Type 1 Diabetes in Finnish Children at Early Life.

    PubMed

    Vaarala, Outi; Jokinen, Jukka; Lahdenkari, Mika; Leino, Tuija

    2017-07-01

    Rotavirus infection has been suggested as a trigger of type 1 diabetes (T1D)-related autoimmunity and celiac disease (CD)-related autoimmunity. We carried out a nationwide, population-based cohort study evaluating whether prevention of rotavirus infection with vaccination affects the risk of CD and T1D diagnosed during 2009-2014 in Finnish children by comparing vaccinated and unvaccinated children in a cohort born in 2009-2010. Nationwide rotavirus vaccination records were collected from healthcare databases during 2009-2011 and validated for a sample of 495 children born from July 2009 to December 2009. Incident diagnoses of CD and T1D during 2009-2014 in the cohort were identified in the National Care Register. The adjusted relative risks (with 95% confidence intervals) were 0.91 (0.69-1.20) for T1D and 0.87 (0.65-1.17) for CD in vaccinated children compared with unvaccinated, suggesting that oral rotavirus vaccination does not alter the risk of CD or T1D during 4-6 years follow-up after vaccination. Our results suggest that oral rotavirus vaccination is considered safe in the individuals at risk of CD and T1D.

  14. Impact of rotavirus vaccination on childhood gastroenteritis-related mortality and hospital discharges in Panama.

    PubMed

    Bayard, Vicente; DeAntonio, Rodrigo; Contreras, Rodolfo; Tinajero, Olga; Castrejon, Maria Mercedes; Ortega-Barría, Eduardo; Colindres, Romulo E

    2012-02-01

    Rotavirus vaccination was introduced in Panama in March 2006. This study was carried out in order to describe the trends in gastroenteritis-related (GER) hospitalizations and mortality in children <5 years of age during the pre- and post-vaccination periods. Data from the Expanded Program on Immunization (Ministry of Health) were used to calculate vaccine coverage. GER mortality and hospitalizations were obtained through database review of the Contraloría General de la República and hospital discharge databases of five sentinel hospitals, for the period 2000-2008. Mean rates of GER mortality and mean numbers of hospitalizations during the baseline pre-vaccination period (2000-2005) were compared to those of 2007 and 2008. National coverage for the second rotavirus vaccine dose increased from 30% in 2006 to 62% in 2007 and 71% in 2008, varying from 62% in the West region to 77% in the Panama region. Overall, at 2-years post-vaccine introduction, the GER mortality rate in Panama had decreased by 50% (95% confidence interval (CI) 46-54). During 2000-2005, the GER mortality rate in children (<1 year) was 73/100 000, decreasing by 45% (95% CI 40-51) in 2008. In children aged 1-4 years, the GER mortality rate was 20.3/100 000 (2000-2005), decreasing by 54% (95% CI 48-60) in 2008. The Panama region registered the highest mortality rate reduction (69%; 95% CI 58-81) for 2008. During 2008, GER hospitalizations among children <5 years of age decreased by 30% (95% CI 21-37) from the mean number of hospitalizations during 2000-2005. A substantial reduction in GER mortality and hospitalizations was observed following the introduction of rotavirus vaccine in Panama. Copyright © 2011 International Society for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.

  15. The impact of Rotavirus mass vaccination on hospitalization rates, nosocomial Rotavirus gastroenteritis and secondary blood stream infections

    PubMed Central

    2013-01-01

    Background The aim of the study was to evaluate the effects of universal mass vaccination (UMV) against rotavirus (RV) on the hospitalization rates, nosocomial RV infections and RV-gastroenteritis (GE)-associated secondary blood stream infections (BSI). Methods The retrospective evaluation (2002–2009) by chart analysis included all clinically diagnosed and microbiologically confirmed RV-GE cases in a large tertiary care hospital in Austria. The pre-vaccination period (2002–2005) was compared with the recommended and early funded (2006–2007) and the funded (2008–2009) vaccination periods. Primary outcomes were RV-GE-associated hospitalizations, secondary outcomes nosocomial RV disease, secondary BSI and direct hospitalization costs for children and their accompanying persons. Results In 1,532 children with RV-GE, a significant reduction by 73.9% of hospitalized RV-GE cases per year could be observed between the pre-vaccination and the funded vaccination period, which was most pronounced in the age groups 0–11 months (by 87.8%), 6–10 years (by 84.2%) and 11–18 years (88.9%). In the funded vaccination period, a reduction by 71.9% of nosocomial RV-GE cases per year was found compared to the pre-vaccination period. Fatalities due to nosocomial RV-GE were only observed in the pre-vaccination period (3 cases). Direct costs of hospitalized, community-acquired RV-GE cases per year were reduced by 72.7% in the funded vaccination period. The reduction of direct costs for patients (by 86.9%) and accompanying persons (86.2%) was most pronounced in the age group 0–11 months. Conclusions UMV may have contributed to the significant decrease of RV-GE-associated hospitalizations, to a reduction in nosocomial RV infections and RV-associated morbidity due to secondary BSI and reduced direct hospitalization costs. The reduction in nosocomial cases is an important aspect considering severe disease courses in hospitalized patients with co-morbidities and death due to

  16. Assessing the risk of intussusception and rotavirus vaccine safety in Canada

    PubMed Central

    Ducharme, Robin; Rosella, Laura C.; Benchimol, Eric I.; Wilson, Kumanan; Crowcroft, Natasha S.; Halperin, Scott A.; Desai, Shalina; Naus, Monika; Sanford, Carolyn J.; Mahmud, Salah M.; Deeks, Shelley L.

    2017-01-01

    ABSTRACT Background: Intussusception has been identified as a rare adverse event following rotavirus immunization. We sought to determine the incidence of intussusception among infants in Canada both before and after introduction of rotavirus immunization programs. Methods: We used Canadian Institute for Health Information (CIHI) Discharge Abstract Database (DAD) to identify infants under 1 y of age who were admitted to a Canadian hospital, which the exception of Quebec, which does not submit data to CIHI, with a diagnosis of intussusception (ICD-10 code K56.1, and ICD-9 code 560) between January 1st, 2003 and December 31, 2013. We compared rates of intussusception hospitalization before and after rotavirus vaccine program introduction. Rates were adjusted for calendar year, age (in months), sex and region using Poisson regression models. Denominator data for infants under 1 year, stratified by age in months, were obtained from Statistics Canada. Results: Annual intussusception hospitalization rates ranged from 20-30 per 100,000 infants over the study period, with no evidence of a trend over time. Intussusception hospitalization rates were highest in infants 4 to <8 months and lowest in those under 2 months or between 10 and <12 months. Males had higher rates than females both overall and within each age group. The rate of intussusception hospitalization after rotavirus vaccine program introduction was 22.4 (95% CI: 18.3, 27.4) compared to 23.4 (95% CI: 21.5, 25.4) per 100,000 before program introduction. Conclusions: We have described baseline intussusception hospitalization rates for infants in Canada and have found no evidence of a change in rate after implementation of routine rotavirus immunization programs. PMID:27835525

  17. Assessing the risk of intussusception and rotavirus vaccine safety in Canada.

    PubMed

    Hawken, Steven; Ducharme, Robin; Rosella, Laura C; Benchimol, Eric I; Langley, Joanne M; Wilson, Kumanan; Crowcroft, Natasha S; Halperin, Scott A; Desai, Shalina; Naus, Monika; Sanford, Carolyn J; Mahmud, Salah M; Deeks, Shelley L

    2017-03-04

    Intussusception has been identified as a rare adverse event following rotavirus immunization. We sought to determine the incidence of intussusception among infants in Canada both before and after introduction of rotavirus immunization programs. We used Canadian Institute for Health Information (CIHI) Discharge Abstract Database (DAD) to identify infants under 1 y of age who were admitted to a Canadian hospital, which the exception of Quebec, which does not submit data to CIHI, with a diagnosis of intussusception (ICD-10 code K56.1, and ICD-9 code 560) between January 1st, 2003 and December 31, 2013. We compared rates of intussusception hospitalization before and after rotavirus vaccine program introduction. Rates were adjusted for calendar year, age (in months), sex and region using Poisson regression models. Denominator data for infants under 1 year, stratified by age in months, were obtained from Statistics Canada. Annual intussusception hospitalization rates ranged from 20-30 per 100,000 infants over the study period, with no evidence of a trend over time. Intussusception hospitalization rates were highest in infants 4 to <8 months and lowest in those under 2 months or between 10 and <12 months. Males had higher rates than females both overall and within each age group. The rate of intussusception hospitalization after rotavirus vaccine program introduction was 22.4 (95% CI: 18.3, 27.4) compared to 23.4 (95% CI: 21.5, 25.4) per 100,000 before program introduction. We have described baseline intussusception hospitalization rates for infants in Canada and have found no evidence of a change in rate after implementation of routine rotavirus immunization programs.

  18. Intussusception in Australia: epidemiology prior to the introduction of rotavirus vaccine.

    PubMed

    Palupi-Baroto, Retno; Lee, Katherine J; Carlin, John B; Bines, Julie E

    2015-02-01

    To describe the incidence rate and clinical outcomes of intussusception in Australia in children aged <24 months prior to the use of rotavirus vaccines in Australia, and to explore associations between patient characteristics and outcomes in children with intussusception. This study used Australian national hospital discharge data on intussusception from July 2000 to June 2006 for children aged <24 months and data from the Australian Bureau of Statistics (ABS) as a proxy for population numbers to estimate incidence. Logistic regression was used to examine associations between patient characteristics (age, sex, ethnicity) and outcomes (length of hospital stay >2 days and the need for surgical intervention). The overall incidence rate of intussusception was 5.4 per 10,000 child-years in children under 24 months (95%CI 5.17-5.70). There was a declining rate over the study period (p<0.001). Age at time of intussusception was strongly associated with length of hospital stay and surgery. This study provides an estimate of the pre-rotavirus vaccine incidence of intussusception across Australia, which is important for monitoring the occurrence of intussusceptions post the introduction of rotavirus vaccine. © 2014 Public Health Association of Australia.

  19. 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.

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

    PubMed Central

    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. PMID:28070453

  1. Dietary rice bran protects against rotavirus diarrhea and promotes Th1-type immune responses to human rotavirus vaccine in gnotobiotic pigs.

    PubMed

    Yang, Xingdong; Wen, Ke; Tin, Christine; Li, Guohua; Wang, Haifeng; Kocher, Jacob; Pelzer, Kevin; Ryan, Elizabeth; Yuan, Lijuan

    2014-10-01

    Rice bran (RB) contains a distinct stoichiometry of phytochemicals that can promote gut mucosal immune responses against enteric pathogens. The effects of RB on rotavirus diarrhea and immunogenicity of an attenuated human rotavirus (HRV) vaccine were evaluated in gnotobiotic pigs. The four treatment groups studied were RB plus vaccine, vaccine only, RB only, and mock control. Pigs in the RB groups were fed the amount of RB that replaced 10% of the pigs' total daily calorie intake from milk starting from 5 days of age until they were euthanized. Pigs in the vaccine groups were orally inoculated with two doses of the attenuated HRV vaccine. A subset of pigs from each group was orally challenged with the homologous virulent HRV on postinoculation day 28. Diarrhea and virus shedding were monitored daily from postchallenge day 0 to day 7. RB feeding significantly protected against diarrhea upon virulent HRV challenge and enhanced the protective rate of the vaccine against rotavirus diarrhea. Consistent with protection, RB significantly increased gamma interferon (IFN-γ)-producing CD4(+) and CD8(+) T cell responses in intestinal and systemic lymphoid tissues. Furthermore, RB also increased the number of total IgM- and IgA-secreting cells, total serum IgM, IgG, and IgA titers, and HRV-specific IgA titers in intestinal contents. RB reduced the numbers of intestinal and systemic HRV-specific IgA and IgG antibody-secreting cells and reduced serum HRV-specific IgA and IgG antibody titers before the challenge. These results demonstrate clear beneficial effects of RB in protection against rotavirus diarrhea and stimulation of nonspecific and HRV-specific immune responses, as well as its biased Th1-type adjuvant effect for the vaccine.

  2. 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

  3. Immunogenicity, safety and efficacy of tetravalent rhesus-human, reassortant rotavirus vaccine in Belém, Brazil.

    PubMed Central

    Linhares, A. C.; Gabbay, Y. B.; Mascarenhas, J. D.; de Freitas, R. B.; Oliveira, C. S.; Bellesi, N.; Monteiro, T. A.; Lins-Lainson, Z.; Ramos, F. L.; Valente, S. A.

    1996-01-01

    A tetravalent rhesus-human reassortant rotavirus (RRV-TV) vaccine (4 x 10(4) plaque-forming units/dose) was evaluated for safety, immunogenicity and efficacy in a prospective, randomized, double-blind, placebo-controlled trial involving 540 Brazilian infants. Doses of vaccine or placebo were given at ages 1, 3 and 5 months. No significant differences were noted in the occurrence of diarrhoea or vomiting in vaccine and placebo recipients following each dose. Low-grade fever occurred on days 3-5 in 2-3% of vaccinees after the first dose, but not after the second or third doses of vaccine. An IgA antibody response to rhesus rotavirus (RRV) occurred in 58% of vaccinees and 33% of placebo recipients. Neutralizing antibody responses to individual serotypes did not exceed 20% when measured by fluorescent focus reduction, but exceeded 40% when assayed by plaque reduction neutralization. There were 91 cases of rotavirus diarrhoea among the 3-dose (vaccine or placebo) recipients during two years of follow-up, 36 of them among children given the vaccine. Overall vaccine efficacy was 8% (P = 0.005) against any diarrhoea and 35% (P = 0.03) against any rotavirus diarrhoea. Protection during the first year of follow-up, when G serotype 1 rotavirus predominated, was 57% (P = 0.008), but fell to 12% in the second year. Similar results were obtained when analysis was restricted to episodes in which rotavirus was the only identified pathogen. There was a tendency for enhanced protection by vaccine against illness associated with an average of 6 or more stools per day. These results are sufficiently encouraging to warrant further studies of this vaccine in developing countries using a higher dosage in an attempt to improve its immunogenicity and efficacy. PMID:9002329

  4. A qualitative assessment of factors influencing acceptance of a new rotavirus vaccine among health care providers and consumers

    PubMed Central

    Patel, Manish M; Janssen, Alan P; Tardif, Richard R; Herring, Mark; Parashar, Umesh D

    2007-01-01

    Background In 2006, a new rotavirus vaccine (RotaTeq) was licensed in the US and recommended for routine immunization of all US infants. Because a previously licensed vaccine (Rotashield) was withdrawn from the US for safety concerns, identifying barriers to uptake of RotaTeq will help develop strategies to broaden vaccine coverage. Methods We explored beliefs and attitudes of parents (n = 57) and providers (n = 10) towards rotavirus disease and vaccines through a qualitative assessment using focus groups and in-depth interviews. Results All physicians were familiar with safety concerns about rotavirus vaccines, but felt reassured by RotaTeq's safety profile. When asked about likelihood of using RotaTeq on a scale of one to seven (1 = "absolutely not;" 7 = "absolutely yes") the mean score was 5 (range = 3–6). Physicians expressed a high likelihood of adopting RotaTeq, particularly if recommended by their professional organizations and expressed specific interest in post-marketing safety data. Similarly, consumers found the RotaTeq safety profile to be favorable and would rely on their physician's recommendation for vaccination. However, when asked to rank likelihood of having their child vaccinated against rotavirus (1 = "definitely not get;" 7 = "definitely get"), 29% ranked 1 or 2, 36% 3 or 4, and 35% 5 to 7. Conclusion Our qualitative assessment provides complementary data to recent quantitative surveys and suggests that physicians and parents are likely to adopt the newly licensed rotavirus vaccine. Increasing parental awareness of the rotavirus disease burden and providing physicians with timely post-marketing surveillance data will be integral to a successful vaccination program. PMID:17945010

  5. Vitamin A Deficiency Impairs Adaptive B and T Cell Responses to a Prototype Monovalent Attenuated Human Rotavirus Vaccine and Virulent Human Rotavirus Challenge in a Gnotobiotic Piglet Model

    PubMed Central

    Chattha, Kuldeep S.; Kandasamy, Sukumar; Vlasova, Anastasia N.; Saif, Linda J.

    2013-01-01

    Rotaviruses (RV) are a major cause of gastroenteritis in children. Widespread vitamin A deficiency is associated with reduced efficacy of vaccines and higher incidence of diarrheal infections in children in developing countries. We established a vitamin A deficient (VAD) gnotobiotic piglet model that mimics subclinical vitamin A deficiency in children to study its effects on an oral human rotavirus (HRV) vaccine and virulent HRV challenge. Piglets derived from VAD and vitamin A sufficient (VAS) sows were orally vaccinated with attenuated HRV or mock, with/without supplemental vitamin A and challenged with virulent HRV. Unvaccinated VAD control piglets had significantly lower hepatic vitamin A, higher severity and duration of diarrhea and HRV fecal shedding post-challenge as compared to VAS control pigs. Reduced protection coincided with significantly higher innate (IFNα) cytokine and CD8 T cell frequencies in the blood and intestinal tissues, higher pro-inflammatory (IL12) and 2-3 fold lower anti-inflammatory (IL10) cytokines, in VAD compared to VAS control pigs. Vaccinated VAD pigs had higher diarrhea severity scores compared to vaccinated VAS pigs, which coincided with lower serum IgA HRV antibody titers and significantly lower intestinal IgA antibody secreting cells post-challenge in the former groups suggesting lower anamnestic responses. A trend for higher serum HRV IgG antibodies was observed in VAD vs VAS vaccinated groups post-challenge. The vaccinated VAD (non-vitamin A supplemented) pigs had significantly higher serum IL12 (PID2) and IFNγ (PID6) compared to vaccinated VAS groups suggesting higher Th1 responses in VAD conditions. Furthermore, regulatory T-cell responses were compromised in VAD pigs. Supplemental vitamin A in VAD pigs did not fully restore the dysregulated immune responses to AttHRV vaccine or moderate virulent HRV diarrhea. Our findings suggest that that VAD in children in developing countries may partially contribute to more severe

  6. [Cost of vaccination and cost of sick leave are determinants of cost-effectiveness vaccination against rotavirus].

    PubMed

    Gyrd-Hansen, Dorte; Olsen, Kim Rose

    2012-02-20

    The literature on cost-effectiveness of oral vaccination against rotavirus infection in high-income European countries is assessed in order to show which parameters are important for evaluation results and recommendations on inclusion in child immunization programs. There is a high degree of variation in results due to variation in country specific incidence rates, unit costs and assumed price of the vaccination. A determining factor is whether only costs to the health care system are included or whether a broader approach to costing is applied. A Danish discussion on this issue is pivotal.

  7. Clinical Severity and Rotavirus Vaccination among Children Hospitalized for Acute Gastroenteritis in Belém, Northern Brazil.

    PubMed

    Justino, Maria Cleonice A; Brasil, Patrícia; Abreu, Erika; Miranda, Yllen; Mascarenhas, Joana D'Arc P; Guerra, Sylvia F S; Linhares, Alexandre C

    2016-08-01

    In March 2006, Brazil introduced the monovalent rotavirus (RV) vaccine (Rotarix™) into the public sector. This study assessed the severity of rotavirus gastroenteritis (RVGE) according to the vaccination status among hospitalized children. We identified 1023 RVGE episodes among not vaccinated (n = 252), partially vaccinated (n = 156) and fully vaccinated (n = 615) children. Very severe gastroenteritis (scored ≥ 15) was reported in 16.7, 17.9 and 13.5% of not vaccinated, partially vaccinated and fully vaccinated children, respectively. There was a trend for a shorter duration of RV diarrhoea among vaccinated children than in not vaccinated children (p = 0.07). A protective effect of vaccination was noted when mean duration of symptoms and hospital stay are analysed, comparing unvaccinated, partially vaccinated and fully vaccinated children (p < 0.05). We showed a vaccination dose effect trend, with fully vaccinated children having less-severe RVGE than not vaccinated and partially vaccinated children. © The Author [2016]. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  8. Impact of Rotavirus Vaccination on Hospitalizations and Deaths From Childhood Gastroenteritis in Botswana.

    PubMed

    Enane, Leslie A; Gastañaduy, Paul A; Goldfarb, David M; Pernica, Jeffrey M; Mokomane, Margaret; Moorad, Banno; Masole, Lingani; Tate, Jacqueline E; Parashar, Umesh D; Steenhoff, Andrew P

    2016-05-01

    A monovalent human rotavirus vaccine (RV1) was introduced in Botswana in July 2012. We assessed the impact of RV1 vaccination on childhood gastroenteritis-related hospitalizations and deaths in 2013 and 2014. We obtained data from registers of 4 hospitals in Botswana on hospitalizations and deaths from gastroenteritis, regardless of cause, among children <5 years of age. Gastroenteritis hospitalizations and deaths during the prevaccine period (January 2009-December 2012) were compared to the postvaccine period (January 2013-December 2014). Vaccine coverage was estimated from data collected through a concurrent vaccine effectiveness study at the same hospitals. By December 2014, coverage with ≥1 dose of RV1 was an estimated 90% among infants <1 year of age and 76% among children 12-23 months of age. In the prevaccine period, the annual median number of gastroenteritis-related hospitalizations in children <5 years of age was 1212, and of gastroenteritis-related deaths in children <2 years of age was 77. In the postvaccine period, gastroenteritis-related hospitalizations decreased by 23% (95% confidence interval [CI], 16%-29%) to 937, and gastroenteritis-related deaths decreased by 22% (95% CI, -9% to 44%) to 60. Declines were most prominent during the rotavirus season (May-October) and among infants <1 year of age, with reductions of 43% (95% CI, 34%-51%) in gastroenteritis hospitalizations and 48% (95% CI, 11%-69%) in gastroenteritis deaths. Following introduction of RV1 into the national immunization program, significant declines in hospitalizations and deaths from gastroenteritis were observed among children in Botswana, suggestive of the beneficial public health impact of rotavirus vaccination. © 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.

  9. Impact of Rotavirus Vaccination on Hospitalizations and Deaths From Childhood Gastroenteritis in Botswana

    PubMed Central

    Enane, Leslie A.; Gastañaduy, Paul A.; Goldfarb, David M.; Pernica, Jeffrey M.; Mokomane, Margaret; Moorad, Banno; Masole, Lingani; Tate, Jacqueline E.; Parashar, Umesh D.; Steenhoff, Andrew P.

    2016-01-01

    Background. A monovalent human rotavirus vaccine (RV1) was introduced in Botswana in July 2012. We assessed the impact of RV1 vaccination on childhood gastroenteritis-related hospitalizations and deaths in 2013 and 2014. Methods. We obtained data from registers of 4 hospitals in Botswana on hospitalizations and deaths from gastroenteritis, regardless of cause, among children <5 years of age. Gastroenteritis hospitalizations and deaths during the prevaccine period (January 2009–December 2012) were compared to the postvaccine period (January 2013–December 2014). Vaccine coverage was estimated from data collected through a concurrent vaccine effectiveness study at the same hospitals. Results. By December 2014, coverage with ≥1 dose of RV1 was an estimated 90% among infants <1 year of age and 76% among children 12–23 months of age. In the prevaccine period, the annual median number of gastroenteritis-related hospitalizations in children <5 years of age was 1212, and of gastroenteritis-related deaths in children <2 years of age was 77. In the postvaccine period, gastroenteritis-related hospitalizations decreased by 23% (95% confidence interval [CI], 16%–29%) to 937, and gastroenteritis-related deaths decreased by 22% (95% CI, −9% to 44%) to 60. Declines were most prominent during the rotavirus season (May–October) and among infants <1 year of age, with reductions of 43% (95% CI, 34%–51%) in gastroenteritis hospitalizations and 48% (95% CI, 11%–69%) in gastroenteritis deaths. Conclusions. Following introduction of RV1 into the national immunization program, significant declines in hospitalizations and deaths from gastroenteritis were observed among children in Botswana, suggestive of the beneficial public health impact of rotavirus vaccination. PMID:27059352

  10. Long-term impact of self-financed rotavirus vaccines on rotavirus-associated hospitalizations and costs in the Valencia Region, Spain.

    PubMed

    Orrico-Sanchez, Alejandro; López-Lacort, Mónica; Pérez-Vilar, Silvia; Díez-Domingo, Javier

    2017-04-11

    Rotavirus vaccines are available in Spain from 2007. They are recommended by the Spanish Pediatric Association, but not funded by the National Health System (NHS) and its coverage rate reached 40-50%. The hospitalization rate reduction of rotavirus caused gastroenteritis (RVAGE) directly attributable to vaccination remains unclear due to the large differences described in published studies, ranging from 14 to 44.5% in children <5 years of age, even with similar vaccination coverage. These results could be partly explained by variability in hospitalization policies, different study designs and the timeframe of observation. In addition, the direct economic impact of the reduction of hospitalizations has never been estimated. Therefore, there is a need to analyze the long-term impact of rotavirus vaccines on RVAGE and all cause gastroenteritis (AGE) hospitalizations and the national health system associated costs, minimizing potential confounders or biases. A population-based, ecological study using the hospital discharge registry's Minimum Basic Data Set (MBDS) and the vaccine register (SIV) was performed, among Valencia Region's children <5 years old, during 2002 - 2015. RVAGE and AGE hospitalization risk was analyzed by vaccine coverage and adjusted by the total hospitalization rate for all causes to avoid external biases. The impact of AGE-associated health care utilization in prevaccine (2003-2006) versus postvaccine (2008-2014) years was also assessed. After vaccines licensure, the incidence of RVAGE-associated hospitalizations decreased markedly. A general vaccine coverage-related reduction in RVAGE or AGE-hospitalizations risk was observed in all age groups. Compared with unvaccinated children, RVAGE hospitalization risk decreased by 67% (95% CI: 55-67), 71% (95% CI: 58-81) and 68% (95% CI: 18-92) in children 0, 1 and 4 years of age, respectively, with a vaccination coverage between 40 and 42%. Overall, the hospital related costs were reduced around EUR 6

  11. Direct, indirect, total, and overall effectiveness of the rotavirus vaccines for the prevention of gastroenteritis hospitalizations in privately insured US children, 2007-2010.

    PubMed

    Panozzo, Catherine A; Becker-Dreps, Sylvia; Pate, Virginia; Weber, David J; Jonsson Funk, Michele; Stürmer, Til; Brookhart, M Alan

    2014-04-01

    We demonstrate how direct, indirect, total, and overall effectiveness estimates and absolute benefits of rotavirus vaccines vary through the years following vaccine introduction. Privately insured US children in a large claims database were followed from age 8 months until they 1) experienced a hospitalization for rotavirus or acute gastroenteritis; 2) lost continuous health plan enrollment; 3) turned 20 months of age; or 4) reached the end of the study period. Vaccine effectiveness estimates in preventing rotavirus and acute gastroenteritis hospitalizations were estimated using Cox proportional hazards regression, stratified by calendar year and adjusted for birth month. Incidence rate differences were estimated to determine the absolute number of gastroenteritis hospitalizations prevented in the cohort. Among 905,718 children, 51%, 66%, 80%, and 86% received 1 or more doses of rotavirus vaccine in each year from 2007 to 2010. The direct vaccine effectiveness of 1 or more doses of rotavirus vaccine in preventing rotavirus gastroenteritis hospitalizations ranged from 87% to 92% each year. Accounting for indirect protection increased estimates of vaccine effectiveness by an additional 3%-8% among those vaccinated. Failing to account for population-level vaccine benefits in 2010, when circulation of rotavirus was low, could underestimate the sustained impact of the vaccine program.

  12. Distributional impact of rotavirus vaccination in 25 GAVI countries: estimating disparities in benefits and cost-effectiveness.

    PubMed

    Rheingans, Richard; Atherly, Deborah; Anderson, John

    2012-04-27

    Other studies have demonstrated that the impact and cost effectiveness of rotavirus vaccination differs among countries, with greater mortality reduction benefits and lower cost-effectiveness ratios in low-income and high-mortality countries. This analysis combines the results of a country level model of rotavirus vaccination published elsewhere with data from Demographic and Health Surveys on within-country patterns of vaccine coverage and diarrhea mortality risk factors to estimate within-country distributional effects of rotavirus vaccination. The study examined 25 countries eligible for funding through the GAVI Alliance. For each country we estimate the benefits and cost-effectiveness of vaccination for each wealth quintile assuming current vaccination patterns and for a scenario where vaccine coverage is equalized to the highest quintile's coverage. In the case of India, variations in coverage and risk proxies by state were modeled to estimate geographic distributional effects. In all countries, rates of vaccination were highest and risks of mortality were lowest in the top two wealth quintiles. However countries differ greatly in the relative inequities in these two underlying variables. Similarly, in all countries examined, the cost-effectiveness ratio for vaccination ($/Disability-Adjusted Life Year averted, DALY) is substantially greater in the higher quintiles (ranging from 2-10 times higher). In all countries, the greatest potential benefit of vaccination was in the poorest quintiles. However, due to reduced vaccination coverage, projected benefits for these quintiles were often lower. Equitable coverage was estimated to result in an 89% increase in mortality reduction for the poorest quintile and a 38% increase overall. Rotavirus vaccination is most cost-effective in low-income groups and regions. However in many countries, simply adding new vaccines to existing systems targets investments to higher income children, due to disparities in vaccination

  13. Rotavirus Genotypes and Vaccine Effectiveness from a Sentinel, Hospital-Based, Surveillance Study for Three Consecutive Rotavirus Seasons in Lebanon.

    PubMed

    Ali, Zainab; Harastani, Houda; Hammadi, Moza; Reslan, Lina; Ghanem, Soha; Hajar, Farah; Sabra, Ahmad; Haidar, Amjad; Inati, Adlette; Rajab, Mariam; Fakhouri, Hassan; Ghanem, Bassam; Baasiri, Ghassan; Gerbaka, Bernard; Zaraket, Hassan; Matar, Ghassan M; Dbaibo, Ghassan

    2016-01-01

    Globally, rotavirus (RV) is the leading cause of gastroenteritis (GE) in children. Longitudinal data about changes in RV genotype distribution and vaccine effectiveness (VE) are scarce. This study was conducted in Lebanon over 3 consecutive RV seasons to estimate the rate of RVGE hospitalization, identify RV genotypes, determine the seasonal and geographical variations, and calculate RV VE. This prospective, multicenter, hospital-based surveillance study was conducted between 2011 and 2013 and enrolled children (<5 years) admitted for GE. Socio-demographic and clinical data about the current episode of GE at admission were collected. Genotypes were determined from stool samples testing positive for RV by PCR. Of 1,414 cases included in the final analysis, 83% were <2 years old and 55.6% were boys. Median duration of hospitalization was 4 days and 91.6% of GE cases were severe (Vesikari score ≥11). PCR testing showed that 30.3% of subjects were RV-positive of which 62.1% had fever versus 71.1% of RV-negative subjects (P = 0.001). RV was predominantly detected in the cold season from November till March (69.9%). G and P genotype pairs for all RV-positive stool specimens showed a predominance of G1P[8] in 36% (n = 154) of specimens, G9P[8] in 26.4% (n = 113), and G2P[4] in 17.8% (n = 76). RV-negative subjects were more likely to be RV-vaccinated (21%) compared to the RV-positive subjects (11.3%) (P<0.001), with a vaccine breakthrough rate of 18.8%. The ratio of RV1-vaccinated for each RV5-vaccinated subject was 7.8 and VE against RV disease was 68.4% (95%CI, 49.6%-80.2%). RV is a major cause of GE requiring hospitalization of children under 5 years of age in Lebanon. A few genotypes predominated over the three RV seasons studied. Mass RV vaccination will likely decrease the burden of hospitalization due to RV. VE is similar to what has been observed for other middle-income countries.

  14. Rotavirus Genotypes and Vaccine Effectiveness from a Sentinel, Hospital-Based, Surveillance Study for Three Consecutive Rotavirus Seasons in Lebanon

    PubMed Central

    Ali, Zainab; Harastani, Houda; Hammadi, Moza; Reslan, Lina; Ghanem, Soha; Hajar, Farah; Sabra, Ahmad; Haidar, Amjad; Inati, Adlette; Rajab, Mariam; Fakhouri, Hassan; Ghanem, Bassam; Baasiri, Ghassan; Gerbaka, Bernard; Zaraket, Hassan; Matar, Ghassan M.; Dbaibo, Ghassan

    2016-01-01

    Introduction Globally, rotavirus (RV) is the leading cause of gastroenteritis (GE) in children. Longitudinal data about changes in RV genotype distribution and vaccine effectiveness (VE) are scarce. This study was conducted in Lebanon over 3 consecutive RV seasons to estimate the rate of RVGE hospitalization, identify RV genotypes, determine the seasonal and geographical variations, and calculate RV VE. Materials and Methods This prospective, multicenter, hospital-based surveillance study was conducted between 2011 and 2013 and enrolled children (<5 years) admitted for GE. Socio-demographic and clinical data about the current episode of GE at admission were collected. Genotypes were determined from stool samples testing positive for RV by PCR. Results Of 1,414 cases included in the final analysis, 83% were <2 years old and 55.6% were boys. Median duration of hospitalization was 4 days and 91.6% of GE cases were severe (Vesikari score ≥11). PCR testing showed that 30.3% of subjects were RV-positive of which 62.1% had fever versus 71.1% of RV-negative subjects (P = 0.001). RV was predominantly detected in the cold season from November till March (69.9%). G and P genotype pairs for all RV-positive stool specimens showed a predominance of G1P[8] in 36% (n = 154) of specimens, G9P[8] in 26.4% (n = 113), and G2P[4] in 17.8% (n = 76). RV-negative subjects were more likely to be RV-vaccinated (21%) compared to the RV-positive subjects (11.3%) (P<0.001), with a vaccine breakthrough rate of 18.8%. The ratio of RV1-vaccinated for each RV5-vaccinated subject was 7.8 and VE against RV disease was 68.4% (95%CI, 49.6%-80.2%). Conclusion RV is a major cause of GE requiring hospitalization of children under 5 years of age in Lebanon. A few genotypes predominated over the three RV seasons studied. Mass RV vaccination will likely decrease the burden of hospitalization due to RV. VE is similar to what has been observed for other middle-income countries. PMID:27571515

  15. Serum IgA levels induced by rotavirus natural infection, but not following immunization with the RRV-TV vaccine (Rotashield), correlate with protection.

    PubMed

    González, Rosabel; Franco, Manuel; Sarmiento, Luis; Romero, Milagros; Schael, Irene Pérez

    2005-08-01

    To directly compare serum rotavirus specific IgA as a marker of protection in children vaccinated with the RRV-TV (Rotashield) vaccine and in naturally infected children, we studied pre-existing rotavirus IgA antibodies by ELISA assays in these groups of children within the first 5 days after the onset of a diarrhea episode, due or not to rotavirus. In immunized children, rotavirus IgA titers were similar between infected and non-RV infected children. In non-immunized children, the proportion with rotavirus IgA titers was significantly greater in non-RV infected children (58%) than in infected children (31%). Additionally, a titer >/=1:800 was associated with 68% protection. Thus, in this study serum rotavirus IgA showed a good correlation with protection in children pre-exposed to natural infection but not in those immunized with the RRV-TV vaccine.

  16. Rotavirus strain surveillance for three years following the introduction of rotavirus vaccine into Belém, Brazil.

    PubMed

    Guerra, Sylvia F S; Linhares, Alexandre C; Mascarenhas, Joana D'Arc P; Oliveira, Alessilva; Justino, Maria Cleonice A; Soares, Luana S; Müller, Elza Caroline; Brasil, Patrícia; Tuboi, Suely; Ortega-Barria, Eduardo; Colindres, Rómulo

    2015-08-01

    The monovalent human rotavirus (RV) vaccine, RIX4414 (Rotarix™, GlaxoSmithKline Biologicals) was introduced into Brazil's Expanded Program on Immunization in March 2006. One year after vaccine introduction, the G2P[4] strain was found to be predominant, with an apparent extinction of many non-G2 strains. This study investigated the diversity of circulating strains in the three years following RIX4414 introduction. Between May 2008 and May 2011, stool samples were collected from children aged ≥12 weeks who were hospitalized for severe lab confirmed RV-gastroenteritis (≥3 liquid or semi-liquid motions over a 24-h period for <14 days, requiring ≥1 overnight hospital stay and intravenous rehydration therapy) in Belém, Brazil. RV-gastroenteritis was detected by ELISA and the G- and P-types were determined by RT-PCR assays. During the first year of surveillance nucleotide sequencing was used for typing those samples not previously typed by RT-PCR. A total of 1,726 of 10,030 severe gastroentertis hospitalizations (17.2%) were due to severe RVGE. G2P[4] was detected in 57.2% of circulating strains over the whole study period, however it predominated during the first 20 months from May 2008 to January 2009. G1P[8] increased in the last part of the study period from May 2010 to May 2011 and represented 36.6% (112/306) of the circulating strains. G2P[4] was the predominant RV strain circulating during the first 20 months of the study, followed by G1P[8]. These findings probably reflect a natural fluctuation in RV strains over time, rather than a vaccine-induced selective pressure.

  17. Risk of Intussusception After Rotavirus Vaccination: Meta-analysis of Postlicensure Studies.

    PubMed

    Rosillon, Dominique; Buyse, Hubert; Friedland, Leonard R; Ng, Su-Peing; Velázquez, F Raúl; Breuer, Thomas

    2015-07-01

    Postlicensure surveillance studies suggest a small temporal increase in the risk for intussusception with both currently available rotavirus vaccines (RV1; Rotarix, GSK and RV5; RotaTeq, Merck & Co., Inc.). This meta-analysis was undertaken to provide a single overall estimate of the relative risk of intussusception during the 7-day period after administration of RV1 and RV5. Meta-analysis based on estimates of relative risk and corresponding 95% confidence intervals from 5 postlicensure studies providing an estimate of risk of intussusception during the 7-day period after administration of dose 1 and/or dose 2 of RV1 and/or RV5, based on active and/or passive surveillance, for confirmed intussusception cases (Brighton or other method of case confirmation). For each vaccine, the relative risk of intussusception was estimated postdose 1 and postdose 2. Results were pooled using the inverse variance method using both fixed-effect and random-effect models. The overall estimate of relative risk of intussusception during the 7 days postdose 1 was 5.4 (95% confidence interval: 3.9-7.4, 3 studies) for RV1 and 5.5 (3.3-9.3, 3 studies) for RV5. The overall estimate of relative risk of intussusception during the 7 days postdose 2 was 1.8 (1.3-2.5, 4 studies) for RV1 and 1.7 (1.1-2.6, 3 studies) for RV5. This meta-analysis showed a similar increased risk of intussusception, during the first 7 days after administration of dose 1 and, to a lesser extent, dose 2, for both currently available rotavirus vaccines. This suggests that intussusception may be a class effect of currently available oral rotavirus vaccines.

  18. Hospitalizations for Intussusception Before and After the Reintroduction of Rotavirus Vaccine in the United States

    PubMed Central

    Zickafoose, Joseph S.; Benneyworth, Brian D.; Riebschleger, Meredith P.; Espinosa, Claudia M.; Davis, Matthew M.

    2012-01-01

    Objective To determine whether hospital discharges for intussusception in children younger than 1 year have changed since the reintroduction of rotavirus vaccine in the United States. Design Serial cross-sectional analysis. Setting US hospitals. Participants Children younger than 1 year with a discharge diagnosis of intussusception identified in the Kids’ Inpatient Database, a series of nationally representative data sets of pediatric hospital discharges in the United States with 4 available years prior to vaccine reintroduction (1997, 2000, 2003, and 2006) and 1 year after (2009). Main Exposures Hospital discharge before vs after rotavirus vaccine reintroduction. Outcome Measures Total number and rate of hospital discharges for infants younger than 1 year with a diagnosis of intussusception (International Classification of Diseases, Ninth Revision, Clinical Modification code 560.0). Results From 1997 to 2006, there was no change in the total number of hospital discharges for intussusception, with a small decrease in the rate of intussusception discharges (41.6 [95% CI, 36.7–46.5] to 36.5 [95% CI, 31.7–41.2] per 100 000 infants). Based on the trend, the predicted rate of discharges for intussusception in 2009 was 36.0 (95% CI, 30.2–41.8) per 100 000 infants. The measured rate of hospital discharges for intussusception in 2009 was 33.3 (95% CI, 29.0–37.6) per 100 000 infants. Conclusion The reintroduction of rotavirus vaccine since 2006 has not resulted in a detectable increase in the number of hospital discharges for intussusception among US infants. PMID:22213609

  19. Rotavirus vaccine response correlates with the infant gut microbiota composition in Pakistan.

    PubMed

    Harris, Vanessa; Ali, Asad; Fuentes, Susana; Korpela, Katri; Kazi, Momin; Tate, Jacqueline; Parashar, Umesh; Wiersinga, W Joost; Giaquinto, Carlo; de Weerth, Carolina; de Vos, Willem M

    2017-09-11

    Rotavirus (RV) is the leading cause of diarrhea-related death in children worldwide and ninety-five percent of rotavirus deaths occur in Africa and Asia. Rotavirus vaccines (RVV) can dramatically reduce RV deaths, but have low efficacy in low-income settings where they are most needed. The intestinal microbiome may contribute to this decreased RVV efficacy. This pilot study hypothesizes that infants' intestinal microbiota composition correlates with RVV immune responses and that RVV responders have different gut microbiota as compared to non-responders. We conducted a nested, matched case-control study comparing the pre-vaccination intestinal microbiota composition between 10 6-week old Pakistani RVV-responders, 10 6-week old Pakistani RVV non-responders, and 10 healthy Dutch infants.  RVV response was defined as an Immunoglobulin A of ≥20 IU/mL following Rotarix™(RV1) vaccination in an infant with a pre-vaccination IgA<20. Infants were matched in a 1:1 ratio using ranked variables: RV1 dosing schedule (6/10/14; 6/10; or 10/14 weeks), RV season, delivery mode, delivery place, breastfeeding practices, age and gender. Fecal microbiota analysis was performed using a highly reproducible phylogenetic microarray. RV1 response correlated with a higher relative abundance of bacteria belonging to Clostridium cluster XI and Proteobacteria, including bacteria related to Serratia and Escherichia coli. Remarkably, abundance of these Proteobacteria was also significantly higher in Dutch infants when compared to RV1-non-responders in Pakistan. This small but carefully matched study showed the intestinal microbiota composition to correlate with RV1 seroconversion in Pakistan infants, identifying signatures shared with healthy Dutch infants.

  20. The First Rotavirus Vaccine and the Politics of Acceptable Risk

    PubMed Central

    Schwartz, Jason L

    2012-01-01

    Context Vaccination in the United States is a frequent source of controversy, with critics alleging failures by public health officials to adequately identify, monitor, and respond to risks associated with vaccines. In response to these charges, the case of RotaShield, a vaccine withdrawn in 1999 following confirmation of a serious adverse event associated with its use, is regularly invoked as evidence of the effectiveness of current vaccine safety activities. Methods This article examines the history of RotaShield, with particular attention paid to decision making regarding its use in the United States and internationally. I reviewed and analyzed federal advisory committee meeting transcripts, international conference reports, government and scientific publications, media coverage, and other primary and secondary source materials. I also conducted six semistructured interviews with former senior officials and advisory committee members at the U.S. Centers for Disease Control and Prevention who participated in decisions regarding the vaccine. Findings Decision making regarding RotaShield, including the ultimate withdrawal of its recommendation for use, was shaped significantly by government health officials’ concern for preserving public confidence in overall U.S. vaccination efforts amid several unrelated vaccine risk controversies ongoing at that time. This attention to public perception and external pressures occurred in tandem with the evaluation of the quantitative evidence regarding the magnitude and severity of the risk associated with the vaccine. The decisions made in the United States resulted in foreseen but unintended consequences for international use of the vaccine, including in nations where the profile of risks and potential benefits was dramatically different. Conclusions As enthusiasm for evidence-based decision making grows throughout medicine and public health, greater explicit attention should be directed to the processes by which decision

  1. 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

  2. Probiotics and colostrum/milk differentially affect neonatal humoral immune responses to oral rotavirus vaccine.

    PubMed

    Chattha, Kuldeep S; Vlasova, Anastasia N; Kandasamy, Sukumar; Esseili, Malak A; Siegismund, Christine; Rajashekara, Gireesh; Saif, Linda J

    2013-04-08

    Breast milk (colostrum [col]/milk) components and gut commensals play important roles in neonatal immune maturation, establishment of gut homeostasis and immune responses to enteric pathogens and oral vaccines. We investigated the impact of colonization by probiotics, Lactobacillus rhamnosus GG (LGG) and Bifidobacterium lactis Bb12 (Bb12) with/without col/milk (mimicking breast/formula fed infants) on B lymphocyte responses to an attenuated (Att) human rotavirus (HRV) Wa strain vaccine in a neonatal gnotobiotic pig model. Col/milk did not affect probiotic colonization in AttHRV vaccinated pigs. However, unvaccinated pigs fed col/milk shed higher numbers of probiotic bacteria in feces than non-col/milk fed colonized controls. In AttHRV vaccinated pigs, col/milk feeding with probiotic treatment resulted in higher mean serum IgA HRV antibody titers and intestinal IgA antibody secreting cell (ASC) numbers compared to col/milk fed, non-colonized vaccinated pigs. In vaccinated pigs without col/milk, probiotic colonization did not affect IgA HRV antibody titers, but serum IgG HRV antibody titers and gut IgG ASC numbers were lower, suggesting that certain probiotics differentially impact HRV vaccine responses. Our findings suggest that col/milk components (soluble mediators) affect initial probiotic colonization, and together, they modulate neonatal antibody responses to oral AttHRV vaccine in complex ways.

  3. Probiotics and colostrum/milk differentially affect neonatal humoral immune responses to oral rotavirus vaccine

    PubMed Central

    Chattha, Kuldeep S; Vlasova, Anastasia N; Kandasamy, Sukumar; Esseili, Malak A; Siegismund, Christine; Rajashekara, Gireesh; Saif, Linda J

    2013-01-01

    Breast milk (colostrum [col]/milk) components and gut commensals play important roles in neonatal immune maturation, establishment of gut homeostasis and immune responses to enteric pathogens and oral vaccines. We investigated the impact of colonization by probiotics, Lactobacillus rhamnosus GG (LGG) and Bifidobacterium lactis Bb12 (Bb12) with/without col/milk (mimicking breast/formula fed infants) on B lymphocyte responses to an attenuated (Att) human rotavirus (HRV) Wa strain vaccine in a neonatal gnotobiotic pig model. Col/milk did not affect probiotic colonization in AttHRV vaccinated pigs. However, unvaccinated pigs fed col/milk shed higher numbers of probiotic bacteria in feces than non-col/milk fed colonized controls. In AttHRV vaccinated pigs, col/milk feeding with probiotic treatment resulted in higher mean serum IgA HRV antibody titers and intestinal IgA antibody secreting cell (ASC) numbers compared to col/milk fed, non-colonized vaccinated pigs. In vaccinated pigs without col/milk, probiotic colonization did not affect IgA HRV antibody titers, but serum IgG HRV antibody titers and gut IgG ASC numbers were lower, suggesting that certain probiotics differentially impact HRV vaccine responses. Our findings suggest that col/milk components (soluble mediators) affect initial probiotic colonization, and together, they modulate neonatal antibody responses to oral AttHRV vaccine in complex ways. PMID:23453730

  4. Acute Gastroenteritis in a Pediatric Hospital in Rio de Janeiro in Pre- and Post-Rotavirus Vaccination Settings

    PubMed Central

    Gouvea, Vera S; Dias, Giselly S; Aguiar, Ericka A; Pedro, Adriana R; Fichman, Elisa R; Chinem, Evelyn S; Gomes, Sandra P; Domingues, André L.S

    2009-01-01

    A 4½-year hospital-based survey was conducted in Rio de Janeiro to determine baseline rates of gastroenteritis-related cases, hospitalizations, and deaths; to examine the prevalence of rotavirus strains causing admissions; and to assess the immediate impact of the nationwide rotavirus immunization program launched in March 2006. From August 2002 to May 2007, 14,473 (10.4%) of the 139,747 consultations had AGE as primary diagnosis, 491 (3.4%) children required hospitalization and two (0.4%) dehydrated children died. Gastroenteritis contribution to hospitalizations varied from ~2.3% in 2004 and 2006 to 6.4% in 2005, being roughly half of them rotavirus-related cases. A gradual decrease in rotavirus strain diversity was observed from 2002 to 2005 when a single G9P[8] prevailed until April 2006. Then only short profile G9P[4] and G2P[4] strains were detected. Gastroenteritis cases were distributed year-round in a trimodal pattern with major winter peaks. Local climate apparently affected the incidence of gastroenteritis: reduction in dry years (2004 and 2007) and explosive outbreaks caused by multiple agents during the heavy rainfalls and recurrent floods of the 2005-early 2006 period. Besides rotavirus, adenovirus and calicivirus were major gastroenteritis agents of these seemingly waterborne outbreaks. In conclusion, rotavirus vaccination impacted marginally, if at all, on the incidence of childhood gastroenteritis, as favorable results obtained by comparing data from the post-vaccine period to the preceding unusual 2005 year all but disappeared when comparing to previous pre-vaccination periods, and the shift towards G2P[4] rotavirus strains may be a global trend unrelated to vaccination. PMID:19572054

  5. Population effectiveness of the pentavalent and monovalent rotavirus vaccines: a systematic review and meta-analysis of observational studies.

    PubMed

    Hungerford, Daniel; Smith, Katie; Tucker, Angela; Iturriza-Gómara, Miren; Vivancos, Roberto; McLeonard, Catherine; A Cunliffe, Nigel; French, Neil

    2017-08-15

    Rotavirus was the leading cause of acute gastroenteritis (AGE) in infants and young children prior to the introduction of routine vaccination. Since 2006 there have been two licensed vaccines available; with successful clinical trials leading the World Health Organization to recommend rotavirus vaccination for all children worldwide. In order to inform immunisation policy we have conducted a systematic review and meta-analysis of observation studies to assess population effectiveness against acute gastroenteritis. We systematically searched PubMed, Medline, Web of Science, Cinhal and Academic Search Premier and grey literature sources for studies published between January 2006 and April 2014. Studies were eligible for inclusion if they were observational measuring population effectiveness of rotavirus vaccination against health care attendances for rotavirus gastroenteritis or AGE. To evaluate study quality we use used the Newcastle-Ottawa Scale for non-randomised studies, categorising studies by risk of bias. Publication bias was assessed using funnel plots. If two or more studies reported a measure of vaccine effectiveness (VE), we conducted a random effects meta-analysis. We stratified analyses by World Bank country income level and used study quality in sensitivity analyses. We identified 30 studies, 19 were from high-income countries and 11 from middle-income countries. Vaccine effectiveness against hospitalization for laboratory confirmed rotavirus gastroenteritis was highest in high-income countries (89% VE; 95% CI 84-92%) compared to middle-income countries (74% VE; 95% CI 67-80%). Vaccine effectiveness was higher for those receiving the complete vaccine schedule (81% VE; 95% CI 75-86%) compared to partial schedule (62% VE; 95% CI 55-69%). Two studies from high-income countries measured VE against community consultations for AGE with a pooled estimate of 40% (95% CI 13-58%; 2 studies). We found strong evidence to further support the continued use of

  6. Risk of intussusception following rotavirus vaccination: An evidence based meta-analysis of cohort and case-control studies.

    PubMed

    Kassim, Priya; Eslick, Guy D

    2017-07-24

    International post-licensure studies on rotavirus vaccines have identified an increased risk of intussusception in infants after administration. The first developed rotavirus vaccine (Rotashield (RRV-TV)) was suspended post-licensure in 1999 after an association with intussusception was found. The currently available second-generation rotavirus vaccines (Rotateq (RV5) and Rotarix (RV1)), are recommended as a routine vaccine by the World Health Organisation (WHO). Post-licensure studies of these vaccines have shown a smaller but temporal increased risk for developing intussusception. A meta-analysis was performed to summarise available evidence and to give an overall risk of developing intussusception from case-control and cohort studies for all rotavirus vaccines that have been manufactured up to date. A search was conducted on MEDLINE, PubMed, EMBASE and Google Scholar up to May 2017. Eligible studies assessed the relationship between the rotavirus vaccine administration and subsequent development of intussusception both after receiving the first dose and after receiving all doses combined. Data was extracted on study characteristics, methods and outcomes. Results were pooled using the random-effect model. Six cohort studies involving 4506265 total first doses and five case-control studies involving a total sample of 9643 children were included in this analysis. The cohort data revealed that there was an associated increased risk of intussusception after the first 7days post first dose of the vaccine (RR:3.71, 95% CI:1.08-12.69) and after receiving all doses of the rotavirus vaccine (RR:3.47, 95% CI:1.23-9.78). Similarly, the case-control data found an increased risk of intussusception following the first dose (OR: 8.45, 95% CI: 4.08-17.50) and following all doses (OR: 1.59, 95% CI: 1.11-2.27). Findings of this meta-analysis suggest that the rotavirus vaccine is associated with an increased risk on the development of intussusception, principally seen after

  7. Virus-specific intestinal IFN-gamma producing T cell responses induced by human rotavirus infection and vaccines are correlated with protection against rotavirus diarrhea in gnotobiotic pigs.

    PubMed

    Yuan, Lijuan; Wen, Ke; Azevedo, Marli S P; Gonzalez, Ana M; Zhang, Wei; Saif, Linda J

    2008-06-19

    We examined rotavirus-specific IFN-gamma producing CD4+, CD8+ and CD4+CD8+ T cell responses in gnotobiotic pigs infected with a virulent human rotavirus (VirHRV) or vaccinated with an attenuated (Att) HRV vaccine (AttHRV3x or AttHRV2x) or an AttHRV oral priming and 2/6-virus-like particle (VLP) intranasal boosting (AttHRV-2/6VLP) regimen. In VirHRV infected pigs, HRV-specific IFN-gamma producing T cells reside primarily in ileum. AttHRV-2/6VLP induced similar frequencies of intestinal IFN-gamma producing T cells as the VirHRV, whereas AttHRV3x or 2x vaccines were less effective. Protection rates against rotavirus diarrhea upon VirHRV challenge significantly correlated (r=0.97-1.0, p<0.005) with frequencies of intestinal IFN-gamma producing T cells, suggesting their role in protective immunity.

  8. Herd immunity after two years of the universal mass vaccination program against rotavirus gastroenteritis in Austria.

    PubMed

    Paulke-Korinek, Maria; Kundi, Michael; Rendi-Wagner, Pamela; de Martin, Alfred; Eder, Gerald; Schmidle-Loss, Birgit; Vecsei, Andreas; Kollaritsch, Herwig

    2011-03-24

    Austria was the first country in Europe implementing a universal mass vaccination program against rotavirus gastroenteritis (RV-GE) for all infants nationwide. Epidemiological data from a hospital based surveillance system show that incidence rates of children hospitalized with RV-GE decreased in 2009 compared to 2008 and compared to the prevaccination period 2001-2005. Decreasing hospitalization-rates from RV-GE were observed in children of all age groups, even in those not eligible for vaccination according to their age, suggesting herd immunity induced by universal mass vaccination against RV-GE. In 2009 the disease burden was highest in children below three months of age stressing the importance of the early start of the immunization course.

  9. Rotavirus VP6 preparations as a non-replicating vaccine candidates.

    PubMed

    Jalilvand, Somayeh; Marashi, Sayed Mahdi; Shoja, Zabihollah

    2015-06-26

    Rotavirus (RV) structural proteins VP4 and VP7, located on the surface of viral particles, elicit neutralizing antibodies (Abs) and are therefore considered to be important components of RV vaccines. However, despite inducing neutralizing Abs, limits of cross-neutralizing activity and lack of full correlation with protection limit the usefulness of these proteins as protective agents against RV disease. VP6 protein, which forms the middle layer of RV particles, is discussed as an alternative vaccine candidate since it can induce cross-protective immune responses against different RV strains although the Ab raised is not neutralizing. This report reviews different functions of VP6 that can lead to considering it as an alternative vaccine against RV disease.

  10. Human rotavirus vaccine (RIX4414) efficacy in the first two years of life

    PubMed Central

    Li, Rong-cheng; Huang, Teng; Li, Yan-Ping; Luo, Dong; Tao, Junhui; Fu, Botao; Si, Guoai; Nong, Yi; Mo, Zhao-Jun; Liao, Xue-Yan; Luan, Ivy; Tang, Haiwen; Rathi, Niraj; Karkada, Naveen; Han, Htay Htay

    2014-01-01

    Rotaviruses (RV) are a major cause of severe gastroenteritis (GE) in children aged <5 y. For the first time in China, we assessed the efficacy of two oral doses of the human rotavirus vaccine (RIX4414) in infants during the first two years of life (113808/NCT01171963). Healthy infants aged 6–16 weeks were randomized (1:1) to receive two oral doses of either the RIX4414 vaccine/placebo according to a 0, 1 month schedule. Vaccine efficacy (VE) against severe RVGE was assessed from two weeks post-Dose 2 up until the end of the second RV season and calculated with its 95% confidence intervals (CI). The primary efficacy objective was met if the lower limit of the 95% CI on VE was ≥10%. Unsolicited symptoms reported during the 31-d post-vaccination follow-up period and serious adverse events (SAEs) reported throughout the study were assessed. Of 3333 enrolled infants, 3148 were included in the according-to-protocol efficacy cohort. Over two consecutive RV seasons, fewer severe RVGE episodes were reported in the RIX4414 group (n = 21) vs. the placebo group (n = 75). VE against severe RVGE was 72% (95% CI: 54.1–83.6); the lower limit of the 95% CI on VE was >10%. The number of unsolicited symptoms and SAEs reported was similar between both groups. Thirteen deaths (RIX4414 = 6; placebo = 7) occurred during the study. All SAEs and deaths in the RIX4414 group were considered unrelated to vaccination. Two oral doses of RIX4414 vaccine provided a substantial level of protection against severe RVGE in Chinese children during the first two years of life. PMID:24013441

  11. 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.

  12. Bone marrow dendritic cells internalize live RF-81 bovine rotavirus and rotavirus-like particles (RF 2/6-GFP-VLP and RF 8*2/6/7-VLP) but are only activated by live bovine rotavirus.

    PubMed

    Istrate, C; Douagi, I; Charpilienne, A; McInerney, G M; Hidmark, A; Johansen, K; Larsson, M; Magnusson, K-E; Poncet, D; Svensson, L; Hinkula, J

    2007-06-01

    Dendritic cells (DC) represent the link between innate and adaptive immunity. They are classified as antigen-presenting cells (APC) and can initiate and modulate the immune response. To investigate the interaction with DCs, live RF-81 bovine rotavirus strain (RFV) and rotavirus-like particles (rota-VLP), RF 2/6-GFP-VLP and rota RF 8*2/6/7-VLP, were added in vitro to murine bone marrow-derived DCs (bmDCs). Live RFV, RF 2/6-GFP-VLP and RF 8*2/6/7-VLP all bound to bmDC and were internalized but only live RFV stimulated phenotypic maturation of the bmDCs as shown by the upregulation of the co-stimulatory molecule CD86. Even though bmDCs internalized RF 2/6-GFP-VLP and RF 8*2/6/7-VLP as efficiently as live RFV, these rota-VLP were not able to activate the cells. Supernatants derived from bmDC cultures treated with live RFV, RF 2/6-GFP-VLP or RF 8*2/6/7-VLP were examined for TNF-alpha production. At 6, 18 and 24 h post-infection, TNF-alpha concentrations were significantly increased in cultures treated with live RFV and rota-VLP compared with untreated cultures. In conclusion, this study showed that live RF-81 bovine rotavirus strain was internalized and induced bmDCs activation, whereas both RF 2/6-GFP-VLP and RF 8*2/6/7-VLP were internalized by bmDCs without triggering their activation.

  13. Intussusception after monovalent rotavirus vaccine-United States, Vaccine Adverse Event Reporting System (VAERS), 2008-2014.

    PubMed

    Haber, Penina; Parashar, Umesh D; Haber, Michael; DeStefano, Frank

    2015-09-11

    In 2006 and 2008, two new rotavirus vaccines (RotaTeq [RV5] and Rotarix [RV1]) were introduced in the United States. US data on intussusception have been mostly related to RV5, with limited data on RV1. We assessed intussusception events following RV1 reported to the Vaccine Adverse Event Reporting System (VAERS), a US national passive surveillance system, during February 2008-December 2014. We conducted a self-controlled risk interval analysis using Poisson regression to estimate the daily reporting ratio (DRR) of intussusception after the first 2 doses of RV1 comparing average daily reports 3-6 versus 0-2 days after vaccination. We calculated the excess risk of intussusception per 100,000 vaccinations based on DRRs and background rates of intussusception. Sensitivity analyses were conducted to assess effects of differential reporting completeness and inaccuracy of baseline rates. VAERS received 108 confirmed insusceptible reports after RV1. A significant clustering was observed on days 3-8 after does1 (p=0.001) and days 2-7 after dose 2 (p=0.001). The DRR comparing the 3-6 day and the 0-2 day periods after RV1 dose 1 was 7.5 (95% CI=2.3, 24.6), translating to an excess risk of 1.6 (95% CI=0.3, 5.8) per 100,000 vaccinations. The DRR was elevated but not significant after dose 2 (2.4 [95% CI=0.8,7.5]). The excess risk ranged from 1.2 to 2.8 per 100,000 in sensitivity analysis. We observed a significant increased risk of intussusception 3-6 days after dose 1 of RV1. The estimated small number of intussusception cases attributable to RV1 is outweighed by the benefits of rotavirus vaccination. Published by Elsevier Ltd.

  14. Etiology of Childhood Diarrhea Following Rotavirus Vaccine Introduction: A Prospective, Population-Based Study in Nicaragua

    PubMed Central

    Becker-Dreps, Sylvia; Bucardo, Filemon; Vilchez, Samuel; Zambrana, Luis Enrique; Liu, Lan; Weber, David J.; Peña, Rodolfo; Barclay, Leslie; Vinjé, Jan; Hudgens, Michael G.; Nordgren, Johan; Svensson, Lennart; Morgan, Douglas R.; Espinoza, Félix; Paniagua, Margarita

    2014-01-01

    Background Nicaragua was the first developing nation to implement routine immunization with the pentavalent rotavirus vaccine (RV5). In this RV5-immunized population, understanding infectious etiologies of childhood diarrhea is necessary to direct diarrhea treatment and prevention efforts. Methods We followed a population-based sample of children less than 5 years in León, Nicaragua for diarrhea episodes through household visits. Information was obtained on RV5 history and sociodemographics. Stool samples collected during diarrhea episodes and among healthy children underwent laboratory analysis for viral, bacterial, and parasitic enteropathogens. Detection frequency and incidence of each enteropathogen was calculated. Results The 826 children in the cohort experienced 677 diarrhea episodes during 607.5 child-years of exposure time (1.1 episodes per child-year). At least one enteropathogen was detected among 61.1% of the 337 diarrheal stools collected. The most common enteropathogens among diarrheal stools were: norovirus (20.4%), sapovirus (16.6%), enteropathogenic Escherichia coli (EPEC, 11.3%), Entamoeba histolytica/dispar (8.3%), Giardia lamblia (8.0%), and enterotoxigenic E.coli (ETEC, 7.7%), with rotavirus detected among 5.3% of diarrheal stools. EPEC and ETEC were frequently detected among stools from healthy children. Among children with diarrhea, norovirus was more commonly detected among younger children (< 2 years) and G. lamblia was more commonly detected among older children (2-4 years). The mean age of rotavirus detection was 34.6 months. Conclusions In this Central American community following RV5 introduction, rotavirus was not commonly detected among children with diarrhea. Prevention and appropriate management of norovirus and sapovirus should be considered to further reduce the burden of diarrheal disease. PMID:24879131

  15. Estimating the costs of implementing the rotavirus vaccine in the national immunisation programme: the case of Malawi.

    PubMed

    Madsen, Lizell B; Ustrup, Marte; Hansen, Kristian S; Nyasulu, Peter S; Bygbjerg, Ib C; Konradsen, Flemming

    2014-02-01

    Worldwide, rotavirus infections cause approximately 453,000 child deaths annually. Two licensed vaccines could be life- and cost-saving in low-income countries where the disease burden is highest. The aim of our study was to estimate the total cost of implementing the rotavirus vaccine in the national immunisation programme of a low-income country. Furthermore, the aim was to examine the relative contribution of different components to the total cost. Following the World Health Organization guidelines, we estimated the resource use and costs associated with rotavirus vaccine implementation, using Malawi as a case. The cost analysis was undertaken from a governmental perspective. All costs were calculated for a 5-years period (2012-2016) and discounted at 5%. The value of key input parameters was varied in a sensitivity analysis. The total cost of rotavirus vaccine implementation in Malawi amounted to US$ 18.5 million over a 5-years period. This translated into US$ 5.8 per child in the birth cohort. With GAVI Alliance financial support, the total cost was reduced to US$ 1.4 per child in the birth cohort. Approximately 83% of the total cost was attributed to vaccine purchase, while 17% was attributed to system costs, with personnel, transportation and cold chain as the main cost components. The total cost of rotavirus vaccine implementation in Malawi is high compared with the governmental health budget of US$ 26 per capita per year. This highlights the need for new financing opportunities for low-income countries to facilitate vaccine implementation and ensure sustainable financing. © 2013 John Wiley & Sons Ltd.

  16. Impact of Withholding Breastfeeding at the Time of Vaccination on the Immunogenicity of Oral Rotavirus Vaccine—A Randomized Trial

    PubMed Central

    Ali, Asad; Kazi, Abdul Momin; Cortese, Margaret M.; Fleming, Jessica A.; Moon, SungSil; Parashar, Umesh D.; Jiang, Baoming; McNeal, Monica M.; Steele, Duncan; Bhutta, Zulfiqar; Zaidi, Anita K. M.

    2015-01-01

    Background Breast milk contains anti-rotavirus IgA antibodies and other innate immune factors that inhibit rotavirus replication in vitro. These factors could diminish the immunogenicity of oral rotavirus vaccines, particularly if breastfeeding occurs close to the time of vaccine administration. Methods Between April 2011 and November 2012, we conducted an open label, randomized trial to compare the immunogenicity of Rotarix (RV1) in infants whose breastfeeding was withheld one hour before through one hour after vaccination with that in infants breastfed at the time of vaccination. The trial was conducted in the peri-urban area of Ibrahim Hyderi in Karachi, Pakistan. Both groups received three doses of RV1 at 6, 10 and 14 weeks of age. Seroconversion (anti-rotavirus IgA antibodies ≥20 U/mL in subjects seronegative at 6 weeks of age) following three vaccine doses (6, 10 and 14 weeks) was determined at 18 weeks of age (primary objective) and seroconversion following two doses (6 and 10 weeks) was determined at 14 weeks of age (secondary objective). Results Four hundred eligible infants were randomly assigned in a 1:1 ratio between the withholding breastfeeding and immediate breastfeeding arms. Overall, 353 (88.3%) infants completed the study according to protocol; 181 in the withholding breastfeeding group and 172 in the immediate breastfeeding group. After three RV1 doses, anti-rotavirus IgA antibody seroconversion was 28.2% (95% CI: 22.1; 35.1) in the withholding arm and 37.8% (95% CI: 30.9; 45.2) in the immediate breastfeeding arm (difference: -9.6% [95% CI: -19.2; 0.2] p=0.07). After two doses of RV1, seroconversion was 16.6% (95% CI: 11.9; 22.7) in the withholding arm and 29.1% (95% CI: 22.8, 36.3) in the immediate breastfeeding arm (difference: -12.5% [95% CI: -21.2,-3.8] p=0.005). Conclusions Withholding breastfeeding around the time of RV1 vaccine administration did not lead to increased anti-rotavirus IgA seroconversion compared with that seen with a

  17. Compliance of mothers following recommendations to breastfeed or withhold breast milk during rotavirus vaccination in North India: a randomized clinical trial

    PubMed Central

    2014-01-01

    Background Neutralizing antibodies in breast milk may adversely influence the immune response to live oral vaccines. Withholding breastfeeding around the time of vaccine administration has been suggested for improving vaccine performance. However, we do not know whether mothers find withholding breastfeeding around the time of vaccination acceptable and how they perceive this recommendation. Methods In a clinical study designed to examine predictors of poor immune response to rotavirus vaccine in infants in India, Rotarix® was administered to infants at 6 and 10 weeks with other childhood vaccines. For the study, 400 mother–infant pairs were randomized into two groups in a 1:1 ratio. Mothers were either recommended to withhold breastfeeding or were encouraged to breastfeed half an hour before and after administration of Rotarix®. The mother–infant pairs were observed and the breastfeeding intervals were recorded during this period. Mothers were administered a questionnaire about their perception of the intervention after the infants received the second dose of Rotarix®. Results Almost 98% (391/400) of the infants received both doses of Rotarix®. Adherence to the recommendations was high in both groups. All mothers in the group who were asked to withhold breastfeeding did so, except one who breastfed her infant before the recommended time after the first dose of Rotarix®. Of the mothers, 4% (7/195) reported that the recommendation to withhold breastfeeding was difficult to follow. All mothers in this group reported that they would withhold breastfeeding at the time of vaccination if they were asked to by a health-care provider. Only one mother responded that withholding breastfeeding would be a reason for not giving rotavirus vaccine to her infant. Conclusions Withholding breastfeeding half an hour before and after vaccination appears to be acceptable to mothers in this setting. If withholding breastfeeding produces an improvement in the performance of the

  18. Do vaccines save lives? Yes they do!

    PubMed

    Lernout, Tinne; Theeten, Heidi; Leuridan, Elke; Van Damme, Pierre

    2014-01-01

    Since their introduction and widespread use, vaccines have been very successful in reducing morbidity and mortality of the diseases they target, at an individual level and through herd immunity. The impact on the mortality has been rapid and easy to measure for some diseases, such as diphtheria, pertussis and measles. For other diseases, including hepatitis B and human papillomavirus infections, deaths averted occur many years after vaccination, and it takes years until the full potential of the vaccine can be established. Finally, in middle and high income countries, the impact of vaccination against some diseases, like invasive pneumococcal disease and rotavirus gastro-enteritis, is measured by decrease in incidence of the disease and reduction in hospitalization rather than impact on mortality. But in the countries with the highest incidence of these diseases, mortality remains high due to low availability of these vaccines, and millions of deaths could be averted by optimal use of vaccines in these regions. Major challenges for vaccination programmes are to maintain and strengthen trust in the benefits of vaccination and adapt immunization schedules according to the changing epidemiological landscape.

  19. Inflammation and Immune Activation in Antiretroviral-Treated Human Immunodeficiency Virus Type 1-Infected African Infants and Rotavirus Vaccine Responses.

    PubMed

    Uprety, Priyanka; Lindsey, Jane C; Levin, Myron J; Rainwater-Lovett, Kaitlin; Ziemniak, Carrie; Bwakura-Dangarembizix, Mutsa; Kaplan, Susan S; Nelson, Micki; Zadzilka, Amanda; Weinberg, Adriana; Persaud, Deborah

    2017-03-15

    Biomarkers of inflammation and immune activation were correlated with rotavirus vaccine responses in 68 human immunodeficiency virus type 1 (HIV-1)–infected (and 116 HIV-exposed but uninfected (HEU) African infants receiving pentavalent rotavirus vaccine (RV5) in a clinical trial. Prevaccination, HIV-1+ infants had significantly higher concentrations of interferon γ (IFNγ), interleukin1β, interleukin 2, interleukin 6, interleukin 10 (IL-10), and soluble CD14 compared with HEU infants. Postvaccination concentrations of neutralizing antibodies to RV5 were negatively correlated with prevaccination concentrations of IL-10 (RV5 surface proteins G1 and P1) and IFNγ (G1) in the HIV-1+ infants, whereas antirotavirus immunoglobulin A (IgA) levels were not. Heightened inflammation and immune activation in HIV-1+ infants did not alter IgA responses associated with protection from rotavirus disease.

  20. Active surveillance for intussusception in a phase III efficacy trial of an oral monovalent rotavirus vaccine in India.

    PubMed

    John, Jacob; Kawade, Anand; Rongsen-Chandola, Temsunaro; Bavdekar, Ashish; Bhandari, Nita; Taneja, Sunita; Antony, Kalpana; Bhatnagar, Veereshwar; Gupta, Arun; Kabra, Madhulika; Kang, Gagandeep

    2014-08-11

    Post licensure studies have identified an increased risk of intussusception following vaccination with currently licensed rotavirus vaccines, raising safety concerns generic to all rotavirus vaccines. We describe the surveillance for intussusception in a phase III clinical trial with an oral monovalent rotavirus vaccine developed from the neonatal 116E strain. Using broad screening criteria and active surveillance, the incidence of intussusception between 6 weeks and 2 years of age was measured in 4532 children who received three doses of vaccine and 2267 children who received a placebo in the clinical trial. Possible intussusceptions were evaluated with a screening ultrasonogram. An independent intussusception case adjudication committee reviewed all intussusceptions and graded them on Brighton Collaboration criteria for diagnostic certainty. We identified twenty-three intussusceptions on ultrasound from 1361 evaluated sentinel events. Eleven were of level 1 diagnostic certainty as determined by the independent intussusception case adjudication committee. None required surgical intervention, and the earliest identified intussusception was at 36 days following the third dose in a placebo recipient. Among vaccine recipients the first event of intussusception occurred 112 days after the third dose. The incidence of ultrasound-diagnosed intussusception was 200/100,000 child-years (95% CI, 120, 320) among those receiving the vaccine and 141/100,000 child-years (95% CI, 50, 310) among those receiving the placebo. The incidence rate of confirmed intussusception among vaccine recipients was 94/100,000 child-years (95% CI, 41, 185) and 71/100,000 child-years (95% CI, 15, 206) among those receiving the placebo. In this licensure study, 23 cases of intussusception were identified through an active surveillance system, but there was no temporal association with rotavirus vaccination. The use of active surveillance with broad criteria intended for ensuring safety of children

  1. 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

  2. Noninterference of Rotavirus Vaccine With Measles-Rubella Vaccine at 9 Months of Age and Improvements in Antirotavirus Immunity: A Randomized Trial

    PubMed Central

    Zaman, K.; Fleming, Jessica A.; Victor, John C.; Yunus, Mohammad; Bari, Tajul Islam A.; Azim, Tasnim; Rahman, Mustafizur; Mowla, Syed Mohammad Niaz; Bellini, William J.; McNeal, Monica; Icenogle, Joseph P.; Lopman, Ben; Parashar, Umesh; Cortese, Margaret M.; Steele, A. Duncan; Neuzil, Kathleen M.

    2016-01-01

    Background. The burden of rotavirus morbidity and mortality is high in children aged <5 years in developing countries, and evaluations indicate waning protection from rotavirus immunization in the second year. An additional dose of rotavirus vaccine may enhance the immune response and lengthen the period of protection against disease, but coadministration of this dose should not interfere with immune responses to concurrently given vaccines. Methods. A total of 480 9-month-old participants from Matlab, Bangladesh, were enrolled in a study with a primary objective to establish noninferiority of concomitant administration of measles-rubella vaccine (MR) and a third dose of human rotavirus vaccine (HRV; MR + HRV), compared with MR given alone. Secondary objectives included noninferiority of rubella antibody seroconversion and evaluating rotavirus IgA/IgG seroresponses in MR + HRV recipients. Results. Two months after vaccination, 75.3% and 74.3% of MR + HRV and MR recipients, respectively, had seroprotective levels of measles virus antibodies; 100.0% and 99.6%, respectively, showed anti–rubella virus immunoglobulin G (IgG) seroprotection. In the MR + HRV group, antirotavirus immunoglobulin A and IgG seropositivity frequencies before vaccination (52.7% and 66.3%, respectively) increased to 69.6% and 88.3% after vaccination. Conclusions. Vaccine-induced measles and rubella antibody responses are not negatively affected by concomitant administration of HRV. The HRV dose increases antirotavirus serum antibody titers and the proportion of infants with detectable antirotavirus antibody. Clinical Trials Registration. NCT01700621. PMID:26823338

  3. 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

  4. High prevalence of G12P[8] rotavirus strains in Rio Branco, Acre, Western Amazon, in the post-rotavirus vaccine introduction period.

    PubMed

    Neves, Mayara A O; Pinheiro, Helder H C; Silva, Rita S U; Linhares, Alexandre C; Silva, Luciana D; Gabbay, Yvone B; Silva, Mônica C M; Loureiro, Edvaldo C B; Soares, Luana S; Mascarenhas, Joana D'Arc P

    2016-05-01

    The present study aimed to provide a molecular characterization of circulating rotavirus (RVA) strains in Rio Branco, Acre, in the post-rotavirus vaccination period, particularly with regard to the emerging, increasingly prevalent G12P[8] genotype. A total of 488 fecal specimens from diarrheic and non-diarrheic children were obtained between January and December 2012. RVA detection was initially performed using enzyme-linked immunosorbent assay (ELISA) method, followed by reverse-transcription polymerase chain reaction (RT-PCR) using specific primers. RVA was detected in 18.3% (44/241) of the children with acute diarrhea and in 1.2% (3/247) of the non-diarrheic children (P < 0.001), with overall RVA-positivity of 9.6% (47/488). The most common genotype was G2P[4] with 43.2% (19/44) of the diarrheic cases, followed by G12P[8] (27.3%, 12/44), G3P[6] (18.2%, 8/44), G3P[8] (4.5%, 2/44), and G12P[6] (2.3%, 1/44). G12 samples belonged to lineage III and were from children aged 4-52 months. All of these children had acute diarrhea associated with fever (83.3%, 10/12) and vomiting (66.7%, 8/12). Most of the cases occurred in August (58.3%, 7/12), 75% (9/12) of which having received the full vaccination scheme with Rotarix™. For the first time G12 was reported at relative high prevalence in Brazil. Our findings warrant further monitoring studies on the molecular characterization of circulating RVA strains after rotavirus vaccine introduction in Brazil and elsewhere, since the occurrence of either unusual our emerging genotypes may pose a challenge to vaccination strategies.

  5. Targeted rotavirus vaccination of high-risk infants; a low cost and highly cost-effective alternative to universal vaccination

    PubMed Central

    2013-01-01

    Background The cost-effectiveness of universal rotavirus (RV) vaccination is controversial in developed countries. As a result, RV vaccination programs do not currently exist in most European countries. Hospitalization is the main driver of RV disease costs, and prematurity, low birth weight (LBW) and underlying medical conditions have been associated with RV hospitalization and complications. We investigated the cost-effectiveness of targeted RV vaccination of high-risk infants and universal RV vaccination versus no vaccination. Methods Disease burden, mortality and healthcare costs of RV hospitalization for children with and without prematurity, LBW and congenital pathology were quantified in two hospital-based observational studies in the Netherlands. Cost-effectiveness analysis was based on an age-structured stochastic multi-cohort model of the Dutch population comparing universal RV vaccination and targeted vaccination of high-risk infants to no vaccination. The primary endpoint was the incremental cost-effectiveness ratio (ICER), with a threshold of €35,000/quality-adjusted life year (QALY) from the healthcare provider perspective. Sensitivity analyses included vaccine price and coverage, herd-immunity and QALY losses. Results A total of 936 children with RV infection were included. Prematurity, LBW and congenital pathology were associated with increased risks of RV hospitalization (relative risks (RR) ranging from 1.6 to 4.4), ICU admission (RR ranging from 4.2 to 7.9), prolonged hospital stay (1.5 to 3.0 excess days) and higher healthcare costs (€648 to €1,533 excess costs). Seven children succumbed due to RV complications, all belonging to the high-risk population. Targeted RV vaccination was highly cost-effective and potentially cost-saving from the healthcare provider perspective with ICERs below €20,000/QALY in all scenarios with total (undiscounted) annual healthcare costs between -€0.1 and €0.5 million/year. Results were most sensitive to

  6. Time series investigation of changes in seasonality of acute diarrhea hospitalizations before and after rotavirus vaccine in Southern Brazil.

    PubMed

    Masukawa, Maria de Lourdes Teixeira; Souza, Eniuce Menezes de; Gimenes, Edilson; Uchimura, Nelson Shozo; Moriwaki, Adriana Mayumi; Uchimura, Taqueco Teruya

    2016-10-20

    Diarrhea by rotavirus is one of the main causes of mortality in children in developing countries, although the hospitalization rates (HR) for acute diarrhea have been found to have fallen since the introduction of the rotavirus vaccine. However, the patterns of the rotavirus are still not well understood and seasonal peaks occur throughout the year, with variations between countries and over time. The main objective of this study was to analyze the temporal behavior of HR caused by acute diarrhea in children under the age of one in the south of Brazil, between 2000 and 2011, and to explore changes in seasonality patters after the introduction of the vaccine against the rotavirus in 2006. Harmonic and multiscale wavelet analyses were used to detect seasonality and the points of change in the temporal scale. The statistical significance of each seasonality that was identified was tested using Fisher's test. The harmonic and wavelet analyses show annual seasonal and six-monthly patterns for HR, as well as a clear change after the introduction of the vaccine in 2006.

  7. Live attenuated vaccines for invasive Salmonella infections.

    PubMed

    Tennant, Sharon M; Levine, Myron M

    2015-06-19

    Salmonella enterica serovar Typhi produces significant morbidity and mortality worldwide despite the fact that there are licensed Salmonella Typhi vaccines available. This is primarily due to the fact that these vaccines are not used in the countries that most need them. There is growing recognition that an effective invasive Salmonella vaccine formulation must also prevent infection due to other Salmonella serovars. We anticipate that a multivalent vaccine that targets the following serovars will be needed to control invasive Salmonella infections worldwide: Salmonella Typhi, Salmonella Paratyphi A, Salmonella Paratyphi B (currently uncommon but may become dominant again), Salmonella Typhimurium, Salmonella Enteritidis and Salmonella Choleraesuis (as well as other Group C Salmonella). Live attenuated vaccines are an attractive vaccine formulation for use in developing as well as developed countries. Here, we describe the methods of attenuation that have been used to date to create live attenuated Salmonella vaccines and provide an update on the progress that has been made on these vaccines.

  8. Live attenuated vaccines for invasive Salmonella infections

    PubMed Central

    Tennant, Sharon M.; Levine, Myron M.

    2015-01-01

    Salmonella enterica serovar Typhi produces significant morbidity and mortality worldwide despite the fact that there are licensed S. Typhi vaccines available. This is primarily due to the fact that these vaccines are not used in the countries that most need them. There is growing recognition that an effective invasive Salmonella vaccine formulation must also prevent infection due to other Salmonella serovars. We anticipate that a multivalent vaccine that targets the following serovars will be needed to control invasive Salmonella infections worldwide: S. Typhi, S. Paratyphi A, S. Paratyphi B (currently uncommon but may become dominant again), S. Typhimurium, S. Enteritidis and S. Choleraesuis (as well as other Group C Salmonella). Live attenuated vaccines are an attractive vaccine formulation for use in developing as well as developed countries. Here, we describe the methods of attenuation that have been used to date to create live attenuated Salmonella vaccines and provide an update on the progress that has been made on these vaccines. PMID:25902362

  9. Impact of enterovirus and other enteric pathogens on oral polio and rotavirus vaccine performance in Bangladeshi infants.

    PubMed

    Taniuchi, Mami; Platts-Mills, James A; Begum, Sharmin; Uddin, Md Jashim; Sobuz, Shihab U; Liu, Jie; Kirkpatrick, Beth D; Colgate, E Ross; Carmolli, Marya P; Dickson, Dorothy M; Nayak, Uma; Haque, Rashidul; Petri, William A; Houpt, Eric R

    2016-06-08

    Oral polio vaccine (OPV) and rotavirus vaccine (RV) exhibit poorer performance in low-income settings compared to high-income settings. Prior studies have suggested an inhibitory effect of concurrent non-polio enterovirus (NPEV) infection, but the impact of other enteric infections has not been comprehensively evaluated. In urban Bangladesh, we tested stools for a broad range of enteric viruses, bacteria, parasites, and fungi by quantitative PCR from infants at weeks 6 and 10 of life, coincident with the first OPV and RV administration respectively, and examined the association between enteropathogen quantity and subsequent OPV serum neutralizing titers, serum rotavirus IgA, and rotavirus diarrhea. Campylobacter and enterovirus (EV) quantity at the time of administration of the first dose of OPV was associated with lower OPV1-2 serum neutralizing titers, while enterovirus quantity was also associated with diminished rotavirus IgA (-0.08 change in log titer per tenfold increase in quantity; P=0.037), failure to seroconvert (OR 0.78, 95% CI: 0.64-0.96; P=0.022), and breakthrough rotavirus diarrhea (OR 1.34, 95% CI: 1.05-1.71; P=0.020) after adjusting for potential confounders. These associations were not observed for Sabin strain poliovirus quantity. In this broad survey of enteropathogens and oral vaccine performance we find a particular association between EV carriage, particularly NPEV, and OPV immunogenicity and RV protection. Strategies to reduce EV infections may improve oral vaccine responses. ClinicalTrials.gov Identifier: NCT01375647. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

  10. Monitoring of children with acute gastroenteritis in Madrid, Spain, during 2010-2011: rotavirus genotype distribution after the vaccines introduction.

    PubMed

    Sánchez-Fauquier, Alicia; González-Galán, Verónica; Arroyo, Sandra; Cabornero, Ana; Ruiz-Burruecos, Ana; Wilhelmi-De Cal, Isabel

    2014-05-01

    A structured surveillance study was conducted on children with diarrhea who were hospitalized in Madrid (Spain) during 2010-2011, in order to describe temporal, geographic, and age-related trends in rotavirus (RV) strains after the introduction of the RV vaccines in our country. A total of 370 children were enrolled, with RV being detected in 117 (31.6%) cases. Coinfections were detected mainly with rotavirus, astrovirus and norovirus. The most prevalent rotavirus G type was G1 (60.7%) followed by G2 (16.09%), G9 (5.9%), and G12 (5.1%). The G12 genotype appeared for the first time in 2008 in Spain, and it has increased to 5.1% of the cases in this report. Some uncommon P genotypes, such as P[14] and P[6], both with a low percentage, were found. The samples with G1 G2, G9 and G12 genotypes appeared in all ages, but were significantly higher in children under 2 years old. A long-term structured surveillance is required in the Spanish post vaccine era, in order to determine the prevalence and variability of RV genotypes. This will especially be needed to distinguish between changes occurring as a result of natural fluctuation in genotype or those (changes) that could be mediated by population immunity to the vaccines. In addition, it will be necessary to study the impact of the current vaccines on the circulating rotavirus strains and on the overall reduction in the prevalence of rotavirus disease among children in Spain. Copyright © 2013 Elsevier España, S.L. y Sociedad Española de Enfermedades Infecciosas y Microbiología Clínica. All rights reserved.

  11. Prevalence and genetic diversity of rotavirus infection in children with acute gastroenteritis in a hospital setting, Nairobi Kenya in post vaccination era: a cross-sectional study.

    PubMed

    Agutu, Mary-Theresa; Ongus, Julliette; Kombich, Janeth; Kamenwa, Rose; Nyangao, James; Kagira, John; Ogutu, Adelaide Ayoyi; Bitek, Austine

    2017-01-01

    Rotavirus is the leading cause of severe diarrhoea among infants and young children. Each year more than 611 000 children die from rotavirus gastroenteritis, and two million are hospitalized, worldwide. In Kenya, the impact of recent rotavirus vaccinations on morbidities has not been estimated. The study aimed at determining the prevalence and identity of rotavirus strains isolated from rotavirus-associated diarrhoea in vaccinated children presenting with acute gastroenteritis. Two hundred and ninety eight specimen from children presented at Gertrude Childrens' Hospital from January to June 2012 were tested by EIA (Enzyme-linked Immunosorbent Assay) for rotavirus antigens. Molecular characterization was conducted on rotavirus-positive specimens. Extracted viral RNA was separated by polyacrylamide gel electrophoresis (PAGE) and the specific rotavirus VP4 (P-types) and VP7 (G-types) determined. The prevalence rate of rotavirus was 31.5% (94/298). Of the rotavirus dsRNA, 57 (60.1%) gave visible RNA profiles, 38 (40.4%) assigned long electropherotypes while 19 (20.2%) were short electropherotypes. The strains among the vaccinated were G3P [4], G12P [6], G3P [6], G9P [4], G mixed G9/3P [4] and G1/3P [4]. Specifically, the G genotypes were G9/3 (5.3%), G9 (4.3%), G3 (4.3%), G12 (2.1%) and mixed G1/3 (1.1%). The P genotypes detected were P [4] (5.3%) and P [6] (5.3%). The present study demonstrates diversity in circulating genotypes with emergence of genotypes G3, G9, G12 and mixed genotypes G9/3 and recommends that vaccines should be formulated with a broad range of strains to include G9 and G12.

  12. The impact of rotavirus vaccination on discounted net tax revenue in Egypt: a government perspective analysis.

    PubMed

    Connolly, Mark P; Topachevskyi, Oleksandr; Standaert, Baudouin; Ortega, Omayra; Postma, Maarten

    2012-08-01

    We evaluated national rotavirus (RV) immunization programme costs to estimate how resulting changes in morbidity and mortality will influence government fiscal accounts over time. The assumption was that increased childhood survival in vaccinated cohorts leads to increased numbers of children consuming government resource, and an increased number of future tax payers. Our objective was to evaluate the difference in lifetime discounted net tax revenue generated by RV vaccinated and unvaccinated cohorts from the Egyptian government perspective. The model framework adopts the Egyptian government perspective for RV immunization costs (year 2009 values) and all government transfers (e.g. education costs, health costs, pensions). To reflect the government tax revenue, we applied a fixed income tax burden to earnings over the lifetime of vaccinated and unvaccinated cohorts. At each year of the model, we derive net taxes (gross taxes less transfers) discounted to the immunization year to reflect the present value of RV vaccination investment costs. Projected incremental net present values of the vaccinated cohort versus the unvaccinated cohort are $US6.1 million, $US58.1 million and $US55.7 million at 25-, 50- and 72-year time horizons, respectively. The internal rate of return for the government based on RV vaccination at years 25, 50 and 72 was 10.8%, 15.1% and 14.9, respectively. Within the first 5 years of vaccination, 76% of vaccine acquisition costs were offset due to direct and indirect cost savings attributed to a reduction in RV-related disease burden. Investments in RV vaccination in a single year are entirely offset when the vaccinated cohort of newborns reach 22 years of age. The government perspective is useful for evaluating investments in RV vaccination because of ongoing government transfers and tax receipts attributed to changes in RV-attributed morbidity and mortality. The analysis described here illustrates that investing in RV offers tangible long

  13. Immunogenicity of porcine P[6], P[7]-specific △VP8* rotavirus subunit vaccines with a tetanus toxoid universal T cell epitope.

    PubMed

    Wen, Xiaobo; Wei, Xiaoman; Ran, Xuhua; Ni, Hongbo; Cao, Si; Zhang, Yao

    2015-08-26

    Currently, commercial porcine rotavirus vaccines remain varied limitations. The objective of this study is to develop an alternative porcine rotavirus subunit vaccine candidate by parenteral administration, which enables to elicit robust immune responses against most prevalence porcine rotavirus strains. The bacterially-expressed porcine rotavirus P[6]- or P[7]-specific truncated VP8* (aa 64-223) recombinant protein with or without a universal tetanus toxoid CD4(+) T cell epitope P2 was generated. All the recombinant subunit proteins △VP8*s or P2-△VP8*s were of high solubility and high yields. The immunogenicity of each purified △VP8* and P2-△VP8* was evaluated in mice (10 μg/dose) or guinea pigs (20 μg/dose) immunized IM with 600 μg aluminum hydroxide three times at 2-week interval. The introduction of P2T cell epitope to P[7]-△VP8* elicited significantly higher IgG titer in mice than its absence. Comparatively, P2 epitope slightly enhanced the immunogenicity of P[6]-△VP8*. P2-P[7]△VP8* elicited high titer of neutralizing antibody against heterotypic P[7]-specific rotaviruses with varied G type combination. Our data indicated that two subunit vaccines could be plausible bivalent rotavirus vaccine candidate to provide antigenic coverage of porcine rotavirus strains of global or regional importance.

  14. 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

  15. 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

  16. Effectiveness of a monovalent rotavirus vaccine in infants in Malawi after programmatic roll-out: an observational and case-control study

    PubMed Central

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

    2015-01-01

    Summary Background Rotavirus is the main cause of severe acute gastroenteritis in children in Africa. Monovalent human rotavirus vaccine (RV1) was added into Malawi's infant immunisation schedule on Oct 29, 2012. We aimed to assess the impact and effectiveness of RV1 on rotavirus gastroenteritis in the 2 years after introduction. Methods From Jan 1, 2012, to June 30, 2014, we recruited children younger than 5 years who were admitted into Queen Elizabeth Central Hospital, Blantyre, Malawi, with acute gastroenteritis. We assessed stool samples from these children for presence of rotavirus with use of ELISA and we genotyped rotaviruses with use of RT-PCR. We compared rotavirus detection rates in stool samples and incidence of hospital admittance for rotavirus in children from Jan 1 to June 30, in the year before vaccination (2012) with the same months in the 2 years after vaccination was introduced (2013 and 2014). In the case-control portion of our study, we recruited eligible rotavirus-positive children from the surveillance platform and calculated vaccine effectiveness (one minus the odds ratio of vaccination) by comparing infants with rotavirus gastroenteritis with infants who tested negative for rotavirus, and with community age-matched and neighbourhood-matched controls. Findings We enrolled 1431 children, from whom we obtained 1417 stool samples (99%). We detected rotavirus in 79 of 157 infants (50%) before the vaccine, compared with 57 of 219 (40%) and 52 of 170 (31%) in successive calendar years after vaccine introduction (p=0·0002). In the first half of 2012, incidence of rotavirus hospital admission was 269 per 100 000 infants compared with 284 in the same months of 2013 (rise of 5·8%, 95% CI −23·1 to 45·4; p=0·73) and 153 in these months in 2014 (a reduction from the prevaccine period of 43·2%, 18·0–60·7; p=0·003). We recruited 118 vaccine-eligible rotavirus cases (median age 8·9 months; IQR 6·6–11·1), 317 rotavirus

  17. Diarrhoea-related hospitalizations in children before and after implementation of monovalent rotavirus vaccination in Mexico

    PubMed Central

    Esparza-Aguilar, Marcelino; Sánchez-Uribe, Edgar; Desai, Rishi; Parashar, Umesh D; Richardson, Vesta; Patel, Manish

    2014-01-01

    Abstract Objective To assess, by socioeconomic setting, the effect of nationwide vaccination against species A rotavirus (RVA) on childhood diarrhoea-related hospitalizations in Mexico. Methods Data on children younger than 5 years who were hospitalized for diarrhoea in health ministry hospitals between 1 January 2003 and 31 December 2011 were collected from monthly discharge reports. Human development indexes were used to categorize the states where hospitals were located as having generally high, intermediate or low socioeconomic status. Annual rates of hospitalization for diarrhoea – per 10 000 hospitalizations for any cause – were calculated. Administrative data were used to estimate vaccine coverage. Findings In the states with high, intermediate and low socioeconomic status, coverage with a two-dose monovalent RVA vaccine – among children younger than 5 years – had reached 93%, 86% and 71%, respectively, by 2010. The corresponding median annual rates of hospitalization for diarrhoea – per 10 000 admissions – fell from 1001, 834 and 1033 in the “prevaccine” period of 2003–2006, to 597, 497 and 705 in the “postvaccine” period from 2008 to 2011, respectively. These decreases correspond to rate reductions of 40% (95% confidence interval, CI: 38–43), 41% (95% CI: 38–43) and 32% (95% CI: 29–34), respectively. Nationwide, RVA vaccination appeared to have averted approximately 16 500 hospitalizations for childhood diarrhoea in each year of the postvaccine period. Conclusion Monovalent RVA vaccination has substantially reduced childhood diarrhoea-related hospitalizations for four continuous years in discretely different socioeconomic populations across Mexico. PMID:24623905

  18. Analysis of hospitalizations due to intussusception in Sicily in the pre-rotavirus vaccination era (2003-2012).

    PubMed

    Costantino, Claudio; Restivo, Vincenzo; Cuccia, Mario; Furnari, Roberto; Amodio, Emanuele; Vitale, Francesco

    2015-08-01

    Intussusception is the most common cause of bowel obstruction in infants with an incidence ranging from 9-328 cases per 100,000 infants aged 0-11 months. Causes underlining this clinical manifestation are still unknown. Possible relationship with a withdrawn tetravalent rotavirus vaccine was not confirmed by post-licensure studies and actually no increased risk of intussusception was found between infants vaccinated with both the recently licensed rotavirus vaccines. Aim of this study is to analyze the intussusception hospitalizations in Sicily from 2003 to 2012 before the introduction of rotavirus universal vaccination and its possible relation with rotavirus gastroenteritis trend. Were collected data from hospital discharge records occurred from 1(st) January 2003 to 31(st) December 2012 in Sicily. Intussusception cases were defined as all hospitalizations with an ICD-9-CM code of 560.0 on any discharge diagnoses. As a proxy for the severity of cases were considered ICD-9-CM procedure codes accounting for surgical or radiologic reduction. A total of 340 intussusception cases were hospitalized in Sicily from 2003 to 2012 in children aged 0-59 months. 46.8 % occurred in the age class 0-11 months. Hospitalization rate for intussusception was 11.4 cases per 100,000 per year (32.6 cases per 100,000 among 0-11 months children; 7.3 cases per 100,000 among 12-59 months children), with a M:F sex ratio of 1.8. During hospitalization only 25 % of intussusceptions had a spontaneous resolution, 56.5 % of cases required a surgical intervention. From 2003 to 2012 intussusception cases were equally distributed during the year without any seasonality, while gastroenteritis hospitalizations due to rotavirus infection have a typically late winter and spring distribution. In Sicily from 2003 to 2012 hospitalizations due to intestinal invagination were higher among children aged 0-11 months with observed rates similar to other European countries. Regional baseline data analysis of

  19. 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…

  20. 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…

  1. Intussusception and Monovalent Rotavirus Vaccination in Singapore: Self-Controlled Case Series and Risk-Benefit Study.

    PubMed

    Yung, Chee-Fu; Chan, Siew Pang; Soh, Sally; Tan, Adriana; Thoon, Koh Cheng

    2015-07-01

    To investigate the association between monovalent human rotavirus vaccine (RV1) and intussusception among Asian infants and the impact of older age of vaccination. To perform risk-benefit analysis of RV1 vaccination programs in Singapore. We performed a self-controlled case series by extracting intussusception cases in infants aged <12 months from hospital databases (2005-2012) and with vaccination histories from a national immunization registry. Relative incidences were calculated by comparing incidence during defined risk periods after vaccination with times outside these periods. In the risk benefit analysis, we estimated excess intussusception hospitalization in relation to the number of infants vaccinated for hypothetical vaccination coverage scenarios. There were 86 infants hospitalized with intussusception; 20 cases had received at least 1 dose of RV1. Nearly all (19) had received their first dose at age >12 weeks old. The age-adjusted relative incidence of intussusception in the 1- to 7-day period post dose one was 8.36 (95% CI 2.42-28.96). Of all childhood hospitalizations because of rotavirus, 71% (570 cases) could be prevented with 90% vaccination coverage. There would be approximately 1 excess intussusception case per 65,000 infants vaccinated. Risk of intussusception increases about 8-fold during 1-7 days after receipt of first dose RV1 in infants of Chinese, Malay, and Indian ethnicity in Singapore, Asia. High vaccine coverage program in Singapore would be beneficial with only a low risk of excess intussusception. The relative risk of intussusception post-RV1 vaccination is not higher in Asia despite differences in background intussusception incidence compared with US and Australia, or older age of vaccination. Copyright © 2015 Elsevier Inc. All rights reserved.

  2. Immune response of pregnant cows to bovine rotavirus immunization.

    PubMed

    Saif, L J; Smith, K L; Landmeier, B J; Bohl, E H; Theil, K W; Todhunter, D A

    1984-01-01

    Fifteen pregnant Holstein cows were freely assigned to 3 experimental groups (5 cows in each group). Cows in group I were inoculated IM and intramammarily (IMm) with Ohio Agricultural Research and Development Center (OARDC) tissue culture-propagated modified-live Nebraska calf diarrhea bovine rotavirus with added adjuvant (OARDC vaccine-immunized cows). Group II cows were given IM injections of a commercial modified-live rotavirus-coronavirus vaccine (commercial vaccine-immunized cows), and the remaining 5 cows were noninoculated controls (group III). Rotavirus antibody in colostrum and milk was mainly associated with immunoglobulin (Ig)G1, and less so with IgG2, IgA, and IgM, as analyzed by the enzyme-linked immunosorbent assay (ELISA), using monospecific anti-bovine IgG1, IgG2, IgM, and IgA sera. In serum, the rotavirus antibody was distributed almost equally between IgG1 and IgG2. The same relationships appeared in both immunized and nonvaccinated cows. All OARDC vaccine-injected cows had virus-neutralization (VN) and ELISA IgG1 rotavirus antibody titers in serum and mammary secretions at significantly increased levels (at least 100-fold; P less than 0.05) compared with the titers in groups II (commercial vaccine-immunized cows) and III (controls). Serum, colostrum, and milk antibody titers from these latter 2 groups did not differ statistically. The ELISA IgG2, IgA, and IgM rotavirus antibody titers also were significantly greater in mammary secretions from OARDC vaccine-immunized cows than in groups II and III cows. There was a high correlation between ELISA IgG1 and VN rotavirus antibody titers for all samples tested (r = 0.97, P less than 0.001), but ELISA IgG1 antibody titers were consistently higher than VN titers. The ELISA IgG1 and VN antibody titers of milk samples collected from cows 30 days after parturition were higher from the OARDC vaccine-immunized cows (ELISA IgG1, geometric mean titer (GMT) = 3,511; VN GMT = 1,689) than were titers from the

  3. Discovery of rotavirus: Implications for child health.

    PubMed

    Bishop, Ruth

    2009-10-01

    For centuries, acute diarrhea has been a major worldwide cause of death in young children, and until 1973, no infectious agents could be identified in about 80% of patients admitted to hospital with severe dehydrating diarrhea. In 1973 Ruth Bishop, Geoffrey Davidson, Ian Holmes, and Brian Ruck identified abundant particles of a 'new' virus (rotavirus) in the cytoplasm of mature epithelial cells lining duodenal villi and in feces, from such children admitted to the Royal Children's Hospital, Melbourne. Rotaviruses have now been shown to cause 40-50% of severe acute diarrhea in young children worldwide in both developing and developed countries, and > 600 000 young children die annually from rotavirus disease, predominantly in South-East Asia and sub-Saharan Africa. Longitudinal surveillance studies following primary infection in young children have shown that rotavirus reinfections are common. However the immune response that develops after primary infection is protective against severe symptoms on reinfection. This observation became the basis for development of live oral rotavirus vaccines. Two safe and effective vaccines are now licensed in 100 countries and in use in 17 countries (including Australia). Rotarix (GSK) is a single attenuated human rotavirus, representative of the most common serotype identified worldwide (G1P[8]). RotaTeq (Merck) is a pentavalent mixture of naturally attenuated bovine/human rotavirus reassortants representing G1, G2, G3, G4, and P(8) serotypes. Preliminary surveillance of the numbers of children requiring hospitalization for severe diarrhea, in USA, Brazil, and Australia, after introduction of these vaccines, encourages the hope that rotavirus infection need no longer be a threat to young children worldwide.

  4. Cocontribution of Rotavirus and Pneumococcal Conjugate Vaccines to the Reduction of Pediatric Hospital Visits in Young Children.

    PubMed

    Ben-Shimol, Shalom; Givon-Lavi, Noga; Greenberg, David; Dagan, Ron

    2017-03-01

    To assess rotavirus vaccine and pneumococcal conjugate vaccines (PCVs) cumulative impact on the pediatric emergency department visits and hospitalization rates in children <2 years of age in southern Israel between April 2006 and March 2014. This prospective, population-based observational study calculated the rates of rotavirus gastroenteritis (RVGE), non-RVGE, community-acquired alveolar pneumonia (CAAP), nonalveolar lower respiratory tract infection, and all-cause hospital visits. PCV7, PCV13, and rotavirus vaccination programs were implemented in Israel in July 2009, November 2010, and January 2011, respectively. From 2006-2009 to 2013-2014, the rates of hospitilizations for RVGE, non-RVGE, CAAP, and nonalveolar lower respiratory tract infection decreased by 78%, 21%, 46%, and 7%, respectively. In outpatients, the respective decreases were 80%, 16%, 67%, and 14%. All-cause outpatient pediatric emergency department visits and hospitalization rates were reduced by 12% and 11%, respectively. During the peak season (October through March), RVGE, non-RVGE, CAAP, and nonalveolar lower respiratory tract infection hospitalization rates decreased significantly by 86%, 44.6%, 23.3%, and 10.5%, respectively. In outpatients, the respective decreases were 81.7%, 73.5%, 13.8%, and 10.7%. The proportion of RVGE and CAAP (grouped) of all-cause hospitalizations and outpatient pediatric ED visits decreased from 19.9% to 12.3% and from 6.9% to 1.8%, respectively. Rotavirus vaccine and PCV introduction cocontributed to a rapid, considerable reduction in hospital burden in children <2 years of age. Because seasonalities of both diseases overlap, this reduction is particularly helpful in relieving burdens of disease and care during the most cumbersome morbidity season. Copyright © 2016 Elsevier Inc. All rights reserved.

  5. Molecular and biological characterization of the 5 human-bovine rotavirus (WC3)-based reassortant strains of the pentavalent rotavirus vaccine, RotaTeq (registered)

    SciTech Connect

    Matthijnssens, Jelle; Joelsson, Daniel B.; Warakomski, Donald J.; Zhou, Tingyi; Mathis, Pamela K.; Maanen, Marc-Henri van; Ranheim, Todd S.; Ciarlet, Max

    2010-08-01

    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 reassortant 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

  6. Epidemiology and Factors Related to Clinical Severity of Acute Gastroenteritis in Hospitalized Children after the Introduction of Rotavirus Vaccination.

    PubMed

    Kim, Ahlee; Chang, Ju Young; Shin, Sue; Yi, Hana; Moon, Jin Soo; Ko, Jae Sung; Oh, Sohee

    2017-03-01

    We aimed to investigate epidemiology and host- and pathogen-related factors associated with clinical severity of acute gastroenteritis (AGE) in children after rotavirus vaccination introduction. Factors assessed included age, co-infection with more than 2 viruses, and virus-toxigenic Clostridium difficile co-detection. Fecal samples and clinical information, including modified Vesikari scores, were collected from hospitalized children with AGE. The presence of enteric viruses and bacteria, including toxigenic C. difficile, was detected by polymerase chain reaction (PCR). Among the 415 children included, virus was detected in stool of 282 (68.0%) children. Co-infection with more than 2 viruses and toxigenic C. difficile were found in 24 (8.5%) and 26 (9.2%) children with viral AGE, respectively. Norovirus (n = 130) infection, including norovirus-associated co-infection, was the most frequent infection, especially in children aged < 24 months (P < 0.001). In the severity-related analysis, age < 24 months was associated with greater diarrheal severity (P < 0.001) and modified Vesikari score (P = 0.001), after adjustment for other severity-related factors including rotavirus status. Although the age at infection with rotavirus was higher than that for other viruses (P = 0.001), rotavirus detection was the most significant risk factor for all severity parameters, including modified Vesikari score (P < 0.001). Viral co-infection and toxigenic C. difficile co-detection were not associated with any severity-related parameter. This information will be helpful in the management of childhood AGE in this era of rotavirus vaccination and availability of molecular diagnostic tests, which often lead to the simultaneous detection of multiple pathogens.

  7. Epidemiology and Factors Related to Clinical Severity of Acute Gastroenteritis in Hospitalized Children after the Introduction of Rotavirus Vaccination

    PubMed Central

    2017-01-01

    We aimed to investigate epidemiology and host- and pathogen-related factors associated with clinical severity of acute gastroenteritis (AGE) in children after rotavirus vaccination introduction. Factors assessed included age, co-infection with more than 2 viruses, and virus-toxigenic Clostridium difficile co-detection. Fecal samples and clinical information, including modified Vesikari scores, were collected from hospitalized children with AGE. The presence of enteric viruses and bacteria, including toxigenic C. difficile, was detected by polymerase chain reaction (PCR). Among the 415 children included, virus was detected in stool of 282 (68.0%) children. Co-infection with more than 2 viruses and toxigenic C. difficile were found in 24 (8.5%) and 26 (9.2%) children with viral AGE, respectively. Norovirus (n = 130) infection, including norovirus-associated co-infection, was the most frequent infection, especially in children aged < 24 months (P < 0.001). In the severity-related analysis, age < 24 months was associated with greater diarrheal severity (P < 0.001) and modified Vesikari score (P = 0.001), after adjustment for other severity-related factors including rotavirus status. Although the age at infection with rotavirus was higher than that for other viruses (P = 0.001), rotavirus detection was the most significant risk factor for all severity parameters, including modified Vesikari score (P < 0.001). Viral co-infection and toxigenic C. difficile co-detection were not associated with any severity-related parameter. This information will be helpful in the management of childhood AGE in this era of rotavirus vaccination and availability of molecular diagnostic tests, which often lead to the simultaneous detection of multiple pathogens. PMID:28145650

  8. 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

  9. Live flavivirus vaccines: reasons for caution.

    PubMed

    Seligman, Stephen J; Gould, Ernest A

    2004-06-19

    Dengue, Japanese encephalitis, tick-borne encephalitis, yellow fever, and West Nile viruses cause substantial morbidity and mortality each year. Modern transportation and the relaxation of mosquito-control measures are largely responsible for the increase of disease caused by flaviviruses. Without effective antiviral drugs, vaccination offers the best chance of decreasing the incidence of these diseases, and live virus vaccines are the most promising and cost effective. However, flaviviruses can recombine, which raises the possibility of recombination between a vaccine strain and wild-type virus resulting in a new virus with potentially undesirable properties. Recently, Arunee Sabchareon and colleagues reported up to 90% seroconversion rates in a phase I trial of live-attenuated dengue-virus vaccines in children (Pediatr Infect Dis J 2004; 23: 99-109). Other live flavivirus vaccines have also been tested against dengue, Japanese encephalitis, and West Nile viruses. Thus far, efficacy seems promising. Safety issues with the live flavivirus vaccines need to be recognised and addressed. The theoretical possibility of untoward recombination events can never be entirely dismissed, but steps can be taken to minimise risk. The development of non-live flavivirus vaccines should be encouraged.

  10. Influenza (Flu) vaccine (Live, Intranasal): What you need to know

    MedlinePlus

    ... is taken in its entirety from the CDC Influenza Live, Intranasal Flu Vaccine Information Statement (VIS): www.cdc.gov/vaccines/ ... flulive.html . CDC review information for Live, Intranasal Influenza VIS: Vaccine Information Statement Influenza Page last reviewed: ...

  11. Divergent immunomodulating effects of probiotics on T cell responses to oral attenuated human rotavirus vaccine and virulent human rotavirus infection in a neonatal gnotobiotic piglet disease model.

    PubMed

    Chattha, Kuldeep S; Vlasova, Anastasia N; Kandasamy, Sukumar; Rajashekara, Gireesh; Saif, Linda J

    2013-09-01

    Rotaviruses (RVs) are a leading cause of childhood diarrhea. Current oral vaccines are not effective in impoverished countries where the vaccine is needed most. Therefore, alternative affordable strategies are urgently needed. Probiotics can alleviate diarrhea in children and enhance specific systemic and mucosal Ab responses, but the T cell responses are undefined. In this study, we elucidated the T cell and cytokine responses to attenuated human RV (AttHRV) and virulent human RV (HRV) in gnotobiotic pigs colonized with probiotics (Lactobacillus rhamnosus strain GG [LGG] and Bifidobacterium lactis Bb12 [Bb12]), mimicking gut commensals in breastfed infants. Neonatal gnotobiotic pigs are the only animal model susceptible to HRV diarrhea. Probiotic colonized and nonvaccinated (Probiotic) pigs had lower diarrhea and reduced virus shedding postchallenge compared with noncolonized and nonvaccinated pigs (Control). Higher protection in the Probiotic group coincided with higher ileal T regulatory cells (Tregs) before and after challenge, and higher serum TGF-β and lower serum and biliary proinflammatory cytokines postchallenge. Probiotic colonization in vaccinated pigs enhanced innate serum IFN-α, splenic and circulatory IFN-γ-producing T cells, and serum Th1 cytokines, but reduced serum Th2 cytokines compared with noncolonized vaccinated pigs (Vac). Thus, LGG+Bb12 induced systemic Th1 immunostimulatory effects on oral AttHRV vaccine that coincided with lower diarrhea severity and reduced virus shedding postchallenge in Vac+Pro compared with Vac pigs. Previously unreported intestinal CD8 Tregs were induced in vaccinated groups postchallenge. Thus, probiotics LGG+Bb12 exert divergent immunomodulating effects, with enhanced Th1 responses to oral AttHRV vaccine, whereas inducing Treg responses to virulent HRV.

  12. Divergent Immunomodulating Effects of Probiotics on T Cell Responses to Oral Attenuated Human Rotavirus Vaccine and Virulent Human Rotavirus Infection in a Neonatal Gnotobiotic Piglet Disease Model

    PubMed Central

    Chattha, Kuldeep S.; Vlasova, Anastasia N.; Kandasamy, Sukumar; Rajashekara, Gireesh; Saif, Linda J.

    2014-01-01

    Rotaviruses (RVs) are a leading cause of childhood diarrhea. Current oral vaccines are not effective in impoverished countries where the vaccine is needed most. Therefore, alternative affordable strategies are urgently needed. Probiotics can alleviate diarrhea in children and enhance specific systemic and mucosal Ab responses, but the T cell responses are undefined. In this study, we elucidated the T cell and cytokine responses to attenuated human RV (AttHRV) and virulent human RV (HRV) in gnotobiotic pigs colonized with probiotics (Lactobacillus rhamnosus strain GG [LGG] and Bifidobacterium lactis Bb12 [Bb12]), mimicking gut commensals in breastfed infants. Neonatal gnotobiotic pigs are the only animal model susceptible to HRV diarrhea. Probiotic colonized and nonvaccinated (Probiotic) pigs had lower diarrhea and reduced virus shedding postchallenge compared with noncolonized and nonvaccinated pigs (Control). Higher protection in the Probiotic group coincided with higher ileal T regulatory cells (Tregs) before and after challenge, and higher serum TGF-β and lower serum and biliary proinflammatory cytokines postchallenge. Probiotic colonization in vaccinated pigs enhanced innate serum IFN-α, splenic and circulatory IFN-γ−producing T cells, and serum Th1 cytokines, but reduced serum Th2 cytokines compared with noncolonized vaccinated pigs (Vac). Thus, LGG+Bb12 induced systemic Th1 immunostimulatory effects on oral AttHRV vaccine that coincided with lower diarrhea severity and reduced virus shedding postchallenge in Vac+Pro compared with Vac pigs. Previously unreported intestinal CD8 Tregs were induced in vaccinated groups postchallenge. Thus, probiotics LGG+Bb12 exert divergent immunomodulating effects, with enhanced Th1 responses to oral AttHRV vaccine, whereas inducing Treg responses to virulent HRV. PMID:23918983

  13. Low Prevalence of Rotavirus and High Prevalence of Norovirus in Hospital and Community Wastewater after Introduction of Rotavirus Vaccine in Nicaragua

    PubMed Central

    Bucardo, Filemón; Lindgren, Per-Eric; Svensson, Lennart; Nordgren, Johan

    2011-01-01

    Rotavirus (RV) and norovirus (NoV) are major causes of pediatric diarrhea and are altogether associated with approximately 800,000 deaths in young children every year. In Nicaragua, national RV vaccination program using the pentavalent RV5 vaccine from Merck was implemented in October 2006. To determine whether RV vaccination decreased the overall number of RV infections, we investigated the occurrence of RV and NoV in wastewater in the city of León from July 2007 to July 2008 and compared these data with pre-vaccination data. The major finding was the low prevalence of RV compared to NoV in all sampling points (11% vs 44%, p<0.05), and that RV concentration was lower as compared to NoV. RV was observed mainly during the rainy season (July–September), and the majority of all RV detected (6/9) belonged to subgroup (SG) I. The partial VP7-gene obtained from one RV positive sample was similar (99% nt identity) to a G6 VP7-gene of bovine origin and similar to the corresponding gene of the vaccine strain (98%). Furthermore RV G-types 2 and 4 were found in the incoming wastewater. NoV strains were detected throughout the year, of which a majority (20/21) were of genotype GII.4. We conclude that the introduction of RV vaccination reduced the transmission of RV in the community in Nicaragua. However, the burden of diarrhea in the country remains high, and the high prevalence of NoVs in hospital and municipal wastewater is noteworthy. This study highlights the need for further assessment of NoV following RV vaccine introduction. PMID:22016794

  14. Decline in rotavirus hospitalizations following the first three years of vaccination in Castile-La Mancha, Spain

    PubMed Central

    Redondo, Olga; Cano, Rosa; Simón, Lorena

    2015-01-01

    Rotavirus is a major burden on the Spanish Healthcare System. Rotarix® and RotaTeq® were simultaneously commercialized in Spain by February, 2007. The objective is to analyze the incidence and seasonality of rotavirus hospitalizations (RH) in Castile-La Mancha (CLM), following the first 3 y of commercialization. A cross-sectional study of the hospital discharge registry's Minimum Basic Data Set (MBDS) in CLM between 2003 and 2009 was performed. We used the Poisson regression model to quantify the percentage of change in the rotavirus incidence rate (IR) for 2007–09 vs. 2003–05, adjusting for age, sex, and province. To analyze changes between epidemic seasons the chi-square test was used. The median IR in 2003–09 was 224.71 per 105 [interquartile range (IQR): 185.24–274.70], which represents 60% of hospital admissions due to infectious acute gastroenteritis. The median rate in 2007–09 decreased [incidence rate ratio (IRR): 0.86, 95% CI: 0.78–0.96], significantly in Toledo (IRR: 0.54, 95% CI: 0.39–0.75). An incipient decline at the beginning of the last cold season was observed, preceded by a significant decrease of 68% in the autumn season of 2009. Despite its limited coverage, the rotavirus vaccine may have contributed to decrease RH in CLM. PMID:25644531

  15. [Contribution of mathematical modeling to vaccination decision making. Examples from varicella, rotavirus and papillomavirus vaccinations].

    PubMed

    Lévy-Bruhl, Daniel

    2010-11-01

    The decision to add a new vaccine to the immunization schedule is a complex and multidisciplinary process based on the risk-benefit balance and, increasingly, on the cost- effectiveness ratio. Such decisions now use mathematical models that can predict the indirect, and potentially detrimental, effects of mass vaccination on the epidemiology of the target disease. The adjunction of an economic component to the modeling process ensures that vaccination represents an efficient allocation of available financial resources in an increasingly constrained environment.

  16. Developing live vaccines against Yersinia pestis

    PubMed Central

    Sun, Wei; Roland, Kenneth L.; Curtiss, Roy

    2014-01-01

    Three great plague pandemics caused by the gram-negative bacterium Yersinia pestis have killed nearly 200 million people and it has been linked to biowarfare in the past. Plague is endemic in many parts of the world. In addition, the risk of plague as a bioweapon has prompted increased research to develop plague vaccines against this disease. Injectable subunit vaccines are being developed in the United States and United Kingdom. However, the live attenuated Y. pestis-EV NIIEG strain has been used as a vaccine for more than 70 years in the former Soviet Union and in some parts of Asia and provides a high degree of efficacy against plague. This vaccine has not gained general acceptance because of safety concerns. In recent years, modern molecular biological techniques have been applied to Y. pestis to construct strains with specific defined mutations designed to create safe, immunogenic vaccines with potential for use in humans and as bait vaccines to reduce the load of Y. pestis in the environment. In addition, a number of live, vectored vaccines have been reported using attenuated viral vectors or attenuated Salmonella strains to deliver plague antigens. Here we summarize the progress of live attenuated vaccines against plague. PMID:21918302

  17. A sham case-control study of effectiveness of DTP-Hib-hepatitis B vaccine against rotavirus acute gastroenteritis in Kenya.

    PubMed

    Khagayi, Sammy; Tate, Jacqueline E; Onkoba, Reuben; Parashar, Umesh; Odhiambo, Frank; Burton, Deron; Laserson, Kayla; Feikin, Daniel R

    2014-02-11

    In many GAVI-eligible countries, effectiveness of new vaccines will be evaluated by case-control methodology. To inform the design and assess selection bias of a future case-control study of rotavirus vaccine effectiveness (VE) in western Kenya, we performed a sham case-control study evaluating VE of pentavalent vaccine (DTP-Hib-HepB) against rotavirus acute gastroenteritis (AGE). From ongoing rotavirus surveillance, we defined cases as children 12 weeks to 23 months old with EIA-confirmed rotavirus AGE. We enrolled one community-based and two hospital-based control groups. We collected vaccination status from cards at enrollment, or later in homes, and evaluated VE by logistic regression. We enrolled 91 cases (64 inpatient, 27 outpatient), 252 non-rotavirus AGE facility-based controls (unmatched), 203 non-AGE facility-based controls (age-matched) and 271 community controls (age-matched). Documented receipt of 3 pentavalent doses was 77% among cases and ranged from 81-86% among controls. One percent of cases and 0-2% of controls had no pentavalent doses. The adjusted odds ratio of three versus zero doses for being a case was 3.27 (95% CI 0.01-1010) for community controls and 0.69 (95% CI 0.06-7.75) for non-rotavirus hospital-based AGE controls, translating to VE of -227% and 31%, respectively, with wide confidence intervals. (No facility-based non-AGE controls were unvaccinated.) Similar results were found for ≥2 pentavalent doses and for severe rotavirus AGE. The study showed that it is feasible to carry out a real case control in the study area, but this needs to be done as soon as the vaccine is introduced to capture the real impact. Sham case-control or pilot studies before vaccine introduction can be useful in designing case-control VE studies.

  18. Recommendation of rotavirus vaccination and herd effect: a budget impact analysis based on German health insurance data.

    PubMed

    Karmann, Alexander; Jurack, Andrea; Lukas, Daniel

    2015-09-01

    The objective of this study was to assess the budget impact and health effects of introducing rotavirus (RV) vaccination in Saxony, Germany, from a health insurance perspective. Special emphasis is given to the herd effect. We analyzed direct medical and non-medical costs of RV infection for Social Health Insurance between 2007 and 2010 based on 360,000 routine data observations from the AOK PLUS for children below 5 years of age. We compared the actual annual number of RV cases (vaccination scenario) with the number derived from 2005 (no vaccination, base case scenario). The vaccination coverage rate has increased from 5% to 61% between 2007 and 2010. The number of RV cases decreased by 21% from 32,274 in 2007 to 25,614 in 2010. Based on vaccination coverage, the total cost savings per 1,000 children due to RV vaccination was estimated to be 39,686 Euros. The overall share of outpatient costs was 60%. Mean gross cost savings were expected to be 304 Euros per avoided case. The net cost savings were expected to be 19 Euros per avoided case. About 59% of total savings was due to herd protection resulting from increasing vaccine rates. The herd effect per avoided case increased with increasing vaccine coverage. Incidence of RV cases, vaccination costs and days absent from work were sensitive parameters. This retrospective analysis showed that the increase in RV vaccination coverage in Saxony has been budget neutral if not cost saving for sick funds.

  19. Development and evaluation of two subunit vaccine candidates containing antigens of hepatitis E virus, rotavirus, and astrovirus

    PubMed Central

    Xia, Ming; Wei, Chao; Wang, Leyi; Cao, Dianjun; Meng, Xiang-Jin; Jiang, Xi; Tan, Ming

    2016-01-01

    Hepatitis E virus (HEV), rotavirus (RV), and astrovirus (AstV) are important pathogens that transmit through a common fecal-oral route, causing hepatitis (HEV) and gastroenteritis (RV and AstV) respectively in humans. In this study, we developed and evaluated two subunit vaccine candidates that consisted of the same protruding or spike protein antigens of the three viruses in two formats, a fusion of the three antigens into one molecule (fused vaccine) vs. a mixture of the three free antigens together (mixed vaccine). Both vaccines were easily made via E. coli expression system. Mouse immunization experiments showed that the fused vaccine elicited significantly higher antibody responses against the three viral antigens than those induced by the mixed vaccine. In addition, the mouse post-immune antisera of the fused vaccine revealed significantly higher neutralizing titers against HEV infection in cell culture, as well as significantly higher 50% blocking titers (BT50) against RV VP8-HBGA receptor interactions than those of the post-immune antisera after immunization of the mixed vaccine. Thus, the fused vaccine is a promising trivalent vaccine candidate against HEV, RV, and AstV, which is worth for further development. PMID:27194006

  20. Impact of rotavirus vaccination in regions with low and moderate vaccine uptake in Germany

    PubMed Central

    Dudareva-Vizule, Sandra; Koch, Judith; an der Heiden, Matthias; Oberle, Doris; Keller-Stanislawski, Brigitte; Wichmann, Ole

    2012-01-01

    In Germany, routine RV-vaccination is not adopted into the national immunization schedule as of 2012. Because RV-vaccines were already on the market since 2006, in 2010 a moderate (58%) and low (22%) vaccine uptake was observed in the 5 eastern federal states (EFS) and the 11 western federal states (WFS), respectively. To assess the impact of RV-vaccination, we compared the incidence rates (IR) of RV-related hospitalizations before (2004‒2006) and in seasons after (2008/09–2010/11) RV-vaccine introduction in Germany by utilizing data from the national mandatory disease reporting system. In the EFS, the IR was significantly reduced in age-groups < 18 mo in 2008/09 and in age-groups < 24 mo in 2009/10–2010/11. In the WFS an IR-reduction was observed only in age-groups < 12 mo in 2008/09 and in age-groups < 18 mo in 2009/10–2010/11. Overall IR-reduction in age-groups < 24 mo comparing 2008–11 with 2004–06 was 36% and 25% in EFS and WFS, respectively. In addition, we computed IR-ratios (IRR) in the seasons after mid-2006 with negative binomial regression. The effect of vaccination was independent from the geographic region. Vaccination was associated with a significant reduction in RV-related hospitalizations in the age-groups 6–23 mo. Most prominently, vaccination of 50% of infants led to an estimated decrease in age group 6–11 mo by 42%. No significant reduction was observed in age-groups ≥ 24 mo. In conclusion, in the German setting with low to moderate vaccine uptake, RV-related hospitalization incidence decreased substantially depending on the achieved vaccination coverage, but only in the first two years of life. PMID:22960495

  1. Methodology and lessons-learned from the efficacy clinical trial of the pentavalent rotavirus vaccine in Bangladesh.

    PubMed

    Zaman, K; Yunus, M; El Arifeen, Shams; Azim, Tasnim; Faruque, A S G; Huq, Ehsanul; Hossain, Ilias; Luby, Stephen P; Victor, John C; Dallas, Michael J; Lewis, Kristen D C; Rivers, Stephen B; Steele, A Duncan; Neuzil, Kathleen M; Ciarlet, Max; Sack, David A

    2012-04-27

    An efficacy clinical trial with pentavalent rotavirus vaccine (PRV), RotaTeq(®), was conducted at Matlab field site of ICDDR,B, Bangladesh from March 2007 to March 2009. The methodology, including operation logistics, and lessons-learned are described in this report. Vaccination was organized at 41 fixed-site clinics twice/month. A total of 1136 infants were randomized 1:1 to receive 3 doses of PRV/placebo at approximately 6-, 10-, and 14-weeks of age with routine vaccines of the Expanded Programme on Immunization (EPI) schedule. Twelve field-workers routinely visited study participants for safety and efficacy follow-up. The study was conducted following good clinical practices and maintaining cold-chain requirements. There were no temperature deviations of clinical vaccine supplies. Data entry was done using the source documents to a central database developed by the sponsor which was linked to web. Among enrolled infants, 1128 (99.3%) received 3 doses of PRV/placebo and efficacy follow-up was conducted for a median of 554 days. For the evaluation of immunogenicity, blood samples were collected from 150 participants predose 1 and from 147 (98%) of the same participants post dose 3. Stool samples were collected from 778 (99.9%) acute gastroenteritis episodes among children who reported to diarrhoea treatment centres. Thirty-nine serious adverse events, including 6 deaths, occurred among study participants. The efficacy of PRV against severe rotavirus gastroenteritis was 42.7% through the entire follow-up period; serum anti-rotavirus IgA response was 78.1%. Inclement weather, difficult transportation, and movement of study participants were some of the challenges identified. This is the first vaccine trial in rural Bangladesh with online data entry. The study was well accepted in the community and was completed successfully.

  2. Rotavirus epidemiology: the Asian Rotavirus Surveillance Network.

    PubMed

    Nelson, E A S; Bresee, J S; Parashar, U D; Widdowson, M-A; Glass, R I

    2008-06-19

    Availability of new rotavirus vaccines has highlighted the need to collect local disease and economic burden data to aid decision makers at global, regional and country level. The World Health Organization and the GAVI Alliance recommended that generic protocols be used and that regional surveillance networks be established to collect these data, thereby helping to fast-track the introduction of these new vaccines into developing countries. Nine countries and regions participated in the first phase of the Asian Rotavirus Surveillance Network (ARSN), which collected data over a 2-year period during 2001-2003. Overall 45% of diarrhoea admissions in the region were positive for rotavirus, which was higher than had been anticipated. Significant rotavirus strain diversity was noted during the surveillance period. Data collection for a second phase of the ARSN commenced in 2004 and included a greater proportion of poorer countries that would in future be eligible for funding support for rotavirus immunization from GAVI. Limited economic evaluations in Asia have demonstrated the potential for new rotavirus vaccines to be cost-effective but more local analyses are required. Despite the ARSN's comprehensive data from a mix of developed and developing countries, Asia has lagged the Americas in terms of the introduction of rotavirus vaccines into National Immunization Programmes (NIPs). Lack on rotavirus vaccine efficacy data in Asia, particularly in poorer populations, will have contributed to this delay. Thus ensuring that all global regions are simultaneously involved in the evaluation of new vaccines from the beginning and also encouraging more regional collaborations of Ministry of Health representatives could help to accelerate the introduction of new vaccines into NIPs.

  3. The assembly conformation of rotavirus VP6 determines its protective efficacy against rotavirus challenge in mice.

    PubMed

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

    2014-05-19

    Viral protein assemblies have shown to be superior immunogens used in commercial vaccines. However, little is known about the effect of protein assembly structure in immunogenicity and the protection conferred by a vaccine. In this work, rotavirus VP6, a polymorphic protein that assembles into nanotubes, icosahedra (dlRLP) or trimers was used to compare the immune response elicited by three different assemblies. VP6 is the most antigenic and abundant rotavirus structural protein. It has been demonstrated that antibodies against VP6 interfere with the replication cycle of rotavirus, making it a vaccine candidate. Groups of mice were immunized with either nanotubes, dlRLP or trimers and the humoral response (IgG and IgA titers) was measured. Immunized mice were challenged with EDIM rotavirus and protection against rotavirus infection, measured as viral shedding, was evaluated. Immunization with nanotubes resulted in the highest IgG titers, followed by immunization with dlRLP. While immunization with one dose of nanotubes was sufficient to reduce viral shedding by 70%, two doses of dlRLP or trimers were required to obtain a similar protection. The results show that the type of assembly of VP6 results in different humoral responses and protection efficacies against challenge with live virus. This information is important for the design of recombinant vaccines in general.

  4. 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

  5. Influenza virus vaccine live intranasal--MedImmune vaccines: CAIV-T, influenza vaccine live intranasal.

    PubMed

    2003-01-01

    MedImmune Vaccines (formerly Aviron) has developed a cold-adapted live influenza virus vaccine [FluMist] that can be administered by nasal spray. FluMist is the first live virus influenza vaccine and also the first nasally administered vaccine to be marketed in the US. The vaccine will be formulated to contain live attenuated (att) influenza virus reassortants of the strains recommended by the US Public Health Service for each 'flu season. The vaccine is termed cold-adapted (ca) because the virus has been adapted to replicate efficiently at 25 degrees C in the nasal passages, which are below normal body temperature. The strains used in the seasonal vaccine will also be made temperature sensitive (ts) so that their replication is restricted at 37 degrees C (Type B strains) and 39 degrees C (Type A strains). The combined effect of the antigenic properties and the att, ca and ts phenotypes of the influenza strains contained in the vaccine enables the viruses to replicate in the nasopharynx to produce protective immunity. The original formulation of FluMist requires freezer storage throughout distribution. Because many international markets do not have distribution channels well suited to the sale of frozen vaccines, Wyeth and MedImmune are collaborating to develop a second generation, refrigerator-stable, liquid trivalent cold-adapted influenza vaccine (CAIV-T), which is in phase III trials. Initially, the frozen formulation will only be available in the US. For the 2003-2004 season, FluMist will contain A/New Caledonia/20/99 (H1N1), A/Panama/2007/99 (H3N2) (A/Moscow/10/99-like) and B/Hong Kong/330/2001. Aviron was acquired by MedImmune on 15 January 2002. Aviron is now a wholly-owned subsidiary of MedImmune and is called MedImmune Vaccines. Aviron acquired FluMist in March 1995 through a Co-operative Research and Development Agreement (CRADA) with the US NIAID, and a licensing agreement with the University of Michigan, Ann Arbor, USA. In June 2000, the CRADA was

  6. Impact of a publicly funded monovalent rotavirus vaccination program in the Province of Quebec (Canada).

    PubMed

    Comeau, Jeannette L; Gagneur, Arnaud; Quach, Caroline

    2016-02-10

    In November 2011, the province of Quebec, Canada implemented a publicly funded rotavirus (RV) vaccination program using the monovalent RV vaccine (RV1). To assess its impact, trends in passive RV laboratory detection and Emergency Department (ED) visits for gastroenteritis (GE) at two pediatric centers were evaluated. RV tests performed were extracted from the virology laboratory databases and ED visits for GE between July 1, 2006 and June 30, 2013, from the ED databases of The Montreal Children's Hospital (MCH) and Centre Hospitalier Universitaire de Sherbrooke (CHUS). The percent positive RV tests over time and season duration were assessed using 5-week moving averages. We defined season start and end as the first two and the last two consecutive weeks where the percent positive RV tests were ≥ 10%, respectively. Comparing the pre- and post-vaccination program periods, a decrease in the proportion of positive RV tests was seen: 15.9% vs. 5.1% (p<0.001). Pre-vaccination program, RV seasons started between December and February, peaked in March or April and ended in May. In 2011-2012, the season started in March, peaked in April, and ended in May. In 2012-2013, the season lasted 3 weeks in May. ED visits for GE decreased post-introduction of the RV1 program: from 4.8% to 3.4% in 2011-2012, and 4.2% in 2012-13 (p<0.001). In children <2 years of age, ED GE visits decreased from 7.5% to 4.8% in 2011-2012, and 5.2% in 2012-2013 (p<0.001). Admissions for GE also decreased significantly from 0.41% of all ED visits to 0.14% in 2011-2012 and 0.22% in 2012-2013 (p<0.005). Implementation of a publicly funded RV vaccination program had a major impact on the epidemiology of RV infections in Quebec: RV seasons have started later and been of shorter duration, peak positives were fewer, and ED visits for GE decreased. Copyright © 2016 Elsevier Ltd. All rights reserved.

  7. Reduction in morbidity and mortality from childhood diarrhoeal disease after species A rotavirus vaccine introduction in Latin America - a review.

    PubMed

    Desai, Rishi; Oliveira, Lucia Helena de; Parashar, Umesh D; Lopman, Benjamin; Tate, Jacqueline E; Patel, Manish M

    2011-12-01

    Countries in Latin America were among the first to implement routine vaccination against species A rotavirus (RVA). We evaluate data from Latin America on reductions in gastroenteritis and RVA disease burden following the introduction of RVA vaccine. Published literature was reviewed to identify case-control studies of vaccine effectiveness and population-based studies examining longitudinal trends of diarrhoeal disease reduction after RVA vaccine introduction in Latin American countries. RVA vaccine effectiveness and impact on gastroenteritis mortality and hospitalization rates and RVA hospitalization rates are described. Among middle-income Latin American countries with published data (Mexico, Brazil, El Salvador and Panama), RVA vaccine contributed to a gastroenteritis-associated mortality reduction of 22-41%, a gastroenteritis-associated hospitalization reduction of 17-51% and a RVA hospitalization reduction of 59-81% among children younger than five years of age. In Brazil and El Salvador, case-control studies demonstrated that a full RVA vaccination schedule was 76-85% effective against RVA hospitalization; a lower effectiveness of 46% was seen in Nicaragua, the only low-income country with available data. A growing body of literature offers convincing evidence of "real world" vaccine program successes in Latin American settings, which may be expanded as more countries in the region include RVA vaccine in their immunization programs.

  8. Retrospective hospital based surveillance of intussusception in children in a sentinel paediatric hospital: benefits and pitfalls for use in post-marketing surveillance of rotavirus vaccines.

    PubMed

    Lloyd-Johnsen, C; Justice, F; Donath, S; Bines, J E

    2012-04-27

    Evaluation of the safety of rotavirus vaccines, particularly with respect to the risk of intussusception, is recommended for countries planning to introduce rotavirus vaccines into the National Immunisation Program. However, as prospective studies are costly, require time to conduct and may be difficult to perform in some settings, retrospective hospital based surveillance at sentinel sites has been suggested as an option for surveillance for intussusception following introduction of rotavirus vaccines. To assess the value of retrospective hospital based surveillance to describe clinical and epidemiological features of intussusception in children aged <24 months and to investigate any temporal association between receipt of a rotavirus vaccine and intussusception. A retrospective chart review of all patients diagnosed with intussusception at Royal Children's Hospital, Melbourne, Australia over an 8-year period including before and after rotavirus vaccine introduction into the National Immunisation Program, was conducted using patients identified by a medical record database (ICD-10-CM 56.1). Patient profile, clinical presentation, treatment and outcome were analysed along with records of immunisation status obtained using the Australian Childhood Immunisation Register. A 9% misclassification rate of discharge diagnosis of intussusception was identified on critical chart review. The incidence rate of intussusception at the Royal Children's Hospital over the study period was 1.91 per 10,000 infants <24 months (95% CI 1.65-2.20). Intestinal resection was required in 6.5% of infants (95% CI 3.6%, 11.0%). Intussusception occurred within 30 days after vaccination in 2 of 27 patients who had received at least 1 dose of a rotavirus vaccine. Valuable data on the incidence, clinical presentation and treatment outcomes of intussusception can be obtained from data retrieved from hospital medical records in a sentinel paediatric hospital using standardised methodology. However

  9. Hospital bed occupancy for rotavirus and all cause acute gastroenteritis in two Finnish hospitals before and after the implementation of the national rotavirus vaccination program with RotaTeq®.

    PubMed

    Hartwig, Susanne; Uhari, Matti; Renko, Marjo; Bertet, Perrine; Hemming, Maria; Vesikari, Timo

    2014-12-11

    Vaccination-impact studies of the live-attenuated pentavalent oral vaccine Rotateq® have demonstrated that the burden of rotavirus gastroenteritis has been reduced significantly after the introduction of RotaTeq® vaccination, but less is known about the benefit of this vaccination on hospital overcrowding. As part of an observational surveillance conducted during the RV seasons 2000/2001 to 2011/2012, we analysed hospital discharge data collected retrospectively from two Finnish hospitals (Oulu and Tampere), concerning ICD 10 codes A00-09 (acute gastroenteritis, AGE) and A08.0 (rotaviral acute gastroenteritis RV AGE). We estimated the reduction in the number of beds occupied and analysed the bed occupancy rate, for RV AGE and all cause AGE, among 0-16 year-old children, before and after the implementation of the RV immunisation program. The rate of bed days occupied for RV AGE was reduced by 86% (95% CI 66%-94%) in Tampere and 79% (95% CI 47%-92%) in Oulu after RV vaccination implementation. For all cause AGE, reduction was 50% (95% CI 29% to 65%) in Tampere and 70% (95% CI 58% to 79%) in Oulu. Results were similar among 0-2 year-old children. This effect was also observed on overcrowding in both hospitals, with a bed occupancy rate for all cause AGE >25% in only 1% of the time in Tampere and 9% in Oulu after the implementation of the immunisation program, compared to 13% and 48% in the pre-vaccination period respectively. After extrapolation to the whole country, the annual number of prevented hospitalizations for all cause AGE in the post-vaccination period in Finland was estimated at 1,646 and 2,303 admissions for 0-2 and 0-16 year-old children respectively. This study demonstrated that universal RV vaccination is associated with a clear decrease in the number of bed days and occupancy rates for RV AGE and all cause AGE. Positive consequences include increase in quality of care and a better healthcare management during winter epidemics.

  10. Molecular epidemiology of rotaviruses in India.

    PubMed

    Broor, Shobha; Ghosh, Dhrubaa; Mathur, Purva

    2003-08-01

    ] was reported from Bangalore. G10P[11] strains also have a high prevalence in calves with diarrhoea, in India. The occurrence of these unusual rotavirus strains which are natural reassortants of human and bovine rotaviruses, suggests that reassortment may be an important mechanism for generation of rotavirus strains of newborns. This is catalyzed by the age old traditions of calves and humans living in the same household and socio-economic conditions in India. The diversity of rotavirus strains and the high prevalence of mixed infections in India are unique features of rotavirus epidemiology in India and emphasizes that vaccines should be formulated against a broad range of strains. Another important aspect is that vaccines in India should also target G9 strains. Since neonates acquiring rotavirus infection are protected against severe diarrhoea, neonatal rotavirus strains can be effective potential vaccine candidates and vaccines based on these neonatal strains are being indigenously developed in India.

  11. Trends in Hospitalizations for Intussusception in California in Relationship to the Introduction of New Rotavirus Vaccines, 1985-2010.

    PubMed

    Contopoulos-Ioannidis, Despina G; Halpern, Meira S; Maldonado, Yvonne

    2015-07-01

    The new rotavirus vaccines RV5 and RV1 have been associated with small increase in intussusception risk in active vaccine surveillance studies. It is unclear what the impact might be on the overall trends of intussusception hospitalizations at a large population basis. We conducted an ecological study of hospital discharges of infants with intussusception discharge diagnosis using the California Office of Statewide Health Planning and Development database (1985-2010). We measured incidence rates (IR) of intussusception hospitalizations per 100,000 births within 3 periods (1985-1997; 2000-2005; 2006-2010) related to past, pre-introduction and post-introduction of the new rotavirus vaccines. We estimated slopes of yearly IRs within each period, changes in slopes between periods and IR ratios (IRR) of the mean IRs between periods. We did subgroup analyses for 5 age-subgroups. We also analyzed intussusception hospitalizations of infants who also had a surgical repair and/or radiologic reduction procedure code (restricted cohort). We identified 6241 intussusception hospitalizations; 4696 also had pertinent procedure codes. There was an upward trend in yearly IRs during 2006-2010 (+2 excess cases per 100,000 births per year; P = 0.023); the change in slopes between 2006-2010 and 2000-2005 was +3.2 excess cases per 100,000 births per year (P = 0.052), and the IR in 2006-2010 was 10% higher than in 2000-2005 (IRR: 1.10; 95% confidence intervals: 1.01-1.19). The IRR in 2006-2010 versus 2000-2005 for the 6-14 weeks age-subgroup was 1.90 (95% confidence intervals: 1.33-2.74). In the restricted cohort, trends were similar, though not nominally significant. We documented at a population-level a small increased risk in intussusception hospitalizations post-introduction of the new rotavirus vaccines.

  12. Significant Correlation Between the Infant Gut Microbiome and Rotavirus Vaccine Response in Rural Ghana

    PubMed Central

    Harris, Vanessa C.; Armah, George; Fuentes, Susana; Korpela, Katri E.; Parashar, Umesh; Victor, John C.; Tate, Jacqueline; de Weerth, Carolina; Giaquinto, Carlo; Wiersinga, Willem Joost; Lewis, Kristen D. C.; de Vos, Willem M.

    2017-01-01

    Background. Rotavirus (RV) is the leading cause of diarrhea-related death in children worldwide and 95% of RV-associated deaths occur in Africa and Asia where RV vaccines (RVVs) have lower efficacy. We hypothesize that differences in intestinal microbiome composition correlate with the decreased RVV efficacy observed in poor settings. Methods. We conducted a nested, case-control study comparing prevaccination, fecal microbiome compositions between 6-week old, matched RVV responders and nonresponders in rural Ghana. These infants' microbiomes were then compared with 154 age-matched, healthy Dutch infants' microbiomes, assumed to be RVV responders. Fecal microbiome analysis was performed in all groups using the Human Intestinal Tract Chip. Results. We analyzed findings in 78 Ghanaian infants, including 39 RVV responder and nonresponder pairs. The overall microbiome composition was significantly different between RVV responders and nonresponders (FDR, 0.12), and Ghanaian responders were more similar to Dutch infants than nonresponders (P = .002). RVV response correlated with an increased abundance of Streptococcus bovis and a decreased abundance of the Bacteroidetes phylum in comparisons between both Ghanaian RVV responders and nonresponders (FDR, 0.008 vs 0.003) and Dutch infants and Ghanaian nonresponders (FDR, 0.002 vs 0.009). Conclusions. The intestinal microbiome composition correlates significantly with RVV immunogenicity and may contribute to the diminished RVV immunogenicity observed in developing countries. PMID:27803175

  13. [Viral vaccines in the national vaccination program--views of the near future].

    PubMed

    Vesikari, Timo

    2013-01-01

    Both conventional virus vaccines and those being introduced in the near future are either live attenuated viruses or nonliving inactivated viruses, mere virus-like particles (VLP) or purified proteins. Live vaccines yield a "more natural" immunity, but in many cases also a nonliving vaccine is sufficient to protect from viral infections. Influenza vaccines are of both types. The commencing HPV vaccination program will be conducted with a VLP vaccine comprising two serotypes. A live chickenpox vaccine will be introduced in the national vaccination program in the next few years. In addition, a shingles vaccine is needed. The live oral rotavirus vaccine works well.

  14. Predominance of Norovirus and Sapovirus in Nicaragua after Implementation of Universal Rotavirus Vaccination

    PubMed Central

    Bucardo, Filemón; Reyes, Yaoska; Svensson, Lennart; Nordgren, Johan

    2014-01-01

    Background Despite significant reduction of rotavirus (RV) infections following implementation of RotaTeq vaccination in Nicaragua, a large burden of patients with diarrhea persists. Methods We conducted a community- and hospital-based study of the burden of RV, norovirus (NV) and sapovirus (SV) infections as cause of sporadic acute gastroenteritis (GE) among 330 children ≤ 5 years of age between September 2009 and October 2010 in two major cities of Nicaragua with a RotaTeq coverage rate of 95%. Results We found that NV, SV and RV infections altogether accounted for 45% of cases of GE. Notably, NV was found in 24% (79/330) of the children, followed by SV (17%, 57/330) and RV (8%, 25/330). The detection rate in the hospital setting was 27%, 15% and 14% for NV, SV and RV respectively, whereas in the community setting the detection rate of RV was < 1%. Among each of the investigated viruses one particular genogroup or genotype was dominant; GII.4 (82%) for NV, GI (46%) for SV and G1P[8] (64%) in RV. These variants were also found in higher proportions in the hospital setting compared to the community setting. The GII.4.2006 Minerva strain circulating globally since 2006 was the most common among genotyped NV in this study, with the GII.4-2010 New Orleans emerging in 2010. Conclusions This study shows that NV has become the leading viral cause of gastroenteritis at hospital and community settings in Nicaragua after implementation of RV vaccination. PMID:24849288

  15. Intellectual property rights and challenges for development of affordable human papillomavirus, rotavirus and pneumococcal vaccines: Patent landscaping and perspectives of developing country vaccine manufacturers.

    PubMed

    Chandrasekharan, Subhashini; Amin, Tahir; Kim, Joyce; Furrer, Eliane; Matterson, Anna-Carin; Schwalbe, Nina; Nguyen, Aurélia

    2015-11-17

    The success of Gavi, the Vaccine Alliance depends on the vaccine markets providing appropriate, affordable vaccines at sufficient and reliable quantities. Gavi's current supplier base for new and underutilized vaccines, such as the human papillomavirus (HPV), rotavirus, and the pneumococcal conjugate vaccine is very small. There is growing concern that following globalization of laws on intellectual property rights (IPRs) through trade agreements, IPRs are impeding new manufacturers from entering the market with competing vaccines. This article examines the extent to which IPRs, specifically patents, can create such obstacles, in particular for developing country vaccine manufacturers (DCVMs). Through building patent landscapes in Brazil, China, and India and interviews with manufacturers and experts in the field, we found intense patenting activity for the HPV and pneumococcal vaccines that could potentially delay the entry of new manufacturers. Increased transparency around patenting of vaccine technologies, stricter patentability criteria suited for local development needs and strengthening of IPRs management capabilities where relevant, may help reduce impediments to market entry for new manufacturers and ensure a competitive supplier base for quality vaccines at sustainably low prices. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

  16. Brucellosis: the case for live, attenuated vaccines.

    PubMed

    Ficht, Thomas A; Kahl-McDonagh, Melissa M; Arenas-Gamboa, Angela M; Rice-Ficht, Allison C

    2009-11-05

    The successful control of animal brucellosis and associated reduction in human exposure has limited the development of human brucellosis vaccines. However, the potential use of Brucella in bioterrorism or biowarfare suggests that direct intervention strategies are warranted. Although the dominant approach has explored the use of live attenuated vaccines, side effects associated with their use has prevented widespread use in humans. Development of live, attenuated Brucella vaccines that are safe for use in humans has focused on the deletion of important genes required for survival. However, the enhanced safety of deletion mutants is most often associated with reduced efficacy. For this reason recent efforts have sought to combine the optimal features of a attenuated live vaccine that is safe, free of side effects and efficacious in humans with enhanced immune stimulation through microencapsulation. The competitive advantages and innovations of this approach are: (1) use of highly attenuated, safe, gene knockout, live Brucella mutants; (2) manufacturing with unique disposable closed system technologies, and (3) oral/intranasal delivery in a novel microencapsulation-mediated controlled release formula to optimally provide the long term mucosal immunostimulation required for protective immunity. Based upon preliminary data, it is postulated that such vaccine delivery systems can be storage stable, administered orally or intranasally, and generally applicable to a number of agents.

  17. Rotavirus Prevalence in the Primary Care Setting in Nicaragua after Universal Infant Rotavirus Immunization

    PubMed Central

    Becker-Dreps, Sylvia; Paniagua, Margarita; Zambrana, Luis Enrique; Bucardo, Filemon; Hudgens, Michael G.; Weber, David J.; Morgan, Douglas R.; Espinoza, Félix

    2011-01-01

    Nicaragua was the first developing nation to implement universal infant rotavirus immunization with the pentavalent rotavirus vaccine (RV5). Initial studies of vaccine effectiveness in Nicaragua and other developing nations have focused on the prevention of hospitalizations and severe rotavirus diarrhea. However, rotavirus diarrhea is more commonly treated in the primary care setting, with only 1–3% of rotavirus cases receiving hospital care. We measured the prevalence of rotavirus infection in primary care clinics in León, Nicaragua, after introduction of the immunization program. In the post-vaccine period, 3.5% (95% confidence interval = 1.9–5.8) of children seeking care for diarrhea tested positive for rotavirus. A high diversity of rotavirus genotypes was encountered among the few positive samples. In conclusion, rotavirus was an uncommon cause of childhood diarrhea in this primary care setting after implementation of a rotavirus immunization program. PMID:22049057

  18. Efficacy, safety and effectiveness of licensed rotavirus vaccines: a systematic review and meta-analysis for Latin America and the Caribbean.

    PubMed

    Velázquez, Raúl F; Linhares, Alexandre C; Muñoz, Sergio; Seron, Pamela; Lorca, Pedro; DeAntonio, Rodrigo; Ortega-Barria, Eduardo

    2017-01-13

    RotaTeq™ (RV5; Merck & Co. Inc., USA) and Rotarix™ (RV1, GlaxoSmithKline, Belgium) vaccines, developed to prevent rotavirus diarrhea in children under five years old, were both introduced into national immunization programs in 2006. As many countries in Latin America and the Caribbean have included either RV5 or RV1 in their routine childhood vaccination programs, we conducted a systematic review and meta-analysis to analyze efficacy, safety and effectiveness data from the region. We conducted a systematic search in PubMed, EMBASE, Scielo, Lilacs and the Cochrane Central Register, for controlled efficacy, safety and effectiveness studies published between January 2000 until December 2011, on RV5 and RV1 across Latin America (where both vaccines are available since 2006). The primary outcome measures were: rotavirus-related gastroenteritis of any severity; rotavirus emergency department visits and hospitalization; and severe adverse events. The results of the meta-analysis for efficacy show that RV1 reduced the risk of any-severity rotavirus-related gastroenteritis by 65% (relative risk (RR) 0.35, 95% confidence interval (CI) 0.25; 0.50), and of severe gastroenteritis by 82% (RR 0.18, 95%CI 0.12; 0.26) versus placebo. In trials, both vaccines significantly reduced the risk of hospitalization and emergency visits by 85% (RR 0.15, 95%CI 0.09; 0.25) for RV1 and by 90% (RR 0.099, 95%CI 0.012; 0.77) for RV5. Vaccination with RV5 or RV1 did not increase the risk of death, intussusception, or other severe adverse events which were previously associated with the first licensed rotavirus vaccine. Real-world effectiveness studies showed that both vaccines reduced rotavirus hospitalization in the region by around 45-50% for RV5 (for 1 to 3 doses, respectively), and, by around 50-80% for RV1 (for 1 to 2 doses, respectively). For RV1, effectiveness against hospitalization was highest (around 80-96%) for children vaccinated before 12 months of age, compared with 5

  19. Data mining in the US Vaccine Adverse Event Reporting System (VAERS): early detection of intussusception and other events after rotavirus vaccination.

    PubMed

    Niu, M T; Erwin, D E; Braun, M M

    2001-09-14

    The Vaccine Adverse Event Reporting System (VAERS) is the US passive surveillance system monitoring vaccine safety. A major limitation of VAERS is the lack of denominator data (number of doses of administered vaccine), an element necessary for calculating reporting rates. Empirical Bayesian data mining, a data analysis method, utilizes the number of events reported for each vaccine and statistically screens the database for higher than expected vaccine-event combinations signaling a potential vaccine-associated event. This is the first study of data mining in VAERS designed to test the utility of this method to detect retrospectively a known side effect of vaccination-intussusception following rotavirus (RV) vaccine. From October 1998 to December 1999, 112 cases of intussusception were reported. The data mining method was able to detect a signal for RV-intussusception in February 1999 when only four cases were reported. These results demonstrate the utility of data mining to detect significant vaccine-associated events at early date. Data mining appears to be an efficient and effective computer-based program that may enhance early detection of adverse events in passive surveillance systems.

  20. [Rotavirus vaccination in 2012. Position of the Pediatric Infections Pathology Group (GPIP) and the French Association of Ambulatory Pediatrics (AFPA)].

    PubMed

    Dommergues, M-A; Gaudelus, J; Weil-Olivier, C; Thiebault, G; Vié le Sage, F; Virey, B; Dufour, V; Romain, O; Cohen, R

    2012-11-01

    In 2008 and 2010, the Comité technique des vaccinations and the Haut Conseil de Santé Publique have not recommended generalized vaccination against rotavirus (RV) in France. The Groupe de Pathologie Infectieuse Pédiatrique (GPIP) and the Association Française de Pédiatrie Ambulatoire (AFPA) believes that it is time to reconsider the recommendation. Indeed, on the one hand, answers were made on the presence of circovirus in vaccines and the risk of intussusception, on the other hand, these vaccines are already implemented in vaccination programs in many developing countries or countries with income intermediate and high. Finally, independent studies have demonstrated the effectiveness in countries with widespread vaccinations (without significant genotypic changes of circulating strains). In addition, implementation would have a major impact on our health care system, changes of the epidemic curve of RV infections (delayed and shortened) to prevent the coexistence of different epidemics occurring during the fall and winter. Remains medico-economic evaluation, which is not of the competence and the responsibility of GPIP and AFPA. However, it seems surprising that developing or middle-income countries have been able to generalize this vaccination and that France can't do it. Copyright © 2012 Elsevier Masson SAS. All rights reserved.

  1. Proceedings of the Consensus Day Meeting: Implications for Rotavirus Vaccination in the 2014 Apulian Lifetime Immunization Schedule. Foggia, 17 April 2015.

    PubMed

    Martinelli, D; Fortunato, F; Cappelli, M G; Gallone, M S; Tafuri, S; Prato, R

    2015-01-01

    Recommendations for vaccination against rotavirus (RV) were issued in Apulia in 2006; the vaccine was free of charge to children who entered day care or nursery school by 1 year of age or those affected by chronic diseases for which diarrhea caused by rotavirus can increase the risk of complications and hospitalization. In 2014, vaccination became available to all healthy children with only a copayment. However, there has not been a significant increase in vaccination coverage. On April 17, 2015, Apulian public health physicians and paediatricians met to share strategies to promote the RV vaccine indications provided in the regional immunization schedule. During the meeting, presentation of data reports were interspersed with discussions that were led with a "bottom-up" approach. The discussants responded to pre-planned questions raised by the participants and encouraged by the discussion.

  2. Mycoplasma gallisepticum: Control by live attenuated vaccines

    USDA-ARS?s Scientific Manuscript database

    Commercially available attenuated strains of Mycoplasma gallisepticum (MG) are commonly used within the layer industry to control MG-induced mycoplasmosis. Among these are two live MG vaccines derived from the moderately pathogenic MG “chick F” strain. In the present study, the commercially availa...

  3. 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.

  4. Intussusception-related Hospitalizations Among Infants Before and After Private Market Licensure of Rotavirus Vaccines in Taiwan, 2001-2013.

    PubMed

    Yen, Catherine; Shih, Shu-Man; Tate, Jacqueline E; Wu, Fang-Tzy; Huang, Yhu-Chering; Parashar, Umesh D; Hsiung, Chao A

    2017-10-01

    Rotavirus is a leading cause of acute gastroenteritis among Taiwanese children. Two globally licensed rotavirus vaccines recommended for inclusion in routine immunization programs that have been available for private market use in Taiwan since 2006 have been associated with a low risk of intussusception in postmarketing studies conducted in several countries. Our objective was to examine trends and characteristics of intussusception hospitalizations in Taiwan among children <12 months of age before and after rotavirus vaccine licensure to provide updated baseline and early postlicensure data. We extracted data on intussusception-related hospitalizations among children <12 months of age during 2001-2013 from the National Health Insurance Research Database. We examined patient demographics, clinical outcome and hospitalization trends, focusing on recommended ages for rotavirus vaccination (6-14, 15-24 and 25-34 weeks). We compared mean hospitalization rates for prevaccine licensure years 2001-2005 with those for postvaccine licensure years 2007-2013 using Poisson regression analysis. During 2001-2013, 1998 intussusceptions hospitalizations were recorded. The mean age of hospitalization was 33 weeks. Almost all children recovered; 3 deaths occurred. The overall intussusception hospitalization rate was 75.1 per 100,000; seasonality was not evident. Hospitalization rates were greatest in children ≥25 weeks of age and occurred more frequently in boys. Prevaccine and postvaccine licensure trends in annual hospitalization rates did not significantly differ. However, mean hospitalization rates were lower during the postvaccine licensure period for children <12 months of age (rate ratio: 0.84, 95% confidence interval: 0.76-0.92) with the greatest decline among children 25-34 weeks of age (rate ratio: 0.66, 95% confidence interval: 0.55-0.78). Infant intussusception in Taiwan occurs at a rate within the range of other Asian countries is rare among children <3 months of age

  5. Health Promotion Through Existing Community Structures: A Case of Churches' Roles in Promoting Rotavirus Vaccination in Rural Zambia.

    PubMed

    Wesevich, Austin; Chipungu, Jenala; Mwale, Mercy; Bosomprah, Samuel; Chilengi, Roma

    2016-04-01

    Rural populations, particularly in Africa, suffer worse health outcomes from poor health services access. Community health workers (CHWs) effectively improve health outcomes, but the best means for CHWs reaching rural populations is unknown. Since Zambia is predominantly Christian, this study explored the use of CHWs through churches as an existing community structure for promoting preventive health behaviors, specifically rotavirus vaccine uptake. A noncontrolled cross-sectional study of 32 churches receiving a packaged intervention of diarrhea prevention and treatment messaging was conducted with repeated time points of data collection over 13 months (2013-2014) in the Kafue District of Zambia. Two churches were selected for each of the 17 catchment areas, and CHWs were identified and trained in the intervention of promoting 4 key messages related to diarrhea prevention and treatment: hand washing with soap, exclusive breast-feeding, rotavirus vaccination, and treating diarrhea with oral rehydration solution and zinc. The intervention was conducted within existing church's women's groups, and data was collected on attendance and the distribution of Rota Cards for tracking rotavirus immunizations. Nineteen (59%) churches completed the study, and CHWs delivered health messages at a total of 890 women's group meetings. The overall reach of the intervention was to 37.0% of church-attending women, and the efficacy was 67.7% (317 of 468 Rota Cards collected at health centers). Implementing community health programs is often expensive and unsustainable, but the reach and efficacy levels achieved through existing structures like churches are encouraging in resource-constrained countries. Churches can be effective channels for delivering health prevention strategies to often difficult-to-reach rural populations. Further research is needed to investigate the impact of the intervention on health outcomes. © The Author(s) 2016.

  6. Use of an immunization information system to assess the effectiveness of pentavalent rotavirus vaccine in US children.

    PubMed

    Sahni, Leila C; Boom, Julie A; Patel, Manish M; Baker, Carol J; Rench, Marcia A; Parashar, Umesh D; Tate, Jacqueline E

    2010-08-31

    Immunization information systems (IISs) are accessible sources of immunization data. We validated immunization information from a local IIS against provider records and assessed the system's utility in evaluating vaccine effectiveness against rotavirus disease using a case-control study. Among the 91% of case and control patients with immunization records, 49% were in the IIS, and 97% had a provider record. Good agreement was observed across record sources (k=0.65). Vaccine effectiveness (VE) was 82% using IIS data compared to 82-88% using provider data. Controls identified through the IIS provided VE estimates similar to hospital control patients. IISs could represent a valuable source of data for effectiveness evaluations. (c) 2010 Elsevier Ltd. All rights reserved.

  7. [Analysis of the mortality due to diarrhea in younger children, before and after the introduction of rotavirus vaccine].

    PubMed

    Esparza-Aguilar, Marcelino; Bautista-Márquez, Aurora; González-Andrade, María del Carmen; Richardson-López-Collada, Vesta Louise

    2009-01-01

    To analyze the mortality due to acute diarrhea in children younger than five years old, before and after the introduction of rotavirus vaccine in Mexico. Number of deaths and mortality rates due to acute diarrhea were compared by children's age and states' vaccine status using annual percentage differences before (2000-2005) and after (2006-2007) the introduction of the HRV. From 2000-2007, deaths due to acute diarrhea in children under five years of age dropped 42%. In those states that received the HRV early in 2006, diarrhea mortality decreased between 2006-2007 15.8% in children younger than one year old and 22.7% in children 1-4 years old. The observed reduction in mortality due to acute diarrhea in children under five years of age after 2005 can be, in part, attributed to the HRV.

  8. Immune responses after live attenuated influenza vaccination.

    PubMed

    Mohn, Kristin G-I; Smith, Ingrid; Sjursen, Haakon; Cox, Rebecca

    2017-09-21

    Since 2003 (US) and 2012 (Europe) the live attenuated influenza vaccine (LAIV) has been used as an alternative to the traditional inactivated influenza vaccines (IIV). The immune responses elicted by LAIV mimic natural infection and have been found to provide broader clinical protection in children compared to the IIVs. However, our knowledge of the detailed immunological mechanisims induced by LAIV remain to be fully elucidated, and despite 14 years on the global market, there exists no correlate of protection. Recently, matters are further complicated by differing efficacy data from the US and Europe which are not understood. Better understanding of the immune responses after LAIV may aid in achieving the ultimate goal of a future "universal influenza vaccine". In this review we aim to cover the current understanding of the immune responses induced after LAIV.

  9. Monitoring the circulation of rotavirus among children after the introduction of the Rotarix™ vaccine in Goiânia, Brazil.

    PubMed

    Borges, Ana Maria Tavares; Dias e Souza, Menira; Fiaccadori, Fabíola Souza; Cardoso, Divina das Dores de Paula

    2011-06-01

    The epidemiological features of rotavirus A (RVA) infection differ between children from developing and developed countries which could result in differences in vaccine efficacy around the world. To evaluate the impact of Rotarix™ on RVA prevalence, we monitored RVA genotypes circulating in Goiânia by monitoring virus in faecal samples from children that had or had not been previously vaccinated. From February-November of 2008, 220 faecal samples were collected from children in seven day-care centres. RVA detection was performed by two methodologies and the results were confirmed by polyacrylamide gel electrophoresis. From the 220 samples, eight were RVA-positive (3.6%) and five were from children that had received either one or two doses of the vaccine. All positive samples were collected from children with diarrhoea during August and September. Genotyping of the RVA characterised five of the viral samples as genotype G2P[4] and one as G8P[4], suggesting that G2P[4] was the predominant circulating genotype in Goiânia during the study. The fact that vaccinated children were also infected by RVA suggests that the vaccine does not fully protect against infection by the G2[P4] RVA genotype.

  10. Do current cost-effectiveness analyses reflect the full value of childhood vaccination in Europe? A rotavirus case study.

    PubMed

    Brüggenjürgen, Bernd; Lorrot, Mathie; Sheppard, Fiona R; Rémy, Vanessa

    2014-01-01

    Economic evaluation of vaccination programs can be challenging and does not always fully capture the benefits provided. Reasons for this include the difficulties incurred in accurately capturing the health and economic impact of infectious diseases and how different diseases may interact with each other. Rotavirus infection, for example, peaks at a similar time than other infectious diseases, such as RSV and influenza, which can cause hospital overcrowding and disruption, and may pose a risk to more vulnerable children due to limited availability of isolation facilities. Another challenge, specific to evaluating childhood vaccination, is that QoL cannot be accurately measured in children due to a lack of validated instruments. Childhood diseases also incur a care giver burden, due to the need for parents to take time off work, and this is important to consider. Finally, for diseases such as RVGE, cost-effectiveness analyses in which longer time horizons are considered may not reflect the short-term benefits of vaccination. Further quantification of the economic impact of childhood diseases is thus required to fully highlight the true benefits of childhood vaccination that may be realized. Herein we explore the limitations of existing economic evaluations for childhood vaccination, and how economic analyses could be better adapted in future.

  11. Impact of five years of rotavirus vaccination in Finland - And the associated cost savings in secondary healthcare.

    PubMed

    Leino, Tuija; Baum, Ulrike; Scott, Peter; Ollgren, Jukka; Salo, Heini

    2017-10-09

    This study aimed to estimate the impact of the national rotavirus (RV) vaccination programme, starting 2009, on the total hospital-treated acute gastroenteritis (AGE) and severe RV disease burden in Finland during the first five years of the programme. This study also evaluated the costs saved in secondary healthcare by the RV vaccination programme. The RV related outcome definitions were based on ICD10 diagnostic codes recorded in the Care Register for Health Care. Incidences of hospitalised and hospital outpatient cases of AGE (A00-A09, R11) and RVGE (A08.0) were compared prior (1999-2005) and after (2010-2014) the start of the programme among children less than five years of age. The reduction in disease burden in 2014, when all children under five years of age have been eligible for RV vaccination, was 92.9% (95%CI: 91.0%-94.5%) in hospitalised RVGE and 68.5% (66.6%-70.3%) in the total hospitalised AGE among children less than five years of age. For the corresponding hospital outpatient cases, there was a reduction of 91.4% (82.4%-96.6%) in the RVGE incidence, but an increase of 6.3% (2.7%-9.9%) in the AGE incidence. The RV vaccination programme prevented 2206 secondary healthcare AGE cases costing €4.5 million annually. As the RV immunisation costs were €2.3 million, the total net savings just in secondary healthcare costs were €2.2 million, i.e. €33 per vaccinated child. The RV vaccination programme clearly controlled the severe, hospital-treated forms of RVGE. The total disease burden is a more valuable end point than mere specifically diagnosed cases as laboratory confirmation practises usually change after vaccine introduction. The RV vaccination programme annually pays for itself at least two times over. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

  12. Rotavirus Infection: A Disease of the Past?

    PubMed

    Dennehy, Penelope H

    2015-12-01

    Rotavirus infection is the most common cause of severe diarrhea disease in infants and young children worldwide. Vaccination is the only control measure likely to have a significant impact on the incidence of severe disease. Rotavirus vaccines have reduced the burden of disease in the United States and Europe and vaccine programs are being introduced in Asia and Africa where it is hoped that vaccine will have significant impact on severe infection. Long-term monitoring and strain surveillance are needed to assess the effects of rotavirus immunization programs and to determine whether changes in strain ecology will affect rotavirus vaccine effectiveness.