[The preliminary analysis of the recognition epitopes of anti-HEV monoclonal antibodies on HEV ORF2].

PubMed

Xiong, Jun-Hui; Guo, Qing-Shun; Ge, Sheng-Xiang; Gu, Ying; Chen, Yi-Xin; Miao, Ji; Du, Hai-Lian; Shi, Wei-Guo; Zhang, Jun; Xia, Ning-Shao

2008-06-01

Western blot, capture-PCR, blocking ELISA and synthetic polypeptides were used to systematically study the recognition epitopes on HEV ORF2 of 23 anti-HEV monoclonal antibodies(McAbs) which were previously generated in our laboratory directed against HEV ORF2. Results showed that seven McAbs recognized linear epitopes that located at aa408-458 of HEV ORF2 and 16 conformation-dependent McAbs, most of which recognized the surface epitopes of native HEV, located at aa459-606 of HEV ORF2. The systematical study of the recognition epitopes of anti-HEV McAbs on HEV ORF2 provides important information for the investigation of virus receptor and HEV infection mechanism, as well as its vaccine and diagnostics development.

The serological markers of acute infection with hepatitis A, B, C, D, E and G viruses revisited.

PubMed

Pondé, Robério Amorim de Almeida

2017-12-01

Viral hepatitis is a liver infection caused by one of the six hepatitis viruses: hepatitis A, B, C, D, E, and G virus (HAV to HEV and HGV). These agents differ in their biological, immunological, pathological and epidemiological characteristics. They cause infections that, when symptomatic, lead to clinical manifestations and laboratory findings that are not specific to a particular virus, often making differential diagnosis difficult, especially when no knowledge is available regarding the patient's medical history or the epidemiological background. A number of acute-phase serological markers, such as anti-HAV, anti-HBc, anti-HDV and anti-HEV IgM antibodies, are able to provide a clear indication of an infection caused by HAV, HBV, HDV or HEV. Anti-HCV antibodies and HGV/RNA are used for the diagnosis of HCV and HGV infections. The importance of each of these markers will be reviewed, and different factors that can interfere with the diagnosis of acute infections caused by these viruses will be described.

Seroprevalence for hepatitis E virus (HEV) infection among volunteer blood donors of the Regional Blood Bank of Londrina, State of Paraná , Brazil.

PubMed

Bortoliero, André Luiz; Bonametti, Ana Maria; Morimoto, Helena Kaminami; Matsuo, Tiemi; Reiche, Edna Maria Vissoci

2006-01-01

A cross-sectional study was carried out among 996 volunteer blood donors enrolled from May 1999 to December 1999 to determine the seroprevalence of hepatitis E virus (HEV) infection among volunteer blood donors of the Regional Blood Bank of Londrina, State of Paraná, Brazil, and to evaluate whether the rate of seroprevalence of IgG anti-HEV antibodies is associated with sociodemographic variables and with seropositivity for hepatitis A virus (HAV) infection. All participants answered the questionnaire regarding the sociodemographic characteristics. Serum samples were tested for IgG antibodies to HEV (anti-HEV) by an enzyme linked immunoassay (ELISA). All serum samples positive for anti-HEV IgG and 237 serum samples negative for anti-HEV were also assayed for IgG anti-HAV antibodies by ELISA. Anti-HEV IgG was confirmed in 23/996 samples, resulting in a seroprevalence of 2.3% for HEV infection, similar to previous results obtained in developed countries. No significant association was found between the presence of anti-HEV IgG antibodies and the sociodemographic variables including gender, age, educational level, rural or urban areas, source of water, and sewer system (p > 0.05). Also, no association with seropositivity for anti-HAV IgG antibodies was observed (p > 0.05). Although this study revealed a low seroprevalence of HEV infection in the population evaluated, the results showed that this virus is circulating among the population from Londrina, South Brazil, and point out the need of further studies to define the clinical and epidemiological importance of HEV infection and to identify additional risk factors involved in the epidemiology and pathogenesis of this infection in this population.

Detection of HEV-specific antibodies in four non-human primate species, including great apes, from different zoos in Germany.

PubMed

Spahr, C; Knauf-Witzens, T; Dähnert, L; Enders, M; Müller, M; Johne, R; Ulrich, R G

2018-01-01

The hepatitis E virus (HEV) has been described in humans and various animal species in different regions of the world. However, the knowledge on natural HEV infection in non-human primates and the corresponding risk of zoonotic transmission is scarce. To determine whether primates in captivity are affected by HEV infection, we investigated 259 individual sera of clinically healthy non-human primates of 14 species from nine German zoos. Using a commercial double-antigen-sandwich ELISA and a commercial IgG ELISA, 10 animals (3·9%) reacted positive in at least one assay. Three ape species and one Old World monkey species were among the seropositive animals: bonobo (Pan paniscus), gorilla (Gorilla gorilla gorilla), lar gibbon (Hylobates lar) and drill (Mandrillus leucophaeus). Testing for anti-HEV-IgM antibodies by commercial ELISA and for viral RNA by reverse-transcription real-time polymerase chain reaction resulted in negative results for all animals indicating the absence of acute HEV infections. In the past, no clinical signs of hepatitis were recorded for the seropositive animals. The results suggest that non-human primates in zoos can get naturally and subclinically infected with HEV or related hepeviruses. Future studies should evaluate potential sources and transmission routes of these infections and their impact on human health.

Estimation of hepatitis E virus (HEV) pig seroprevalence using ELISA and Western blot and comparison between human and pig HEV sequences in Belgium.

PubMed

Thiry, Damien; Mauroy, Axel; Saegerman, Claude; Thomas, Isabelle; Wautier, Magali; Miry, Cora; Czaplicki, Guy; Berkvens, Dirk; Praet, Nicolas; van der Poel, Wim; Cariolet, Roland; Brochier, Bernard; Thiry, Etienne

2014-08-27

Zoonotic transmission of hepatitis E virus (HEV) is of special concern, particularly in high income countries were waterborne infections are less frequent than in developing countries. High HEV seroprevalences can be found in European pig populations. The aims of this study were to obtain prevalence data on HEV infection in swine in Belgium and to phylogenetically compare Belgian human HEV sequences with those obtained from swine. An ELISA screening prevalence of 73% (95% CI 68.8-77.5) was determined in Belgian pigs and a part of the results were re-evaluated by Western blot (WB). A receiver operating characteristic curve analysis was performed and scenarios varying the ELISA specificity relative to WB were analysed. The seroprevalences estimated by the different scenarios ranged between 69 and 81% and are in agreement with the high exposure of the European pig population to HEV. Pig HEV sequences were genetically compared to those detected in humans in Belgium and a predominance of genotype 3 subtype f was shown in both swine and humans. The high HEV seroprevalence in swine and the close phylogenetic relationships between pig and human HEV sequences further support the risk for zoonotic transmission of HEV between humans and pigs. Copyright © 2014 Elsevier B.V. All rights reserved.

Host Immune Status and Response to Hepatitis E Virus Infection

PubMed Central

Krain, Lisa J.; Nelson, Kenrad E.

2014-01-01

SUMMARY Hepatitis E virus (HEV), identified over 30 years ago, remains a serious threat to life, health, and productivity in developing countries where access to clean water is limited. Recognition that HEV also circulates as a zoonotic and food-borne pathogen in developed countries is more recent. Even without treatment, most cases of HEV-related acute viral hepatitis (with or without jaundice) resolve within 1 to 2 months. However, HEV sometimes leads to acute liver failure, chronic infection, or extrahepatic symptoms. The mechanisms of pathogenesis appear to be substantially immune mediated. This review covers the epidemiology of HEV infection worldwide, the humoral and cellular immune responses to HEV, and the persistence and protection of antibodies produced in response to both natural infection and vaccines. We focus on the contributions of altered immune states (associated with pregnancy, human immunodeficiency virus [HIV], and immunosuppressive agents used in cancer and transplant medicine) to the elevated risks of chronic infection (in immunosuppressed/immunocompromised patients) and acute liver failure and mortality (among pregnant women). We conclude by discussing outstanding questions about the immune response to HEV and interactions with hormones and comorbid conditions. These questions take on heightened importance now that a vaccine is available. PMID:24396140

Pig model mimicking chronic hepatitis E virus infection in immunocompromised patients to assess immune correlates during chronicity

PubMed Central

Cao, Dianjun; Cao, Qian M.; Subramaniam, Sakthivel; Yugo, Danielle M.; Heffron, C. Lynn; Rogers, Adam J.; Kenney, Scott P.; Tian, Debin; Matzinger, Shannon R.; Overend, Christopher; Catanzaro, Nicholas; LeRoith, Tanya; Wang, Heng; Piñeyro, Pablo; Lindstrom, Nicole; Clark-Deener, Sherrie; Yuan, Lijuan; Meng, Xiang-Jin

2017-01-01

Chronic hepatitis E virus (HEV) infection is a significant clinical problem in immunocompromised individuals such as organ transplant recipients, although the mechanism remains unknown because of the lack of an animal model. We successfully developed a pig model of chronic HEV infection and examined immune correlates leading to chronicity. The conditions of immunocompromised patients were mimicked by treating pigs with an immunosuppressive regimen including cyclosporine, azathioprine, and prednisolone. Immunocompromised pigs infected with HEV progressed to chronicity, because 8/10 drug-treated HEV-infected pigs continued fecal virus shedding beyond the acute phase of infection, whereas the majority (7/10) of mock-treated HEV-infected pigs cleared fecal viral shedding at 8 wk postinfection. During chronic infection, serum levels of the liver enzyme γ-glutamyl transferase and fecal virus shedding were significantly higher in immunocompromised HEV-infected pigs. To identify potential immune correlates of chronic infection, we determined serum levels of cytokines and cell-mediated immune responses in pigs. Results showed that HEV infection of immunocompromised pigs reduced the serum levels of Th1 cytokines IL-2 and IL-12, and Th2 cytokines IL-4 and IL-10, particularly during the acute phase of infection. Furthermore IFN-γ–specific CD4+ T-cell responses were reduced in immunocompromised pigs during the acute phase of infection, but TNF-α–specific CD8+ T-cell responses increased during the chronic phase of infection. Thus, active suppression of cell-mediated immune responses under immunocompromised conditions may facilitate the establishment of chronic HEV infection. This pig model will aid in delineating the mechanisms of chronic HEV infection and in developing effective therapeutics against chronic hepatitis E. PMID:28630341

Pig model mimicking chronic hepatitis E virus infection in immunocompromised patients to assess immune correlates during chronicity.

PubMed

Cao, Dianjun; Cao, Qian M; Subramaniam, Sakthivel; Yugo, Danielle M; Heffron, C Lynn; Rogers, Adam J; Kenney, Scott P; Tian, Debin; Matzinger, Shannon R; Overend, Christopher; Catanzaro, Nicholas; LeRoith, Tanya; Wang, Heng; Piñeyro, Pablo; Lindstrom, Nicole; Clark-Deener, Sherrie; Yuan, Lijuan; Meng, Xiang-Jin

2017-07-03

Chronic hepatitis E virus (HEV) infection is a significant clinical problem in immunocompromised individuals such as organ transplant recipients, although the mechanism remains unknown because of the lack of an animal model. We successfully developed a pig model of chronic HEV infection and examined immune correlates leading to chronicity. The conditions of immunocompromised patients were mimicked by treating pigs with an immunosuppressive regimen including cyclosporine, azathioprine, and prednisolone. Immunocompromised pigs infected with HEV progressed to chronicity, because 8/10 drug-treated HEV-infected pigs continued fecal virus shedding beyond the acute phase of infection, whereas the majority (7/10) of mock-treated HEV-infected pigs cleared fecal viral shedding at 8 wk postinfection. During chronic infection, serum levels of the liver enzyme γ-glutamyl transferase and fecal virus shedding were significantly higher in immunocompromised HEV-infected pigs. To identify potential immune correlates of chronic infection, we determined serum levels of cytokines and cell-mediated immune responses in pigs. Results showed that HEV infection of immunocompromised pigs reduced the serum levels of Th1 cytokines IL-2 and IL-12, and Th2 cytokines IL-4 and IL-10, particularly during the acute phase of infection. Furthermore IFN-γ-specific CD4 + T-cell responses were reduced in immunocompromised pigs during the acute phase of infection, but TNF-α-specific CD8 + T-cell responses increased during the chronic phase of infection. Thus, active suppression of cell-mediated immune responses under immunocompromised conditions may facilitate the establishment of chronic HEV infection. This pig model will aid in delineating the mechanisms of chronic HEV infection and in developing effective therapeutics against chronic hepatitis E.

Autochthonous sporadic acute hepatitis E caused by two distinct subgenotype 3b hepatitis E virus strains with only 90% nucleotide identity.

PubMed

Yamaguchi, Yasuko; Takagi, Hitoshi; Suzuki, Yuhei; Maruhashi, Kyoko; Kosone, Takashi; Kakizaki, Satoru; Sato, Ken; Yamada, Masanobu; Nagashima, Shigeo; Takahashi, Masaharu; Okamoto, Hiroaki

2017-04-01

Hepatitis E, which is caused by hepatitis E virus (HEV), is a public health concern in Japan, where the zoonotic food-borne transmission of HEV from domestic pigs and wild boars plays an important role. A 44-year-old Japanese man with autochthonous sporadic acute hepatitis E was admitted with general fatigue and moderate liver dysfunction. In the present study, two distinct HEV strains were recovered from the patient, who had consumed the raw or undercooked pig liver and intestine two or three times per week for 3 months before the disease onset. The recovered HEV strains were segregated into two clusters within subgenotype 3b, the open reading frame (ORF)1 and ORF2 sequences of which each showed ~10% difference, indicating HEV mixed infection. Because most notified patients with clinical HEV infection in Japan are diagnosed based on the detection of IgA-class HEV antibodies and because serum samples from only a limited number of HEV-infected patients are subjected to HEV RNA detection and nucleotide sequencing, it is very likely that patients with HEV mixed infection remain largely overlooked. The identification of sources of autochthonous HEV infection remains an important goal. Continued efforts to trace the sources of acute or chronic autochthonous HEV infection are warranted.

Serological evidence for a hepatitis E virus (HEV)-related agent in goats in the United States

PubMed Central

Sanford, B.J.; Emerson, S.U.; Purcell, R.H.; Engle, R.E.; Dryman, B.A.; Cecere, T.E.; Buechner-Maxwell, V.; Sponenberg, D.P.; Meng, X.J.

2012-01-01

Summary Hepatitis E virus (HEV) causes an important public health disease in many developing countries and is also endemic in some industrialized countries. In addition to humans, strains of HEV have been genetically identified from pig, chicken, rat, mongoose, deer, rabbit and fish. While the genotypes 1 and 2 HEV are restricted to humans, the genotypes 3 and 4 HEV are zoonotic and infect humans and other animal species. As a part of our ongoing efforts to search for potential animal reservoirs for HEV, we tested goats from Virginia for evidence of HEV infection and showed that 16% (13/80) of goat sera from Virginia herds were positive for IgG anti-HEV. Importantly, we demonstrated that neutralizing antibodies to HEV were present in selected IgG anti-HEV positive goat sera. Subsequently, in an attempt to genetically identify the HEV-related agent from goats, we conducted a prospective study in a closed goat herd with known anti-HEV seropositivity and monitored a total of 11 kids from the time of birth until 14 weeks of age for evidence of HEV infection. Seroconversion to IgG anti-HEV was detected in 7 of the 11 kids, although repeated attempts to detect HEV RNA by a broad-spectrum nested RT-PCR from the fecal and serum samples of the goats that had seroconverted were unsuccessful. In addition, we also attempted to experimentally infect laboratory goats with three well-characterized mammalian strains of HEV but with no success. The results indicate that a HEV-related agent is circulating and maintained in the goat population in Virginia and that the goat HEV is likely genetically very divergent from the known HEV strains. PMID:22909079

Hepatitis E virus co-infection in HIV-infected patients in Foggia and Naples in southern Italy.

PubMed

Scotto, Gaetano; Grisorio, Benvenuto; Filippini, Pietro; Ferrara, Sergio; Massa, Salvatore; Bulla, Fabio; Martini, Salvatore; Filippini, Alberico; Tartaglia, Alessandra; Lo Muzio, Lorenzo; Fazio, Vincenzina

2015-01-01

Hepatitis E virus (HEV) infection represents an emerging infection in developed countries and is thought to be a zoonotic infection. It has recently been described as a new causative agent of acute and chronic hepatitis in immunosuppressed subjects, including HIV-infected patients. The aim of this study was to assess the sero-virological prevalence of HEV in HIV patients and in the general population as control group. A prospective and observational cohort study was carried out in two hospitals in southern Italy. The seroprevalence of HEV was determined in a cohort of 959 subjects, 509 (53%) of whom were HIV-positive patients and 450 were from the general population. Serum samples were tested for anti-HEV antibodies; repeatedly positive results were confirmed by a Western blot assay. In positive patients HEV RNA and genotypes were also determined. A total of 46 (4.8%) of the 959 serum samples examined were reactive to anti-HEV Ig and confirmed by Western blotting. The prevalence of HEV antibodies (IgG and/or IgM) was 2.7% in the control group and 6.7% in HIV-infected patients. Anti-HEV IgM was found in 6/46 (13.0%) of the anti-HEV Ig-positive serum samples, in 5/34 HIV patients and in 1/12 of the general population. No HIV-infected patient presented chronic hepatitis with HEV infection alone. This study indicates a higher circulation of HEV in HIV-infected patients, whereas a low prevalence of HEV antibodies in the general Italian population was shown. Chronic hepatitis with HEV alone was absent, while it was present in subjects with HIV-HEV, co-infected with hepatitis B virus (HBV) and/or hepatitis C virus (HCV).

Population Movement and Virus Spreading: HEV Spreading in a Pilgrimage City, Mashhad in Northeast Iran; an Example

PubMed Central

Ahmadi Ghezeldasht, Sanaz; Miri, Rahele; Hedayatimoghadam, Mohamadreza; Shamsian, Aliakbar; Bidkhori, Hamidreza; Fathimoghadam, Fahad; Rezaee, Seyyed Abdorrahim

2013-01-01

Background Hepatitis E Virus (HEV) infection is a significant public health concern and responsible for large outbreaks of acute hepatitis in poor sanitary and living conditions. Objectives To investigate the impact of population movements on virus spreading, a large-scale population-based survey was performed in a pilgrimage- tourism area, the great Mashhad, capital city of Khorasan province. Patients and Methods A cross-sectional study was carried out among 1582 randomly selected individuals from general population of Mashhad, north east of Iran, between May to September 2009. Serum samples were tested for total anti-HEV antibody using a specific enzyme linked immunoassay (ELISA) kit. Results The prevalence of HEV infection was 14.2% (225/1582) with a maximum of 25.5 % (14/55) in densely populated areas. The highest prevalence was observed in visitant areas (≥ 20%) near the holly shrine with crowded hotels and inns. The differences between these areas and other districts were statistically significant (P < 0.001). The findings indicated that 13.2% (95/718) of males and 15.0% (130/864) of females were HEV positive; this difference is not significant. Seroprevalence increases with age rising , from 12.8% in subjects less than five years to 28.6% in individuals with more than 65 years old. Although, there were no meaningful differences between HEV seropositivity and socio-economic status, Illiterate individuals were significantly at higher risk for infection than educated persons (P < 0.001). Conclusions These findings demonstrated that, high prevalence of HEV is related to populated district, which can reach to the highest rate in hotels and inns close to visitants. Traditional sanitation and water supplying systems are the second important factor for the virus transmission. Therefore, it can be concluded that such areas need efficient surveillance systems to prevent the spreading of infectious diseases. PMID:24171006

Population Movement and Virus Spreading: HEV Spreading in a Pilgrimage City, Mashhad in Northeast Iran; an Example.

PubMed

Ahmadi Ghezeldasht, Sanaz; Miri, Rahele; Hedayatimoghadam, Mohamadreza; Shamsian, Aliakbar; Bidkhori, Hamidreza; Fathimoghadam, Fahad; Rezaee, Seyyed Abdorrahim

2013-01-01

Hepatitis E Virus (HEV) infection is a significant public health concern and responsible for large outbreaks of acute hepatitis in poor sanitary and living conditions. To investigate the impact of population movements on virus spreading, a large-scale population-based survey was performed in a pilgrimage- tourism area, the great Mashhad, capital city of Khorasan province. A cross-sectional study was carried out among 1582 randomly selected individuals from general population of Mashhad, north east of Iran, between May to September 2009. Serum samples were tested for total anti-HEV antibody using a specific enzyme linked immunoassay (ELISA) kit. The prevalence of HEV infection was 14.2% (225/1582) with a maximum of 25.5 % (14/55) in densely populated areas. The highest prevalence was observed in visitant areas (≥ 20%) near the holly shrine with crowded hotels and inns. The differences between these areas and other districts were statistically significant (P < 0.001). The findings indicated that 13.2% (95/718) of males and 15.0% (130/864) of females were HEV positive; this difference is not significant. Seroprevalence increases with age rising , from 12.8% in subjects less than five years to 28.6% in individuals with more than 65 years old. Although, there were no meaningful differences between HEV seropositivity and socio-economic status, Illiterate individuals were significantly at higher risk for infection than educated persons (P < 0.001). These findings demonstrated that, high prevalence of HEV is related to populated district, which can reach to the highest rate in hotels and inns close to visitants. Traditional sanitation and water supplying systems are the second important factor for the virus transmission. Therefore, it can be concluded that such areas need efficient surveillance systems to prevent the spreading of infectious diseases.

Acute Hepatitis E Virus infection with coincident reactivation of Epstein-Barr virus infection in an immunosuppressed patient with rheumatoid arthritis: a case report.

PubMed

Schultze, Detlev; Mani, Bernhard; Dollenmaier, Günter; Sahli, Roland; Zbinden, Andrea; Krayenbühl, Pierre Alexandre

2015-10-29

Hepatitis E virus (HEV) is the most recently discovered of the hepatotropic viruses, and is considered an emerging pathogen in developed countries with the possibility of fulminant hepatitis in immunocompromised patients. Especially in the latter elevated transaminases should be taken as a clue to consider HEV infection, as it can be treated by discontinuation of immunosuppression and/or ribavirin therapy. To our best knowledge, this is a unique case of autochthonous HEV infection with coincident reactivation of Epstein-Barr virus (EBV) infection in an immunosuppressed patient with rheumatoid arthritis (RA). A 68-year-old Swiss woman with RA developed hepatitis initially diagnosed as methotrexate-induced liver injury, but later diagnosed as autochthonous HEV infection accompanied by reactivation of her latent EBV infection. She showed confounding serological results pointing to three hepatotropic viruses (HEV, Hepatitis B virus (HBV) and EBV) that could be resolved by detection of HEV and EBV viraemia. The patient recovered by temporary discontinuation of immunosuppressive therapy. In immunosuppressed patients with RA and signs of liver injury, HEV infection should be considered, as infection can be treated by discontinuation of immunosuppression. Although anti-HEV-IgM antibody assays can be used as first line virological tools, nucleic acid amplification tests (NAAT) for detection of HEV RNA are recommended--as in our case--if confounding serological results from other hepatotropic viruses are obtained. After discontinuation of immunosuppressive therapy, our patient recovered from both HEV infection and reactivation of latent EBV infection without sequelae.

Epidemiology of hepatitis E virus infection during pregnancy in Benin.

PubMed

De Paschale, Massimo; Ceriani, Cristina; Romanò, Luisa; Cerulli, Teresa; Cagnin, Debora; Cavallari, Serena; Ndayake, Joseph; Zaongo, Dieudonné; Diombo, Kouma; Priuli, Gianbattista; Viganò, Paolo; Clerici, Pierangelo

2016-01-01

Hepatitis E virus (HEV) is the cause of enterically transmitted non-A, non-C hepatitis (an infection that is particularly severe during pregnancy) in tropical and subtropical countries. As there are no published data concerning the prevalence of HEV antibodies in Benin, their presence was investigated in pregnant women undergoing routine HIV screening in a rural area in northern Benin and in pregnant women with acute non-A, non-C hepatitis. A total of 278 serum samples were collected from asymptomatic pregnant women in 2011 were tested for HEV and hepatitis A virus (HAV) antibodies, and the HEV IgM-positive samples were further tested for HEV-RNA. A further seven samples of pregnant women with acute non-A, non-C hepatitis collected during episodes of acute hepatitis in 2005 were also analysed. Of the 278 samples collected in 2011, 16.19% were positive for HEV IgG and 1.44% for HEV IgM (none positive for HEV-RNA), and 99.64% were positive for total HAV antibodies (none positive for HAV IgM). Six of the seven samples collected in 2005 were positive for HEV IgG and IgM, and two were also positive for HEV-RNA. The circulation of HEV infection is significant among pregnant women in Benin, in whom the consequences may be fatal. © 2015 John Wiley & Sons Ltd.

Acute hepatitis E in a renal transplantation recipient: a case report.

PubMed

Shindo, Mitsutoshi; Takemae, Hiroaki; Kubo, Takafumi; Soeno, Masatsugu; Ando, Tetsuo; Morishita, Yoshiyuki

2018-01-01

Hepatitis E is caused by infection with the hepatitis E virus (HEV). HEV is transmitted orally via HEV-contaminated food or drink. Hepatitis E usually shows mild symptoms and is self-limiting in the general population; however, it may progress to chronic hepatitis in immunosuppressed patients such as recipients of organ transplantation. However, a few cases of acute hepatitis E have been reported in organ transplantation recipients. We herein report a case of acute hepatitis E in a 31-year-old male renal transplant recipient. The patient underwent renal transplantation 2 years ago, and his postoperative course was uneventful without rejection. After complaining of general fatigue and low-grade fever for 1 week, he was referred to and admitted to our hospital. Careful interview revealed that he ate undercooked pork 10 weeks prior. Blood analysis revealed liver dysfunction but was serologically negative for hepatitis A, B and C virus, cytomegalovirus infection and collagen diseases. Immunoglobulin A antibody against hepatitis E virus (HEV-IgA) was also negative at that point. After 2 weeks of admission, HEV-IgA and HEV-RNA were measured again as hepatitis E could not be ruled out due to history of ingestion of undercooked meat that may have been contaminated with HEV. At that time, HEV-IgA and HEV-RNA (genotype 3) were positive. Thus, an acute hepatitis E was diagnosed. His liver function gradually improved to within the normal range, and HEV-IgA and HEV-RNA were negative at 11 weeks after admission. In conclusion, we describe here a case of acute hepatitis E in a renal transplant recipient. Careful interview regarding the possibility of ingestion of HEV-contaminated food and repeated measurements of HEV-IgA were helpful in finalizing a diagnosis.

High prevalence of hepatitis E virus infection in goats.

PubMed

Long, Feiyan; Yu, Wenhai; Yang, Chenchen; Wang, Jue; Li, Yunlong; Li, Yi; Huang, Fen

2017-11-01

Hepatitis E virus (HEV) is a major cause of acute hepatitis worldwide, primarily transmitted by fecal-oral route. Zoonotic transmission of HEV from HEV-infected pigs (pork) or cows (milk) to human or non-human primate has been confirmed, but the risk of HEV in goat is still rarely assessed. In the present study, stool, blood, tissues, and milk of goat were collected for HEV infection investigation from Dali City of Yunnan Province in China, where raw mutton and goat milk are traditionally consumed. Surprisingly, a high prevalence of HEV infection in goat was found. Phylogenetic analysis revealed that all HEV isolates from goat belong to genotype 4 and subtype 4h, and shared a high similarity homology (>99.6%) with HEV isolated from human, swine, and cows in the same area. Results suggested that goats are a previously unrecognized HEV host. © 2017 Wiley Periodicals, Inc.

Clinical features and risk factors of acute hepatitis E with severe jaundice

PubMed Central

Xu, Bin; Yu, Hai-Bin; Hui, Wei; He, Jia-Li; Wei, Lin-Lin; Wang, Zheng; Guo, Xin-Hui

2012-01-01

AIM: To compares the clinical features of patients infected with hepatitis E virus (HEV) with or without severe jaundice. In addition, the risk factors for HEV infection with severe jaundice were investigated. METHODS: We enrolled 235 patients with HEV into a cross-sectional study using multi-stage sampling to select the study group. Patients with possible acute hepatitis E showing elevated liver enzyme levels were screened for HEV infection using serologic and molecular tools.HEV infection was documented by HEV antibodies and by the detection of HEV-RNA in serum. We used χ2 analysis, Fisher’s exact test, and Student’s t test where appropriate in this study. Significant predictors in the univariate analysis were then included in a forward, stepwise multiple logistic regression model. RESULTS: No significant differences in symptoms, alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, or hepatitis B virus surface antigen between the two groups were observed. HEV infected patients with severe jaundice had significantly lower peak serum levels of γ-glutamyl-transpeptidase (GGT) (median: 170.31 U/L vs 237.96 U/L, P = 0.007), significantly lower ALB levels (33.84 g/L vs 36.89 g/L, P = 0.000), significantly lower acetylcholine esterase (CHE) levels (4500.93 U/L vs 5815.28 U/L, P = 0.000) and significantly higher total bile acid (TBA) levels (275.56 μmol/L vs 147.03 μmol/L, P = 0.000) than those without severe jaundice. The median of the lowest point time tended to be lower in patients with severe jaundice (81.64% vs 96.12%, P = 0.000). HEV infected patients with severe jaundice had a significantly higher viral load (median: 134 vs 112, P = 0.025) than those without severe jaundice. HEV infected patients with severe jaundice showed a trend toward longer median hospital stay (38.17 d vs 18.36 d, P = 0.073). Multivariate logistic regression indicated that there were significant differences in age, sex, viral load, GGT, albumin, TBA, CHE

Clinical features and risk factors of acute hepatitis E with severe jaundice.

PubMed

Xu, Bin; Yu, Hai-Bin; Hui, Wei; He, Jia-Li; Wei, Lin-Lin; Wang, Zheng; Guo, Xin-Hui

2012-12-28

To compares the clinical features of patients infected with hepatitis E virus (HEV) with or without severe jaundice. In addition, the risk factors for HEV infection with severe jaundice were investigated. We enrolled 235 patients with HEV into a cross-sectional study using multi-stage sampling to select the study group. Patients with possible acute hepatitis E showing elevated liver enzyme levels were screened for HEV infection using serologic and molecular tools.HEV infection was documented by HEV antibodies and by the detection of HEV-RNA in serum. We used χ(2) analysis, Fisher's exact test, and Student's t test where appropriate in this study. Significant predictors in the univariate analysis were then included in a forward, stepwise multiple logistic regression model. No significant differences in symptoms, alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, or hepatitis B virus surface antigen between the two groups were observed. HEV infected patients with severe jaundice had significantly lower peak serum levels of γ-glutamyl-transpeptidase (GGT) (median: 170.31 U/L vs 237.96 U/L, P = 0.007), significantly lower ALB levels (33.84 g/L vs 36.89 g/L, P = 0.000), significantly lower acetylcholine esterase (CHE) levels (4500.93 U/L vs 5815.28 U/L, P = 0.000) and significantly higher total bile acid (TBA) levels (275.56 μmol/L vs 147.03 μmol/L, P = 0.000) than those without severe jaundice. The median of the lowest point time tended to be lower in patients with severe jaundice (81.64% vs 96.12%, P = 0.000). HEV infected patients with severe jaundice had a significantly higher viral load (median: 134 vs 112, P = 0.025) than those without severe jaundice. HEV infected patients with severe jaundice showed a trend toward longer median hospital stay (38.17 d vs 18.36 d, P = 0.073). Multivariate logistic regression indicated that there were significant differences in age, sex, viral load, GGT, albumin, TBA, CHE, prothrombin index, alcohol

Hepatitis E virus infection: Epidemiology and treatment implications

PubMed Central

Lee, Ga Young; Poovorawan, Kittiyod; Intharasongkroh, Duangnapa; Sa-nguanmoo, Pattaratida; Vongpunsawad, Sompong; Chirathaworn, Chintana; Poovorawan, Yong

2015-01-01

Hepatitis E virus (HEV) infection is now established as an emerging enteric viral hepatitis. Standard treatments in acute and chronic hepatitis E remain to be established. This study undertakes a review of the epidemiology, treatment implication and vaccine prevention from published literature. HEV infection is a worldwide public health problem and can cause acute and chronic hepatitis E. HEV genotypes 1 and 2 are primarily found in developing countries due to waterborne transmission, while the zoonotic potential of genotypes 3 and 4 affects mostly industrialized countries. An awareness of HEV transmission through blood donation, especially in the immunocompromised and solid organ transplant patients, merits an effective anti-viral therapy. There are currently no clear indications for the treatment of acute hepatitis E. Despite concerns for side effects, ribavirin monotherapy or in combination with pegylated interferon alpha for at least 3 mo appeared to show significant efficacy in the treatment of chronic hepatitis E. However, there are no available treatment options for specific patient population groups, such as women who are pregnant. Vaccination and screening of HEV in blood donors are currently a global priority in managing infection. New strategies for the treatment and control of hepatitis E are required for both acute and chronic infections, such as prophylactic use of medications, controlling large outbreaks, and finding acceptable antiviral therapy for pregnant women and other patient groups for whom the current options of treatment are not viable. PMID:26568916

Distinct changing profiles of hepatitis A and E virus infection among patients with acute hepatitis, patients on maintenance hemodialysis and healthy individuals in Japan.

PubMed

Mitsui, Takehiro; Tsukamoto, Yukie; Hirose, Akinori; Suzuki, Shigeru; Yamazaki, Chikao; Masuko, Kazuo; Tsuda, Fumio; Endo, Kazunori; Takahashi, Masaharu; Okamoto, Hiroaki

2006-08-01

To compare the epidemiologic profiles of hepatitis A virus (HAV) and hepatitis E virus (HEV) infections in Japan, the prevalence of clinical or subclinical HAV and HEV infections was investigated serologically and molecularly among 128 consecutive patients (age, mean +/- standard deviation, 37.5 +/- 14.7 years) who contracted acute hepatitis between 1989 and 2005 in a city hospital, and among 416 hemodialysis patients (60.1 +/- 12.6 years) and 266 medical staff members (34.6 +/- 11.4 years) at the same hospital, using stored periodic serum samples collected since the start of hemodialysis or employment, respectively. Between 1989 and 1995, among 93 patients with acute hepatitis, 51 (54.8%) were diagnosed with hepatitis A and only one patient with hepatitis E. Between 1996 and 2005, however, among 35 patients, only 3 (8.6%) were diagnosed with hepatitis A and 2 (5.7%) with hepatitis E. Although subclinical HEV infection was recognized in four hemodialysis patients (one each in 1979, 1980, 1988, and 2003) and two medical staff members (1978 and 2003) in previous studies, none of the 191 hemodialysis patients who had been negative for anti-HAV at the start of hemodialysis contracted HAV infection during the observation period of 7.6 +/- 6.4 years. Only one (0.4%) of the 246 medical staff members who had been negative for anti-HAV at the start of employment acquired hepatitis A during the observation period of 7.9 +/- 8.0 years: none had subclinical HAV infection. Clinical or subclinical HEV infection has occurred rarely during the last three decades, while HAV infection has markedly decreased at least since 1996. 2006 Wiley-Liss, Inc.

Chronically infected wild boar can transmit genotype 3 hepatitis E virus to domestic pigs.

PubMed

Schlosser, Josephine; Vina-Rodriguez, Ariel; Fast, Christine; Groschup, Martin H; Eiden, Martin

2015-10-22

Hepatitis E virus (HEV) causes acute hepatitis E in humans in developing countries, but sporadic and autochthonous cases do also occur in industrialized nations. In Europe, food-borne zoonotic transmission of genotype 3 (gt3) has been associated with the consumption of raw and undercooked products from domestic pig and wild boar. As shown recently, naturally acquired HEV gt3 replicates efficiently in experimentally infected wild boar and is transmissible from a wild boar to domestic pigs. Generally, following an acute infection swine suffer from a transient febrile illness and viremia in connection with fecal virus shedding. However, little is known about sub-acute or chronic HEV infections in swine, and how and where HEV survives the immune response. In this paper, we describe the incidental finding of a chronic HEVgt3 infection in two naturally infected European wild boar which were raised and housed at FLI over years. The wild boar displayed fecal HEV RNA excretion and viremia over nearly the whole observation period of more than five months. The animal had mounted a substantial antibody response, yet without initial clearance of the virus by the immune system. Further analysis indicated a subclinical course of HEV with no evidence of chronic hepatitis. Additionally, we could demonstrate that this chronic wild boar infection was still transmissible to domestic pigs, which were housed together with this animal. Sentinel pigs developed fecal virus shedding accompanied by seroconversion. Wild boar should therefore be considered as an important reservoir for transmission of HEV gt3 in Europe. Copyright © 2015 Elsevier B.V. All rights reserved.

Guillain-Barre syndrome caused by hepatitis E infection: case report and literature review.

PubMed

Zheng, Xiaoqin; Yu, Liang; Xu, Qiaomai; Gu, Silan; Tang, Lingling

2018-01-23

Hepatitis E infection is a global disorder that causes substantial morbidity. Numerous neurologic illnesses, including Guillain-Barre syndrome (GBS), have occurred in patients with hepatitis E virus (HEV) infection. We report a 58 year-old non-immunocompromised man who presented with progressive muscle weakness in all extremities during an episode of acute HEV infection, which was confirmed by measuring the anti-HEV IgM antibodies in the serum. Both cerebrospinal fluid examination and electrophysiological study were in agreement with the diagnosis of HEV-associated GBS. Following the treatment with intravenous immunoglobulin, the patient's neurological condition improved rapidly. HEV infection should be strongly considered in patients with neurological symptoms, especially those with elevated levels of liver enzymes.

Molecular characterization of hepatitis E virus in patients with acute hepatitis in Venezuela.

PubMed

García, Cristina Gutiérrez; Sánchez, Doneyla; Villalba, Maria Caridad Montalvo; Pujol, Flor Helene; de Los Ángeles Rodríguez Lay, Licel; Pinto, Belquis; Chacón, Elsa Patricia; Guzmán, Maria Guadalupe

2012-07-01

Hepatitis E virus (HEV) causes a common infection in developing countries. HEV infection occurs as outbreaks, as sporadic clinical cases and as large epidemics in endemic areas. The objective of this study was to determine the presence of HEV infection in patients with clinical suspicion of hepatitis A virus (HAV) infection, referred to the Instituto Nacional de Higiene "Rafael Rangel" in Venezuela. Seventy-four sera were tested for anti-HAV and anti-HEV IgM antibodies. HEV-RNA was amplified from anti-HEV IgM positive sera using nested reverse transcription polymerase chain reaction for ORF1 (RNA dependent RNA polymerase region) and the amplicons sequenced for phylogenetic analysis. The frequency of anti-HEV IgM was 22/74 (30%) in the samples tested. Dual infection with HAV and HEV was found in 31% (12/39) of anti-HAV IgM positive patients. Viremia was detected in 3/22 (14%) of sera positive for anti-HEV IgM. Two HEV strains were classified as genotype 1 and one as genotype 3, which were closely related to Yam 67 (north of India) and US1 isolates from the USA, respectively. These findings suggest that HEV is an important cause of acute viral hepatitis in Venezuela as a single infection or co-infection with HAV, with high morbidity in children and young adults suggesting that this infection is endemic in Venezuela. Copyright © 2012 Wiley Periodicals, Inc.

Production of monoclonal antibodies against the ORF3 protein of rat hepatitis E virus (HEV) and demonstration of the incorporation of the ORF3 protein into enveloped rat HEV particles.

PubMed

Takahashi, Masaharu; Kobayashi, Tominari; Tanggis; Jirintai, Suljid; Mulyanto; Nagashima, Shigeo; Nishizawa, Tsutomu; Kunita, Satoshi; Okamoto, Hiroaki

2016-12-01

Eight murine monoclonal antibodies (MAbs) against a synthetic peptide corresponding to the C-terminal 15-amino-acid portion of the ORF3 protein of rat hepatitis E virus (ratHEV) were produced and characterized. Immunofluorescence assays using the anti-ratHEV ORF3 MAbs revealed the accumulation of ORF3 protein in the cytoplasm of PLC/PRF/5 cells transfected with ORF3-expressing plasmids or inoculated with cell-culture-generated ratHEV strains. Anti-ORF3 MAbs could capture ratHEV particles in culture supernatant and serum following treatment with 0.5 % deoxycholate, but not those without prior detergent treatment or fecal ratHEV particles. Following treatment with 0.5 % deoxycholate and 0.5 % trypsin, the buoyant density of ratHEV particles in culture supernatant with ORF3 protein on the surface shifted from 1.15 g/cm 3 to 1.26 g/cm 3 in a sucrose gradient; the resulting particles were capturable by an anti-ORF2 MAb but not by an anti-ORF3 MAb. This indicates that the ORF3 protein (at least its C-terminal portion) is incorporated into the enveloped ratHEV virions released from infected cells but that it is not found in the virions in the feces, supporting the hypothesis that the ratHEV ORF3 protein is associated with the egress of virions from infected cells, similar to human HEV, despite the fact that the ratHEV ORF3 protein lacks a PSAP amino acid motif.

Acute viral hepatitis E presenting with haemolytic anaemia and acute renal failure in a patient with glucose-6-phosphate dehydrogenase deficiency.

PubMed

Tomar, Laxmikant Ramkumarsingh; Aggarwal, Amitesh; Jain, Piyush; Rajpal, Surender; Agarwal, Mukul P

2015-10-01

The association of acute hepatitis E viral (HEV) infection with glucose-6-phosphate dehydrogenase (G6PD) deficiency leading to extensive intravascular haemolysis is a very rare clinical entity. Here we discuss such a patient, who presented with acute HEV illness, developed severe intravascular haemolysis and unusually high levels of bilirubin, complicated by acute renal failure (ARF), and was later on found to have a deficiency of G6PD. The patient recovered completely with haemodialysis and supportive management. © The Author(s) 2014.

Seroprevalence of hev antibodies in a sample of pregnant women in the city of Messina.

PubMed

La Fauci, V; Facciolà, A; Riso, R; Calimeri, S; Lo Giudice, D; Squeri, R

2017-01-01

Hepatitis E virus (HEV) is widespread in developing countries and the disease is also increasing in the developed ones. This infection in pregnancy can cause spontaneous abortion and neonatal death in 56% of newborns. The study was conducted on a sample of 352 pregnant women, 326 Italian and 26 foreign, in order to confirm the presence of HEV in our territory, to analyze wrong habits of the population and to suggest preventive actions against the risk to contract the infection during pregnancy. We asked all women under study to fill an anonymous questionnaire immediately before taking a venous blood samples to determine the presence of anti-HEV antibodies. The questionnaire contained a set of questions to gain information about lifestyles and risk factors to contract HEV. The questionnaire revealed that a portion of the tested women have risk behaviours, as consumption of raw or undercooked food, eating unwashed food and traveling to endemic areas. The percentage of women positive for HEV antibodies was 3.4%, in agreement with national data; all the women were Italian. This study confirms the circulation of HEV in the city of Messina. For this reason, it is highly recommended to disseminate hygienic and appropriate behaviours and feeding habits in order to prevent the risk to contract the infection.

Hepatitis E Virus (HEV) Detection and Quantification by a Real-Time Reverse Transcription-PCR Assay Calibrated to the World Health Organization Standard for HEV RNA.

PubMed

Germer, Jeffrey J; Ankoudinova, Irina; Belousov, Yevgeniy S; Mahoney, Walt; Dong, Chen; Meng, Jihong; Mandrekar, Jayawant N; Yao, Joseph D

2017-05-01

Hepatitis E virus (HEV) has emerged as a cause of chronic hepatitis among immunocompromised patients. Molecular assays have become important tools for the diagnosis and management of these chronically infected patients. A real-time reverse transcription-quantitative PCR (RT-qPCR) assay utilizing Pleiades probe chemistry and an RNA internal control for the simultaneous detection and quantification of HEV RNA in human serum was developed based on an adaptation of a previously described and broadly reactive primer set targeting the overlapping open reading frame 2/3 (ORF2/3) nucleotide sequence of HEV. A chimeric bovine viral diarrhea virus construct containing an HEV RNA insert (SynTura HEV) was developed, value assigned with the first World Health Organization (WHO) international standard for HEV RNA (code 6329/10), and used to prepare working assay calibrators and controls, which supported an assay quantification range of 100 to 5,000,000 IU/ml. The analytical sensitivity (95% detection rate) of this assay was 25.2 IU/ml (95% confidence interval [CI], 19.2 to 44.1 IU/ml). The assay successfully amplified 16 different HEV sequences with significant nucleotide mismatching in primer/probe binding regions, while evaluation of a WHO international reference panel for HEV genotypes (code 8578/13) showed viral load results falling within the result ranges generated by WHO collaborative study participants for all panel members (genotypes 1 to 4). Broadly reactive RT-qPCR primers targeting HEV ORF2/3 were successfully adapted for use in an assay based on Pleiades probe chemistry. The availability of secondary standards calibrated to the WHO HEV international standard can improve the standardization and performance of assays for the detection and quantification of HEV RNA. Copyright © 2017 American Society for Microbiology.

Hepatitis E Virus (HEV) Detection and Quantification by a Real-Time Reverse Transcription-PCR Assay Calibrated to the World Health Organization Standard for HEV RNA

PubMed Central

Germer, Jeffrey J.; Ankoudinova, Irina; Belousov, Yevgeniy S.; Mahoney, Walt; Dong, Chen; Meng, Jihong; Mandrekar, Jayawant N.

2017-01-01

ABSTRACT Hepatitis E virus (HEV) has emerged as a cause of chronic hepatitis among immunocompromised patients. Molecular assays have become important tools for the diagnosis and management of these chronically infected patients. A real-time reverse transcription-quantitative PCR (RT-qPCR) assay utilizing Pleiades probe chemistry and an RNA internal control for the simultaneous detection and quantification of HEV RNA in human serum was developed based on an adaptation of a previously described and broadly reactive primer set targeting the overlapping open reading frame 2/3 (ORF2/3) nucleotide sequence of HEV. A chimeric bovine viral diarrhea virus construct containing an HEV RNA insert (SynTura HEV) was developed, value assigned with the first World Health Organization (WHO) international standard for HEV RNA (code 6329/10), and used to prepare working assay calibrators and controls, which supported an assay quantification range of 100 to 5,000,000 IU/ml. The analytical sensitivity (95% detection rate) of this assay was 25.2 IU/ml (95% confidence interval [CI], 19.2 to 44.1 IU/ml). The assay successfully amplified 16 different HEV sequences with significant nucleotide mismatching in primer/probe binding regions, while evaluation of a WHO international reference panel for HEV genotypes (code 8578/13) showed viral load results falling within the result ranges generated by WHO collaborative study participants for all panel members (genotypes 1 to 4). Broadly reactive RT-qPCR primers targeting HEV ORF2/3 were successfully adapted for use in an assay based on Pleiades probe chemistry. The availability of secondary standards calibrated to the WHO HEV international standard can improve the standardization and performance of assays for the detection and quantification of HEV RNA. PMID:28228493

Incidence and characteristics of hepatitis E virus infection in children in Assiut, Upper Egypt.

PubMed

Hasan, Gamal; Assiri, Asaad; Marzuuk, Naglaa; Daef, Enas; Abdelwahab, Sayed; Ahmed, Ahmed; Mohamad, Ismail; Al-Eyadhy, Ayman; Alhaboob, Ali; Temsah, Mohamad-Hani

2016-10-01

Objective To describe the characteristics of hepatitis E virus (HEV) infection in a cohort of children from Upper Egypt using data from a large multicentre prospective study of acute viral hepatitis (AVH). Methods Data from subjects aged 2-18 years with AVH or close contacts of those with AVH found to have asymptomatic AVH were included in the analysis. Information concerning medical history, clinical examination, liver function tests and screening for hepatotropic viruses was recorded and analysed. Results A total of 123 patients (73 boys, 50 girls) were included in the analysis. Of these, 33 (26.8%) had HEV infection, 17 (13.8%) had hepatitis A virus infection, 10 (8.1%) had hepatitis B virus infection, 14 (11.4%) had cytomegalovirus hepatitis, five (4.1%) had autoimmune hepatitis, 11 (8.9%) had hepatitis due to mixed viral infections and 33 (26.8%) had non A-E hepatitis. Overall, 38 (30.9%) had infection with HEV. HEV infection was significantly higher among those using underground wells as a water source compared with tap water. Liver enzymes were significantly raised in patients with non-HEV infection compared with those with HEV infection. Conclusions HEV is a significant cause of AVH among children in Upper Egypt. Contamination of drinking water appears to be a major source of infection. Screening for HEV should be considered in all Egyptian children with AVH.

Serological and virological survey of hepatitis E virus (HEV) in animal reservoirs from Uruguay reveals elevated prevalences and a very close phylogenetic relationship between swine and human strains.

PubMed

Mirazo, Santiago; Gardinali, Noemí R; Cecilia, D'Albora; Verger, Lorenzo; Ottonelli, Florencia; Ramos, Natalia; Castro, Gustavo; Pinto, Marcelo A; Ré, Viviana; Pisano, Belén; Lozano, Alejandra; de Oliveira, Jaqueline Mendes; Arbiza, Juan

2018-01-01

Hepatitis E virus (HEV) infection is an issue of public health concern in high-income and non-endemic countries. Increasing evidence supports the hypothesis of a zoonotic route as the main mode of infection in this epidemiological setting, since the transmission of genotypes HEV-3 and HEV-4 from reservoirs to humans has been demonstrated. In America, studies have confirmed the circulation of HEV in pig herds but the zoonotic role of wild boars has never been evaluated. Uruguay has a high burden of HEV- associated acute hepatitis, and a close phylogenetic relationship was observed among human HEV-3 strains and European isolates detected in swine. However in this context, swine herds have never been surveyed. Herein is reported a survey of HEV in swine herds, pigs at slaughter-house and free-living wild boar populations. Two-hundred and twenty sera and 150 liver tissue samples from domestic pigs, and 140 sera from wild boars were tested for HEV by ELISA and PCR-based approaches. All tested swine farms resulted seropositive with an overall rate of 46.8%. In turn, 22.1% of the wild boars had anti-HEV antibodies. HEV RNA was detected in 16.6% and 9.3% of liver samples from slaughter-age pigs and adult wild boars sera, respectively. Three strains from domestic pig were also amplified by nested-PCR approaches. By contrast, none of the positive samples obtained from wild boars could be confirmed by nested-PCR. Phylogenetic analysis revealed a very high nucleotide identity among swine strains and sequences obtained from humans in Uruguay. Results showed that HEV is widely distributed among swine herds in Uruguay. Additionally, this study evidences for the first time in the American continent that wild boar populations are a reservoir for HEV, though its zoonotic role remains to be elucidated. Altogether, data presented here suggest a high zoonotic risk of HEV transmission from swine to humans. Copyright © 2017 Elsevier B.V. All rights reserved.

Detection of hepatitis E virus (HEV) through the different stages of pig manure composting plants

PubMed Central

García, M; Fernández-Barredo, S; Pérez-Gracia, M T

2014-01-01

Hepatitis E virus (HEV) is an increasing cause of acute hepatitis in industrialized countries. The aim of this study was to evaluate the presence of HEV in pig manure composting plants located in Spain. For this purpose, a total of 594 samples were taken in 54 sampling sessions from the different stages of composting treatment in these plants as follows: slurry reception ponds, anaerobic ponds, aerobic ponds, fermentation zone and composting final products. HEV was detected by reverse transcription polymerase chain reaction (RT-nested PCR) in four (80%) of five plants studied, mainly in the first stages of the process. HEV was not detected in any final product (compost) sample, destined to be commercialized as a soil fertilizer, suggesting that composting is a suitable method to eliminate HEV and thus, to reduce the transmission of HEV from pigs to humans. PMID:24206540

Comparative Pathology of Hepatitis A Virus and Hepatitis E Virus Infection.

PubMed

Cullen, John M; Lemon, Stanley M

2018-04-30

Hepatitis A virus (HAV) and hepatitis E virus (HEV) cause acute, self-limiting hepatic infections that are usually spread by the fecal-oral route in humans. Naturally occurring and experimental infections are possible in a variety of nonhuman primates and, in the case of HEV, a number of other species. Many advances in understanding the pathogenesis of these viruses have come from studies in experimental animals. In general, animals infected with these viruses recapitulate the histologic lesions seen in infected humans, but typically with less severe clinical and histopathological manifestations. This review describes the histopathologic changes associated with HAV and HEV infection in humans and experimental animals. Copyright © 2018 Cold Spring Harbor Laboratory Press; all rights reserved.

Clinical features of acute hepatitis E super-infections on chronic hepatitis B

PubMed Central

Chen, Chong; Zhang, Shu-Ye; Zhang, Dan-Dan; Li, Xin-Yan; Zhang, Yu-Ling; Li, Wei-Xia; Yan, Jing-Jing; Wang, Min; Xun, Jing-Na; Lu, Chuan; Ling, Yun; Huang, Yu-Xian; Chen, Liang

2016-01-01

AIM To examine the clinical features and risk factors for adverse outcomes in chronic hepatitis B (CHB) superimposed with hepatitis E virus (HEV). METHODS This retrospective cohort study included 228 patients with acute HEV infection (showing clinical acute hepatitis symptomology and positivity for anti-HEV immunoglobulin M) with underlying CHB (confirmed by positivity for hepatitis B surface antigen and/or hepatitis B virus (HBV) DNA over 6 mo) who had been admitted to the Shanghai Public Health Clinical Center, which represents the regional tertiary hospital for infectious diseases in Shanghai city, China. Data for adverse outcomes were collected, and included severe liver diseases (defined as liver failure and/or acute liver decompensation) and liver-related mortality. Logistic regression modeling was performed to determine the risk factors for adverse outcomes. RESULTS The symptoms caused by superimposed acute hepatitis E (AHE) were much more severe in cirrhotic patients (n = 94) than in non-cirrhotic patients (n = 134), as evidenced by significantly higher liver complications (77.7% vs 28.4%, P < 0.001) and mortality rate (21.3% vs 7.5%, P = 0.002). Most of the cirrhotic patients (n = 85, 90.4%) had no prior decompensation. Among the non-cirrhotic patients, superimposed AHE caused progressively more severe diseases that corresponded with the CHB disease stages, from immune tolerant to immune reactivation phases. Few risk factors were identified in the cirrhotic patients, but risk factors for non-cirrhotic patients were found to be intermediate HBV DNA levels (OR: 5.1, P = 0.012), alcohol consumption (OR: 6.4, P = 0.020), and underlying diabetes (OR: 7.5, P = 0.003) and kidney diseases (OR: 12.7, P = 0.005). Only 28.7% of the cirrhotic patients and 9.0% of the non-cirrhotic patients had received anti-HBV therapy previously and, in all cases, the efficacy had been suboptimal. CONCLUSION CHB-related cirrhosis and intermediate HBV DNA level were associated with

Molecular Investigation on the Presence of Hepatitis E Virus (HEV) in Wild Game in North-Western Italy.

PubMed

Serracca, Laura; Battistini, Roberta; Rossini, Irene; Mignone, Walter; Peletto, Simone; Boin, Claudia; Pistone, Giancarlo; Ercolini, Riccardo; Ercolini, Carlo

2015-09-01

Meat products from HEV-infected reservoir animal species are capable of transmitting HEV to humans and represent a public health concern. Human HEV cases have been linked to the consumption of raw or undercooked pig liver sausages, pork, and game meats, such as wild boars and deer worldwide. Direct exposure to swine or wild game species might also represent a source of HEV transmission especially for veterinarians, hunters, or butchers. A limited amount of data is available on HEV prevalence in wild boars in Italy and no data are available for other wild game species intended for human consumption. In this study, the circulation of HEV in four different animal species hunted in north-western Italy was evaluated to gain insight into the infection levels and the genetic diversity of the virus in such animal populations. Liver samples of 372 wild boars, 30 roe deer, 47 European hares and 38 coypus were analyzed for HEV RNA by real-time RT-PCR; positive samples were then sequenced and submitted to phylogenetic analysis. HEV RNA was detected in the livers of 7/372 (1.9%) wild boars tested, while no sample was positive for roe deer, European hare, and coypu. Phylogenetic analysis showed that wild boar HEV sequences belonged to HEV subtypes 3e, 3c, and 3f. Our results indicate that HEV is circulating only in wild boar among the considered game species in north-western Italy and suggest a potential zoonotic risk related to handling and/or consumption of raw or undercooked meat and products made of the liver from this species.

Rural habitat as risk factor for hepatitis E virus seroconversion in HIV-infected patients: A prospective longitudinal study.

PubMed

Rivero-Juarez, A; Cuenca-Lopez, F; Martinez-Peinado, A; Camacho, A; Real, L M; Frias, M; Gordon, A; Cantisán, S; Torre-Cisneros, J; Pineda, J A; Rivero, A

2017-11-01

Our objective was to determine the incidence and clinical manifestations of acute hepatitis E virus (HEV) in HIV-infected patients. A prospective longitudinal study including HIV-infected HEV-seronegative patients was conducted; HEV seroconversion (to IgG and/or IgM) was the main outcome variable. All patients were tested for HEV antibodies every 3-6 months. For patients who developed HEV seroconversion, a data collection protocol was followed to identify associated clinical manifestations and analytical alterations. A total of 627 patients (89.9%) were followed during a median of 11.96 months (IQR: 8.52-14.52 months) and formed the study population. Forty-one patients developed detectable anti-HEV antibodies (7.2 cases per 100 patients/year). Our study found a high incidence of HEV in HIV-infected patients in southern Spain strongly associated with a rural habitat. © 2017 Blackwell Verlag GmbH.

Evaluation of antiviral efficacy of Chinese traditional medicine Babao Dan in rabbits infected with hepatitis E virus.

PubMed

Gong, Wanyun; Liu, Lin; Li, Manyu; Wang, Lin; Zhang, Mingyu; Luo, Zhengxin; Sridhar, Siddharth; Woo, Patrick C Y; Wang, Ling

2018-06-20

Hepatitis E virus (HEV) is a major cause of acute viral hepatitis. Patients with chronic hepatitis B superinfected with HEV may progress to liver failure. Babao Dan (BD) is a traditional Chinese medicine widely used as an auxiliary option for the treatment of chronic hepatitis and liver cancer in China. This study aimed to evaluate the effect of BD on the management of HEV infection in a rabbit model. Sixty-two specific-pathogen-free (SPF) rabbits were divided randomly into five groups and treated with BD or placebo for 2 weeks. All rabbits were inoculated intravenously with rabbit HEV after initial administration. Then, rabbits were administered BD or ribavirin or placebo at 2 weeks post-inoculation (wpi) until faecal virus shedding showed negative. The duration of faecal virus shedding and levels of HEV RNA in faeces were reduced, and anti-HEV antibodies were detected in all rabbits in groups treated with BD before or after inoculation. Ribavirin treatment rapidly cleared HEV infection in SPF rabbits, but anti-HEV antibodies remained negative in 50 % of rabbits treated with ribavirin. These results indicate that ribavirin treatment was more effective in clearing HEV infection, while administration of BD before or after inoculation was effective in clearing HEV infection. Further clinical studies are warranted.

More powerful virus inhibitors from structure-based analysis of HEV71 capsid-binding molecules

PubMed Central

Spyrou, John A. B.; Kelly, James; Ren, Jingshan; Grimes, Jonathan; Puerstinger, Gerhard; Stonehouse, Nicola; Walter, Thomas S.; Hu, Zhongyu; Wang, Junzhi; Li, Xuemei; Peng, Wei; Rowlands, David; Fry, Elizabeth E.; Rao, Zihe; Stuart, David I.

2014-01-01

Enterovirus 71 (HEV71) epidemics amongst children and infants result mainly in mild symptoms, however, especially in the Asia-Pacific region, infection can be fatal. At present no therapies are available. We have used structural analysis of the complete virus to guide the design of HEV71 inhibitors. Analysis of complexes with four 3-(-4-pyridyl)-2-imidazolidinone derivatives with varying anti-HEV71 activities, pinpointed key structure-activity correlates. We then identified additional potentially beneficial substitutions, developed methods to reliably triage compounds by quantum mechanics-enhanced ligand docking, and synthesized two candidates. Structural analysis and in vitro assays confirmed the predicted binding modes and their ability to block viral infection. One ligand (IC50 = 25 pM) is an order of magnitude more potent than the best previously reported inhibitor, and is also more soluble. Our approach may be useful in the design of effective drugs for enterovirus infections. PMID:24509833

Brainstem encephalitis and acute polyneuropathy associated with hepatitis E infection.

PubMed

Salim, Omar Jabbar; Davidson, Amy; Li, Kathy; Leach, John Paul; Heath, Craig

2017-09-11

A 59-year-old man presented with feverish illness. His Glasgow Coma Scale was 15, had reduced visual acuity in the left eye with partial left ptosis and mild left hemiparesis with an extensor left plantar. Over 48 hours, he accrued multiple cranial nerves palsies and progressed to a flaccid paralysis necessitating admission to an intensive care unit.Cerebrospinal fluid (CSF) study showed 20 lymphocytes and raised protein. Viral and bacterial PCRs were negative. Samples for Lyme, blood-borne viruses, syphilis and autoantibodies were also negative. MRI brain showed T2 abnormalities within the brainstem. Nerve conduction studies revealed an acute motor and sensory axonal neuropathy pattern of Guillian Barre Syndrome (GBS). The patient was treated for both infective and inflammatory causes of brainstem encephalitis and GBS.Retrospective studies confirmed the presence of hepatitis E virus (HEV) RNA in CSF and serum studies showed positive HEV IgG and IgM prior to intravenous infusion. After 3 months of intensive rehabilitation, the patient was discharged home walking with a frame. © BMJ Publishing Group Ltd (unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Prevalence of hepatitis A virus, hepatitis B virus, hepatitis C virus, hepatitis D virus and hepatitis E virus as causes of acute viral hepatitis in North India: a hospital based study.

PubMed

Jain, P; Prakash, S; Gupta, S; Singh, K P; Shrivastava, S; Singh, D D; Singh, J; Jain, A

2013-01-01

Acute viral hepatitis (AVH) is a major public health problem and is an important cause of morbidity and mortality. The aim of the present study is to determine the prevalence of hepatitis A virus (HAV), hepatitis B virus (HBV), hepatitis C virus (HCV), hepatitis D virus (HDV) and hepatitis E virus (HEV) as causes of AVH in a tertiary care hospital of North India. Blood samples and clinical information was collected from cases of AVH referred to the Grade I viral diagnostic laboratory over a 1-year period. Samples were tested for hepatitis B surface antigen, anti-HCV total antibodies, anti-HAV immunoglobulin M (IgM) and anti-HEV IgM by the enzyme-linked immunosorbent assay. PCR for nucleic acid detection of HBV and HCV was also carried out. Those positive for HBV infection were tested for anti-HDV antibodies. Fisher's exact test was used and a P < 0.05 was considered to be statistically significant. Of the 267 viral hepatitis cases, 62 (23.22%) patients presented as acute hepatic failure. HAV (26.96%) was identified as the most common cause of acute hepatitis followed by HEV (17.97%), HBV (16.10%) and HCV (11.98%). Co-infections with more than one virus were present in 34 cases; HAV-HEV co-infection being the most common. HEV was the most important cause of acute hepatic failure followed by co-infection with HAV and HEV. An indication towards epidemiological shift of HAV infection from children to adults with a rise in HAV prevalence was seen. To the best of our knowledge, this is the first report indicating epidemiological shift of HAV in Uttar Pradesh.

Genetic and physicochemical analyses of a novel ferret hepatitis E virus, and clinical signs of infection after birth.

PubMed

Li, Tian-Cheng; Yoshizaki, Sayaka; Kataoka, Michiyo; Ami, Yasushi; Suzaki, Yuriko; Doan, Yen Hai; Haga, Kei; Ishii, Koji; Takeda, Naokazu; Wakita, Takaji

2017-07-01

A novel cluster of five ferret hepatitis E virus (HEV) strains was detected from nine laboratory ferrets (Mustela putorius furo) imported from a ferret farm in the U.S. Our detection of ferret HEV RNA and anti-HEV antibodies, and alanine aminotransferase (ALT) value assessment indicated that all of the 9 ferrets were infected with ferret HEV, and that the infection exhibited three patterns: sub-clinical infection (n=2), acute hepatitis (n=6) and persistent infection (n=1). Next-generation sequence analyses of the entire genome sequences of the five strains revealed that their nucleotide sequence identities ranged from 99.5% to 99.9%, indicating that genetically similar ferret HEVs had been circulating at this the U.S. ferret farm. In contrast, the strains shared 82% and 89% nucleotide sequence identities with other ferret HEV that isolated from the Netherlands (JN998607) and the U.S. (AB890374), suggesting that these strains form a novel cluster of ferret HEV with diverse genomes depending on the region where their host. Particles with a diameter of ~35nm at a density of 1.201g/cm 3 were observed in the fecal specimens by electron microscopy. There was no evidence that the particles were associated with the cell membrane. The ferret HEV RNA was not constantly detected in urine, suggesting that the excretion of ferret HEV into urine is not a common feature of HEV infection. Copyright © 2017 Elsevier B.V. All rights reserved.

Burden and Seasonality of Viral Acute Respiratory Tract Infections among Outpatients in Southern Sri Lanka.

PubMed

Shapiro, David; Bodinayake, Champica K; Nagahawatte, Ajith; Devasiri, Vasantha; Kurukulasooriya, Ruvini; Hsiang, Jeremy; Nicholson, Bradley; De Silva, Aruna Dharshan; Østbye, Truls; Reller, Megan E; Woods, Christopher W; Tillekeratne, L Gayani

2017-07-01

In tropical and subtropical settings, the epidemiology of viral acute respiratory tract infections varies widely between countries. We determined the etiology, seasonality, and clinical presentation of viral acute respiratory tract infections among outpatients in southern Sri Lanka. From March 2013 to January 2015, we enrolled outpatients presenting with influenza-like illness (ILI). Nasal/nasopharyngeal samples were tested in duplicate using antigen-based rapid influenza testing and multiplex polymerase chain reaction (PCR) for respiratory viruses. Monthly proportion positive was calculated for each virus. Bivariable and multivariable logistic regression were used to identify associations between sociodemographic/clinical information and viral detection. Of 571 subjects, most (470, 82.3%) were ≥ 5 years of age and 53.1% were male. A respiratory virus was detected by PCR in 63.6% ( N = 363). Common viral etiologies included influenza (223, 39%), human enterovirus/rhinovirus (HEV/HRV, 14.5%), respiratory syncytial virus (RSV, 4.2%), and human metapneumovirus (hMPV, 3.9%). Both ILI and influenza showed clear seasonal variation, with peaks from March to June each year. RSV and hMPV activity peaked from May to July, whereas HEV/HRV was seen year-round. Patients with respiratory viruses detected were more likely to report pain with breathing (odds ratio [OR] = 2.60, P = 0.003), anorexia (OR = 2.29, P < 0.001), and fatigue (OR = 2.00, P = 0.002) compared with patients with no respiratory viruses detected. ILI showed clear seasonal variation in southern Sri Lanka, with most activity during March to June; peak activity was largely due to influenza. Targeted infection prevention activities such as influenza vaccination in January-February may have a large public health impact in this region.

Cross-species infections of cultured cells by hepatitis E virus and discovery of an infectious virus-host recombinant.

PubMed

Shukla, Priyanka; Nguyen, Hanh T; Torian, Udana; Engle, Ronald E; Faulk, Kristina; Dalton, Harry R; Bendall, Richard P; Keane, Frances E; Purcell, Robert H; Emerson, Suzanne U

2011-02-08

The RNA virus, hepatitis E virus (HEV) is the most or second-most important cause of acute clinical hepatitis in adults throughout much of Asia, the Middle East, and Africa. In these regions it is an important cause of acute liver failure, especially in pregnant women who have a mortality rate of 20-30%. Until recently, hepatitis E was rarely identified in industrialized countries, but Hepatitis E now is reported increasingly throughout Western Europe, some Eastern European countries, and Japan. Most of these cases are caused by genotype 3, which is endemic in swine, and these cases are thought to be zoonotically acquired. However, transmission routes are not well understood. HEV that infect humans are divided into nonzoonotic (types 1, 2) and zoonotic (types 3, 4) genotypes. HEV cell culture is inefficient and limited, and thus far HEV has been cultured only in human cell lines. The HEV strain Kernow-C1 (genotype 3) isolated from a chronically infected patient was used to identify human, pig, and deer cell lines permissive for infection. Cross-species infections by genotypes 1 and 3 were studied with this set of cultures. Adaptation of the Kernow-C1 strain to growth in human hepatoma cells selected for a rare virus recombinant that contained an insertion of 174 ribonucleotides (58 amino acids) of a human ribosomal protein gene.

Hepatitis E virus: do locally acquired infections in Australia necessitate laboratory testing in acute hepatitis patients with no overseas travel history?

PubMed Central

Shrestha, Ashish C.; Faddy, Helen M.; Flower, Robert L. P.; Seed, Clive R.; Keller, Anthony J.

2015-01-01

Summary Hepatitis E virus (HEV) is emerging as a global public health threat. Water-borne HEV outbreaks are common in developing countries and are associated with genotypes 1 and 2. In industrialised countries, sporadic cases of zoonotic transmission associated with genotypes 3 and 4 are increasingly being reported. Transfusion- and transplantation-transmitted HEV have been documented, although ingestion of contaminated food is thought to be the major transmission route. Severe disease is possible and chronic hepatitis infection occurs in solid-organ-transplant recipients and in patients with immunosuppressive disorders. In Australia, HEV cases are mainly travellers returning from disease endemic countries. Indeed, there are few reported cases of locally acquired HEV. Pigs in Australia have been shown to be infected with HEV, which indicates the possibility of zoonotic transmission. The extent of locally acquired infection is not known, however it may be greater than expected and may necessitate laboratory testing in patients reporting no overseas travel. PMID:25560836

Identification of genotype 4 hepatitis E virus strains from a patient with acute hepatitis E and farm pigs in Bali, Indonesia.

PubMed

Wibawa, I Dewa Nyoman; Suryadarma, I G A; Mulyanto; Tsuda, Fumio; Matsumoto, Yasunobu; Ninomiya, Masashi; Takahashi, Masaharu; Okamoto, Hiroaki

2007-08-01

A previous study revealed that antibodies to hepatitis E virus (HEV) (anti-HEV) are highly prevalent among healthy individuals and farm pigs in Bali, Indonesia, and suggested that HEV infection may occur via zoonosis among Balinese people. However, there were no reports of acute hepatitis E in Bali. To elucidate whether Balinese HEV strains recovered from infected humans and pigs have significant sequence similarity, serum samples obtained from 57 patients (age, mean +/- standard deviation, 31.1 +/- 11.9 years) with sporadic acute hepatitis and from one hundred and one 2- or 3-month-old farm pigs in Bali were tested for anti-HEV and HEV RNA. Among the 57 patients, 2 (3.5%) had high-titer IgM/IgA class anti-HEV antibodies and one of them had detectable HEV RNA (BaliE03-46). Overall, 58 pigs (57.4%) tested positive for anti-HEV, while 5 pigs (5.0%) had detectable HEV RNA. Based on the 412-nucleotide sequence within open reading frame 2, the BaliE03-46 isolate and the 5 swine HEV isolates recovered from the viremic pigs were phylogenetically classified in genotype 4, but were only 77.3-90.8% identical to the genotype 4 HEV isolates reported thus far in China, India, Japan, Taiwan, and Vietnam. The BaliE03-46 isolate of human origin shared high identities of 97.3-98.3% with 4 of the 5 Balinese swine isolates, but differed by 16.1% from the remaining swine isolate. These results suggest that indigenous HEV strains of genotype 4 with marked heterogeneity are circulating in Bali, Indonesia, and that pigs are reservoirs of HEV for Balinese people who have a habit of ingesting uncooked pigs.

Constant Hepatitis E Virus (HEV) Circulation in Wild Boar and Red Deer in Spain: An Increasing Concern Source of HEV Zoonotic Transmission.

PubMed

Kukielka, D; Rodriguez-Prieto, V; Vicente, J; Sánchez-Vizcaíno, J M

2016-10-01

Hepatitis E is a viral zoonosis that affects multiple hosts. The complete dynamics of infection in wildlife are still unknown, but the previous fact facilitates the maintenance and circulation of the virus, posing a risk to human health in the case of meat consumption from susceptible animals. In Spain, it has been shown how domestic pigs, cattle and wildlife (i.e. wild boar and red deer) clearly interact in hunting farms, generating a complex epidemiological situation in terms of interspecies pathogen transmission. Therefore, in this study, we aimed to (i) evaluate the circulation of the virus in geographically close domestic (Iberian pigs) and wild animals (wild boar and deer) living in hunting areas from central Spain over an 8-year period (2003-2010) and (ii) to determine whether HEV could be used as a marker of domestic-wildlife contact. For these purposes, a longitudinal analysis of Iberian pig, wild boar and red deer samples (n = 287) through virological and serological tests was conducted to shed light upon the circulation events of HEV. Regarding HEV RNA detection by real-time RT-PCR, 10.12% samples (95% CI: 5.44-14.8) from wild boar and 16.05% samples (95% CI: 8.06-24.04) from red deer were positive. As for the Iberian pigs, none of the 48 samples was positive for HEV RNA detection. In the serological analysis, 43.75% (95% CI: 29.75-57.75) from Iberian pig, 57.40% (95% CI: 48.10-66.70) from wild boar and 12.85% (95% CI: 5.01-20.69) samples from red deer presented anti-HEV antibodies. Positive samples were distributed among all study years (2003-2010). These results depict the urgent need to improve the inspection and surveillance of these species and their products. In the case of HEV, it is clear that the stable and constant presence of the virus in wildlife and its contact with Iberian pigs pose a risk for human health as they are all destined for human consumption. © 2015 Blackwell Verlag GmbH.

A longitudinal study revealing hepatitis E virus infection and transmission at a swine test station.

PubMed

Kantala, T; Oristo, S; Heinonen, M; von Bonsdorff, C-H; Maunula, L

2013-12-01

Hepatitis E virus (HEV) is a zoonotic agent that causes acute hepatitis in humans, and infects several animal species, most importantly swine. In the current study, that presents the first evidence of HEV infections in pigs in Finland, genetic divergence and transmission of HEV was investigated among pigs at a swine test station at two occasions. In 2007, HEV RNA was found in 25% of pens, and 35% of 2-3 month-old pigs at the station. Three different isolates, comprising 13 sequences of HEV genotype 3 e that were imported from different farms were detected. In 2010, 39% of pigs were HEV RNA positive on weeks 1, 3, or 5 of a 3-month follow-up, and 11 sequences, all representing one of the isolates that was also present in 2007, were detected. The isolate was considered to be either re-introduced to, or to persist at the station, and it was transmitted between the pigs. The study sheds light on the rate and time of HEV transmission in swine, and describes the epidemiologic variability of HEV isolates over time. Copyright © 2013 Elsevier Ltd. All rights reserved.

Swine and rabbits are the main reservoirs of hepatitis E virus in China: detection of HEV RNA in feces of farmed and wild animals.

PubMed

Xia, Junke; Zeng, Hang; Liu, Lin; Zhang, Yulin; Liu, Peng; Geng, Jiabao; Wang, Lin; Wang, Ling; Zhuang, Hui

2015-11-01

Hepatitis E virus (HEV) infection is recognized as a zoonosis. The prevalence of HEV RNA and anti-HEV antibodies in many animal species has been reported, but the host range of HEV is unclear. The aims of this study were to investigate HEV infection in various animal species and to determine the reservoirs of HEV. Eight hundred twenty-two fecal samples from 17 mammal species and 67 fecal samples from 24 avian species were collected in China and tested for HEV RNA by RT-nPCR. The products of PCR were sequenced and analyzed phylogenetically. The positive rates of HEV RNA isolated from pigs in Beijing, Shandong, and Henan were 33%, 30%, and 92%, respectively, and that from rabbits in Beijing was 5%. HEV RNA was not detectable in farmed foxes, sheep or sika deer, or in wild animals in zoos, including wild boars, yaks, camels, Asiatic black bears, African lions, red pandas, civets, wolves, jackals and primates. Sequence analysis revealed that swine isolates had 97.8%-98.4% nucleotide sequence identity to genotype 4d isolates from patients in Shandong and Jiangsu of China. Phylogenetic analysis showed that swine HEV isolates belong to genotype 4, including subgenotype 4h in Henan and 4d in Beijing and Shandong. The rabbit HEV strains shared 93%-99% nucleotide sequence identity with rabbit strains isolated from Inner Mongolia. In conclusion, swine and rabbits have been confirmed to be the main reservoirs of HEV in China.

Hepatitis E Virus Genotype 3 in Sewage and Genotype 1 in Acute Hepatitis Cases, Israel

PubMed Central

Ram, Daniela; Manor, Yossi; Gozlan, Yael; Schwartz, Eli; Ben-Ari, Ziv; Mendelson, Ella; Mor, Orna

2016-01-01

Hepatitis E virus (HEV) is an emerging infectious agent in developed countries. HEV genotypes 1 (G1) and 3 (G3) have been identified in environmental and clinical samples in Europe. In Israel, the overall prevalence of anti-HEV IgG antibodies was found to be 10.6%; however, reports of HEV infection are scarce. In this study, the presence of HEV in Israel was investigated using 169 sewage samples from 32 treatment facilities and 49 samples from acute hepatitis patients, all collected between 2013 and 2015. Fourteen sewage samples, from Haifa (11/18 samples), Tel Aviv (2/29 samples), and Beer Sheva (1/17 samples), regions with good sanitary conditions and middle-high socioeconomic populations, were HEV positive. Among the patient samples, 6.1% (3/49) were HEV positive, all returning travelers from India. Genotype analysis revealed G1 HEV in patients and G3 HEV sequences in sewage. Evidence that HEV could be establishing itself in our region may justify more active surveillance to monitor its spread. PMID:27246446

Hepatitis E virus infection in Europe: surveillance and descriptive epidemiology of confirmed cases, 2005 to 2015.

PubMed

Aspinall, Esther J; Couturier, Elisabeth; Faber, Mirko; Said, Bengü; Ijaz, Samreen; Tavoschi, Lara; Takkinen, Johanna; Adlhoch, Cornelia

2017-06-29

Hepatitis E virus (HEV) is an under-recognised cause of acute hepatitis in high-income countries. The purpose of this study was to provide an overview of testing, diagnosis, surveillance activities, and data on confirmed cases in the European Union/European Economic Area (EU/EEA). A semi-structured survey was developed and sent to 31 EU/EEA countries in February 2016, 30 responded. Twenty of these countries reported that they have specific surveillance systems for HEV infection. Applied specific case definition for HEV infection varied widely across countries. The number of reported cases has increased from 514 cases per year in 2005 to 5,617 in 2015, with most infections being locally acquired. This increase could not be explained by additional countries implementing surveillance for HEV infections over time. Hospitalisations increased from less than 100 in 2005 to more than 1,100 in 2015 and 28 fatal cases were reported over the study period. EU/EEA countries are at different stages in their surveillance, testing schemes and policy response to the emergence of HEV infection in humans. The available data demonstrated a Europe-wide increase in cases. Standardised case definitions and testing policies would allow a better understanding of the epidemiology of HEV as an emerging cause of liver-related morbidity. This article is copyright of The Authors, 2017.

 Autochthonous infection with hepatitis E virus related to subtype 3a, France: a case report.

PubMed

Saint-Jacques, Pauline; Tissot-Dupont, Hervé; Colson, Philippe

2016-01-01

Hepatitis E virus (HEV) recently emerged in Europe as a cause of autochthonous acute hepatitis and a porcine zoonosis. European autochthonous cases almost exclusively involved viruses of genotype 3, subtype 3a being only recently reported in France, from farm pigs. We report an autochthonous human infection with a HEV related to subtype 3a in Southeastern France. A 55-year-old human immunodeficiency virus-infected man presented liver cytolysis in June 2014. HEV RNA was detected in serum and three months later, anti-HEV IgM and IgG were positive whereas HEV RNA was no more detectable in serum. No biological or clinical complication did occur. HEV phylogeny based on two capsid gene fragments showed clustering of sequences obtained from the case-patient with HEV-3a, mean nucleotide identity being 91.7 and 91.3% with their 10 best GenBank matches that were obtained in Japan, South Korea, USA, Canada, Germany and Hungria from humans, pigs and a mongoose. Identity between HEV sequence obtained here and HEV-3a sequences obtained at our laboratory from farm pigs sampled in 2012 in Southeastern France was only 90.2-91.4%. Apart from these pig sequences, best hits from France were of subtypes 3i, 3f, or undefined. The patient consumed barely cooked wild-boar meat; no other risk factor for HEV infection was documented. In Europe, HEV-3a has been described in humans in England and Portugal, in wild boars in Germany, and in pigs in Germany, the Netherlands, and, recently, France. These findings suggest to gain a better knowledge of HEV-3a circulation in France.

Cryptic Hepatitis B and E in Patients With Acute Hepatitis of Unknown Etiology.

PubMed

Ganova-Raeva, Lilia; Punkova, Lili; Campo, David S; Dimitrova, Zoya; Skums, Pavel; Vu, Nga H; Dat, Do T; Dalton, Harry R; Khudyakov, Yury

2015-12-15

Up to 30% of acute viral hepatitis has no known etiology. To determine the disease etiology in patients with acute hepatitis of unknown etiology (HUE), serum specimens were obtained from 38 patients residing in the United Kingdom and Vietnam and from 26 healthy US blood donors. All specimens tested negative for known viral infections causing hepatitis, using commercially available serological and nucleic acid assays. Specimens were processed by sequence-independent complementary DNA amplification and next-generation sequencing (NGS). Sufficient material for individual NGS libraries was obtained from 12 HUE cases and 26 blood donors; the remaining HUE cases were sequenced as a pool. Read mapping was done by targeted and de novo assembly. Sequences from hepatitis B virus (HBV) were detected in 7 individuals with HUE (58.3%) and the pooled library, and hepatitis E virus (HEV) was detected in 2 individuals with HUE (16.7%) and the pooled library. Both HEV-positive cases were coinfected with HBV. HBV sequences belonged to genotypes A, D, or G, and HEV sequences belonged to genotype 3. No known hepatotropic viruses were detected in the tested normal human sera. NGS-based detection of HBV and HEV infections is more sensitive than using commercially available assays. HBV and HEV may be cryptically associated with HUE. Published by Oxford University Press on behalf of the Infectious Diseases Society of America 2015. This work is written by (a) US Government employee(s) and is in the public domain in the US.

Seroprevalence of Hepatitis A and E Virus Infections Among Healthy Population in Shiraz, Southern Iran.

PubMed

Asaei, Sadaf; Ziyaeyan, Mazyar; Moeini, Mahsa; Jamalidoust, Marzieh; Behzadi, Mohammad Amin

2015-07-01

Enterically-transmitted acute viral hepatitis is caused predominantly by hepatitis A virus (HAV) and hepatitis E virus (HEV). The prevalence of HEV and HAV infections varies in different geographical regions. This study was conducted to determine the prevalence of HEV and HAV infections among Iranian healthy individuals in southern Iran. Totally, 1030 samples were collected from healthy subjects in schools, those referred to tertiary outpatient clinics and health centers in Shiraz between November 2011 and May 2012. Their ages ranged between six months and 95 years. The presence of total anti-HAV and anti-HEV immunoglobulin M (IgM) in plasma was assessed by ELISA. The results showed that 66.2% and 0.6% of the general population in this area were positive for total anti-HAV and IgM antibodies by ELISA, respectively. As seen, 13.4% and 0.9% were positive for total anti-HEV and IgM antibodies, respectively. The difference in total anti-HAV and anti-HEV antibodies was significant among the age groups (P < 0.001). This study showed that the prevalence rates of HAV and HEV antibodies were positively correlated with age. The results demonstrated that the infection with these two viruses in the region was high and some high-risk individuals including females at child-bearing age were more susceptible. HAV vaccination could be recommended for antibody-negative adults.

[Vaccination of rhesus monkeys with recombinant antigen fragments and protection from hepatitis E virus infection].

PubMed

Ma, Yan-bing; Xie, Tian-hong; Zhang, Guang-ming; Li, Chun-hong; Dai, Xie-Jie; Dai, Chang-bai; Sun, Mao-sheng; Lu, Jian; Bi, Sheng-li

2002-12-01

To observe anti-HEV IgG response to vaccination of recombinant antigen fragments and evaluate its protection from Hepatitis E Virus infection in rhesus monkeys (Macaca mulatta). Twelve monkeys were divided into three groups and immunized respectively with three different recombinant antigens: namely Ag1 (carboxyl terminal 431 amino acids of ORF2), Ag2 (128aa fragment at the carboxyl terminal of ORF2), and Ag3 (full length ORF3 ligated with two ORF2 fragments encoded by 6743-7126nt and 6287-6404nt). The monkeys were challenged intravenously with fecal suspension from experimentally infected rhesus monkeys, and the other three monkeys served as the placebo group for challenge with HEV. The dynamic changes of the levels of ALT and anti-HEV IgG were examined. Pathological changes of liver tissue were observed by light microscope. Excretion of virus was detected by RT-nPCR. Hepatic histopathology of two monkeys in the placebo group was consistent with acute viral hepatitis, and ALT was elevated 3-4 weeks after inoculated with virus, up to 10-20 times higher than normal level. The liver tissue of monkeys immunized with antigen kept normal, ALT in several monkeys elevated mildly, and anti-HEV IgG conversation occurred at 1-2 weeks after vaccination, with the titer reaching 1:12,800. The virus RNA could be detected by RT-nPCR from days 7 to 50 in monkeys of control group, and from days 7 to 21 in vaccinated monkeys after challenged with virus. The recombinant antigens could induce the production of anti-HEV IgG, which protected rhesus monkeys from acute Hepatitis symptoms related to HEV infection.

Epidemiology and Transmission of Hepatitis A Virus and Hepatitis E Virus Infections in the United States.

PubMed

Hofmeister, Megan G; Foster, Monique A; Teshale, Eyasu H

2018-04-30

There are many similarities in the epidemiology and transmission of hepatitis A virus (HAV) and hepatitis E virus (HEV) genotype (gt)3 infections in the United States. Both viruses are enterically transmitted, although specific routes of transmission are more clearly established for HAV than for HEV: HAV is restricted to humans and primarily spread through the fecal-oral route, while HEV is zoonotic with poorly understood modes of transmission in the United States. New cases of HAV infection have decreased dramatically in the United States since infant vaccination was recommended in 1996. In recent years, however, outbreaks have occurred among an increasingly susceptible adult population. Although HEV is the most common cause of acute viral hepatitis in developing countries, it is rarely diagnosed in the United States. Copyright © 2018 Cold Spring Harbor Laboratory Press; all rights reserved.

Epidemiology and Risk Factors of Incident Hepatitis E Virus Infections in Rural Bangladesh

PubMed Central

Labrique, Alain B.; Zaman, K.; Hossain, Zahid; Saha, Parimalendu; Yunus, Mohammad; Hossain, Anowar; Ticehurst, John R.; Nelson, Kenrad E.

2010-01-01

Hepatitis E virus (HEV) is the most common cause of acute viral hepatitis in the world. Most of South Asia is HEV endemic, with frequent seasonal epidemics of hepatitis E and continuous sporadic cases. This author group's epidemiologic work and clinical reports suggest that Bangladesh is HEV endemic, but there have been few population-based studies of this country's HEV burden. The authors calculated HEV infection rates, over an 18-month interval between 2003 and 2005, by following a randomly selected cohort of 1,134 subjects between the ages of 1 and 88 years, representative of rural communities in southern Bangladesh. Baseline prevalence of antibody to hepatitis E virus (anti-HEV) was 22.5%. Seroincidence was 60.3 per 1,000 person-years during the first 12 months and 72.4 per 1,000 person-years from >12 to 18 months (during the monsoon season), peaking by age 50 years and with low rates during childhood. Few of the seroconverting subjects reported hepatitis-like illness. Overall incidence was calculated to be 64 per 1,000 person-years, with 1,172 person-years followed. No significant associations were found between anti-HEV incidence and demographic or socioeconomic factors for which data were available. This is the first study to document annual HEV infection rates among “healthy” and very young to elderly subjects in a rural Bangladeshi population. PMID:20801864

Differences in capabilities of different enzyme immunoassays to detect anti-hepatitis E virus immunoglobulin G in pigs infected experimentally with hepatitis E virus genotype 3 or 4 and in pigs with unknown exposure.

PubMed

Zhang, H; Mohn, U; Prickett, J R; Schalk, S; Motz, M; Halbur, P G; Feagins, A R; Meng, X J; Opriessnig, T

2011-08-01

Hepatitis E virus (HEV), a major cause of acute viral hepatitis in humans in many developing countries, is highly prevalent in the pig population worldwide. The objective of this study was to assess the capability of three porcine prototypes of a human enzyme-linked immunosorbent assay (ELISA), an in-house ELISA and a line-immunoassay (LIA) to detect anti-HEV antibodies in pigs infected experimentally with HEV (n = 57), known to be negative for HEV infection (n = 27), or with unknown exposure to HEV infection (field samples, n = 90). All 27 samples from non-infected pigs were negative with all five assays. The earliest detection of anti-HEV antibodies occurred at 14 days post-inoculation (dpi) with four of five assays. From 42 dpi, all samples from infected pigs were detected correctly as anti-HEV positive. Kappa analysis demonstrated substantial agreement among tests (0.62-1.00) at 14 dpi and complete agreement (1.00) at 56 dpi. The overall area under the curve for all quantitative tests as determined by receiver operator characteristic analysis ranged from 0.794 to 0.831 indicating moderate accuracy. The results showed that all five assays can detect anti-HEV IgG antibodies accurately in pigs infected experimentally with HEV. In field samples, a higher prevalence of anti-HEV IgG was found in breeding herds than in growing pigs (100% versus 66.7-93.9%). These serological assays should be very useful in veterinary diagnostic labs for HEV diagnosis in swine. Copyright © 2011 Elsevier B.V. All rights reserved.

Role of Envelopment in the HEV Life Cycle

PubMed Central

Yin, Xin; Li, Xinlei; Feng, Zongdi

2016-01-01

Hepatitis E virus (HEV), an enterically transmitted hepatotropic virus, was thought to be non-enveloped for decades. However, recent studies have revealed that the virus circulating in the patient’s blood is completely cloaked in host membranes and resistant to neutralizing antibodies. The discovery of this novel enveloped form of HEV has raised a series of questions about the fundamental biology of HEV and the way this virus, which has been understudied in the past, interacts with its host. Here, we review recent advances towards understanding this phenomenon and discuss its potential impact on various aspects of the HEV life cycle and immunity. PMID:27548201

Incidence and seroprevalence of hepatitis E virus infection in pregnant women infected with hepatitis B virus and antibody placental transfer in infants.

PubMed

Huang, Hongyu; Xu, Chenyu; Zhou, Xuan; Liu, Lanhua; Dai, Yimin; Xu, Biao; Yang, Jishi; Chen, Tingmei; Hu, Yali; Zhou, Yi-Hua

2016-09-01

Hepatitis E has poor outcomes in pregnant women. Superinfection of hepatitis E virus (HEV) in patients infected with hepatitis B virus (HBV) may worsen liver disease. To estimate the incidence and seroprevalence of HEV infection among HBV-infected pregnant women, to investigate the transplacental transfer of maternal anti-HEV IgG, and to compare the maternal and neonatal outcomes in anti-HEV positive and negative pregnant women. Totally 391 HBV-infected pregnant women were recruited from April 2012 to October 2014. Paired mothers and infants were followed up at an average 9.8 months postpartum. Anti-HEV IgG and IgM were tested by ELISA. Of the pregnant women, none was anti-HEV IgM positive and 42 (10.7%) were IgG positive. At the follow-up, 3 seronegative women converted to anti-HEV IgG positive, with an estimated incidence of 17 per 1000 person-years. No significant differences of gestational age, preterm birth rate, Apgar score and birthweight were observed between newborns of anti-HEV IgG positive and negative mothers. Of the 42 neonates born to anti-HEV IgG positive mothers, 38 (90.5%) had anti-HEV IgG in their cord blood. The neonatal and maternal anti-HEV IgG levels were positively correlated (r=0.827, p<0.05). All infants were negative for both anti-HEV IgM and IgG at the follow-up. HBV-infected pregnant women rarely have novel HEV infection during late pregnancy in Jiangsu, China. Maternal anti-HEV IgG efficiently transfers into the fetuses, and disappears in infants before 10 months old. Copyright © 2016 Elsevier B.V. All rights reserved.

Detection of serum antibodies to hepatitis E virus in domestic pigs in Italy using a recombinant swine HEV capsid protein.

PubMed

Ponterio, Eleonora; Di Bartolo, Ilaria; Orrù, Ginevra; Liciardi, Manuel; Ostanello, Fabio; Ruggeri, Franco Maria

2014-06-16

The hepatitis E virus (HEV) has been detected in both humans and animals, particularly pigs, worldwide. Several evidences, including human infection following consumption of raw contaminated meat, suggest a zoonotic transmission of HEV. In Italy, large circulation of genotype 3 HEV has been reported in swine, and recent studies have confirmed the involvement of this genotype in autochthonous human cases. In this study 111 sera collected from healthy pigs in two Italian regions were tested for anti-HEV IgG antibodies. For specific HEV antibody detection in swine, we developed ELISA and Western blotting methods, using a truncated capsid (ORF2) protein lacking the first 111 amino acids of a swine HEV genotype 3 strain. The ORF2-based ELISA revealed anti-HEV antibodies in 104 out of 111 pigs compared with 102 detected with a commercial ELISA kit. A lower number of sera reacted with the recombinant ORF2 protein in a Western blotting format (81/111). Using a Latent class analysis (LCA), the estimated sensitivities for ELISA-ORF2 and ELISA-kit tests were 0.961 and 0.936, respectively, whereas specificities were 0.599 and 0.475. The estimated sensitivity of Western blotting was 0.775, and the specificity was 0.944. The overall results confirm the high prevalence of HEV seropositive healthy pigs in Italy. Through comparisons with a commercial ELISA test, the swine genotype 3 HEV antigen produced in this study was proven suitable to detect anti-HEV antibodies in pig sera by both ELISA and Western Blotting.

Occurrence and prevalence of selected zoonotic agents: Echinococcus multilocularis, Trichinella spiralis and hepatitis E virus (HEV) in the population of Polish hunters--results of the study conducted in 2010-2012.

PubMed

Sadkowska-Todys, Małgorzata; Baumann-Popczyk, Anna; Wnukowska, Natalia; Popczyk, Bartłomiej; Kucharczyk, Bożena; Gołąb, Elżbieta

2015-01-01

In Poland the development of the knowledge concerning zoonotic pathogens, of which free-living animals are the reservoir of is gaining in importance both in epidemiological aspect as well as in the context of prevention for improving public health. Dietary habits such as the consumption of forest undergrowth products and wild game meat, and the way of those products being prepared (in the process of barbequing) pose a risk factors of infection with the foodborne pathogens such as Echinococcus multilocularis, Trichinella spp., and HEV. The aim of this study is to estimate the prevalence of infections caused by Trichinella spp., Echinococcus multilocularis, and HEV in the population of Polish hunters, describing their geographical distribution in Poland, and to try to define basic factors, which may contribute to their occurrence. In 2010-2012 a cross-sectional study was carried out among Polish hunters. A blood samples were collected as well as a survey of 1027 participants recruited in the 16 provinces was also carried out. Serological tests were performed for the presence of specific antibodies against Echinococcus multilocularis, Trichinella spp. and HEV using commercial or "in home" ELISA tests. In case of positive result for Echinococcus, an Em2plus ELISA or/and western blot test were carried out, and for positive results for IgM for HEV a recomLine HEV IgM test was carried out. In the studied population a total number of 2 cases of Echinococcus multilocularis infection were found. Moreover in 47 (4,6%) participants presence of antibodies against Trichinella spp. were found, including 17 positive and 30 borderline results. In 206 persons (25%) IgG anti-HEV antibodies were found (by ELISA test). Geographical diversity in prevalence of both, the Trichinella spp. and HEV cases was observed. The study confirmed presence of zoonotic infections such as Echinococcus multilocularis, Trichinella spp., and hepatitis E (HEV) among Polish hunters. In the case of

Genetic variability of HEV isolates: inconsistencies of current classification.

PubMed

Oliveira-Filho, Edmilson F; König, Matthias; Thiel, Heinz-Jürgen

2013-07-26

Many HEV and HEV-like sequences have been reported during the last years, including isolates which may represent a number of potential new genera, new genotypes or new subtypes within the family Hepeviridae. Using the most common classification system, difficulties in the establishment of subtypes have been reported. Moreover the relevance of subtype classification for epidemiology can be questioned. In this study we have performed phylogenetic analyses based on whole capsid gene and complete HEV genomic sequences in order to evaluate the current classification of HEV at genotype and subtype levels. The results of our analyses modify the current taxonomy of genotype 3 and refine the established system for typing of HEV. In addition we suggest a classification for hepeviruses recently isolated from bats, ferrets, rats and wild boar. Copyright © 2013 Elsevier B.V. All rights reserved.

Coexistence of IgM antihepatitis A virus and IgM antihepatitis E virus in acute viral hepatitis: a prospective, multicentre study in Korea.

PubMed

Jang, J-H; Jung, Y M; Kim, J S; Lee, S H; Kim, J-W; Hwang, S G; Rim, K S; Park, S J; Park, Y M; Kang, S-K; Lee, H S; Yun, H; Kim, J-H; Jeong, S-H

2011-10-01

This study investigated the clinical, serological and molecular characteristics of coexistence of both immunoglobulin M (IgM) antihepatitis A virus (HAV) and IgM antihepatitis E virus (HEV) in acute viral hepatitis using a prospective, multicentre design. Among a total of 771 symptomatic cases with acute viral hepatitis enrolled in a Korean city from September 2006 to August 2008, coexistence of IgM anti-HAV and IgM anti-HEV was found in 43 patients (A+E group; 6%), while the existence of IgM anti-HAV alone was found in 595 patients (A group; 77%) and that of IgM anti-HEV alone in 14 patients (E group; 2%). Clinical data analysis and measurement of IgM and IgG anti-HEV were performed using two different commercial kits, and HAV RNA and HEV RNA were detected in available serum or stool samples. The clinical features of the A+E group were similar to those of the A group. HAV RNA detection rates in the A+E and A group were similar, while HEV RNA was detected only in the stool samples of the E group, not in the A+E group. Comparative testing of anti-HEV using two different ELISA kits showed markedly discordant results for IgM anti-HEV positivity and consistently low positivity for IgG anti-HEV in the A+E group. Coexistence of IgM anti-HEV measured by the Genelabs ELISA kit in the setting of hepatitis A appears to yield false-positive results in nonendemic areas of HEV infection. Diagnosis of hepatitis E using IgM anti-HEV should be made with caution. © 2011 Blackwell Publishing Ltd.

Hepatitis A and E virus infections among children in Mongolia.

PubMed

Davaalkham, Dambadarjaa; Enkhoyun, Tsogzolbaatar; Takahashi, Masaharu; Nakamura, Yosikazu; Okamoto, Hiroaki

2009-08-01

To compare the epidemiologic profiles of hepatitis A virus (HAV) and hepatitis E virus (HEV) infections in children in Mongolia, the prevalence of HAV and HEV infections was studied serologically and molecularly among 520 apparently healthy children 7-12 years of age (mean +/- standard deviation, 8.5 +/- 0.8 years) using serum samples obtained in 2004. Total antibody against HAV (anti-HAV) was detected in 438 children (84.2%), whereas IgG antibody against HEV (anti-HEV IgG) was detected in only three subjects (0.6%). All three subjects with anti-HEV IgG were negative for anti-HEV IgM and HEV RNA. The presence of HAV RNA was tested in all 520 subjects, and one child (9-year-old girl) was found to have detectable HAV RNA (subgenotype IA). In conclusion, HEV infection was uncommon, but subclinical HAV infection was highly prevalent among children in Mongolia.

Hepatitis E in Israel: A nation-wide retrospective study

PubMed Central

Erez-Granat, Ortal; Lachish, Tamar; Daudi, Nili; Shouval, Daniel; Schwartz, Eli

2016-01-01

AIM: To investigate the epidemiology, risk factors and clinical course of acute hepatitis E virus (HEV) infection in Israel, an industrialized country. METHODS: A retrospective analysis of acute HEV cases diagnosed in Israel from 1993 to 2013. Acute HEV was defined by ALT/AST elevation and a positive HEV PCR test or positive anti-HEV-IgM serology. HEV RNA was tested by quantitative reverse transcription PCR. Antibodies to HEV were tested retrospectively using an ELISA assay. HEV-RNA was sequenced using RT-PCR of ORF1 and ORF2 regions to diagnose genotype of the virus. Epidemiologic and clinical data were collected by reviewing the clinical files and through a telephone interview according to a structured questionnaire. RESULTS: Acute HEV was diagnosed in 68 patients. Among the 59 patients who gave an informed consent and were interviewed, 41% of infections were autochthonous (acquired in Israel), 44% travel-related and 15% imported by foreign workers. Autochthonous patients were mainly females (62.5%), more than half of them pregnant, 26% recalled consuming food or water in areas with poor sanitation, 44% ate non-kosher meat. Fulminant hepatitis developed in 3 patients (5%), all of them were females, two of them with post-partum infection, all acquired the disease in Israel (autochthonous). Israeli travelers with imported infection were predominantly males (73%), acquired the disease in the Indian subcontinent (81%), with 100% reporting having consumed fresh vegetables and drinks with ice cubes abroad. Six patients’ sera were tested for genotype and revealed HEV genotype 1 (all cases acquired in the Indian subcontinent). CONCLUSION: This is the first report which highlights the existence of hepatitis E as an autochthonous infection in Israel. Imported HEV originates mostly from the Indian subcontinent. PMID:27350735

Hepatitis E in Israel: A nation-wide retrospective study.

PubMed

Erez-Granat, Ortal; Lachish, Tamar; Daudi, Nili; Shouval, Daniel; Schwartz, Eli

2016-06-28

To investigate the epidemiology, risk factors and clinical course of acute hepatitis E virus (HEV) infection in Israel, an industrialized country. A retrospective analysis of acute HEV cases diagnosed in Israel from 1993 to 2013. Acute HEV was defined by ALT/AST elevation and a positive HEV PCR test or positive anti-HEV-IgM serology. HEV RNA was tested by quantitative reverse transcription PCR. Antibodies to HEV were tested retrospectively using an ELISA assay. HEV-RNA was sequenced using RT-PCR of ORF1 and ORF2 regions to diagnose genotype of the virus. Epidemiologic and clinical data were collected by reviewing the clinical files and through a telephone interview according to a structured questionnaire. Acute HEV was diagnosed in 68 patients. Among the 59 patients who gave an informed consent and were interviewed, 41% of infections were autochthonous (acquired in Israel), 44% travel-related and 15% imported by foreign workers. Autochthonous patients were mainly females (62.5%), more than half of them pregnant, 26% recalled consuming food or water in areas with poor sanitation, 44% ate non-kosher meat. Fulminant hepatitis developed in 3 patients (5%), all of them were females, two of them with post-partum infection, all acquired the disease in Israel (autochthonous). Israeli travelers with imported infection were predominantly males (73%), acquired the disease in the Indian subcontinent (81%), with 100% reporting having consumed fresh vegetables and drinks with ice cubes abroad. Six patients' sera were tested for genotype and revealed HEV genotype 1 (all cases acquired in the Indian subcontinent). This is the first report which highlights the existence of hepatitis E as an autochthonous infection in Israel. Imported HEV originates mostly from the Indian subcontinent.

Hepatitis E virus as an etiology of acute exacerbation of previously unrecognized asymptomatic patients with hepatitis B virus-related chronic liver disease.

PubMed

Kumar, Manoj; Sharma, Barjesh C; Sarin, Shiv K

2008-06-01

Hepatitis E virus (HEV) has recently been implicated in episodes of acute decompensation in patients having underlying chronic liver disease (CLD) of varying etiology. However, HEV as a cause of acute exacerbation of previously asymptomatic and unrecognized hepatitis B virus (HBV)-infected patients is less well described. The aim of the present study was to investigate the etiology of acute exacerbation of previously asymptomatic and unrecognized HBV-infected patients and to evaluate the relative role of HEV. We also investigated the effect of superinfection on the clinical spectrum of underlying HBV infection. Forty-three patients presented with the following were retrospectively analyzed: (i) clinical features suggestive of acute hepatitis; (ii) with hepatitis B surface antigen (HBsAg) (+); (iii) IgM hepatitis B core antibody (IgM anti-HBc) (-); (iv) no previous history of liver disease; (v) no features suggestive of CLD at presentation; (vi) HBsAg remaining (+) for at least 12 months on follow up; and (vii) having a follow-up biopsy during the convalescent phase showing evidence of chronic hepatitis B. Of the 43 patients, 21 were hepatitis e antigen (HBeAg) (+) (Gr.1) and 22 HBeAg (-) (Gr.2) at presentation. In Gr.1, only two (9.5%) had superinfection (both with hepatitis A virus), whereas in Gr.2, 11 (50%) had superinfection (27.3% hepatitis E, 13.6% hepatitis A and 9.1% both) (P = 0.007). In Gr.1, the remaining 19 (90.5%) patients had spontaneous exacerbation (immune clearance with spontaneous seroconversion) whereas in Gr.2, the remaining 11 (50%) had spontaneous exacerbation (due to reactivation). Overall, HEV superinfection contributed to 20% of acute exacerbation episodes and, in particular, 36% of episodes in initially HBeAg (-) patients. Time to alanine aminotransferase normalization was longer in patients with superinfection (n = 13) as compared to spontaneous exacerbation (n = 30) (median [range] 36 [8-48]vs 16 [6-36] weeks, P = 0.001). During

Hepatitis E-induced severe myositis.

PubMed

Mengel, Annerose M; Stenzel, Werner; Meisel, Andreas; Büning, Carsten

2016-02-01

Hepatitis E virus (HEV) is endemic in Asian and African countries but is rarely reported in Western countries. Although there are some prominent neurological manifestations, HEV is rarely recognized by neurologists. This is a case report of myositis induced by HEV. We report the life-threatening case of a 57-year-old man with flaccid tetraparesis due to myositis, acute hepatitis, and renal failure caused by HEV infection. Muscle biopsy revealed scattered myofiber necrosis with a diffuse, mild lymphomonocytic infiltrate in the endomysium and perimysium. Because the patient suffered from an acute HEV infection with a rapidly progressive course of severe myopathy, we started ribavirin treatment. He recovered partially within 3 weeks and recovered fully within 6 months. This case highlights a neurological manifestation of endemic HEV infection with severe myositis in a patient with alcoholic chronic liver disease. Ribavirin treatment is effective in severe HEV infection and may also lead to rapid neurological recovery. © 2015 Wiley Periodicals, Inc.

Characterization of the non-polio enterovirus infections associated with acute flaccid paralysis in South-Western India.

PubMed

Laxmivandana, Rongala; Yergolkar, Prasanna; Gopalkrishna, Varanasi; Chitambar, Shobha D

2013-01-01

Non-polio enteroviruses (NPEVs) have been reported frequently in association with acute flaccid paralysis (AFP) cases during Polio Surveillance Programs (PSPs) worldwide. However, there is limited understanding on the attributes of their infections. This study reports characteristics of NPEVs isolated from AFP cases, investigated during PSPs held in 2009-2010, in Karnataka and Kerala states of south-western India having varied climatic conditions. NPEV cell culture isolates derived from stool specimens that were collected from 422 of 2186 AFP cases (<1-14 years age) and 17 of 41 asymptomatic contacts; and details of all AFP cases/contacts were obtained from National Polio Laboratory, Bangalore. The distribution of NPEV infections among AFP cases and circulation pattern of NPEV strains were determined by statistical analysis of the data. Genotyping of all NPEV isolates was carried out by partial VP1 gene sequencing and phylogenetic analysis. NPEV positive AFP cases were significantly higher in children aged <2 years; with residual paralysis; in summer months; and in regions with relatively hot climate. Genotyping of NPEVs identified predominance of human enteroviruses (HEV)-B species [81.9%-Echoviruses (E): 57.3%; coxsackieviruses (CV) B: 15%; numbered EVs: 8.9%; CVA9: 0.7%] and low levels of HEV-A [14.5%-CVA: 6%; numbered EVs: 8.5%] and HEV-C [3.6%-CVA: 2.6%; numbered EVs: 1%] species, encompassing 63 genotypes. EV76 (6.3%) and each of E3, CVB3 and E9 (4.97%) were found frequently during 2009 while E11 (6.7%), CVB1 (6.1%), E7 (5.1%) and E20 (5.1%) were detected commonly in 2010. A marked proportion of AFP cases from children aged <2 years; presenting with fever; and from north and south interior parts of Karnataka state was detected with E/numbered EVs than that found with CVA/CVB. This study highlights the extensive genetic diversity and diverse circulation patterns of NPEV strains in AFP cases from different populations and climatic conditions.

Production of infectious dromedary camel hepatitis E virus by a reverse genetic system: Potential for zoonotic infection.

PubMed

Li, Tian-Cheng; Zhou, Xianfeng; Yoshizaki, Sayaka; Ami, Yasushi; Suzaki, Yuriko; Nakamura, Tomofumi; Takeda, Naokazu; Wakita, Takaji

2016-12-01

The pathogenicity, epidemiology and replication mechanism of dromedary camel hepatitis E virus (DcHEV), a novel hepatitis E virus (HEV), has been unclear. Here we used a reverse genetic system to produce DcHEV and examined the possibility of zoonotic infection. Capped genomic RNA derived from a synthetic DcHEV cDNA was transfected into human hepatocarcinoma cells PLC/PRF/5. The DcHEV capsid protein and RNA were detected by an enzyme-linked immunosorbent assay (ELISA) or RT-qPCR. A neutralization test for DcHEV was carried out by using antisera against HEV-like particles. DcHEV was used to inoculate two cynomolgus monkeys to examine the potential for cross-species infection. The transfection of PLC/PRF/5 cells with capped DcHEV RNA resulted in the production of infectious DcHEV. The genome sequence analysis demonstrated that both nucleotide and amino acid changes accumulated during the passages in PLC/PRF/5 cells. The cynomolgus monkeys showed serological signs of infection when DcHEV was intravenously inoculated. DcHEV was neutralized by not only anti-DcHEV-LPs antibody, but also anti-genotype 1 (G1), G3 and G4 HEV-LPs antibodies. Moreover, the monkeys immunized with DcHEV escaped the G3 HEV challenge, indicating that the serotype of DcHEV is similar to those of other human HEVs. Infectious DcHEV was produced using a reverse genetic system and propagated in PLC/PRF/5 cells. The antigenicity and immunogenicity of DcHEV are similar to those of G1, G3 and G4 HEV. DcHEV was experimentally transmitted to primates, demonstrating the possibility of a zoonotic infection by DcHEV. Dromedary camel hepatitis E virus (DcHEV) was produced by a reverse genetic system and grows well in PLC/PRF/5 cells. Cynomolgus monkeys experimentally infected with DcHEV indicated serological signs of infection, suggesting that DcHEV has the potential to cause zoonotic HEV infection. Copyright © 2016 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.

Identification of Genotype 3 Hepatitis E Virus (HEV) in Serum and Fecal Samples from Pigs in Thailand and Mexico, Where Genotype 1 and 2 HEV Strains Are Prevalent in the Respective Human Populations

PubMed Central

Cooper, K.; Huang, F. F.; Batista, L.; Rayo, C. D.; Bezanilla, J. C.; Toth, T. E.; Meng, X. J.

2005-01-01

Hepatitis E virus (HEV), the causative agent of hepatitis E, is an important public health concern in many developing countries. Increasing evidence indicates that hepatitis E is a zoonotic disease. There exist four major genotypes of HEV, and HEV isolates identified in samples from pigs belong to either genotype 3 or 4. Genotype 1 and 2 HEVs are found exclusively in humans. To determine whether genotype 1 and 2 HEVs also exist in pigs, a universal reverse transcription-PCR assay that is capable of detecting all four HEV genotypes was used to test for the presence of HEV RNA in serum and/or fecal samples from pigs in Thailand, where genotype 1 human HEV is prevalent, and from pigs in Mexico, where genotype 2 human HEV was epidemic. In Thailand, swine HEV RNA was detected in sera from 10/26 pigs of 2 to 4 months of age but not in sera from 50 pigs of other ages. In Mexico, swine HEV RNA was detected in 8/125 sera and 28/92 fecal samples from 2- to 4-month-old pigs. Antibodies to swine HEV were also detected in about 81% of the Mexican pigs. A total of 44 swine HEV isolates were sequenced for the open reading frame 2 gene region. Sequence analyses revealed that all swine HEV isolates identified in samples from pigs in Thailand and Mexico belong to genotype 3. Phylogenetic analyses revealed that minor branches associated with geographic origin exist among the swine HEV isolates. The results indicated that genotype 1 or 2 swine HEV does not exist in pigs from countries where the respective human HEV genotype 1 or 2 is prevalent. It is likely that only genotype 3 and 4 HEV strains have zoonotic potential. PMID:15814985

Southern Tunisia: A still high endemicity area for hepatitis A.

PubMed

Neffatti, Houcine; Lebraud, Patricia; Hottelet, Corinne; Gharbi, Jawher; Challouf, Taieb; Roque-Afonso, Anne-Marie

2017-01-01

Hepatitis A (HAV) and E (HEV) viruses are responsible for enterically transmitted hepatitis. Tunisia is reported to be of intermediate endemicity for HAV and of low seroprevalence for HEV; however, data from rural areas of South Tunisia are lacking. Sera from 216 asymptomatic pregnant women and from 92 patients with acute hepatitis were collected between October 2014 and November 2015. Total and IgM anti-HAV immunoglobulins and anti-HEV IgG and IgM were investigated. Anti-HAV IgM-positive samples were subjected to RT-PCR targeting the VP1/2A region and sequenced. HEV IgM positive samples and all samples from acute hepatitis patients were assessed for HEV RNA. Among pregnant women (mean age 32+/-8), HAV seroprevalence was 98.6%, none presented anti-HAV IgM; HEV seroprevalence was 5.1% and three presented weakly reactive anti-HEV IgM without detectable RNA. Among acute hepatitis patients (mean age 18.5 +/- 14), HEV seroprevalence was 19,5%, none presented anti-HEV IgM, nor HEV RNA. HAV seroprevalence exceeded 90% by age 5 and acute HAV infection was detected in 20 patients (21,7%), younger than patients with other hepatitis causes (9,8 years vs. 20,4 years, p = 0,004); 65% were male. Most acute HAV infections were observed in a coastal area where HAV infections represented 52% of hepatitis etiology. Phylogenetic analysis identified genotype IA strains, clustering close to previously published Tunisian sequences. The present study confirmed a low HEV endemicity and evidenced a still high level of HAV circulation in Southern Tunisia, suggesting distinct dissemination patterns for these viruses.

Southern Tunisia: A still high endemicity area for hepatitis A

PubMed Central

Neffatti, Houcine; Lebraud, Patricia; Hottelet, Corinne; Gharbi, Jawher; Challouf, Taieb

2017-01-01

Background Hepatitis A (HAV) and E (HEV) viruses are responsible for enterically transmitted hepatitis. Tunisia is reported to be of intermediate endemicity for HAV and of low seroprevalence for HEV; however, data from rural areas of South Tunisia are lacking. Methods Sera from 216 asymptomatic pregnant women and from 92 patients with acute hepatitis were collected between October 2014 and November 2015. Total and IgM anti-HAV immunoglobulins and anti-HEV IgG and IgM were investigated. Anti-HAV IgM-positive samples were subjected to RT-PCR targeting the VP1/2A region and sequenced. HEV IgM positive samples and all samples from acute hepatitis patients were assessed for HEV RNA. Results Among pregnant women (mean age 32+/-8), HAV seroprevalence was 98.6%, none presented anti-HAV IgM; HEV seroprevalence was 5.1% and three presented weakly reactive anti-HEV IgM without detectable RNA. Among acute hepatitis patients (mean age 18.5 +/- 14), HEV seroprevalence was 19,5%, none presented anti-HEV IgM, nor HEV RNA. HAV seroprevalence exceeded 90% by age 5 and acute HAV infection was detected in 20 patients (21,7%), younger than patients with other hepatitis causes (9,8 years vs. 20,4 years, p = 0,004); 65% were male. Most acute HAV infections were observed in a coastal area where HAV infections represented 52% of hepatitis etiology. Phylogenetic analysis identified genotype IA strains, clustering close to previously published Tunisian sequences. Conclusion The present study confirmed a low HEV endemicity and evidenced a still high level of HAV circulation in Southern Tunisia, suggesting distinct dissemination patterns for these viruses. PMID:28426700

Distinct changing profiles of hepatitis A and E virus infection among patients with acute hepatitis in Mongolia: The first report of the full genome sequence of a novel genotype 1 hepatitis E virus strain.

PubMed

Tsatsralt-Od, Bira; Primadharsini, Putu Prathiwi; Nishizawa, Tsutomu; Ohnishi, Hiroshi; Nagashima, Shigeo; Takahashi, Masaharu; Jirintai, Suljid; Nyamkhuu, Dulmaa; Okamoto, Hiroaki

2018-01-01

In January 2012, Mongolia started a hepatitis A vaccination program, which has not yet been evaluated. The first occurrence of autochthonous acute hepatitis E in 2013, caused by genotype 4 hepatitis E virus (HEV), suggests the need for a routine study to monitor its prevalence. One hundred fifty-four consecutive patients who were clinically diagnosed with acute hepatitis between 2014 and 2015 in Ulaanbaatar, Mongolia were studied. By serological and molecular testing followed by sequencing and phylogenetic analysis, only one patient (0.6%) was diagnosed with acute hepatitis A, caused by genotype IA hepatitis A virus (HAV), and 32 (20.8%) patients were diagnosed with acute hepatitis E, caused by genotype 1 HEV. The 32 HEV isolates obtained in this study shared 99.5-100% nucleotide identity and were grouped into a cluster separated from those of subtypes 1a to 1f. Upon comparison of p-distances over the entire genome, the distances between one representative HEV isolate (MNE15-072) and 1a-1f strains were 0.071-0.137, while those between 1b and 1c were 0.062-0.070. In conclusion, the prevalence of acute hepatitis A has decreased in Mongolia since the start of the vaccination program, while the monophyletic genotype 1 HEV strain of a probably novel subtype has been prevalent. © 2017 Wiley Periodicals, Inc.

Hepatitis E in blood donors: investigation of the natural course of asymptomatic infection, Germany, 2011.

PubMed

Vollmer, Tanja; Diekmann, Juergen; Eberhardt, Matthias; Knabbe, Cornelius; Dreier, Jens

2016-09-01

Asymptomatic hepatitis E virus (HEV) infections have been found in blood donors from various European countries, but the natural course is rarely specified. Here, we compared the progression of HEV viraemia, serostatus and liver-specific enzymes in 10 blood donors with clinically asymptomatic genotype 3 HEV infection, measuring HEV RNA concentrations, plasma concentrations of alanine/aspartate aminotransferase, glutamate dehydrogenase and bilirubin and anti-HEV IgA, IgM and IgG antibodies. RNA concentrations ranged from 77.2 to 2.19×10(5) IU/mL, with viraemia lasting from less than 10 to 52 days. Donors showed a typical progression of a recent HEV infection but differed in the first detection of anti-HEV IgA, IgM and IgG and seropositivity of the antibody classes. The diagnostic window between HEV RNA detection and first occurrence of anti-HEV antibodies ranged from eight to 48 days, depending on the serological assay used. The progression of laboratory parameters of asymptomatic HEV infection was largely comparable to the progression of symptomatic HEV infection, but only four of 10 donors showed elevated liver-specific parameters. Our results help elucidate the risk of transfusion-associated HEV infection and provide a basis for development of screening strategies. The diagnostic window illustrates that infectious blood donors can be efficiently identified only by RNA screening. This article is copyright of The Authors, 2016.

Hepatitis E virus coinfection with hepatotropic viruses in Egyptian children.

PubMed

Zaki, Maysaa El Sayed; Salama, Osama Saad; Mansour, Fathy Awaad; Hossein, Shaimaa

2008-06-01

Major hepatotropic viruses continue to be important causes of acute viral hepatitis in developing countries. This work was carried out to detect the seroprevalence of hepatitis E virus (HEV) markers in children with acute viral hepatitis due to hepatotropic viruses (A, B and C) and non-A, non-B, non-C acute hepatitis, and to ascertain the influence of HEV superinfection in individuals infected with hepatitis viruses (A, B and C). We studied prospectively 162 children with sporadic acute hepatitis who reported to our hospital. Thirteen healthy controls were also included in the study. Laboratory investigations were performed, including complete liver function tests. Complete serological profiles for hepatitis viruses A, B, C and E were evaluated. HEV immunoglobulin G was detected with highest percentage among patients with hepatitis B (56.7%), followed by patients with hepatitis C virus (52.0%), hepatitis A virus (34.1%) and combined hepatitis B and C viruses (30.0%). The detection rate among patients with non-A, non-B, non-C hepatitis was 7.1%. HEV immunoglobulin M was found in 4.5% of hepatitis A virus patients and in 3.3% of hepatitis B patients. The prevalence of HEV immunoglobulin G and immunoglobulin M correlated with the levels of hepatic aspartate aminotransferase and alanine aminotransferase in patients with dual markers of infection with hepatitis E and other viruses compared to patients with acute hepatitis due to A and C viruses. HEV serological markers are common among children with acute viral hepatitis, especially from hepatitis C and B viruses. There may be increased sensitivity to HEV coinfection in association with hepatitis B and C infections. Dual infection with HEV and other hepatotropic viruses was associated with greater elevation of aspartate and alanine aminotransferases.

Why is the market for hybrid electric vehicles (HEVs) moving slowly?

PubMed

Rahmani, Djamel; Loureiro, Maria L

2018-01-01

Hybrid electric vehicles (HEVs) could be a good short term option to help achieve global targets regarding road transport greenhouse gas emissions. Several common and country-specific public policies based on price or tax rebates are established in order to encourage the adoption of HEVs. The present research empirically assesses market preferences for HEVs in Spain, looking at the role of subsidies. An interactive internet-based survey was conducted in a representative sample (N = 1,200) of Spanish drivers. Drivers are willing to pay an extra amount of €1,645 for a HEV model compared to a conventional vehicle, premium which is well below the price markup for these cars. Therefore, current levels of economic subsidies applied in isolation to promote these types of vehicles may have a quite limited effect in extending their use. Overall, it is found that drivers have clear misconceptions about HEVs, which affect their purchasing choices and perceptions. Therefore, a policy mix of various incentives (including informational campaigns) may be required in order to stimulate the demand for HEVs.

Why is the market for hybrid electric vehicles (HEVs) moving slowly?

PubMed Central

Rahmani, Djamel; Loureiro, Maria L.

2018-01-01

Hybrid electric vehicles (HEVs) could be a good short term option to help achieve global targets regarding road transport greenhouse gas emissions. Several common and country-specific public policies based on price or tax rebates are established in order to encourage the adoption of HEVs. The present research empirically assesses market preferences for HEVs in Spain, looking at the role of subsidies. An interactive internet-based survey was conducted in a representative sample (N = 1,200) of Spanish drivers. Drivers are willing to pay an extra amount of €1,645 for a HEV model compared to a conventional vehicle, premium which is well below the price markup for these cars. Therefore, current levels of economic subsidies applied in isolation to promote these types of vehicles may have a quite limited effect in extending their use. Overall, it is found that drivers have clear misconceptions about HEVs, which affect their purchasing choices and perceptions. Therefore, a policy mix of various incentives (including informational campaigns) may be required in order to stimulate the demand for HEVs. PMID:29561860

First reported outbreak of locally acquired hepatitis E virus infection in Australia.

PubMed

Yapa, Chaturangi M; Furlong, Catriona; Rosewell, Alexander; Ward, Kate A; Adamson, Sheena; Shadbolt, Craig; Kok, Jen; Tracy, Samantha L; Bowden, Scott; Smedley, Elizabeth J; Ferson, Mark J; Sheppeard, Vicky; McAnulty, Jeremy M

2016-04-18

To determine the source and extent of a locally acquired hepatitis E virus (HEV) infection outbreak. A cluster of notified cases of HEV infection linked to a single restaurant (X) was identified in May 2014. People with laboratory-confirmed HEV infection in New South Wales between January 2013 and December 2014 were interviewed about potential risk factors for HEV infection. Co-diners at restaurant X and patients with suspected but unexplained viral hepatitis were retrospectively tested. Foods eaten by the infected persons were compared with those of seronegative co-diners. HEV RNA detected in sera from infected persons was sequenced and genotyped. Implicated foods were traced back to their sources. Potential sources of infection, including overseas travel and foods eaten, and origin of implicated food products. In 55 serologically confirmed cases of HEV infection, 24 people had not travelled overseas during their incubation periods. Of the 24, 17 reported having eaten at restaurant X, 15 of whom could be interviewed. All reported consuming pork liver pâté, compared with only four of seven uninfected co-diners (P < 0.05). The other seven people with locally acquired infections each reported consuming a pork product during their incubation periods. HEV RNA was detected in 16 of the 24 cases; all were of genotype 3. Sequencing indicated greater than 99% homology among restaurant X isolates. HEV RNA was isolated from pork sausages from a batch implicated in one of the locally acquired infections not linked with restaurant X. The pork livers used for pâté preparation by restaurant X were traced to a single Australian farm. This is the first reported HEV outbreak in Australia. HEV should be considered in patients presenting with a compatible illness, even without a history of overseas travel. Pork products should be thoroughly cooked before consumption.

Advances in hepatitis E - II: Epidemiology, clinical manifestations, treatment and prevention.

PubMed

Goel, Amit; Aggarwal, Rakesh

2016-09-01

Infection with hepatitis E virus (HEV) is the commonest cause of acute hepatitis worldwide. This infection, with fecal-oral transmission, was previously thought to be limited to humans residing in developing countries with poor sanitation, spreading via contaminated drinking water. In recent years, our understanding of epidemiology and clinical spectrum of this infection have changed markedly. This article reviews the epidemiology, including routes of transmission, and clinical manifestations of HEV infection around the world. In addition, recent findings on transmission-associated HEV infection, extrahepatic manifestations of hepatitis E and chronic infection with HEV, and treatment and prevention of this infection are discussed. Expert commentary: HEV infection has two distinct epidemiologic forms and clinical patterns of disease: (i) acute epidemic or sporadic hepatitis caused by fecal-oral (usually water-borne) transmission of genotype 1 and 2 HEV from a human reservoir in areas with poor hygiene and frequent water contamination, and (ii) infrequent sporadic hepatitis E caused by zoonotic infection, possibly from an animal source through ingestion of undercooked animal meal, of genotype 3 or 4 virus. In disease-endemic areas, pregnant women are at a particular risk of serious disease and high mortality. In less-endemic areas, chronic infection with HEV among immunosuppressed persons is observed. HEV can also be transmitted through Transfusion of blood and blood products. Ribivirin treatment is effective in chronic hepatitis E. Two efficacious vaccines have been tried in humans; one of these has received marketing approval in its country of origin.

Identification of European-type hepatitis E virus subtype 3e isolates in Japanese wild boars: molecular tracing of HEV from swine to wild boars.

PubMed

Nakano, Tatsunori; Takahashi, Kazuaki; Arai, Masahiro; Okano, Hiroshi; Kato, Hideaki; Ayada, Minoru; Okamoto, Hiroaki; Mishiro, Shunji

2013-08-01

Nucleotide sequences of hepatitis E virus (HEV) isolates infecting wild boars in Mie prefecture, which is located in the central region of Japan and is far from the most prevalent regions of HEV infection in Japan, were determined and characterised. Among 144 serum samples of wild boars captured in Mie prefecture, 7 were positive for HEV-RNA. The nucleotide sequence of nearly the entire genome was determined for 4 of the 7 positive samples. Phylogenetic tree analyses indicated that 6 samples were subtype 3e and 1 was subtype 3a among the 7 isolates. We identified the indigenization of subtype 3e isolates in Japanese wild boars. Furthermore, 5 subtype 3e isolates were closely related and were located in the peripheral branch of subtype 3e isolates from European countries in the phylogenetic tree. The structure indicated that the ancestor of the 5 subtype 3e isolates originated in Europe. The phylogenetic structure and coalescent analyses suggested that the subtype 3e isolates entered Japan from Europe by importation of large-race pigs around 1966. The results also indicated that several lineages of subtype 3e expanded to a wide area of Japan around 1992 and 1 of the lineages was indigenized in wild boars in Mie prefecture between 1992 and 2009. The appearance of a wild boar cluster in the peripheral branch in the phylogenetic lineage may indicate the direction of gene flow of HEV subtype 3e from swine to wild boars. Clarification of the transmission direction or route should be helpful to prevent a future endemic or epidemic of HEV infection. Copyright © 2013 Elsevier B.V. All rights reserved.

Cutthroat trout virus as a surrogate in vitro infection model for testing inhibitors of hepatitis E virus replication

USGS Publications Warehouse

Debing, Yannick; Winton, James; Neyts, Johan; Dallmeier, Kai

2013-01-01

Hepatitis E virus (HEV) is one of the most important causes of acute hepatitis worldwide. Although most infections are self-limiting, mortality is particularly high in pregnant women. Chronic infections can occur in transplant and other immune-compromised patients. Successful treatment of chronic hepatitis E has been reported with ribavirin and pegylated interferon-alpha, however severe side effects were observed. We employed the cutthroat trout virus (CTV), a non-pathogenic fish virus with remarkable similarities to HEV, as a potential surrogate for HEV and established an antiviral assay against this virus using the Chinook salmon embryo (CHSE-214) cell line. Ribavirin and the respective trout interferon were found to efficiently inhibit CTV replication. Other known broad-spectrum inhibitors of RNA virus replication such as the nucleoside analog 2′-C-methylcytidine resulted only in a moderate antiviral activity. In its natural fish host, CTV levels largely fluctuate during the reproductive cycle with the virus detected mainly during spawning. We wondered whether this aspect of CTV infection may serve as a surrogate model for the peculiar pathogenesis of HEV in pregnant women. To that end the effect of three sex steroids on in vitro CTV replication was evaluated. Whereas progesterone resulted in marked inhibition of virus replication, testosterone and 17β-estradiol stimulated viral growth. Our data thus indicate that CTV may serve as a surrogate model for HEV, both for antiviral experiments and studies on the replication biology of the Hepeviridae.

Hepatitis E and pregnancy: current state.

PubMed

Pérez-Gracia, María Teresa; Suay-García, Beatriz; Mateos-Lindemann, María Luisa

2017-03-20

Hepatitis E virus (HEV) is responsible for more than 50% of acute viral hepatitis cases in endemic countries. Approximately 2 billion individuals live in hepatitis E-endemic areas and, therefore, are at risk of infection. According to World Health Organization, HEV causes about 20.1 million infections and 70 000 deaths every year. In developing countries with poor sanitation, this disease is transmitted through contaminated water and is associated with large outbreaks, affecting hundreds or thousands of people. In developed countries, autochthonous cases of HEV have been increasingly recognized in the past several years. Hepatitis E virus typically causes an acute, self-limiting illness similar to other acute viral hepatitis, such as hepatitis A or B, with about 0.2% to 1% mortality rate in the general population. However, the course of hepatitis E in pregnancy is different than the mild self-constraining infection described in other populations. During pregnancy, HEV infection can take a fulminant course, resulting in fulminant hepatic failure, membrane rupture, spontaneous abortions, and stillbirths. Studies from various developing countries have shown a high incidence of HEV infection in pregnancy with a significant proportion of pregnant women progressing to fulminant hepatitis with a fatality rate of up to 30%. The present review will highlight new aspects of the HEV infection and pregnancy. Copyright © 2017 John Wiley & Sons, Ltd.

First Report of Hepatitis E Virus Infection in Sika Deer in China

PubMed Central

Zhang, Xiao-Xuan; Qin, Si-Yuan; Zhang, Yuan; Meng, Qing-Feng; Jiang, Jing; Yang, Gui-Lian; Zhao, Quan; Zhu, Xing-Quan

2015-01-01

Hepatitis E virus (HEV), a single stranded RNA, nonenveloped virus, belongs to the genus Hepevirus, in the family of Hepeviridae. In this study, 46 (5.43%) out of the 847 serum samples from sika deer (Cervus nippon) were detected as seropositive with hepatitis E virus (HEV) by enzyme linked immunosorbent assay (ELISA). These samples were collected from Inner Mongolia and Jilin and Heilongjiang provinces in China, between October 2012 and October 2013. Seroprevalence of HEV infection in male and female deer was 4.82% and 6.52%, respectively. HEV seroprevalence in sika deer from different geographical locations varied from 3.13% to 6.73%. There was no significant difference in HEV seroprevalence between sika deer collected in autumn (5.65%) and winter (4.85%). This is the first report of HEV seroprevalence in sika deer in China, which will provide foundation information for estimating the effectiveness of future measures to control HEV infection in sika deer in China and assessing the potential risk of humans infected with HEV after consumption of undercooked or raw meat from infected sika deer. PMID:25949999

First report of hepatitis E virus infection in sika deer in China.

PubMed

Zhang, Xiao-Xuan; Qin, Si-Yuan; Zhang, Yuan; Meng, Qing-Feng; Jiang, Jing; Yang, Gui-Lian; Zhao, Quan; Zhu, Xing-Quan

2015-01-01

Hepatitis E virus (HEV), a single stranded RNA, nonenveloped virus, belongs to the genus Hepevirus, in the family of Hepeviridae. In this study, 46 (5.43%) out of the 847 serum samples from sika deer (Cervus nippon) were detected as seropositive with hepatitis E virus (HEV) by enzyme linked immunosorbent assay (ELISA). These samples were collected from Inner Mongolia and Jilin and Heilongjiang provinces in China, between October 2012 and October 2013. Seroprevalence of HEV infection in male and female deer was 4.82% and 6.52%, respectively. HEV seroprevalence in sika deer from different geographical locations varied from 3.13% to 6.73%. There was no significant difference in HEV seroprevalence between sika deer collected in autumn (5.65%) and winter (4.85%). This is the first report of HEV seroprevalence in sika deer in China, which will provide foundation information for estimating the effectiveness of future measures to control HEV infection in sika deer in China and assessing the potential risk of humans infected with HEV after consumption of undercooked or raw meat from infected sika deer.

Infection with hepatitis A, B, C, and delta viruses among patients with acute hepatitis in Mongolia.

PubMed

Tsatsralt-Od, Bira; Takahashi, Masaharu; Endo, Kazunori; Buyankhuu, Osorjin; Baatarkhuu, Oidov; Nishizawa, Tsutomu; Okamoto, Hiroaki

2006-05-01

One hundred ten consecutive patients (60 males and 50 females; age, mean +/- standard deviation [SD], 22.6 +/- 6.4 years; range 16-48 years) who were clinically diagnosed with sporadic acute hepatitis between December 2004 and January 2005 in Ulaanbaatar, Mongolia, were studied. IgM antibodies to hepatitis A virus were detected in 18 patients (16.4%), IgM antibodies to hepatitis B core (anti-HBc IgM) in 38 patients (34.5%) including two patients with concurrent hepatitis delta virus (HDV) infection, and hepatitis C virus RNA in nine patients (8.2%). There were 30 hepatitis B virus (HBV) carriers who had detectable hepatitis B surface antigen and antibodies to HDV but were negative for anti-HBc IgM, suggesting that they acquired type D acute hepatitis due to superinfection of HDV on a background of chronic HBV infection. None had IgM antibodies to hepatitis E virus (HEV). Consequently, 16.4, 32.7, 6.4, 1.8, and 27.3% of the patients were diagnosed as having acute hepatitis of type A, B, C, type B + D (HBV/HDV coinfection), and type D (superinfection of HDV), respectively. The cause of hepatitis was not known in the remaining 17 patients (15.5%). All 18 HAV isolates were genotyped as IA, all 9 HCV isolates were genotyped as 1b, and all 32 HDV isolates were classified into genotype I. The distribution of HBV genotypes among the 67 HBV isolates was A (1.5%, n = 1) and D (98.5%, n = 66). The present study indicates that de novo infections of HAV, HBV, HCV, and HDV are prevalent among young adults in Mongolia. Copyright 2006 Wiley-Liss, Inc.

Hepatitis E virus infections in travellers: assessing the threat to the Australian blood supply.

PubMed

Shrestha, Ashish C; Flower, Robert L P; Seed, Clive R; Keller, Anthony J; Hoad, Veronica; Harley, Robert; Leader, Robyn; Polkinghorne, Ben; Furlong, Catriona; Faddy, Helen M

2017-05-01

In many developed countries hepatitis E virus (HEV) infections have occurred predominantly in travellers to countries endemic for HEV. HEV is a potential threat to blood safety as the virus is transfusion-transmissible. To minimise this risk in Australia, individuals diagnosed with HEV are deferred. Malarialdeferrals, when donors are restricted from donating fresh blood components following travel toanareain which malaria is endemic, probably also decrease the HEV risk, by deferring donors who travel to many countries also endemic for HEV. The aim of this study is to describe overseas-acquired HEV cases in Australia, in order to determine whether infection in travellers poses a risk to Australian blood safety. Details of all notified HEV cases in Australia from 2002 to 2014 were accessed, and importation rates estimated. Countries in which HEV was acquired were compared to those for which donations are restricted following travel because of a malaria risk. Three hundred and thirty-two cases of HEV were acquired overseas. Travel to India accounted for most of these infections, although the importation rate was highest for Nepal and Bangladesh. Countries for which donations are restricted following travel due to malaria risk accounted for 94% of overseas-acquired HEV cases. The vast majority of overseas-acquired HEV infections were in travellers returning from South Asian countries, which are subject to donation-related travel restrictions for malaria. This minimises the risk HEV poses to the Australian blood supply.

Hepatitis E virus infections in travellers: assessing the threat to the Australian blood supply

PubMed Central

Shrestha, Ashish C.; Flower, Robert L.P.; Seed, Clive R.; Keller, Anthony J.; Hoad, Veronica; Harley, Robert; Leader, Robyn; Polkinghorne, Ben; Furlong, Catriona; Faddy, Helen M.

2017-01-01

Background In many developed countries hepatitis E virus (HEV) infections have occurred predominantly in travellers to countries endemic for HEV. HEV is a potential threat to blood safety as the virus is transfusion-transmissible. To minimise this risk in Australia, individuals diagnosed with HEV are deferred. Malarialdeferrals, when donors are restricted from donating fresh blood components following travel toanareain which malaria is endemic, probably also decrease the HEV risk, by deferring donors who travel to many countries also endemic for HEV. The aim of this study is to describe overseas-acquired HEV cases in Australia, in order to determine whether infection in travellers poses a risk to Australian blood safety. Materials and methods Details of all notified HEV cases in Australia from 2002 to 2014 were accessed, and importation rates estimated. Countries in which HEV was acquired were compared to those for which donations are restricted following travel because of a malaria risk. Results Three hundred and thirty-two cases of HEV were acquired overseas. Travel to India accounted for most of these infections, although the importation rate was highest for Nepal and Bangladesh. Countries for which donations are restricted following travel due to malaria risk accounted for 94% of overseas-acquired HEV cases. Discussion The vast majority of overseas-acquired HEV infections were in travellers returning from South Asian countries, which are subject to donation-related travel restrictions for malaria. This minimises the risk HEV poses to the Australian blood supply. PMID:27483488

Serological evidence of hepatitis E virus infection in dromedary camels in Ethiopia.

PubMed

Li, Tian-Cheng; Yoshizaki, Sayaka; Zhou, Xianfeng; Sentsui, Hiroshi; Shirato, Kazuya; Matsuyama, Shutoku; Melaku, Simenew Keskes; Bazartseren, Boldbaatar; Takeda, Naokazu; Wakita, Takaji

2017-08-01

The genome of dromedary camel hepatitis E virus (DcHEV) has been detected in stool and serum samples from dromedary camels, but the sero-epidemiological information of DcHEV infection remains unclear. A total of 246 serum samples collected from dromedary camels (Camelus dromedarius) in Ethiopia, and 40 serum samples from Bactrian camels (Camelus ferus) in Mongolia were examined for the detection of anti-DcHEV IgG antibody by a newly developed enzyme-linked immunosorbent assay (ELISA) by using DcHEV-like particles (DcHEV-LPs) as the antigen. The results revealed that 55 of the 246 (22.4%) dromedary camels were positive for anti-DcHEV IgG, whereas all 40 samples from the Bactrian camels were negative for DcHEV IgG antibody. A total of 98 serum samples from dromedary camels, including 25 anti-DcHEV-IgG positive samples, were used for the detection of DcHEV RNA by reverse transcription-polymerase chain reaction (RT-PCR), however, no positive samples were identified. These results suggested that the DcHEV infection occurred in the dromedary camels in Ethiopia. Further studies are required to determine whether Bactrian camels are susceptible to DcHEV infection. In addition, not only DcHEV-LPs, but also virus-like particles (VLPs) delivered from G1, G3 and G5 HEV are likely applicable for the detection of the anti-DcHEV IgG antibody. Copyright © 2017 Elsevier B.V. All rights reserved.

Cutthroat trout virus as a surrogate in vitro infection model for testing inhibitors of hepatitis E virus replication.

PubMed

Debing, Yannick; Winton, James; Neyts, Johan; Dallmeier, Kai

2013-10-01

Hepatitis E virus (HEV) is one of the most important causes of acute hepatitis worldwide. Although most infections are self-limiting, mortality is particularly high in pregnant women. Chronic infections can occur in transplant and other immune-compromised patients. Successful treatment of chronic hepatitis E has been reported with ribavirin and pegylated interferon-alpha, however severe side effects were observed. We employed the cutthroat trout virus (CTV), a non-pathogenic fish virus with remarkable similarities to HEV, as a potential surrogate for HEV and established an antiviral assay against this virus using the Chinook salmon embryo (CHSE-214) cell line. Ribavirin and the respective trout interferon were found to efficiently inhibit CTV replication. Other known broad-spectrum inhibitors of RNA virus replication such as the nucleoside analog 2'-C-methylcytidine resulted only in a moderate antiviral activity. In its natural fish host, CTV levels largely fluctuate during the reproductive cycle with the virus detected mainly during spawning. We wondered whether this aspect of CTV infection may serve as a surrogate model for the peculiar pathogenesis of HEV in pregnant women. To that end the effect of three sex steroids on in vitro CTV replication was evaluated. Whereas progesterone resulted in marked inhibition of virus replication, testosterone and 17β-estradiol stimulated viral growth. Our data thus indicate that CTV may serve as a surrogate model for HEV, both for antiviral experiments and studies on the replication biology of the Hepeviridae. Copyright © 2013 Elsevier B.V. All rights reserved.

Further demonstration of the VRLA-type UltraBattery under medium-HEV duty and development of the flooded-type UltraBattery for micro-HEV applications

NASA Astrophysics Data System (ADS)

Furukawa, J.; Takada, T.; Monma, D.; Lam, L. T.

The UltraBattery has been invented by the CSIRO Energy Technology in Australia and has been developed and produced by the Furukawa Battery Co., Ltd., Japan. This battery is a hybrid energy storage device which combines a super capacitor and a lead-acid battery in single unit cells, taking the best from both technologies without the need of extra, expensive electronic controls. The capacitor enhances the power and lifespan of the lead-acid battery as it acts as a buffer during high-rate discharging and charging, thus enabling it to provide and absorb charge rapidly during vehicle acceleration and braking. The laboratory results of the prototype valve-regulated UltraBatteries show that the capacity, power, available energy, cold cranking and self-discharge of these batteries have met, or exceeded, all the respective performance targets set for both minimum and maximum power-assist HEVs. The cycling performance of the UltraBatteries under micro-, mild- and full-HEV duties is at least four times longer than that of the state-of-the-art lead-acid batteries. Importantly, the cycling performance of UltraBatteries is proven to be comparable or even better than that of the Ni-MH cells. On the other hand, the field trial of UltraBatteries in the Honda Insight HEV shows that the vehicle has surpassed 170,000 km and the batteries are still in a healthy condition. Furthermore, the UltraBatteries demonstrate very good acceptance of the charge from regenerative braking even at high state-of-charge, e.g., 70% during driving. Therefore, no equalization charge is required for the UltraBatteries during field trial. The HEV powered by UltraBatteries gives slightly higher fuel consumption (cf., 4.16 with 4.05 L/100 km) and CO 2 emissions (cf., 98.8 with 96 g km -1) compared with that by Ni-MH cells. There are no differences in driving experience between the Honda Insight powered by UltraBatteries and by Ni-MH cells. Given such comparable performance, the UltraBattery pack costs

Seroepidemiology of hepatitis E virus infection in pigs in Durango State, Mexico.

PubMed

Alvarado-Esquivel, Cosme; Sánchez-Anguiano, Luis F; Hernández-Tinoco, Jesús; Alvarado-Félix, Ángel O

2018-02-01

No information about hepatitis E virus (HEV) infection in pigs in the northern Mexican state of Durango exists. We determined the seroprevalence and correlates of anti-HEV IgG antibodies in pigs in Durango, Mexico. Through a cross-sectional study, we studied 427 pigs raised in backyards (n = 328), or slaughtered (n = 99) in Durango. Sera of pigs were analyzed for anti-HEV IgG antibodies using a commercially available enzyme-linked immunoassay. Antibodies to HEV were found in 193 (45.2%) of the 427 pigs studied. A significantly higher seroprevalence was observed in slaughtered pigs (79.8%) than in backyard pigs (34.8%). Bivariate analysis showed that HEV seropositivity was associated with age, sex, breed, climate, altitude, mean annual temperature, mean annual rainfall, and farm raising. Logistic regression analysis showed that HEV seropositivity was associated with the origin (Sonora State) of pigs (OR=6.51; 95%CI: 3.74-11.32; P < 0.001), and mean annual rainfall (≤600 mm) (OR=1.78; 95%CI: 1.01-3.15; P = 0.04). A high seroprevalence of HEV infection in pigs slaughtered for human consumption in Durango City was found. This is the first report of an association between HEV seropositivity in pigs and climatic factors. Infection factors found may help for the optimal planning of preventive measures against HEV infection. © 2017 Wiley Periodicals, Inc.

Infectivity titration of a prototype strain of hepatitis E virus in cynomolgus monkeys.

PubMed

Tsarev, S A; Tsareva, T S; Emerson, S U; Yarbough, P O; Legters, L J; Moskal, T; Purcell, R H

1994-06-01

The infectivity titer of a standard stock of the SAR-55 strain of hepatitis E virus (HEV) was determined in cynomolgus macaques (Macaca fascicularis) and the effect of dose on the course of the infection was examined by weekly monitoring of alanine aminotransferase (ALT) and anti-HEV levels. Antibody to HEV (anti-HEV) was measured with ELISAs based on ORF-2 recombinant antigens consisting of either a 55 kDa region expressed in insect cells or shorter regions expressed as fusion proteins in bacteria. The ELISA based on the 55 kDa antigen was generally more sensitive. The infectivity titer of SAR-55 was 10(6) cynomolgus 50% infectious doses per gram of feces. The infectivity titer corresponded to the HEV genome titer of the inoculum as determined by reverse transcriptase-polymerase chain reaction (RT-PCR). Anti-HEV IgM was detected in only a portion of the animals that had an anti-HEV IgG response. Biochemical evidence of hepatitis was most prominent in animals that were inoculated with the higher concentrations of virus and the incubation period to seroconversion was prolonged in animals that received the lower doses.

Dual infection with hepatitis A and E viruses in outbreaks and in sporadic clinical cases: Cuba 1998-2003.

PubMed

Rodríguez Lay, Licel de los Angeles; Quintana, Ariel; Villalba, María Caridad Montalvo; Lemos, Gilda; Corredor, Marité Bello; Moreno, Aidonis Gutiérrez; Prieto, Pablo Aguiar; Guzmán, María G; Anderson, David

2008-05-01

Viral hepatitis ranks as the fifth cause of morbidity for infectious diseases in Cuba. Epidemics are observed frequently in the population, the hepatitis A virus being the main agent responsible for such epidemics. Previous reports also confirmed the circulation of the hepatitis E virus. From 1998 to 2003, 258 serum samples were collected by the Reference Laboratory on Viral Hepatitis during 33 outbreaks of acute viral hepatitis as well as from 39 sporadic clinical cases. Sera were tested for anti-HAV and anti-HEV IgM by EIA. Overall of the 33 outbreaks studied sera from 12 (36.4%) were positive for anti-HAV IgM only, from 7 (21.2%) were positive for anti-HEV IgM only, and from 14 (42.4%) were positive for antibodies to both viruses. Individually of the 258 sera collected, 137 (53.1%) were positives for anti-HAV IgM, 20 (7.8%) were positives for anti-HEV IgM, 33 (12.8%) were positives for both markers and 68 (26.4%) were negative to both. Of the clinical cases, 4 (10.3%) were positives for anti-HAV IgM, 13 (33.3%) were positives for anti-HEV IgM and 5 (12.8%) were positives for both markers. Seventeen (43.6%) sera were negatives for all viral hepatitis markers available (A-E). A high positivity for HEV was found in outbreaks tested with the kit produced by CIGB. In particular HEV seems to infect individuals of all ages. The results demonstrate the co-circulation of and co-infection with two enterically transmitted viruses; however a higher positivity was observed for anti-HAV than to anti-HEV (53.1% vs. 7.8%) in outbreaks.

Prevalence of hepatitis viruses in patients with acute hepatitis and characterization of the detected genotype 4 hepatitis E virus sequences in Mongolia.

PubMed

Tsatsralt-Od, Bira; Baasanjav, Nachin; Nyamkhuu, Dulmaa; Ohnishi, Hiroshi; Takahashi, Masaharu; Okamoto, Hiroaki

2016-02-01

Hepatitis E is considered to be a worldwide public health problem. Although the prevalence of hepatitis E virus (HEV) antibodies in healthy individuals is noted to be 11%, no patients with acute hepatitis E have previously been identified in Mongolia. Three hundred two consecutive patients (183 males and 119 females; median age of 22.0 [Interquartile range: 18.3-25.0] years) who were clinically diagnosed with sporadic acute hepatitis during 2012-2013 in Ulaanbaatar, Mongolia, were studied. By serological and/or molecular approaches, 77 (25.5%), 93 (30.8%), 19 (6.3%), 48 (15.9%), and 12 (4.0%) of the patients were diagnosed with acute hepatitis of types A, B, C, D (superinfection of hepatitis delta virus on a background of chronic hepatitis B virus infection) and E, respectively, while the cause of hepatitis was unknown in the remaining 53 patients (17.5%). The 12 hepatitis E patients had no history of travel abroad in the 3 months before the onset of disease, and lived separately in fixed or movable houses with water supplied via pipe, tank or well, denying transmission from a common water supply. The 12 HEV isolates obtained from the patients showed high nucleotide identities of 99.7-100%, and a representative HEV isolate, MNE13-227, was closest to the Chinese isolates of genotype 4, with the highest identity of 97.3% in the 304-nt ORF2 sequence and 92.1% over the entire genome. The present study revealed the occurrence of autochthonous acute hepatitis E in Mongolia, caused by a monophyletic genotype 4 HEV strain. © 2015 Wiley Periodicals, Inc.

Determination of the full-genome sequence of hepatitis E virus (HEV) SAAS-FX17 and use as a reference to identify putative HEV genotype 4 virulence determinants.

PubMed

Zhu, Yumin; Yu, Xiaoming; Huang, Fenfen; Yu, Ruisong; Dong, Shijuan; Si, Fusheng; Zhang, Yuanshu; Li, Zhen

2012-11-08

Four major genotypes of hepatitis E virus (HEV), the causative agent of hepatitis E, have so far been recognized. While genotypes 3 and 4 are both zoonotic, the disease symptoms caused by the latter tend to be more severe. To examine if specific nucleotide/amino acid variations between genotypes 3 and 4 play a role in determining the severity of hepatitis E disease, the complete genome of one swine HEV genotype 4 isolate, SAAS-FX17, was determined and compared with other genotype 4 and genotype 3 genomes to identify putative HEV genotype 4 virulence determinants. A total of 42 conformable nt/aa variations between genotype 3 and 4 HEVs were detected, of which 19 were proposed to be potential disease severity determinants for genotype 4 strains. One potential determinant was located in each of the 5'-UTR and 3'-UTR, 3 and 12 within ORF1 and ORF2 respectively, and 2 in the junction region.

Construction of an infectious cDNA clone of avian hepatitis E virus (avian HEV) recovered from a clinically healthy chicken in the United States and characterization of its pathogenicity in specific-pathogen-free chickens.

PubMed

Kwon, Hyuk Moo; LeRoith, Tanya; Pudupakam, R S; Pierson, F William; Huang, Yao-Wei; Dryman, Barbara A; Meng, Xiang-Jin

2011-01-27

A genetically distinct strain of avian hepatitis E virus (avian HEV-VA strain) was isolated from a healthy chicken in Virginia, and thus it is important to characterize and compare its pathogenicity with the prototype strain (avian HEV-prototype) isolated from a diseased chicken. Here we first constructed an infectious clone of the avian HEV-VA strain. Capped RNA transcripts from the avian HEV-VA clone were replication-competent after transfection of LMH chicken liver cells. Chickens inoculated intrahepatically with RNA transcripts of avian HEV-VA clone developed active infection as evidenced by fecal virus shedding, viremia, and seroconversion. To characterize the pathogenicity, RNA transcripts of both avian HEV-VA and avian HEV-prototype clones were intrahepatically inoculated into the livers of chickens. Avian HEV RNA was detected in feces, serum and bile samples from 10/10 avian HEV-VA-inoculated and 9/9 avian HEV-prototype-inoculated chickens although seroconversion occurred only in some chickens during the experimental period. The histopathological lesion scores were lower for avian HEV-VA group than avian HEV-prototype group in the liver at 3 and 5 weeks post-inoculation (wpi) and in the spleen at 3 wpi, although the differences were not statistically significant. The liver/body weight ratio, indicative of liver enlargement, of both avian HEV-VA and avian HEV-prototype groups were significantly higher than that of the control group at 5 wpi. Overall, the avian HEV-VA strain still induces histological liver lesions even though it was isolated from a healthy chicken. The results also showed that intrahepatic inoculation of chickens with RNA transcripts of avian HEV infectious clone may serve as an alternative for live virus in animal pathogenicity studies. Copyright © 2010 Elsevier B.V. All rights reserved.

Comparison of hepatitis A and E virus infections among healthy children in Mongolia: evidence for infection with a subgenotype IA HAV in children.

PubMed

Tsatsralt-Od, Bira; Takahashi, Masaharu; Endo, Kazunori; Agiimaa, Dondog; Buyankhuu, Osorjin; Okamoto, Hiroaki

2007-01-01

To compare the epidemiologic profiles of hepatitis A virus (HAV) and hepatitis E virus (HEV) infections in children in Mongolia, the prevalence of HAV and HEV infections was investigated serologically and molecularly among 717 apparently healthy individuals of 0-20 years of age (mean +/- standard deviation, 8.6 +/- 4.9 years) using serum samples obtained between October 2005 and January 2006. Total antibody against HAV (anti-HAV [total]) was detected in 494 (68.9%) of the 717 subjects, while IgG antibody against HEV (anti-HEV IgG) was detected in only five subjects (0.7%) (P < 0.0001). All five subjects who had anti-HEV IgG, were negative for anti-HEV IgM and HEV RNA. Anti-HAV was detectable in 24 (75.0%) of the 32 infants aged 7 days to 6 months, but not in any of the 8 infants aged 7 to <12 months. The prevalence of anti-HAV was 19.5% (17/87) in the age group of 1-3 years, and it increased to 50.0% (69/138) in the age group of 4-6 years, and further to 81.4% (105/129) in the age group of 7-9 years. Of note, 97.2% of the subjects in the age group of 16-20 years had anti-HAV. The presence of HAV RNA was tested in all 717 subjects, and three children of 1, 4, or 8 years of age were found to have detectable HAV RNA (subgenotype IA). No subject had a history of hepatitis or jaundice. In conclusion, HEV infection was uncommon, but HAV infection lacking overt clinical features was prevalent among children in Mongolia.

Zoonotic hepatitis E: animal reservoirs and emerging risks

PubMed Central

Pavio, Nicole; Meng, Xiang-Jin; Renou, Christophe

2010-01-01

Hepatitis E virus (HEV) is responsible for enterically-transmitted acute hepatitis in humans with two distinct epidemiological patterns. In endemic regions, large waterborne epidemics with thousands of people affected have been observed, and, in contrast, in non-endemic regions, sporadic cases have been described. Although contaminated water has been well documented as the source of infection in endemic regions, the modes of transmission in non-endemic regions are much less known. HEV is a single-strand, positive-sense RNA virus which is classified in the Hepeviridae family with at least four known main genotypes (1–4) of mammalian HEV and one avian HEV. HEV is unique among the known hepatitis viruses, in which it has an animal reservoir. In contrast to humans, swine and other mammalian animal species infected by HEV generally remain asymptomatic, whereas chickens infected by avian HEV may develop a disease known as Hepatitis-Splenomegaly syndrome. HEV genotypes 1 and 2 are found exclusively in humans while genotypes 3 and 4 are found both in humans and other mammals. Several lines of evidence indicate that, in some cases involving HEV genotypes 3 and 4, animal to human transmissions occur. Furthermore, individuals with direct contact with animals are at higher risk of HEV infection. Cross-species infections with HEV genotypes 3 and 4 have been demonstrated experimentally. However, not all sources of human infections have been identified thus far and in many cases, the origin of HEV infection in humans remains unknown. PMID:20359452

Serological evidence of hepatitis E virus infection in zoo animals and identification of a rodent-borne strain in a Syrian brown bear.

PubMed

Spahr, Carina; Ryll, René; Knauf-Witzens, Tobias; Vahlenkamp, Thomas W; Ulrich, Rainer G; Johne, Reimar

2017-12-01

Hepatitis E virus (HEV) is the causative agent of hepatitis E, an emerging infectious disease of humans. HEV infections have also been described in various animal species. Whereas domestic pigs and wild boars are well-known animal reservoirs for HEV, the knowledge on natural HEV infection in zoo animals is scarce so far. Here, we analysed 244 sera from 66 mammal species derived from three zoos in Germany using a commercial double antigen sandwich ELISA. HEV-specific antibodies were detected in 16 animal species, with the highest detection rates in suids (33.3%) and carnivores (27.0%). However, RNA of the human pathogenic HEV genotypes 1-4 was not detected in the serum samples from suids or carnivores. Using a broad spectrum RT-PCR, a ratHEV-related sequence was identified in a sample of a female Syrian brown bear (Ursus arctos syriacus). Subsequent serum samples within a period of five years confirmed a HEV seroconversion in this animal. No symptoms of hepatitis were recorded. In a follow-up investigation at the same location, closely related ratHEV sequences were identified in free-living Norway rats (Rattus norvegicus), whereas feeder rats (Rattus norvegicus forma domestica) were negative for HEV-specific antibodies and RNA. Therefore, a spillover infection of ratHEV from free-living Norway rats is most likely. The results indicate that a wide range of zoo animals can be naturally infected with HEV or HEV-related viruses. Their distinct role as possible reservoir animals for HEV and sources of HEV infection for humans and other animals remains to be investigated. Copyright © 2017 Elsevier B.V. All rights reserved.

Epidemic of hepatitis E in a military unit in Abbotrabad, Pakistan.

PubMed

Bryan, Joe P; Iqbal, Mohammad; Tsarev, Sergei; Malik, Iftikhar A; Duncan, J Fred; Ahmed, Aftab; Khan, Asad; Khan, Ahmed; Rafiqui, Abdul Rauf; Purcell, Robert H; Legters, Llewellyn J

2002-12-01

An outbreak of hepatitis caused by hepatitis E virus (HEV) in Abbottabad, Pakistan was traced to fecal contamination of a water system. Of 109 men hospitalized with hepatitis, 104 (95%) had serologic evidence of acute hepatitis E (IgM antibody to HEV [anti-HEV]), three (3%) probably had acute hepatitis E (high titers of IgG anti-HEV without IgM), and two had acute hepatitis A. Among a subset of 44 men with acute hepatitis E from whom three serum specimens were obtained over a four-month period, the anti-HEV IgG geometric mean titers (GMTs) decreased from 1,519 during the outbreak to 657 at four months. The IgM anti-HEV was detected in 40 (91%) of 44 sera obtained at admission (GMT = 533 during acute disease), but in only six (14%) four months later. The prevalence of anti-HEV in this population before the outbreak was estimated to be 30%. The presence of IgG anti-HEV appeared to protect against clinical hepatitis or development of serologic evidence of new infection with HEV. This is the second major epidemic of hepatitis E in the Pakistani military confirmed by an anti-HEV enzyme-linked immunosorbent assay (ELISA). Evidence that pre-existing antibody as measured by this ELISA protects against disease is important for assessment of vaccine development.

Prevalence of Hepatitis E Virus Infection in Pigs at the Time of Slaughter, United Kingdom, 2013.

PubMed

Grierson, Sylvia; Heaney, Judith; Cheney, Tanya; Morgan, Dilys; Wyllie, Stephen; Powell, Laura; Smith, Donald; Ijaz, Samreen; Steinbach, Falko; Choudhury, Bhudipa; Tedder, Richard S

2015-08-01

Since 2010, reports of infection with hepatitis E virus (HEV) have increased in England and Wales. Despite mounting evidence regarding the zoonotic potential of porcine HEV, there are limited data on its prevalence in pigs in the United Kingdom. We investigated antibody prevalence, active infection, and virus variation in serum and cecal content samples from 629 pigs at slaughter. Prevalence of antibodies to HEV was 92.8% (584/629), and HEV RNA was detected in 15% of cecal contents (93/629), 3% of plasma samples (22/629), and 2% of both (14/629). However, although HEV is prevalent in pigs in the United Kingdom and viremic pigs are entering the food chain, most (22/23) viral sequences clustered separately from the dominant type seen in humans. Thus, pigs raised in the United Kingdom are unlikely to be the main source of human HEV infections in the United Kingdom. Further research is needed to identify the source of these infections.

The 14.6 kd rubber elongation factor (Hev b 1) and 24 kd (Hev b 3) rubber particle proteins are recognized by IgE from patients with spina bifida and latex allergy.

PubMed

Yeang, H Y; Cheong, K F; Sunderasan, E; Hamzah, S; Chew, N P; Hamid, S; Hamilton, R G; Cardosa, M J

1996-09-01

Two major water-insoluble proteins are located on the surface of rubber particles in Hevea brasiliensis latex. A 14.6 kd protein (Hev b 1), found mainly on large rubber particles (> 350 mm in diameter), and a 24 kd protein (Hev b 3), found mainly on small rubber particles (average diameter, 70 nm), are recognized by IgE from patients with spina bifida and latex allergy. Although Hev b 1 (also called the rubber elongation factor [REF]) has previously been reported as a major latex allergen, this conclusion has been disputed on the basis of results from other studies. The allergenicity of Hev b 1 is verified in this study by testing the recombinant protein generated from its gene. Because allergenicity is confined to patients with spina bifida and not observed in adults sensitive to latex, it is not a major latex allergen. The identification of Hev b 3 as another allergen originating from rubber particles is confirmed by immunogold labeling and electron microscopy. Observations with the monoclonal antibody USM/RC2 developed against Hev b 3 show that the protein has a tendency to fragment into several polypeptides of lower molecular weight (from 24 kd to about 5 kd) when stored at -20 degrees C. There is also indication of protein aggregation from the appearance of proteins with molecular weights greater than 24 kd. Fragmentation of Hev b 3 is induced immediately on he addition of latex B-serum, which is normally compartmentalized in the lutoids in fresh latex. In the preparation of ammoniated latex (used for the manufacture of latex products), the lutoids are ruptured, and the released B-serum reacts with Hev b 3 on the rubber particles to give rise to an array of low molecular weight polypeptides that are allergenic to patients with spina bifida.

High prevalence of antibodies against hepatitis E virus in HIV-infected patients with unexplained liver disease.

PubMed

Merchante, Nicolás; Parra-Sánchez, Manuel; Rivero-Juárez, Antonio; Cifuentes, Celia; Camacho, Ángela; Macías, Juan; Martínez-Dueñas, Loreto; Pérez-Navarro, Elisabet; Rivero, Antonio; Pineda, Juan A

2015-10-01

To look for evidence of hepatitis E virus (HEV) exposure in HIV-infected patients with unexplained elevations of liver stiffness (LS). Case-control study conducted in 31 HIV-infected patients with unexplained elevations of LS and in 31 HIV-controls with normal LS, matched by age, sex and CD4 cell-counts. Serum HEV antibodies were tested by two ELISA procedures and by Immunoblot. We defined exposure to HEV as the detection of serum HEV antibodies by at least one of the two ELISA assays, provided that it was confirmed by Immunoblot. A real-time PCR RNA assay was conducted in all plasma samples to identify subjects with active HEV infection. Exposure to HEV was demonstrated, according to the criteria used in this study, in 9 (29%) of the cases, whereas it was shown in 5 (16%) of the controls (p=.3). Serum HEV RNA was detected in none of the controls and in only in one case. This patient had a documented chronic hepatitis E with progression to cirrhosis. HEV antibodies are frequently found in HIV-infected patients with unexplained liver disease. Copyright © 2014 Elsevier España, S.L.U. y Sociedad Española de Enfermedades Infecciosas y Microbiología Clínica. All rights reserved.

Self-Reported Mental Health Predicts Acute Respiratory Infection.

PubMed

Maxwell, Lizzie; Barrett, Bruce; Chase, Joseph; Brown, Roger; Ewers, Tola

2015-06-01

Poor mental health conditions, including stress and depression, have been recognized as a risk factor for the development of acute respiratory infection. Very few studies have considered the role of general mental health in acute respiratory infection occurrence. The aim of this analysis is to determine if overall mental health, as assessed by the mental component of the Short Form 12 Health Survey, predicts incidence, duration, or severity of acute respiratory infection. Data utilized for this analysis came from the National Institute of Health-funded Meditation or Exercise for Preventing Acute Respiratory Infection (MEPARI) and MEPARI-2 randomized controlled trials examining the effects of meditation or exercise on acute respiratory infection among adults aged > 30 years in Madison, Wisconsin. A Kendall tau rank correlation compared the Short Form 12 mental component, completed by participants at baseline, with acute respiratory infection incidence, duration, and area-under-the-curve (global) severity, as assessed by the Wisconsin Upper Respiratory Symptom Survey. Participants were recruited from Madison, Wis, using advertisements in local media. Short Form 12 mental health scores significantly predicted incidence (P = 0.037) of acute respiratory infection, but not duration (P = 0.077) or severity (P = 0.073). The Positive and Negative Affect Schedule (PANAS) negative emotion measure significantly predicted global severity (P = 0.036), but not incidence (P = 0.081) or duration (P = 0.125). Mindful Attention Awareness Scale scores significantly predicted incidence of acute respiratory infection (P = 0.040), but not duration (P = 0.053) or severity (P = 0.70). The PHQ-9, PSS-10, and PANAS positive measures did not show significant predictive associations with any of the acute respiratory infection outcomes. Self-reported overall mental health, as measured by the mental component of Short Form 12, predicts acute respiratory infection incidence.

Evaluation of an antigen-capture EIA for the diagnosis of hepatitis E virus infection.

PubMed

Zhao, C; Geng, Y; Harrison, T J; Huang, W; Song, A; Wang, Y

2015-11-01

An enzyme immunoassay (EIA) has been developed for hepatitis E virus (HEV) antigen (HEV-Ag) detection and marketed in China. This study aimed to evaluate the sensitivity of the assay and assess the value of HEV-Ag detection in the diagnosis of HEV infection in comparison with HEV RNA detection. Using serial dilutions of a genotype 4 HEV strain, significant correlation was found between the EIA (S/CO) and HEV RNA (IU/mL) concentration in the range 10(3.5) to 10(0.5) IU/mL HEV RNA, the Pearson correlation coefficient r approached 0.97. The EIA detection limit was 54.6 IU/mL, compared to 24 IU/mL for HEV RNA using real-time RT-PCR. In clinical samples from hepatitis E patients, the HEV-Ag and HEV RNA positivity rates were 55.6% (65/117) and 60.7% (71/117) in sera and 76.7% (56/73) and 84.9% (62/73) in stools, and the concordance of these two markers was 77.8% in sera and 80.8% in stools. In serum samples, the HEV-Ag positivity rate and the concordance between HEV-Ag and HEV RNA were inversely proportional to the presence of anti-HEV antibody. The presence of anti-HEV IgG could reduce the S/CO of the HEV-Ag EIA. These results reveal a significant correlation between the detection of HEV-Ag and HEV RNA. The sensitivity of the HEV-Ag EIA was lower than real-time RT-PCR but could be higher than conventional nested RT-PCR. Therefore, the detection of HEV-Ag in serum and faeces is valuable for the diagnosis and prognosis of HEV infection in developing regions where real-time RT-PCR is not available. © 2015 John Wiley & Sons Ltd.

Unexplained abnormal liver function in patients with primary antibody deficiency: could it be chronic hepatitis E infection?

PubMed

Mohamed, Omar E; Jones, Julie; Osman, Husam; Huissoon, Aarnoud P

2017-08-09

Data from recent studies suggest rising incidence rate of hepatitis E virus (HEV) infection in the UK. HEV infection may take a severe and persistent course in immunocompromised patients, including transplant recipients on immunosuppressives, patients with HIV, haematological malignancies and in idiopathic CD4 + T lymphocytopenia. The prevalence of HEV in primary antibody deficiency (PAD) disorders is still unknown. The aim of this study was to investigate HEV infection in 27 patients with PAD with unexplained, persistently elevated liver enzymes. Although all the 27 patients tested negative for HEV-RNA, we would still strongly recommend that HEV should be considered in any immunodeficient patient with impaired liver function. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Vaccine Development against Zoonotic Hepatitis E Virus: Open Questions and Remaining Challenges

PubMed Central

Nan, Yuchen; Wu, Chunyan; Zhao, Qin; Sun, Yani; Zhang, Yan-Jin; Zhou, En-Min

2018-01-01

Hepatitis E virus (HEV) is a fecal-orally transmitted foodborne viral pathogen that causes acute hepatitis in humans and is responsible for hepatitis E outbreaks worldwide. Since the discovery of HEV as a zoonotic agent, this virus has been isolated from a variety of hosts with an ever-expanding host range. Recently, a subunit HEV vaccine developed for the prevention of human disease was approved in China, but is not yet available to the rest of the world. Meanwhile, notable progress and knowledge has been made and revealed in recent years to better understand HEV biology and infection, including discoveries of quasi-enveloped HEV virions and of a new function of the HEV-ORF3 product. However, the impact of these new findings on the development of a protective vaccine against zoonotic HEV infection requires further discussion. In this review, hallmark characteristics of HEV zoonosis, the history of HEV vaccine development, and recent discoveries in HEV virology are described. Moreover, special attention is focused on quasi-enveloped HEV virions and the potential role of the HEV-ORF3 product as antibody-neutralization target on the surface of quasi-enveloped HEV virions to provide new insights for the future development of improved vaccines against zoonotic HEV infection. PMID:29520257

Vaccine Development against Zoonotic Hepatitis E Virus: Open Questions and Remaining Challenges.

PubMed

Nan, Yuchen; Wu, Chunyan; Zhao, Qin; Sun, Yani; Zhang, Yan-Jin; Zhou, En-Min

2018-01-01

Hepatitis E virus (HEV) is a fecal-orally transmitted foodborne viral pathogen that causes acute hepatitis in humans and is responsible for hepatitis E outbreaks worldwide. Since the discovery of HEV as a zoonotic agent, this virus has been isolated from a variety of hosts with an ever-expanding host range. Recently, a subunit HEV vaccine developed for the prevention of human disease was approved in China, but is not yet available to the rest of the world. Meanwhile, notable progress and knowledge has been made and revealed in recent years to better understand HEV biology and infection, including discoveries of quasi-enveloped HEV virions and of a new function of the HEV-ORF3 product. However, the impact of these new findings on the development of a protective vaccine against zoonotic HEV infection requires further discussion. In this review, hallmark characteristics of HEV zoonosis, the history of HEV vaccine development, and recent discoveries in HEV virology are described. Moreover, special attention is focused on quasi-enveloped HEV virions and the potential role of the HEV-ORF3 product as antibody-neutralization target on the surface of quasi-enveloped HEV virions to provide new insights for the future development of improved vaccines against zoonotic HEV infection.

Seroepidemiological study of hepatitis E virus infection in Japan using a newly developed antibody assay.

PubMed

Tanaka, E; Takeda, N; Tian-Chen, L; Orii, K; Ichijo, T; Matsumoto, A; Yoshizawa, K; Iijima, T; Takayama, T; Miyamura, T; Kiyosawa, K

2001-05-01

A seroepidemiological study of hepatitis E virus (HEV) infection was conducted in Japan, where HEV infection is not considered endemic. IgG and IgM class antibodies to HEV were measured with a newly developed enzyme-linked immunosorbent assay in which recombinant virus-like particles were used as an antigen. A total of 1253 individuals (401 males and 852 females; age range, 6-89 years) were enrolled from two different areas: area 1 (n = 478), in which hepatitis C was endemic; and area 2 (n = 775), in which it was not endemic. The HEV antibody (IgG class) positive rate was 6.7% in area 1 and 4.6% in area 2. Similarly, the HAV antibody (IgG class) positive rates were 65.3% and 72.3%. The age- and sex-specific prevalence of both HAV and HEV antibodies was quite similar in the two areas, and the HAV antibody positive rate clearly increased with age in both males and females. On the other hand, the HEV antibody positive rate showed a slight tendency to increase with age in males, but not in females. None of the 32 individuals with the HEV antibody who were interviewed had a history of visiting countries in which hepatitis E was endemic. In both areas, the mean age, percentage of males, and HAV antibody positive rate were significantly higher in the group of individuals with the HEV antibody than in the group of those without it, according to conventional statistical analyses. Of the three factors age, male sex, presence of HAV antibody, and the area factor, only male sex was statistically significant (P < 0.001) on multivariate logistic regression analysis. Two (0.2%) of the total of 1253 individuals were positive for the IgM class antibody to HEV. Our results suggest the possibility that HEV infection is circulating in Japan at a low level. HEV infection was associated with male sex, but not with HAV infection.

Therapeutic and prevention strategies against human enterovirus 71 infection

PubMed Central

Kok, Chee Choy

2015-01-01

Human enterovirus 71 (HEV71) is the cause of hand, foot and mouth disease and associated neurological complications in children under five years of age. There has been an increase in HEV71 epidemic activity throughout the Asia-Pacific region in the past decade, and it is predicted to replace poliovirus as the extant neurotropic enterovirus of highest global public health significance. To date there is no effective antiviral treatment and no vaccine is available to prevent HEV71 infection. The increase in prevalence, virulence and geographic spread of HEV71 infection over the past decade provides increasing incentive for the development of new therapeutic and prevention strategies against this emerging viral infection. The current review focuses on the potential, advantages and disadvantages of these strategies. Since the explosion of outbreaks leading to large epidemics in China, research in natural therapeutic products has identified several groups of compounds with anti-HEV71 activities. Concurrently, the search for effective synthetic antivirals has produced promising results. Other therapeutic strategies including immunotherapy and the use of oligonucleotides have also been explored. A sound prevention strategy is crucial in order to control the spread of HEV71. To this end the ultimate goal is the rapid development, regulatory approval and widespread implementation of a safe and effective vaccine. The various forms of HEV71 vaccine designs are highlighted in this review. Given the rapid progress of research in this area, eradication of the virus is likely to be achieved. PMID:25964873

Production of Hev b5 as a fluorescent biotin-binding tripartite fusion protein in insect cells.

PubMed

Nordlund, Henri R; Laitinen, Olli H; Uotila, Sanna T H; Kulmala, Minna; Kalkkinen, Nisse; Kulomaa, Markku S

2005-10-14

The presented green fluorescent protein and streptavidin core-based tripartite fusion system provides a simple and efficient way for the production of proteins fused to it in insect cells. This fusion protein forms a unique tag, which serves as a multipurpose device enabling easy optimization of production, one-step purification via streptavidin-biotin interaction, and visualization of the fusion protein during downstream processing and in applications. In the present study, we demonstrate the successful production, purification, and detection of a natural rubber latex allergen Hev b5 with this system. We also describe the production of another NRL allergen with the system, Hev b1, which formed large aggregates and gave small yields in purification. The aggregates were detected at early steps by microscopical inspection of the infected insect cells producing this protein. Therefore, this fusion system can also be utilized as a fast indicator of the solubility of the expressed fusion proteins and may therefore be extremely useful in high-throughput expression approaches.

Serologic evidence for hepatitis E virus infection in mongoose.

PubMed

Li, Tian-Cheng; Saito, Mika; Ogura, Go; Ishibashi, Osamu; Miyamura, Tatsuo; Takeda, Naokazu

2006-05-01

Although pig and wild boar are considered to be the reservoirs of hepatitis E virus (HEV) in Japan, the spread of HEV to other animals is unknown. Serum samples from 84 mongooses (Small Asian mongoose; Herpestes javanicus) collected in Okinawa, Japan were examined for antibodies to HEV by enzyme-linked immunosorbent assay and RNA was analyzed by reverse transcription-polymerase chain reaction. Seven (8.3%) of 84 mongooses were positive for IgG antibodies to HEV, and the antibody-positive rate increased with body weight and size, whereas HEV RNA was not detected in these samples. These results are consistent with the possibility that mongooses in Okinawa are occasionally infected with HEV; however, they are not considered the major zoonotic reservoir of HEV.

Seroepidemiology of hepatitis e virus infection in general population in rural durango, Mexico.

PubMed

Alvarado-Esquivel, Cosme; Sanchez-Anguiano, Luis Francisco; Hernandez-Tinoco, Jesus

2014-06-01

The seroepidemiology of hepatitis E virus (HEV) infection in rural areas in Mexico has been poorly studied. The aim of the study was to determine the seroprevalence and correlates of anti-HEV IgG antibodies in adults in rural areas in Durango, Mexico. We performed a cross-sectional study to determine the frequency of anti-HEV IgG antibodies in 273 adults living in rural Durango, Mexico using an enzyme-linked immunoassay. In addition, we searched for an association of HEV exposure with the socio-demographic and behavioral characteristics of the subjects studied. One hundred (36.6%) of the 273 rural adults (mean age: 39.85 ± 17.15 years) had anti-HEV IgG antibodies. Multivariate analysis of socio-demographic and behavioral characteristics of the participants showed that HEV exposure was associated with increasing age (OR = 1.04; 95% CI: 1.04-1.05; P < 0.001), consumption of untreated water (OR = 1.92; 95% CI: 1.06-3.46; P = 0.03), and availability of water at home (OR = 1.87; 95% CI: 1.07-3.27; P = 0.02). In contrast, other socio-demographic and behavioral characteristics including educational level, occupation, socio-economic status, foreign travel, consumption of unwashed raw fruits, consumption of raw or undercooked meat and raising animals did not show associations with HEV exposure. The seroprevalence of HEV infection found in rural Durango is higher than those reported in other Mexican populations. Consumption of untreated water is an important factor for HEV exposure in rural areas in Durango. The correlates of HEV seropositivity found in the present study can be used for an optimal planning of preventive measures against HEV infection.

Why Human Papillomavirus Acute Infections Matter

PubMed Central

2017-01-01

Most infections by human papillomaviruses (HPVs) are ‘acute’, that is non-persistent. Yet, for HPVs, as for many other oncoviruses, there is a striking gap between our detailed understanding of chronic infections and our limited data on the early stages of infection. Here we argue that studying HPV acute infections is necessary and timely. Focusing on early interactions will help explain why certain infections are cleared while others become chronic or latent. From a molecular perspective, descriptions of immune effectors and pro-inflammatory pathways during the initial stages of infections have the potential to lead to novel treatments or to improved handling algorithms. From a dynamical perspective, adopting concepts from spatial ecology, such as meta-populations or meta-communities, can help explain why HPV acute infections sometimes last for years. Furthermore, cervical cancer screening and vaccines impose novel iatrogenic pressures on HPVs, implying that anticipating any viral evolutionary response remains essential. Finally, hints at the associations between HPV acute infections and fertility deserve further investigation given their high, worldwide prevalence. Overall, understanding asymptomatic and benign infections may be instrumental in reducing HPV virulence. PMID:28994707

Hepatitis E in liver transplant recipients in the Rhône-Alpes region in France.

PubMed

Buffaz, C; Scholtes, C; Dron, A-G; Chevallier-Queyron, P; Ritter, J; André, P; Ramière, C

2014-06-01

In developed countries, hepatitis E virus (HEV) is considered an emerging pathogen, but prevalence seems highly variable according to previous European studies. As HEV can lead to chronic infections in immunosuppressed patients, it is thus essential to evaluate the prevalence and incidence of this infection. We determined retrospectively, in a cohort of 206 pediatric and adult liver transplant recipients from the Rhône-Alpes region in France, pre-transplant anti-HEV-IgG prevalence and incidence of HEV infections during post-transplant follow-up (HEV IgG and IgM ± HEV-RNA). Transplantations were carried out between 2005 and 2012 and mean post-transplant follow-up was 32.8 months. Global pre-transplant prevalence of anti-HEV IgG was 29%, increasing regularly with age from 7% for children under 15 to 49% for patients older than 60. From the 142 seronegative patients before transplant, 11 seroconversions (7.7%) were observed during follow-up (incidence of 2.83 cases per 100 person-years). HEV RNA-tested at transaminases peak or randomly-was detected in only one case of seroconversion. For at least 2 HEV-seropositive patients, who had negative RNAemia before transplantation, viral RNA was detected chronically during follow-up, suggesting reinfection with HEV. Acute infections were largely more frequent than chronic infections and were asymptomatic or misdiagnosed, suggesting that liver transplant patients may not be particularly prone to developing severe HEV hepatitis. In addition, the presence of IgG anti-HEV may not protect against re-infection. Serological testing, therefore, appears to be of limited interest for the diagnosis of HEV infections in liver transplant recipients.

Clinical presentation and course of acute hepatitis C infection in HIV-infected patients.

PubMed

Luetkemeyer, Annie; Hare, C Bradley; Stansell, John; Tien, Phyllis C; Charlesbois, Edwin; Lum, Paula; Havlir, Diane; Peters, Marion

2006-01-01

Hepatitis C virus (HCV) has become a significant source of morbidity and mortality in HIV-infected patients. However, little is known about the clinical presentation and course of acute HCV infection in this population. This study reports the outcomes of acute HCV infection in 9 HIV-infected men. Sex with men was the only reported risk factor for HCV infection in 6 of the subjects. Clinical presentation of acute HCV ranged from incidentally discovered elevated transaminases to severe liver dysfunction requiring hospitalization. At the time of HCV diagnosis, 8 of 9 patients had CD4+ counts >250 cells/mm(3), and 6 had HIV viral loads of < or =5000 copies/mL. Eight patients were receiving antiretroviral therapy. Outcome of these acute HCV infections varied. Five patients experienced virologic clearance, 2 in whom virus cleared spontaneously and 3 who were treated with pegylated interferon and ribavirin. Four patients developed chronic infection, one of whom had a relapse during HCV treatment and 3 of whom were untreated. All 4 patients to whom HCV therapy was administered experienced significant anemia or neutropenia, necessitating dose reduction or support with growth factors. Prompt recognition of acute HCV infection may minimize antiretroviral treatment interruption and will allow early treatment, which may improve virologic clearance. Unexplained transaminase elevations in HIV-infected patients, including men who have sex with men, should trigger an evaluation for acute HCV infection.

From Barnyard to Food Table: the Omnipresence of Hepatitis E virus and Risk for Zoonotic Infection and Food Safety

PubMed Central

Meng, Xiang-Jin

2011-01-01

Hepatitis E virus (HEV) is an important but extremely understudied pathogen. The mechanisms of HEV replication and pathogenesis are poorly understood, and a vaccine against HEV is not yet available. HEV is classified in the family Hepeviridae consisting of at least four recognized major genotypes. Genotypes 1 and 2 HEV are restricted to humans and associated with epidemics in developing countries, whereas genotypes 3 and 4 HEV are zoonotic and responsible for sporadic cases worldwide. The identification and characterization of a number of animal strains of HEV from pigs, chickens, rabbits, rats, mongoose, deer, and possibly cattle and sheep have significantly broadened the host range and diversity of HEV. The demonstrated ability of cross-species infection by some animal strains of HEV raises public health concerns for zoonotic HEV infection. Pigs are a recognized reservoir for HEV, and pig handlers are at increased risk of zoonotic HEV infection. Sporadic cases of hepatitis E have been definitively linked to the consumption of raw or undercooked animal meats such as pig livers, sausages, and deer meats. In addition, since large amounts of viruses excreted in feces, animal manure land application and runoffs can contaminate irrigation and drinking water with concomitant contamination of produce or shellfish. HEV RNA of swine origin has been detected in swine manure, sewage water and oysters, and consumption of contaminated shellfish has also been implicated in sporadic cases of hepatitis E. Therefore, the animal strains of HEV pose not only a zoonotic risk but also food and environmental safety concerns. PMID:21316404

Zinc Salts Block Hepatitis E Virus Replication by Inhibiting the Activity of Viral RNA-Dependent RNA Polymerase.

PubMed

Kaushik, Nidhi; Subramani, Chandru; Anang, Saumya; Muthumohan, Rajagopalan; Shalimar; Nayak, Baibaswata; Ranjith-Kumar, C T; Surjit, Milan

2017-11-01

Hepatitis E virus (HEV) causes an acute, self-limiting hepatitis in healthy individuals and leads to chronic disease in immunocompromised individuals. HEV infection in pregnant women results in a more severe outcome, with the mortality rate going up to 30%. Though the virus usually causes sporadic infection, epidemics have been reported in developing and resource-starved countries. No specific antiviral exists against HEV. A combination of interferon and ribavirin therapy has been used to control the disease with some success. Zinc is an essential micronutrient that plays crucial roles in multiple cellular processes. Zinc salts are known to be effective in reducing infections caused by few viruses. Here, we investigated the effect of zinc salts on HEV replication. In a human hepatoma cell (Huh7) culture model, zinc salts inhibited the replication of genotype 1 (g-1) and g-3 HEV replicons and g-1 HEV infectious genomic RNA in a dose-dependent manner. Analysis of a replication-defective mutant of g-1 HEV genomic RNA under similar conditions ruled out the possibility of zinc salts acting on replication-independent processes. An ORF4-Huh7 cell line-based infection model of g-1 HEV further confirmed the above observations. Zinc salts did not show any effect on the entry of g-1 HEV into the host cell. Furthermore, our data reveal that zinc salts directly inhibit the activity of viral RNA-dependent RNA polymerase (RdRp), leading to inhibition of viral replication. Taken together, these studies unravel the ability of zinc salts in inhibiting HEV replication, suggesting their possible therapeutic value in controlling HEV infection. IMPORTANCE Hepatitis E virus (HEV) is a public health concern in resource-starved countries due to frequent outbreaks. It is also emerging as a health concern in developed countries owing to its ability to cause acute and chronic infection in organ transplant and immunocompromised individuals. Although antivirals such as ribavirin have been used

Familial Hepatitis E Outbreak Linked to Wild Boar Meat Consumption.

PubMed

Rivero-Juarez, A; Frias, M; Martinez-Peinado, A; Risalde, M A; Rodriguez-Cano, D; Camacho, A; García-Bocanegra, I; Cuenca-Lopez, F; Gomez-Villamandos, J C; Rivero, A

2017-11-01

An HIV-infected patient was diagnosed with acute hepatitis E infection in our hospital. An epidemiological inquiry was performed to collect demographic, food and animal exposure variables in order to identify the potential route of transmission. The patient reported that his family traditionally hunted wild boar for food. All family members were analysed for hepatitis E virus infection. Additionally, route of transmission by wild boar meat consumption and prevalence of HEV infection among wild boar from the same hunting area were investigated. In all-family members (n = 8), HEV-RNA was amplified. Two wild boar meat slices consumed was analysed, showing the presence of HEV. The virus isolated was consistent with genotype 3, revealing 100% homology between family members and meat. Additionally, we tested nine wild boar hunted in the same hunting area. All of them were RNA-HEV positive, isolating the same HEV genotype 3 viral strain. We demonstrated by phylogenetic analysis zoonotic transmission of HEV by wild boar meat consumption. The prevalence of HEV infection among wild boar found in our study suggests that this species is an important route of transmission to human. © 2017 Blackwell Verlag GmbH.

Seroepidemiology of Hepatitis E Virus Infection in General Population in Rural Durango, Mexico

PubMed Central

Alvarado-Esquivel, Cosme; Sanchez-Anguiano, Luis Francisco; Hernandez-Tinoco, Jesus

2014-01-01

Background: The seroepidemiology of hepatitis E virus (HEV) infection in rural areas in Mexico has been poorly studied. Objectives: The aim of the study was to determine the seroprevalence and correlates of anti-HEV IgG antibodies in adults in rural areas in Durango, Mexico. Materials and Methods: We performed a cross-sectional study to determine the frequency of anti-HEV IgG antibodies in 273 adults living in rural Durango, Mexico using an enzyme-linked immunoassay. In addition, we searched for an association of HEV exposure with the socio-demographic and behavioral characteristics of the subjects studied. Results: One hundred (36.6%) of the 273 rural adults (mean age: 39.85 ± 17.15 years) had anti-HEV IgG antibodies. Multivariate analysis of socio-demographic and behavioral characteristics of the participants showed that HEV exposure was associated with increasing age (OR = 1.04; 95% CI: 1.04-1.05; P < 0.001), consumption of untreated water (OR = 1.92; 95% CI: 1.06-3.46; P = 0.03), and availability of water at home (OR = 1.87; 95% CI: 1.07-3.27; P = 0.02). In contrast, other socio-demographic and behavioral characteristics including educational level, occupation, socio-economic status, foreign travel, consumption of unwashed raw fruits, consumption of raw or undercooked meat and raising animals did not show associations with HEV exposure. Conclusions: The seroprevalence of HEV infection found in rural Durango is higher than those reported in other Mexican populations. Consumption of untreated water is an important factor for HEV exposure in rural areas in Durango. The correlates of HEV seropositivity found in the present study can be used for an optimal planning of preventive measures against HEV infection. PMID:24976837

[Hepatitis E as zoonosis].

PubMed

Baumann-Popczyk, Anna

2011-01-01

The hepatitis E virus (HEV) the causative agent of hepatitis E, is a non-enveloped RNA virus. HEV is transmitted through oral consumption of contaminated food and water According to the currently knowledge now be considered as zoonosis. The main reservoir of HEV are pigs, boars and deer. For the first time HEV was isolated from animals (pigs) in 1997 in the U.S. Genetic analysis of strains isolated from pigs showed high similarity to strains HEV isolated from humans. This was the first evidence showing that HEV is a zoonosis. Further studies have shown that occupational groups e.g. veterinarians, swine breeders with close contact to pigs have an increased risk for HEV infections. The additional evidence supported the zoonotic potential of HEV were reports of acute hepatitis E after the consumption of undercooked meat from deer and wild boar. Infection of HEV in the domestic pig and wild boar population in Europe is widespread.

Seroprevalence of hepatitis E virus infection among dogs in several developed cities in the Guangdong province of China.

PubMed

Wang, Lifang; Zheng, Yun; Fu, Cheng; Huang, San; Hong, Malin; Yan, Zhongshan; Jia, Kun; Zhou, Pei; Li, Shoujun

2016-08-01

Hepatitis E virus (HEV), as a zoonotic disease virus, was seldom studied in dogs especially in stray dogs. As previously reported, dog might be an accidental host of HEV for human beings and some risk factors might play an important role in HEV transmission. Thus, we designed this study to evaluate the seroprevalence of HEV infection among dogs in several cities in Guangdong province of China. This surveillance may help us understand risk factors including location, gender, live type, and diet habit for HEV transmission. The overall seroprevalence of anti-HEV antibodies in dogs was 19.00%. Positive rate of anti-HEV antibodies in other food groups (21.13%) was higher than that in dog food groups (9.77%) (P < 0.05), which suggested that diet habit might be a vital element of infecting HEV for dogs and play an important role in living environment. However, the analysis indicated that no strong relationship was observed among different cities, gender groups, and live type. Our study demonstrated that HEV is prevalent in dogs in the Guangdong province of China. As diet habit might become a vital element of infecting HEV for dogs and play an important role in living environment, similar studies of dogs should be conducted in the future. J. Med. Virol. 88:1404-1407, 2016. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Screening for acute HIV infection in South Africa: finding acute and chronic disease

PubMed Central

Bassett, Ingrid V.; Chetty, Senica; Giddy, Janet; Reddy, Shabashini; Bishop, Karen; Lu, Zhigang; Losina, Elena; Freedberg, Kenneth A.; Walensky, Rochelle P.

2010-01-01

Background The yield of screening for acute HIV infection among general medical patients in resource-scarce settings remains unclear. Our objective was to evaluate a strategy of pooled HIV plasma RNA to diagnose acute HIV infection in patients with negative or discordant rapid HIV antibody tests in Durban, South Africa. Methods We prospectively enrolled patients with negative or discordant rapid HIV antibody tests from a routine HIV screening program in an outpatient department in Durban with an HIV prevalence of 48%. Study participants underwent venipuncture for pooled qualitative HIV RNA, and if positive, quantitative RNA, enzyme immunoassay and Western Blot (WB). Patients with negative or indeterminate WB and positive quantitative HIV RNA were considered acutely infected. Those with chronic infection (positive RNA and WB) despite negative or discordant rapid HIV tests were considered false negative rapid antibody tests. Results Nine hundred ninety-four participants were enrolled with either negative (N=976) or discordant (N=18) rapid test results. Eleven (1.1%, 95% CI: 0.6–2.0%) had acute HIV infection. Of the 994 patients, an additional 20 (2.0%, 95% CI: 1.3–.3.1%) had chronic HIV infection (false negative rapid test). Conclusions One percent of outpatients with negative or discordant rapid HIV tests in Durban, South Africa had acute HIV infection readily detectable through pooled serum HIV RNA screening. Pooled RNA testing also identified an additional 2% of patients with chronic HIV infection. HIV RNA screening has the potential to identify both acute and chronic HIV infections that are otherwise missed by standard HIV testing algorithms. PMID:20553336

Hepatitis E Virus in Wild Boars and Spillover Infection in Red and Roe Deer, Germany, 2013–2015

PubMed Central

Anheyer-Behmenburg, Helena E.; Szabo, Kathrin; Schotte, Ulrich; Binder, Alfred; Klein, Günter

2017-01-01

To determine animal hepatitis E virus (HEV) reservoirs, we analyzed serologic and molecular markers of HEV infection among wild animals in Germany. We detected HEV genotype 3 strains in inner organs and muscle tissues of a high percentage of wild boars and a lower percentage of deer, indicating a risk for foodborne infection of humans. PMID:27983488

Hepatitis E virus: An ancient hidden enemy in Latin America

PubMed Central

Fierro, Nora A; Realpe, Mauricio; Meraz-Medina, Tzintli; Roman, Sonia; Panduro, Arturo

2016-01-01

Hepatitis E virus (HEV) infection is a common cause of acute clinical hepatitis worldwide. HEV is an RNA-containing virus and the only member of the genus Hepevirus in the family Hepeviridae. Human HEV is classified into four genotypes widely distributed across the world. The virus is mainly transmitted via the fecal-oral route, and water-borne epidemics have become characteristic of hepatitis E in developing countries, including those in Latin America. The zoonotic potential of HEV is broadly recognized. Thus, there is an urgent need to re-evaluate virus transmission scenarios and to enforce epidemiological surveillance systems. Additionally, it is known that HEV infections, initially defined as self-limiting, can also take chronic courses in immunocompromised patients. Moreover, we recently reported a high seroprevalence of HEV in samples from cirrhotic patients with no other etiological agents present, suggesting the potential role of HEV in the development of chronic liver illness. In this review, HEV genomic variability, transmission, chronic infectious course, zoonotic potential and treatment are discussed. Focus is placed on the impact of HEV infection in Latin America, to support the development of specific control strategies and the handling of this important and typically imperceptible viral infection. PMID:26900289

Retransplant Due to Fulminant Hepatic Failure From Hepatitis E Virus: A Case Report.

PubMed

Tenorio González, E; Robles Díaz, M; Sanjuan Jiménez, R; González Grande, R; Olmedo Martín, R V; Rodrigo López, J M; Jiménez Pérez, M

2018-03-01

Hepatitis E virus (HEV) usually causes self-limiting acute liver infections from fecal or oral transmission, though other routes of infection exist (vertical transmission, blood transfusion, zoonosis). It may give rise to fulminant hepatic failure in 1% of cases. Cases have recently been reported of chronic infection evolving to cirrhosis in immunosuppressed patients, such as those with a liver or kidney transplant. Nonetheless, development of acute liver failure in these patients is exceptional, with few cases published. We present a case of acute liver failure due to HEV in a liver transplant patient who required a liver retransplant 9 years after receiving the original transplant. Copyright © 2017 Elsevier Inc. All rights reserved.

A case of transfusion-transmitted hepatitis E caused by blood from a donor infected with hepatitis E virus via zoonotic food-borne route.

PubMed

Matsubayashi, Keiji; Kang, Jong-Hon; Sakata, Hidekatsu; Takahashi, Kazuaki; Shindo, Motohiro; Kato, Masaru; Sato, Shinichiro; Kato, Toshiaki; Nishimori, Hiroyuki; Tsuji, Kunihiko; Maguchi, Hiroyuki; Yoshida, Jun-Ichi; Maekubo, Hiroshi; Mishiro, Shunji; Ikeda, Hisami

2008-07-01

Five cases of transfusion transmission of hepatitis E virus (HEV) have been reported so far. The infection routes of the causative donors remain unclear, however. Also, the progress of virus markers in the entire course of HEV infection has not been well documented. Nucleic acid testing was performed by real-time reverse transcription-polymerase chain reaction targeting the open reading frame 2 region of HEV. Full-length nucleotide sequences of HEV RNA were detected by direct sequencing. Lookback study of a HEV-positive donor revealed that the platelets (PLTs) donated from him 2 weeks previously contained HEV RNA and were transfused to a patient. Thirteen relatives including the donor were ascertained to enjoy grilled pork meats together in a barbecue restaurant 23 days before the donation. Thereafter, his father died of fulminant hepatitis E and the other 6 members showed serum markers of HEV infection. In the recipient, HEV was detected in serum on Day 22 and reached the peak of 7.2 log copies per mL on Day 44 followed by the steep increase of alanine aminotransferase. Immunoglobulin G anti-HEV emerged on Day 67; subsequently, hepatitis was resolved. HEV RNA sequences from the donor and recipient were an identical, Japan-indigenous strain of genotype 4. HEV RNA was detectable up to Day 97 in serum, Day 85 in feces, and Day 71 in saliva. A transfusion-transmitted hepatitis E case by blood from a donor infected via the zoonotic food-borne route and the progress of HEV markers in the entire course are demonstrated. Further studies are needed to clarify the epidemiology and the transfusion-related risks for HEV even in industrialized countries.

Seroprevalence of anti-hepatitis E virus antibodies in domestic pigs in Mexico.

PubMed

García-Hernández, Montserrat Elemi; Cruz-Rivera, Mayra; Sánchez-Betancourt, José Iván; Rico-Chávez, Oscar; Vergara-Castañeda, Arely; Trujillo, María E; Sarmiento-Silva, Rosa Elena

2017-09-21

Hepatitis E virus (HEV) infection is one of the most common causes of acute liver diseases in humans worldwide. In developing countries, HEV is commonly associated with waterborne outbreaks. Conversely, in industrialized countries, HEV infection is often associated with travel to endemic regions or ingestion of contaminated animal products. Limited information on both, human and animal HEV infection in Mexico is available. As a consequence, the distribution of the virus in the country is largely unknown. Here, we assessed the seroprevalence of HEV among swine in different geographical regions in Mexico. Seroprevalence of anti-HEV antibodies in swine herds in Mexico was evaluated in a representative sample including 945 pig serum specimens from different regions of the country using a commercial enzyme-linked immunosorbent assay (ELISA). The overall prevalence of anti-HEV antibodies in swine was 59.4%. The northern region of Mexico exhibited the highest seroprevalence in the country (86.6%), while the central and southern regions in Mexico showed lower seroprevalence, 42.7% and 51.5%, respectively. In Mexico, HEV seroprevalence in swine is high. Importantly, northern Mexico showed the highest seroprevalence in the country. Thus, further studies are required to identify the risk factors contributing to HEV transmission among pigs in the country. Assessment of HEV human infection in the context of viral transmission in swine is required to better understand the epidemiology of hepatitis E in Mexico.

Acute infection contributes to racial disparities in stroke mortality.

PubMed

Levine, Deborah A; Langa, Kenneth M; Rogers, Mary A M

2014-03-18

It is unknown whether racial differences in exposure to acute precipitants of stroke, specifically infection, contribute to racial disparities in stroke mortality. Among participants in the nationally representative Health and Retirement Study with linked Medicare data (1991-2007), we conducted a case-crossover study employing within-person comparisons to study racial/ethnic differences in the risks of death and hospitalization from ischemic stroke following acute infection. There were 964 adults hospitalized for ischemic stroke. Acute infection increased the 30-day risks of ischemic stroke death (5.82-fold) and ischemic stroke hospitalization (1.87-fold). Acute infection was a more potent trigger of acute ischemic stroke death in non-Hispanic blacks (odds ratio [OR] 39.21; 95% confidence interval [CI] 9.26-166.00) than in non-Hispanic whites (OR 4.50; 95% CI 3.14-6.44) or Hispanics (OR 5.18; 95% CI 1.34-19.95) (race-by-stroke interaction, p = 0.005). When adjusted for atrial fibrillation, infection remained more strongly associated with stroke mortality in blacks (OR 34.85) than in whites (OR 3.58) and Hispanics (OR 3.53). Acute infection increased the short-term risk of incident stroke similarly across racial/ethnic groups. Infection occurred often before stroke death in non-Hispanic blacks, with 70% experiencing an infection in the 30 days before stroke death compared to a background frequency of 15%. Acute infection disproportionately increases the risk of stroke death for non-Hispanic blacks, independently of atrial fibrillation. Stroke incidence did not explain this finding. Acute infection appears to be one factor that contributes to the black-white disparity in stroke mortality.

Hepatitis Virus Infections in Poultry.

PubMed

Yugo, Danielle M; Hauck, Ruediger; Shivaprasad, H L; Meng, Xiang-Jin

2016-09-01

Viral hepatitis in poultry is a complex disease syndrome caused by several viruses belonging to different families including avian hepatitis E virus (HEV), duck hepatitis B virus (DHBV), duck hepatitis A virus (DHAV-1, -2, -3), duck hepatitis virus Types 2 and 3, fowl adenoviruses (FAdV), and turkey hepatitis virus (THV). While these hepatitis viruses share the same target organ, the liver, they each possess unique clinical and biological features. In this article, we aim to review the common and unique features of major poultry hepatitis viruses in an effort to identify the knowledge gaps and aid the prevention and control of poultry viral hepatitis. Avian HEV is an Orthohepevirus B in the family Hepeviridae that naturally infects chickens and consists of three distinct genotypes worldwide. Avian HEV is associated with hepatitis-splenomegaly syndrome or big liver and spleen disease in chickens, although the majority of the infected birds are subclinical. Avihepadnaviruses in the family of Hepadnaviridae have been isolated from ducks, snow geese, white storks, grey herons, cranes, and parrots. DHBV evolved with the host as a noncytopathic form without clinical signs and rarely progressed to chronicity. The outcome for DHBV infection varies by the host's ability to elicit an immune response and is dose and age dependent in ducks, thus mimicking the pathogenesis of human hepatitis B virus (HBV) infections and providing an excellent animal model for human HBV. DHAV is a picornavirus that causes a highly contagious virus infection in ducks with up to 100% flock mortality in ducklings under 6 wk of age, while older birds remain unaffected. The high morbidity and mortality has an economic impact on intensive duck production farming. Duck hepatitis virus Types 2 and 3 are astroviruses in the family of Astroviridae with similarity phylogenetically to turkey astroviruses, implicating the potential for cross-species infections between strains. Duck astrovirus (DAstV) causes

Fatal disease associated with Swine Hepatitis E virus and Porcine circovirus 2 co-infection in four weaned pigs in China.

PubMed

Yang, Yifei; Shi, Ruihan; She, Ruiping; Mao, Jingjing; Zhao, Yue; Du, Fang; Liu, Can; Liu, Jianchai; Cheng, Minheng; Zhu, Rining; Li, Wei; Wang, Xiaoyang; Soomro, Majid Hussain

2015-03-26

In recent decades, Porcine circovirus 2 (PCV2) infection has been recognized as the causative agent of postweaning multisystemic wasting syndrome, and has become a threat to the swine industry. Hepatitis E virus (HEV) is another high prevalent pathogen in swine in many regions of the world. PCV2 and HEV are both highly prevalent in pig farms in China. In this study, we characterized the HEV and PCV2 co-infection in 2-3 month-old piglets, based on pathogen identification and the pathological changes observed, in Hebei Province, China. The pathological changes were severe, and general hyperemia, hemorrhage, inflammatory cell infiltration, and necrosis were evident in the tissues of dead swine. PCR was used to identify the pathogen and we tested for eight viruses (HEV, Porcine reproductive and respiratory syndrome virus, PCV2, Classical swine fever virus, Porcine epidemic diarrhea virus, Transmissible gastroenteritis coronavirus, Porcine parvovirus and Pseudorabies virus) that are prevalent in Chinese pig farms. The livers, kidneys, spleens, and other organs of the necropsied swine were positive for HEV and/or PCV2. Immunohistochemical staining showed HEV- and PCV2-antigen-positive signals in the livers, kidneys, lungs, lymph nodes, and intestine. HEV and PCV2 co-infection in piglets was detected in four out of seven dead pigs from two pig farms in Hebei, China, producing severe pathological changes. The natural co-infection of HEV and PCV2 in pigs in China has rarely been reported. We speculate that co-infection with PCV2 and HEV may bring some negative effect on pig production and recommend that more attention should be paid to this phenomenon.

Acute infection contributes to racial disparities in stroke mortality

PubMed Central

Langa, Kenneth M.; Rogers, Mary A.M.

2014-01-01

Objective: It is unknown whether racial differences in exposure to acute precipitants of stroke, specifically infection, contribute to racial disparities in stroke mortality. Methods: Among participants in the nationally representative Health and Retirement Study with linked Medicare data (1991–2007), we conducted a case-crossover study employing within-person comparisons to study racial/ethnic differences in the risks of death and hospitalization from ischemic stroke following acute infection. Results: There were 964 adults hospitalized for ischemic stroke. Acute infection increased the 30-day risks of ischemic stroke death (5.82-fold) and ischemic stroke hospitalization (1.87-fold). Acute infection was a more potent trigger of acute ischemic stroke death in non-Hispanic blacks (odds ratio [OR] 39.21; 95% confidence interval [CI] 9.26–166.00) than in non-Hispanic whites (OR 4.50; 95% CI 3.14–6.44) or Hispanics (OR 5.18; 95% CI 1.34–19.95) (race-by-stroke interaction, p = 0.005). When adjusted for atrial fibrillation, infection remained more strongly associated with stroke mortality in blacks (OR 34.85) than in whites (OR 3.58) and Hispanics (OR 3.53). Acute infection increased the short-term risk of incident stroke similarly across racial/ethnic groups. Infection occurred often before stroke death in non-Hispanic blacks, with 70% experiencing an infection in the 30 days before stroke death compared to a background frequency of 15%. Conclusions: Acute infection disproportionately increases the risk of stroke death for non-Hispanic blacks, independently of atrial fibrillation. Stroke incidence did not explain this finding. Acute infection appears to be one factor that contributes to the black–white disparity in stroke mortality. PMID:24510494

Acute Toxoplasma infection among family members of patients with acute lymphadenopathic toxoplasmosis.

PubMed

Luft, B J; Remington, J S

1984-01-01

Studies were performed to determine how frequently acute infections with Toxoplasma gondii occur among family members of patients with acute acquired lymphadenopathic toxoplasmosis. In five of the nine families studied, more than one family member had serologic evidence of recent acute infection with T gondii. In three of the families, the immunoglobulin M and immunoglobulin G antibody titers to T gondii among infected family members were similar irrespective of whether lymphadenopathy was present. Lymphadenopathy developed in one family member in each of two families (families VIII and IX) three and eight months after lymphadenopathy had developed in the index case (proband). These results suggest that common-source outbreaks occur with surprising frequency among family members of patients with lymphadenopathic toxoplasmosis and that the humoral response is similar with different manifestations of the infection.

The Role of Infected Cell Proliferation in the Clearance of Acute HBV Infection in Humans

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

Goyal, Ashish; Ribeiro, Ruy Miguel; Perelson, Alan S.

Around 90–95% of hepatitis B virus (HBV) infected adults do not progress to the chronic phase and, instead, recover naturally. The strengths of the cytolytic and non-cytolytic immune responses are key players that decide the fate of acute HBV infection. In addition, it has been hypothesized that proliferation of infected cells resulting in uninfected progeny and/or cytokine-mediated degradation of covalently closed circular DNA (cccDNA) leading to the cure of infected cells are two major mechanisms assisting the adaptive immune response in the clearance of acute HBV infection in humans. We employed fitting of mathematical models to human acute infection datamore » together with physiological constraints to investigate the role of these hypothesized mechanisms in the clearance of infection. Results suggest that cellular proliferation of infected cells resulting in two uninfected cells is required to minimize the destruction of the liver during the clearance of acute HBV infection. In contrast, we find that a cytokine-mediated cure of infected cells alone is insufficient to clear acute HBV infection. Lastly, our modeling indicates that HBV clearance without lethal loss of liver mass is associated with the production of two uninfected cells upon proliferation of an infected cell.« less

The Role of Infected Cell Proliferation in the Clearance of Acute HBV Infection in Humans

DOE PAGES

Goyal, Ashish; Ribeiro, Ruy Miguel; Perelson, Alan S.

2017-11-18

Around 90–95% of hepatitis B virus (HBV) infected adults do not progress to the chronic phase and, instead, recover naturally. The strengths of the cytolytic and non-cytolytic immune responses are key players that decide the fate of acute HBV infection. In addition, it has been hypothesized that proliferation of infected cells resulting in uninfected progeny and/or cytokine-mediated degradation of covalently closed circular DNA (cccDNA) leading to the cure of infected cells are two major mechanisms assisting the adaptive immune response in the clearance of acute HBV infection in humans. We employed fitting of mathematical models to human acute infection datamore » together with physiological constraints to investigate the role of these hypothesized mechanisms in the clearance of infection. Results suggest that cellular proliferation of infected cells resulting in two uninfected cells is required to minimize the destruction of the liver during the clearance of acute HBV infection. In contrast, we find that a cytokine-mediated cure of infected cells alone is insufficient to clear acute HBV infection. Lastly, our modeling indicates that HBV clearance without lethal loss of liver mass is associated with the production of two uninfected cells upon proliferation of an infected cell.« less

Natural and experimental hepatitis E virus genotype 3-infection in European wild boar is transmissible to domestic pigs.

PubMed

Schlosser, Josephine; Eiden, Martin; Vina-Rodriguez, Ariel; Fast, Christine; Dremsek, Paul; Lange, Elke; Ulrich, Rainer G; Groschup, Martin H

2014-11-26

Hepatitis E virus (HEV) is the causative agent of acute hepatitis E in humans in developing countries, but sporadic and autochthonous cases do also occur in industrialised countries. In Europe, food-borne zoonotic transmission of genotype 3 (gt3) has been associated with domestic pig and wild boar. However, little is known about the course of HEV infection in European wild boar and their role in HEV transmission to domestic pigs. To investigate the transmissibility and pathogenesis of wild boar-derived HEVgt3, we inoculated four wild boar and four miniature pigs intravenously. Using quantitative real-time RT-PCR viral RNA was detected in serum, faeces and in liver, spleen and lymph nodes. The antibody response evolved after fourteen days post inoculation. Histopathological findings included mild to moderate lymphoplasmacytic hepatitis which was more prominent in wild boar than in miniature pigs. By immunohistochemical methods, viral antigens were detected mainly in Kupffer cells and liver sinusoidal endothelial cells, partially associated with hepatic lesions, but also in spleen and lymph nodes. While clinical symptoms were subtle and gross pathology was inconspicuous, increased liver enzyme levels in serum indicated hepatocellular injury. As the faecal-oral route is supposed to be the most likely transmission route, we included four contact animals to prove horizontal transmission. Interestingly, HEVgt3-infection was also detected in wild boar and miniature pigs kept in contact to intravenously inoculated wild boar. Given the high virus loads and long duration of viral shedding, wild boar has to be considered as an important HEV reservoir and transmission host in Europe.

[Hepatitis E: a Third World's hepatitis found in Belgium].

PubMed

Seivert, M; Belaiche, J; Delwaide, J

2008-09-01

Hepatitis E virus is the second cause of acute viral hepatitis of oral-fecal origin in the world. This virus has a vast distribution throughout the world and manifests itself either in epidemic or endemic-sporadic form in many developing countries. Usually, the cases of HEV infection in industrialized countries are observed after a history of travel in an endemic area. However, an increasing number of cases have been attributed to a HEV zoonotic form transmitted by swine. HEV infection can lead to deadly fulminant hepatic failure in 1-4% in the common population, but the mortality incidence reaches 20% in case of third trimester pregnant women infection. The diagnosis of HEV infection can be made using serological tests but today, RT-PCR is considered as the gold standard test. Unfortunately, this technique is not widely available in Belgium yet. There is no treatment for HEV infection, only prophylactic measures as hygiene and sewage treatment can stop epidemics. Recently, a new vaccine, still in research phase, has showed promising outcomes.

Host Innate Immunity against Hepatitis E Virus and Viral Evasion Mechanisms.

PubMed

Kang, Sangmin; Myoung, Jinjong

2017-10-28

Hepatitis E virus (HEV) infections cause epidemic or sporadic acute hepatitis, which are mostly self-limiting. However, viral infection in immunocompromised patients and pregnant women may result in serious consequences, such as chronic hepatitis and liver damage, mortality of the latter of which reaches up to 20-30%. Type I interferon (IFN)-induced antiviral immunity is known to be the first-line defense against virus infection. Upon HEV infection in the cell, the virus genome is recognized by pathogen recognition receptors, leading to rapid activation of intracellular signaling cascades. Expression of type I IFN triggers induction of a barrage of IFN-stimulated genes, helping the cells cope with viral infection. Interestingly, some of the HEV-encoded genes seem to be involved in disrupting signaling cascades for antiviral immune responses, and thus crippling cytokine/chemokine production. Antagonistic mechanisms of type I IFN responses by HEV have only recently begun to emerge, and in this review, we summarize known HEV evasion strategies and compare them with those of other hepatitis viruses.

Hepatitis E Virus: Time to Change the Textbooks.

PubMed

Dalton, Harry R; Webb, Glynn W; Norton, Ben C; Woolson, Kathy L

Until recently, hepatitis E virus (HEV) was thought not to occur in developed countries. It is now clear that locally acquired HEV is common in such settings. HEV infection acquired in these areas differs from that in developing countries in a number of important aspects: it is caused by genotype 3 (and 4 in China and Japan), it mainly affects middle-aged/elderly males and it is zoonotic with a porcine primary host. Pig herds worldwide are infected with HEV genotype 3 and HEV has been found in the human food chain in a number of developed countries. However, the route of transmission is not fully understood, since most cases are not obviously associated with pigs/pig products. HEV can be transmitted by blood transfusion and surprisingly high numbers of asymptomatic blood donors are viremic at the time of donation: Germany 1:1,200, Netherlands 1:2,671, England 1:2,848. Our understanding of the clinical phenotype of HEV infection in humans has undergone a sea-change in recent years. Previously, HEV was thought to cause only acute self-limiting hepatitis. However, HEV may cause persistent disease in the immunocompromised. Patients with chronic HEV infection have no symptoms, but some develop rapidly progressive liver cirrhosis. The full clinical spectrum of HEV is still emerging. HEV has important extra-hepatic manifestations, which deserve further investigation. For example, HEV can cause a wide range of neurological illness. In particular, very recent data suggest that Guillain-Barré syndrome and neuralgic amyotrophy are associated with locally acquired HEV in approximately 5 and 10% of the cases, respectively. © 2016 S. Karger AG, Basel.

Markers for Ongoing or Previous Hepatitis E Virus Infection Are as Common in Wild Ungulates as in Humans in Sweden

PubMed Central

Roth, Anette; Lin, Jay; Magnius, Lars; Karlsson, Marie; Belák, Sándór; Widén, Frederik; Norder, Heléne

2016-01-01

Hepatitis E virus (HEV) is a human pathogen with zoonotic spread, infecting both domestic and wild animals. About 17% of the Swedish population is immune to HEV, but few cases are reported annually, indicating that most infections are subclinical. However, clinical hepatitis E may also be overlooked. For identified cases, the source of infection is mostly unknown. In order to identify whether HEV may be spread from wild game, the prevalence of markers for past and/or ongoing infection was investigated in sera and stool samples collected from 260 hunted Swedish wild ungulates. HEV markers were found in 43 (17%) of the animals. The most commonly infected animal was moose (Alces alces) with 19 out of 69 animals (28%) showing HEV markers, followed by wild boar (Sus scrofa) with 21 out of 139 animals (15%), roe deer (Capreolus capreolus) with 2 out of 30 animals, red deer (Cervus elaphus) with 1 out of 15 animals, and fallow deer (Dama dama) 0 out of 7 animals. Partial open reading frame 1 (ORF1) of the viral genomes from the animals were sequenced and compared with those from 14 endemic human cases. Phylogenetic analysis revealed that three humans were infected with HEV strains similar to those from wild boar. These results indicate that wild animals may be a source of transmission to humans and could be an unrecognized public health concern. PMID:27657108

Markers for Ongoing or Previous Hepatitis E Virus Infection Are as Common in Wild Ungulates as in Humans in Sweden.

PubMed

Roth, Anette; Lin, Jay; Magnius, Lars; Karlsson, Marie; Belák, Sándór; Widén, Frederik; Norder, Heléne

2016-09-19

Hepatitis E virus (HEV) is a human pathogen with zoonotic spread, infecting both domestic and wild animals. About 17% of the Swedish population is immune to HEV, but few cases are reported annually, indicating that most infections are subclinical. However, clinical hepatitis E may also be overlooked. For identified cases, the source of infection is mostly unknown. In order to identify whether HEV may be spread from wild game, the prevalence of markers for past and/or ongoing infection was investigated in sera and stool samples collected from 260 hunted Swedish wild ungulates. HEV markers were found in 43 (17%) of the animals. The most commonly infected animal was moose ( Alces alces ) with 19 out of 69 animals (28%) showing HEV markers, followed by wild boar ( Sus scrofa ) with 21 out of 139 animals (15%), roe deer ( Capreolus capreolus ) with 2 out of 30 animals, red deer ( Cervus elaphus ) with 1 out of 15 animals, and fallow deer ( Dama dama ) 0 out of 7 animals. Partial open reading frame 1 (ORF1) of the viral genomes from the animals were sequenced and compared with those from 14 endemic human cases. Phylogenetic analysis revealed that three humans were infected with HEV strains similar to those from wild boar. These results indicate that wild animals may be a source of transmission to humans and could be an unrecognized public health concern.

Serological evidence for hepatitis e virus infection in laboratory monkeys and pigs in animal facilities in Japan.

PubMed

Yamamoto, Hiroshi; Li, Tian-Cheng; Koshimoto, Chihiro; Ito, Kaori; Kita, Masakazu; Miyashita, Nobumoto; Arikawa, Jiro; Yagami, Kenichi; Asano, Masahide; Tezuka, Hideo; Suzuki, Noboru; Kurosawa, Tsutomu; Shibahara, Toshiyuki; Furuya, Masato; Mohri, Shirou; Sato, Hiroshi; Ohsawa, Kazutaka; Ibuki, Kentaro; Takeda, Naokazu

2008-07-01

In laboratory animal facilities, monkeys and pigs are used for animal experiments, but the details of hepatitis E virus (HEV) infection in these animals are unknown. The risk of infection from laboratory animals to humans has become a concern; therefore, much attention should be paid to the handling of these animals during their care and use, including surgical procedures performed on infected animals. In this connection, serum samples collected from 916 monkeys and 77 pigs kept in 23 animal facilities belonging to the Japanese Association of Laboratory Animal Facilities of National University Corporations (JALAN) and the Japanese Association of Laboratory Animal Facilities of Public and Private Universities (JALAP) in Japan were examined for the purpose of detecting antibodies to HEV and HEV RNA by using ELISA and RT-PCR, respectively. One hundred and seven serum samples of 916 (11.7%) monkeys were positive for anti-HEV IgG, and 7 and 17 serum samples of 916 (0.8% and 5.3%) monkeys were positive for anti-HEV IgM and IgA, respectively. Thirty-six samples from 62 (58.1%) farm pigs were positive for anti-HEV IgG, whereas all samples tested from miniature pigs were negative (0/15, 0%). Seven samples from 62 (9.1%) farm pigs and 7 samples from 916 (0.8%) monkeys were positive for IgM antibody, but these HEV-IgM antibody positive serum samples were HEV-RNA negative by RT-PCR. The IgM antibody positive rate (9.1%) of farm pigs was much higher than that of monkeys (0.8%). These results suggest the relative levels of risk of HEV infection from these animals to animal handlers and researchers who work with them in laboratory animal facilities.

Excretion of infectious hepatitis E virus into milk in cows imposes high risks of zoonosis.

PubMed

Huang, Fen; Li, Yunlong; Yu, Wenhai; Jing, Shenrong; Wang, Jue; Long, Feiyan; He, Zhanlong; Yang, Chenchen; Bi, Yanhong; Cao, Wentao; Liu, Chengbo; Hua, Xiuguo; Pan, Qiuwei

2016-08-01

Hepatitis E virus (HEV) represents the main cause of acute hepatitis worldwide. HEV infection in immunocompromised patients involves a high risk for the development of chronic hepatitis. Because HEV is recognized as a zoonotic pathogen, it is currently believed that swine is the primary reservoir. However, this is not sufficient to justify the strikingly high seroprevalence of HEV in both developing and Western countries. Thus, this study aimed to identify new zoonotic sources that bear a high risk of transmission to humans. We collected fecal, blood, and milk samples of cows in a typical rural region of Yunnan Province in southwest China, where mixed farming of domestic animals is a common practice. HEV RNA was quantified by quantitative real-time polymerase chain reaction, and the whole genome was sequenced. HEV infectivity was assessed in rhesus macaques. We found a high prevalence of active HEV infection in cows as determined by viral RNA positivity in fecal samples. Surprisingly, we discovered that HEV is excreted into milk that is produced by infected cows. Phylogenetic analysis revealed that all HEV isolates from cow/milk belong to genotype 4 and subtype 4h. Gavage with HEV-contaminated raw and even pasteurized milk resulted in active infection in rhesus macaques. Importantly, a short period of boiling, but not pasteurization, could completely inactivate HEV. Infectious HEV-contaminated cow milk is recognized as a new zoonotic source that bears a high risk of transmission to humans; these results call attention to understanding and establishing proper measurement and control of HEV zoonotic transmission, particularly in the setting of mixed farming of domestic animals. (Hepatology 2016;64:350-359). © 2016 by the American Association for the Study of Liver Diseases.

Association of hepatitis E virus with an outbreak of hepatitis in Pakistan: serologic responses and pattern of virus excretion.

PubMed

Ticehurst, J; Popkin, T J; Bryan, J P; Innis, B L; Duncan, J F; Ahmed, A; Iqbal, M; Malik, I; Kapikian, A Z; Legters, L J

1992-02-01

Hepatitis E virus (HEV), a positive-strand RNA agent, has been associated with enterically transmitted non-A, non-B hepatitis in Asia, Africa, and Mexico. To evaluate the role of HEV in an outbreak of hepatitis in Pakistan, we used immune electron microscopy to detect 1) antibody to HEV, for evidence of infection, and 2) virus, to determine the pattern of HEV excretion. Paired sera from 2 patients were assayed for antibody by using reference HEV: one seroconverted, an atypical finding for HEV infections; the other had high levels of anti-HEV in both sera. Virus particles with the size (29 x 31 nm) and morphology of HEV were detected in feces from 10 of 85 patients and serologically identified as HEV by using reference antibodies from an HEV-infected chimpanzee. One of these HEV-containing specimens was collected 9 days before the onset of jaundice; it was among feces from 38 outpatients with nonspecific symptoms and biochemical hepatitis, 12 of whom subsequently developed jaundice. The other 9 feces with HEV were among 36 collected within 7 days of the onset of acute icteric hepatitis; all 11 feces from days 8 to 15 were negative for HEV. Fecal concentrations of HEV appeared to be lower than those of many enteric viruses: only one specimen contained as many as 5 particles per EM grid square. It is concluded that HEV was etiologically associated with the epidemic and was predominantly excreted at very low levels during the first week of jaundice.

[Human enterovirus infection status and clinical characteristics of 274 patients with viral encephalitis in Henan Province, 2011-2012].

PubMed

Ma, H X; Pan, J J; Li, Y; Kang, K; Huang, X Y; You, A G; Xu, B L

2017-02-06

Objective: To investigate human enterovirus (HEV) infection and clinical characteristics of viral encephalitis patients in Pingdingshan, Henan Province. Methods: Cerebrospinal fluid specimens and epidemiological information were collected from 274 viral encephalitis patients in the departments of pediatrics and neurology in hospitals in Pingdingshan, Henan Province, from April 2011 to August 2012. Patients with bacterial infections were excluded from the study. Demographic information was collected by questionnaires and clinical information was mainly obtained from hospital examinations. Viral RNA was extracted using magnetic bead extraction. Real-time RT-PCR was then performed for HEV, CV-A16, and EV-A71 testing. SPSS statistical software was statistical analyses. Significant differences were determined using the chi-squared test ( P< 0.05). Results: Among 274 cases of viral encephalitis, 180 cases (65.7%) were male and 94 cases were female (34.3%). The median age was 2.17 years. Approximately 61.3% (168) of patients were younger than 3 years of age. A total of 107 (39.1%), 2 (0.7%), and 42 (15.3%) cases were positive for HEV, CV-A16, and EV-A71, respectively. Eleven patients were younger than 6 months of age and one patient was co-infected with HEV and EV-A71. In the<3, 3-5, 6-15, and>15 years old age groups, HEV infections comprised 31.5% (53/168), 52.9% (18/34), 53.0% (35/66), and 16.7% (1/6) (χ(2)=13.10, P= 0.003), respectively. The EV-A71 infection rates were 17.9% (30/168), 23.5% (8/34), 6.1% (4/66), and 0 (χ(2)=8.04, P= 0.045), respectively. The other enterovirus (OEV) infection rates were 12.5% (21/168), 29.4% (10/34), 48.5% (32/66), and 16.7% (1/6) (χ(2)=35.19, P< 0.001), respectively. The rate of vomiting in OEV and EV-A71 infected patients was 73% (44/60) and 26% (11/42), respectively, while the frequency of skin rash in OEV and EV-A71 infected patients was 32% (19/60) and 79% (33/42), respectively. Approximately 95% (99/104) of patients infected

Sero-prevalence and risk factors for hepatitis E virus infection among pregnant women in the Cape Coast Metropolis, Ghana.

PubMed

Obiri-Yeboah, Dorcas; Asante Awuku, Yaw; Adu, Joseph; Pappoe, Faustina; Obboh, Evans; Nsiah, Paul; Amoako-Sakyi, Daniel; Simpore, Jacques

2018-01-01

Hepatitis E virus is an emerging infection in Africa with poor maternal and foetal outcomes. There is scanty data on the sero-prevalence of HEV infection among pregnant women in Ghana. This study highlighted the prevalence and risk factors associated with HEV infection among pregnant women in Cape Coast Metropolis, Central Region of Ghana. A multicenter (3 selected sites) analytical cross sectional study involving 398 pregnant women in the Cape Coast metropolis was conducted. HEV (Anti-HEV IgG and Anti-HEV IgM) ELISA was performed. Sero-positive women had liver chemistries done and data collected on maternal and neonatal outcomes. Data analyses were performed using Stata version 13 software (STATA Corp, Texas USA). Mean age was 28.01 (± 5.93) years. HEV sero-prevalence was 12.2% (n = 48) for IgG and 0.2% (n = 1) for IgM with overall of 12.3%. The odds of being HEV sero-positive for women aged 26-35 years was 3.1 (95% CI: 1.1-8.1), p = 0.02 and ≥36 years it was 10.7 (95% CI; 3.4-33.5), p = 0.0001. Living in urban settlement was associated with lowest odds of HEV infection {OR 0.4 (95% CI; 0.2-0.8), p = 0.01}. Factors with no statistical evidence of association include main source of drinking water and history of blood transfusion. The sero-prevalence of HEV IgG increased progressively across trimesters with the highest among women in their third trimester (55.3%). None of the 49 HEV sero-positive women had elevated ALT level. Ten (N = 41) of the neonates born to sero-positive women developed jaundice in the neonatal period. The mean birth weight was 3.1kg (SD 0.4). HEV sero-prevalence among pregnant women in the Cape Coast Metropolis is high enough to deserve more attention than it has received so far. It is therefore important to conduct further research on the potential impact on maternal and neonatal mortality and morbidity in Ghana.

Cross-species infection of hepatitis E virus in a zoo-like location, including birds

PubMed Central

ZHANG, W.; SHEN, Q.; MOU, J.; YANG, Z. B.; YUAN, C. L.; CUI, L.; ZHU, J. G.; HUA, X. G.; XU, C. M.; HU, J.

2008-01-01

SUMMARY Hepatitis E virus (HEV) is a zoonotic pathogen of which several species of animals are considered to be reservoirs. Thirty-eight faecal samples, obtained from 22 species of animals including birds in a wildlife first-aid centre in Eastern China, were tested for HEV RNA. Our survey revealed that in total 28·9% (95% confidence interval 14·5–43·4) of the faecal samples from various mammals and birds were HEV RNA positive. Sequence and phylogenetic analyses of the 11 isolates demonstrated that all sequences clustered in genotype 4 with 96–100% identity to each other. In addition, serum samples from seven animal handlers have shown that five (71·4%) were seropositive. The findings imply that cross-species infection of HEV had probably occurred in this zoo-like location, and moreover, birds can be infected naturally with mammalian HEV. PMID:17961279

Hepatitis E virus and related viruses in wild, domestic and zoo animals: A review.

PubMed

Spahr, C; Knauf-Witzens, T; Vahlenkamp, T; Ulrich, R G; Johne, R

2018-02-01

Hepatitis E is a human disease mainly characterized by acute liver illness, which is caused by infection with the hepatitis E virus (HEV). Large hepatitis E outbreaks have been described in developing countries; however, the disease is also increasingly recognized in industrialized countries. Mortality rates up to 25% have been described for pregnant women during outbreaks in developing countries. In addition, chronic disease courses could be observed in immunocompromised transplant patients. Whereas the HEV genotypes 1 and 2 are mainly confined to humans, genotypes 3 and 4 are also found in animals and can be zoonotically transmitted to humans. Domestic pig and wild boar represent the most important reservoirs for these genotypes. A distinct subtype of genotype 3 has been repeatedly detected in rabbits and a few human patients. Recently, HEV genotype 7 has been identified in dromedary camels and in an immunocompromised transplant patient. The reservoir animals get infected with HEV without showing any clinical symptoms. Besides these well-known animal reservoirs, HEV-specific antibodies and/or the genome of HEV or HEV-related viruses have also been detected in many other animal species, including primates, other mammals and birds. In particular, genotypes 3 and 4 infections are documented in many domestic, wildlife and zoo animal species. In most cases, the presence of HEV in these animals can be explained by spillover infections, but a risk of virus transmission through contact with humans cannot be excluded. This review gives a general overview on the transmission pathways of HEV to humans. It particularly focuses on reported serological and molecular evidence of infections in wild, domestic and zoo animals with HEV or HEV-related viruses. The role of these animals for transmission of HEV to humans and other animals is discussed. © 2017 Blackwell Verlag GmbH.

Seroepidemiology of hepatitis A, B, C, and E viruses infection among preschool children in Taiwan.

PubMed

Lin, Jye-Bin; Lin, Ding-Bang; Chen, Shiuan-Chih; Chen, Pao-San; Chen, Wen-Kang

2006-01-01

Taiwan was a hyperendemic area for hepatitis A and B viruses (HAV and HBV) infection before late 1980s. To study the seroprevalence of hepatitis A, B, C, and E viruses (HCV and HEV) infection among preschool children in Taiwan, a community-based survey was carried out in 54 kindergartens in 10 urban areas, 10 rural areas, and 2 aboriginal areas randomly selected through stratified sampling. Serum specimens of 2,538 preschool children were screened for the hepatitis A, C, and E antibodies by a commercially available enzyme immunoassay and for HBV markers by radioimmunoassay methods. The multivariate-adjusted odd ratios (OR) with their 95% confidence intervals (CI) were estimated through the multiple logistic regression analysis. Females had a statistically significantly higher HAV seroprevalence than males. The seroprevalence of HCV infection increased significantly with age. The larger the sibship size, the higher the seroprevalence of HBV infection. Aboriginal children had a significantly higher seroprevalence of HBV and HEV infection and lower seroprevalence of HCV infection than non-aboriginal children. A significantly higher seroprevalence of HBV infection was found in rural children than urban children. There was no significant association between serostatus of HAV and HEV infection and between serostatus of HBV and HCV infection among preschool children in Taiwan. The poor environmental and hygienic conditions in the aboriginal areas might play a role in infection with HBV and HEV.

Evaluation of candidate genes associated with hepatitis A and E virus infection in Chinese Han population.

PubMed

Gu, Maolin; Qiu, Jing; Guo, Daoxia; Xu, Yunfang; Liu, Xingxiang; Shen, Chong; Dong, Chen

2018-03-20

Recent GWAS-associated studies reported that single nucleotide polymorphisms (SNPs) in ABCB1, TGFβ1, XRCC1 genes were associated with hepatitis A virus (HAV) infection, and variants of APOA4 and APOE genes were associated with and hepatitis E virus (HEV) infection in US population. However, the associations of these loci with HAV or HEV infection in Chinese Han population remain unclear. A total of 3082 Chinese Han persons were included in this study. Anti-HAV IgG and anti-HEV IgG were detected by enzyme-linked immunosorbent assay (ELISA). Genotypes in ABCB1, TGFβ1, XRCC1, APOA4 and APOE SNPs were determined by TaqMan MGB technology. In Chinese Han population, rs1045642 C to T variation in ABCB1 was significantly associated with the decreased risk of HAV infection (P < 0.05). However, the effect direction was different with the previous US study. Rs1001581 A to G variation in XRCC1, which was not identified in US population, was significantly associated with the protection against HAV infection in our samples (P < 0.05). In addition, our results suggested that rs7412 C to T variation in APOE was significantly associated with lower risk of HEV infection in males (adjusted OR < 1.0, P < 0.05) but not in females. ABCB1 and XRCC1 genes variants are significantly associated with the protection against HAV infection. Additionally, Chinese Han males with rs7412 C to T variation in APOE gene are less prone to be infected by HEV.

Prevalence, risk factors and molecular evaluation of hepatitis E virus infection among pregnant women resident in the northern shores of Persian Gulf, Iran

PubMed Central

Farshadpour, Fatemeh; Ravanbod, Mohamad Reza; Eghbali, Seyed Sajjad; Taherkhani, Sakineh; Mahdavi, Easa

2018-01-01

Background Although Iran is reported to be an endemic country for hepatitis E virus (HEV), data on the prevalence of HEV infection among pregnant women are scarce and the epidemiology of HEV is unknown in most parts of the country. Therefore, this study was conducted to elucidate the prevalence, risk factors and genotypic pattern of HEV infection among pregnant women resident in the northern shores of Persian Gulf. This is the first report on the epidemiology of HEV infection among pregnant women in this territory. Methods From October 2016 to May 2017, 1331 pregnant women participated in this study. The mean age ± SD of participants was 27.93±5.7 years with a range of 14–45 years. Serum samples of pregnant women were screened for the presence of anti-HEV total antibodies, anti-HEV IgG and anti-HEV IgM using commercially available ELISA kits (DIA.PRO, Milan, Italy). All anti-HEV IgG and anti-HEV IgM positive samples were tested for HEV RNA using two independent reverse transcriptase polymerase chain reaction (RT-PCR) assays, targeting ORF2 and ORF3 of HEV genome. In addition, 92 anti-HEV seronegative samples as well as 50 pooled seronegative samples were evaluated by two independent RT-PCR assays for validation of results. Results Of the 1331 pregnant women, 84 women (6.3%, 95% CI: 5.1%-7.7%) were positive for anti-HEV antibodies, of which 83 women had anti-HEV IgG, and 11 women (0.83%, 95% CI: 0.47%-1.47%) had anti-HEV IgM. The highest rate of HEV seroprevalence was observed among Afghan immigrants (68.0%), uneducated pregnant women (46.51%) and those residents in Bushehr city (8.75%). All anti-HEV IgG and/or IgM positive samples were found to be negative for HEV RNA. In addition, all of the evaluated anti-HEV seronegative samples were negative for HEV RNA. HEV seropositivity among pregnant women was statistically associated with age, ethnicity, place of residence, number of pregnancies, and level of education. So that, low education levels, Afghan, residence

Epidemiologic and clinical features of non-polio enteroviral infections in northern Taiwan in 2008.

PubMed

Hsu, Chien-Hui; Lu, Chun-Yi; Shao, Pei-Lan; Lee, Ping-Ing; Kao, Chuan-Liang; Chung, Ming-Yi; Chang, Luan-Yin; Huang, Li-Min

2011-08-01

Non-polio enteroviruses may cause different diseases, including herpangina, hand-foot-mouth disease (HFMD), meningitis, and nonspecific febrile illness; and cause epidemic outbreak annually. This study delineates the diversity of clinical presentations based on different serotypes and different groups [human enterovirus (HEV)-A and HEV-B] of enteroviruses (EVs) during the 2008 epidemic in National Taiwan University Hospital (NTUH). We retrospectively identified patients younger than 18 years who had positive isolates of non-polio EV in throat swabs, rectal swabs, or cerebrospinal fluid, in NTUH from January 1 to December 31, 2008. For serotyping, immunofluorescence assay and polymerase chain reaction followed by viral structure protein-1 sequencing were applied. We analyzed and compared their clinical features among different serotypes and different groups of EVs. Among 172 patients who were enrolled, 16 serotypes were identified. The major serotype in NTUH was EV71 (25.6%) followed by coxsackievirus A (CA)16 and coxsackievirus B (CB)4. EV71 manifested mostly as HFMD (89%) and was complicated with encephalomyelitis in three patients. Serotypes of HFMD included EV71 (70%), CA16 (27%), CA4, and CA6. Serotypes of herpangina were heterogeneous, and the major serotype was CA2 (35.7%) followed by CB4 (23.8%). Aseptic meningitis was entirely caused by HEV-B and mostly infected by echovirus 30 (50%). Among children with EV-related respiratory tract infection, CB4 (32%) was dominant in upper respiratory tract infection, whereas echovirus 4 (71%) was the major cause of lower respiratory tract infection. Cases of HEV-A were significantly younger than the cases of HEV-B (p = 0.04). Multivariate analysis revealed that the most significant factor associated with hospitalization is HEV-B (odds ratio, 2.2; 95% confidence interval, 1.1-4.2; p = 0.02). At least 16 serotypes circulated in northern Taiwan in 2008. EV71 is the predominant strain in this outbreak. All patients with HFMD

A large outbreak of Hepatitis E virus genotype 1 infection in an urban setting in Chad likely linked to household level transmission factors, 2016-2017.

PubMed

Spina, Alexander; Lenglet, Annick; Beversluis, David; de Jong, Marja; Vernier, Larissa; Spencer, Craig; Andayi, Fred; Kamau, Charity; Vollmer, Simone; Hogema, Boris; Irwin, Andrea; Ngueremi Yary, Roger; Mahamat Ali, Açyl; Moussa, Ali; Alfani, Prince; Sang, Sibylle

2017-01-01

In September 2016, three acutely jaundiced (AJS) pregnant women were admitted to Am Timan Hospital, eastern Chad. We described the outbreak and conducted a case test-negative study to identify risk factors for this genotype of HEV in an acute outbreak setting. Active case finding using a community based surveillance network identified suspected AJS cases. Pregnant or visibly ill AJS cases presenting at hospital were tested with Assure® IgM HEV rapid diagnostic tests (RDTs) and some with Polymerase Chain Reaction (PCR) in Amsterdam; confirmed cases were RDT-positive and controls were RDT-negative. All answered questions around: demographics, household makeup, area of residence, handwashing practices, water collection behaviour and clinical presentation. We calculated unadjusted odds ratios (ORs) and 95% confidence intervals (95% CI). Between September and April 2017, 1443 AJS cases (1293 confirmed) were detected in the town(attack rate: 2%; estimated 65,000 population). PCR testing confirmed HEV genotype 1e. HEV RDTs were used for 250 AJS cases; 100 (40%) were confirmed. Risk factors for HEV infection, included: having at least two children under the age of 5 years (OR 2.1, 95%CI 1.1-4.3), having another household member with jaundice (OR 2.4, 95%CI 0.90-6.3) and, with borderline significance, living in the neighbourhoods of Riad (OR 3.8, 95%CI 1.0-1.8) or Ridina (OR 3.3, 95%CI 1.0-12.6). Cases were more likely to present with vomiting (OR 3.2, 9%CI 1.4-7.9) than controls; possibly due to selection bias. Cases were non-significantly less likely to report always washing hands before meals compared with controls (OR 0.33, 95%CI 0.1-1.1). Our study suggests household factors and area of residence (possibly linked to access to water and sanitation) play a role in HEV transmission; which could inform future outbreak responses. Ongoing sero-prevalence studies will elucidate more aspects of transmission dynamics of this virus with genotype 1e.

Antibiotic treatment of acute respiratory infections in acute care settings.

PubMed

Gonzales, Ralph; Camargo, Carlos A; MacKenzie, Thomas; Kersey, Ayanna S; Maselli, Judith; Levin, Sara K; McCulloch, Charles E; Metlay, Joshua P

2006-03-01

To examine the patterns of antibiotic use for acute respiratory tract infections (ARIs) in acute care settings. Chart reviews were performed retrospectively on a random sample of adult ARI visits to seven Veterans Affairs (VA) and seven non-VA emergency departments (EDs) for the period of November 2003 to February 2004. Visits were limited to those discharged to home and those with primary diagnoses of antibiotic-responsive (pneumonia, acute exacerbation of chronic bronchitis, pharyngitis, sinusitis) and antibiotic-nonresponsive conditions (acute bronchitis, nonspecific upper respiratory tract infection [URI]). Results are expressed as adjusted odds ratios with 95% confidence intervals. Of 2,270 ARI visits, 62% were for antibiotic-nonresponsive diagnoses. Seventy-two percent of acute bronchitis and 38% of URI visits were treated with antibiotics (p < 0.001). Stratified analyses show that antibiotic prescription rates were similar among attending-only and housestaff-associated visits for antibiotic-responsive diagnoses (p = 0.11), and acute bronchitis (76% vs. 59%; p = 0.31). However, the antibiotic prescription rate for URIs was greater for attending-only visits compared with housestaff-associated visits (48% vs. 15%; p = 0.01). Antibiotic prescription rates for total ARIs varied between sites, ranging from 42% to 89%. Patient age, gender, race and ethnicity, smoking status, comorbidities, and clinical setting (VA vs. non-VA) were not independently associated with antibiotic prescribing. Acute care settings are important targets for reducing inappropriate antibiotic prescribing. The mechanisms accounting for lower antibiotic prescription rates observed with housestaff-associated visits merit further study.

Analysis of B-cell epitopes from the allergen Hev b 6.02 revealed by using blocking antibodies.

PubMed

Pedraza-Escalona, Martha; Becerril-Luján, Baltazar; Agundis, Concepción; Domínguez-Ramírez, Lenin; Pereyra, Ali; Riaño-Umbarila, Lidia; Rodríguez-Romero, Adela

2009-02-01

Hev b 6.02 (hevein), identified as a major allergen from natural rubber latex (NRL), is involved in the latex-fruit syndrome and also acts as a pathogenesis defense-related protein. Its 3D structure has been solved at high resolution, and its linear epitopes have already been reported. However, information about conformational epitopes is still controversial, even though it is relevant for an accurate diagnosis and treatment, as well as for the study of allergen-antibody molecular interactions. We sought to analyze the B-cell epitopes of Hev b 6.02 at a molecular and structural level, using specific recombinant antibodies. We obtained a murine monoclonal antibody (mAb 6E7) and three human single chain fragments (scFvs A6, H8, and G7) anti-Hev b 6.02 that were able to compete for hevein binding with serum IgEs from latex allergic patients. In vitro assays showed that the mAb 6E7 and scFv H8 recognized the area of Hev b 6.02 where the aromatic residues are exposed; while the scFv G7 defined the amino and carboxy-terminal regions that lie close to each other, as a different epitope. The structural modeling of the Hev b 6.02-scFv H8 and Hev b 6.02-scFv G7 complexes revealed the putative regions of two conformational epitopes. In one of these, the aromatic residues, as well as polar side chains are important for the interaction, suggesting that they are part of a dominant conformational epitope also presented on the Hev b 6.02-IgE interactions. Antibodies recognizing this important allergen have potential to be used to diagnose and ultimately treat latex allergy.

Hepatitis E Virus Infection in Dromedaries, North and East Africa, United Arab Emirates, and Pakistan, 1983-2015.

PubMed

Rasche, Andrea; Saqib, Muhammad; Liljander, Anne M; Bornstein, Set; Zohaib, Ali; Renneker, Stefanie; Steinhagen, Katja; Wernery, Renate; Younan, Mario; Gluecks, Ilona; Hilali, Mosaad; Musa, Bakri E; Jores, Joerg; Wernery, Ulrich; Drexler, Jan Felix; Drosten, Christian; Corman, Victor Max

2016-07-01

A new hepatitis E virus (HEV-7) was recently found in dromedaries and 1 human from the United Arab Emirates. We screened 2,438 dromedary samples from Pakistan, the United Arab Emirates, and 4 African countries. HEV-7 is long established, diversified and geographically widespread. Dromedaries may constitute a neglected source of zoonotic HEV infections.

Environmental hepatitis E virus detection supported by serological evidence in the northwest of Argentina.

PubMed

Pisano, María B; Lugo, Belén C; Poma, Ramiro; Cristóbal, Héctor A; Raskovsky, Viviana; Martínez Wassaf, Maribel G; Rajal, Verónica B; Ré, Viviana E

2018-05-23

Hepatitis E virus (HEV) is an emergent cause of acute hepatitis worldwide. Water contamination is a possible source of viral infection. In South America, particularly in Argentina, little is known about environmental HEV circulation, including recreational water. The aim of this work was to provide evidence of current environmental and human circulation of HEV in northern Argentina. Molecular detection of HEV in water samples from the Arias-Arenales River in the city of Salta by nested polymerase chain reaction (ORF2 region) and anti-HEV immunoglobulin G (IgG) and IgM detection in the general population by enzyme-linked immunosorbent assay was carried out. HEV RNA was detected in 1.6% (3/189) of the environmental samples. All sequences belonged to HEV genotype 3 and were very similar to those previously detected in the country. The prevalence of IgG anti-HEV was 9% (13/143) and three samples were positive for specific IgM. Circulation of HEV in the northwest of Argentina was demonstrated for the first time, showing viral presence in environmental samples and infections in people who attended health care centres for routine control. These findings show that recreational waters are a possible source of virus and highlight the need to carry out HEV detection when a case of hepatitis occurs.

A case of undulating fevers and elevated liver tests after pancreas-kidney transplantation.

PubMed

Im, Gene Y; Sehgal, Vinita; Ward, Stephen C

2013-02-01

The patient is a 50-year-old Caucasian woman with a history of a pancreas and two kidney transplants complicated by chronic rejection of her latest kidney allograft and currently undergoing hemodialysis, who was referred for fever of unknown origin and elevated liver tests. She suffered a self-limited acute diarrheal illness with fever 3 months prior to referral and then experienced a persistent, undulating fever pattern. An exhaustive evaluation involving many consultants was undertaken, but failed to determine the etiology of her symptoms. Given her history, persistently elevated liver tests, and abnormal but nonspecific liver biopsy findings, infection with hepatitis E virus (HEV) was entertained. Several serum and stool samples were sent to the Centers for Disease Control for detection of HEV that were positive and ultimately consistent with autochthonous chronic HEV infection. The patient was treated with ribavirin and achieved normalization of her transaminase activities and resolution of her fever after 1 month, and undetectable HEV polymerase chain reaction at treatment month 6 and 10, at which time treatment was stopped. There has been renewed interest in HEV in light of recent studies demonstrating the existence of a chronic form of HEV infection occurring in immunosuppressed patients, such as solid-organ-transplant recipients. This report highlights a case of chronic HEV infection in a pancreas-kidney-transplant recipient with an unusual clinical presentation and highlights the need for increased awareness of chronic HEV infection in the hepatology and transplant community. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

A systematic review of hepatitis E virus infection in children.

PubMed

Verghese, Valsan Philip; Robinson, Joan L

2014-09-01

A systematic review was conducted, seeking all literature relevant to the epidemiology, clinical and laboratory features, and outcome of hepatitis E virus (HEV) infection in children. Transmission is thought to be primarily from fecal-oral transmission, with the role of transmission from animal reservoirs not being clear in children. Worldwide, seroprevalence is <10% up to 10 years of age, with the exception of 1 of 5 studies from India and the sole study from Egypt. Seroprevalence increases with age, but it is not clear if it is increasing over time. The clinical presentation of HEV infection has broad similarities to hepatitis A virus (HAV) infection, with most cases being subclinical. However, HEV differs from HAV in that infectivity is lower, perinatal transmission can result in neonatal morbidity and even mortality, and a chronic carrier state exists, accounting for chronic hepatitis in some pediatric solid organ transplant recipients. © The Author 2014. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Cross Talk between Nucleotide Synthesis Pathways with Cellular Immunity in Constraining Hepatitis E Virus Replication

PubMed Central

Wang, Yijin; Wang, Wenshi; Xu, Lei; Zhou, Xinying; Shokrollahi, Ehsan; Felczak, Krzysztof; van der Laan, Luc J. W.; Pankiewicz, Krzysztof W.; Sprengers, Dave; Raat, Nicolaas J. H.; Metselaar, Herold J.; Peppelenbosch, Maikel P.

2016-01-01

Viruses are solely dependent on host cells to propagate; therefore, understanding virus-host interaction is important for antiviral drug development. Since de novo nucleotide biosynthesis is essentially required for both host cell metabolism and viral replication, specific catalytic enzymes of these pathways have been explored as potential antiviral targets. In this study, we investigated the role of different enzymatic cascades of nucleotide biosynthesis in hepatitis E virus (HEV) replication. By profiling various pharmacological inhibitors of nucleotide biosynthesis, we found that targeting the early steps of the purine biosynthesis pathway led to the enhancement of HEV replication, whereas targeting the later step resulted in potent antiviral activity via the depletion of purine nucleotide. Furthermore, the inhibition of the pyrimidine pathway resulted in potent anti-HEV activity. Interestingly, all of these inhibitors with anti-HEV activity concurrently triggered the induction of antiviral interferon-stimulated genes (ISGs). Although ISGs are commonly induced by interferons via the JAK-STAT pathway, their induction by nucleotide synthesis inhibitors is completely independent of this classical mechanism. In conclusion, this study revealed an unconventional novel mechanism of cross talk between nucleotide biosynthesis pathways and cellular antiviral immunity in constraining HEV infection. Targeting particular enzymes in nucleotide biosynthesis represents a viable option for antiviral drug development against HEV. HEV is the most common cause of acute viral hepatitis worldwide and is also associated with chronic hepatitis, especially in immunocompromised patients. Although often an acute and self-limiting infection in the general population, HEV can cause severe morbidity and mortality in certain patients, a problem compounded by the lack of FDA-approved anti-HEV medication available. In this study, we have investigated the role of the nucleotide synthesis pathway

A Single Lineage of Hepatitis E Virus Causes both Outbreaks and Sporadic Hepatitis in Sudan

PubMed Central

Elduma, Adel Hussein; Zein, Mai Mohammed Adam; Karlsson, Marie; Elkhidir, Isam M.E.; Norder, Heléne

2016-01-01

Few studies have reported sporadic hepatitis E virus (HEV) infections during non-outbreak periods in Africa. In this study, the prevalence of HEV infection in Sudan was investigated in 432 patients with acute hepatitis from 12 localities in North Kordofan, and from 152 patients involved in smaller outbreaks of hepatitis in the neighbouring Darfur. HEV infection was diagnosed in 147 (25%) patients: 98 from Kordofan and 49 from Darfur. The mortality was 10%; six of the patients who died from the infection were pregnant women. HEV RNA was detected by quantitative real-time polymerase chain reaction (RT-qPCR) in 38 (26%) patients: 22 from Kordofan and 16 from Darfur. Partial open reading frame (ORF) 1 and ORF2 were sequenced from HEV from nine and three patients, respectively. Phylogenetic analysis showed that the Sudanese strains belonged to genotype 1 (HEV1), and confirmed the segregation of African HEV1 strains into one branch divergent from Asian HEV1. It also revealed that the Sudanese strains from this study and from an outbreak in 2004 formed a separate clade with a common ancestor, distinct from strains from the neighbouring Chad and Egypt. This HEV strain has thus spread in a large area of Sudan, where it has caused both sporadic hepatitis E and outbreaks from at least 2004 and onwards. These data demonstrate that hepatitis E is a constant, on-going public health problem in Sudan and that there is a need for hepatitis E surveillance, outbreak preparedness, and general improvements of the sanitation in these remote areas of the country. PMID:27782061

Characterization of the Quasi-Enveloped Hepatitis E Virus Particles Released by the Cellular Exosomal Pathway

PubMed Central

Nagashima, Shigeo; Takahashi, Masaharu; Kobayashi, Tominari; Nishizawa, Tsutomu; Nishiyama, Takashi; Primadharsini, Putu Prathiwi

2017-01-01

ABSTRACT Our previous studies demonstrated that membrane-associated hepatitis E virus (HEV) particles—now considered “quasi-enveloped particles”—are present in the multivesicular body with intraluminal vesicles (exosomes) in infected cells and that the release of HEV virions is related to the exosomal pathway. In this study, we characterized exosomes purified from the culture supernatants of HEV-infected PLC/PRF/5 cells. Purified CD63-, CD9-, or CD81-positive exosomes derived from the culture supernatants of HEV-infected cells that had been cultivated in serum-free medium were found to contain HEV RNA and the viral capsid (ORF2) and ORF3 proteins, as determined by reverse transcription-PCR (RT-PCR) and Western blotting, respectively. Furthermore, immunoelectron microscopy, with or without prior detergent and protease treatment, revealed the presence of virus-like particles in the exosome fraction. These particles were 39.6 ± 1.0 nm in diameter and were covered with a lipid membrane. After treatment with detergent and protease, the diameter of these virus-like particles was 26.9 ± 0.9 nm, and the treated particles became accessible with an anti-HEV ORF2 monoclonal antibody (MAb). The HEV particles in the exosome fraction were capable of infecting naive PLC/PRF/5 cells but were not neutralized by an anti-HEV ORF2 MAb which efficiently neutralizes nonenveloped HEV particles in cell culture. These results indicate that the membrane-wrapped HEV particles released by the exosomal pathway are copurified with the exosomes in the exosome fraction and suggest that the capsids of HEV particles are individually covered by lipid membranes resembling those of exosomes, similar to enveloped viruses. IMPORTANCE Hepatitis E, caused by HEV, is an important infectious disease that is spreading worldwide. HEV infection can cause acute or fulminant hepatitis and can become chronic in immunocompromised hosts, including patients after organ transplantation. The HEV particles

Multiplex hydrolysis probe real-time PCR for simultaneous detection of hepatitis A virus and hepatitis E virus.

PubMed

Qiu, Feng; Cao, Jingyuan; Su, Qiudong; Yi, Yao; Bi, Shengli

2014-05-30

Detection of hepatitis viral infections has traditionally relied on the circulating antibody test using the enzyme-linked immunosorbent assay. However, multiplex real-time PCR has been increasingly used for a variety of viral nucleic acid detections and has proven to be superior to traditional methods. Hepatitis A virus (HAV) and hepatitis E virus (HEV) are the major causes of acute hepatitis worldwide; both HAV and HEV infection are a main public health problem. In the present study, a one-step multiplex reverse transcriptase quantitative polymerase chain reaction assay using hydrolysis probes was developed for simultaneously detecting HAV and HEV. This novel detection system proved specific to the target viruses, to be highly sensitive and to be applicable to clinical sera samples, making it useful for rapid, accurate and feasible identification of HAV and HEV.

Seroprevalence of hepatitis E virus differs in Dutch and first generation migrant populations in Amsterdam, the Netherlands: a cross-sectional study.

PubMed

Sadik, S; van Rijckevorsel, G G C; van Rooijen, M S; Sonder, G J B; Bruisten, S M

2016-11-08

In the last decade hepatitis E virus (HEV) is increasingly recognized as a cause of acute viral hepatitis in developed countries. HEV is transmitted via the fecal-oral route. In countries like the Netherlands, HEV infection is suspected to be a zoonosis but HEV may also be introduced by migrants. We studied the seroprevalence of HEV among different migrants, mainly Moroccans and Turks, and compared this to that of the native Dutch population in Amsterdam, the Netherlands. Data were obtained from a cross-sectional survey of the adult Amsterdam population performed in 2004; the Amsterdam Health Monitor. A total of 1199 plasma samples were tested for IgG-and IgM antibodies to HEV using the Wantai kit according to instructions of the manufacturer. Basic demographic data (gender, age, country of birth, and age at immigration) were used in the analyses. Hepatitis A virus (HAV) serology data were available from a previous study. The total weighted anti-HEV IgG seroprevalence in the overall Amsterdam population was 26.7 %, based on 1199 samples. In the study population (not-weighted) this HEV seroprevalence was 157/426 (36.9 %) for the Dutch participants and it was 161/257 (62.6 %) for Moroccans, 99/296 (33.4 %) for Turks and 42/220 (19.1 %) for other ethnicities. HEV seroprevalence increased significantly with age. First-generation Moroccan migrants (44.0 %) had a significantly higher weighted HEV seroprevalence than the Dutch participants (29.7 %). In the first generation Turks (20.3 %) and first generation migrants from other countries (16.7 %) this weighted seroprevalence was lower, but this was only significant for the 'other ethnicities'. The median age of migration was significantly higher in the Moroccan and Turkish migrants who were HEV IgG positive versus HEV IgG negative. However, when stratifying for age at time of study, median migration age was only significantly different for HEV sero-status for younger Turks and younger 'other ethnicities'. HEV Ig

The burden of acute respiratory infections in Ecuador 2011-2015.

PubMed

Chicaiza-Ayala, Wilson; Henríquez-Trujillo, Aquiles R; Ortiz-Prado, Esteban; Douce, Richard W; Coral-Almeida, Marco

2018-01-01

Burden of disease studies intend to improve public health decision-making and to measure social and economic impact in population. The objective of this study was to describe the burden of acute respiratory infections (ARI) in Ecuador between 2011 and 2015. Five-year period morbidity and mortality data available from national agencies of statistics was analyzed to estimate the burden of disease attributable to acute respiratory infections. Cases and deaths registered were grouped according to their ICD-10 code into three diagnostic groups: Acute upper respiratory infections (J00-J06), Influenza and pneumonia (J09-J18), and Bronchitis and other acute lower respiratory infections (J20-J22, J85, J86). Disability-adjusted life years stratified by diagnostic and age group were calculated using the "DALY" package for R. The productivity loss in monetary terms was estimated using the human capital method. Over the 5-year period studied there were a total of 14.84 million cases of acute respiratory infections, with 17 757 deaths reported (0.12%). The yearly burden of disease ranged between 98 944 to 118 651 disability-adjusted life years, with an estimated average loss of productivity of US$152.16 million (±19.6) per year. Approximately 99% of the burden can be attributed to years life lost due to premature mortality in population under 5 years old and over 60 years-old. The burden of acute respiratory infections remained steady during the analyzed period. Evidence-based prevention and control policies to tackle acute respiratory infections in Ecuador should focus on the population at extreme ages of life.

The burden of acute respiratory infections in Ecuador 2011-2015

PubMed Central

2018-01-01

Background Burden of disease studies intend to improve public health decision-making and to measure social and economic impact in population. The objective of this study was to describe the burden of acute respiratory infections (ARI) in Ecuador between 2011 and 2015. Methods Five-year period morbidity and mortality data available from national agencies of statistics was analyzed to estimate the burden of disease attributable to acute respiratory infections. Cases and deaths registered were grouped according to their ICD-10 code into three diagnostic groups: Acute upper respiratory infections (J00-J06), Influenza and pneumonia (J09-J18), and Bronchitis and other acute lower respiratory infections (J20-J22, J85, J86). Disability-adjusted life years stratified by diagnostic and age group were calculated using the “DALY” package for R. The productivity loss in monetary terms was estimated using the human capital method. Results Over the 5-year period studied there were a total of 14.84 million cases of acute respiratory infections, with 17 757 deaths reported (0.12%). The yearly burden of disease ranged between 98 944 to 118 651 disability-adjusted life years, with an estimated average loss of productivity of US$152.16 million (±19.6) per year. Approximately 99% of the burden can be attributed to years life lost due to premature mortality in population under 5 years old and over 60 years-old. Conclusions The burden of acute respiratory infections remained steady during the analyzed period. Evidence-based prevention and control policies to tackle acute respiratory infections in Ecuador should focus on the population at extreme ages of life. PMID:29715314

Comparison of autochthonous and imported cases of hepatitis A or hepatitis E.

PubMed

Hartl, J; Kreuels, B; Polywka, S; Addo, M; Luethgehetmann, M; Dandri, M; Dammermann, W; Sterneck, M; Lohse, A W; Pischke, S

2015-07-01

Hepatitis A and hepatitis E are not limited to tropical countries but are also present in industrialized countries. Both infections share similar clinical features. There is no comparative study evaluating the clinical parameters of autochthonous and imported hepatitis A virus and hepatitis E virus infections. The aim of this study was to determine differences between autochthonous and imported hepatitis A virus (HAV) and hepatitis E virus (HEV) infections. Medical charts of all patients at our center with acute HAV and HEV infections were analyzed retrospectively (n = 50, study period 01/2009 - 08/2013). Peak bilirubin (median 8.6 vs. 4.4 mg/dL, p = 0.008) and ALT levels (median 2998 vs. 1666 IU/mL, p = 0.04) were higher in patients with hepatitis A compared to hepatitis E. In comparison to autochthones hepatitis E cases, patients with imported infections had significantly higher peak values for AST, ALT, bilirubin and INR (p = 0.009, p = 0.002, p = 0.04 and p = 0.049, respectively). In HAV infection, AST levels tended to be higher in imported infections (p = 0.08). (i) It is not possible to differentiate certainly between acute HAV and HEV infections by clinical or biochemical parameters, however, HAV infections might be associated with more cholestasis and higher ALT values. (ii) Imported HEV infections are associated with higher transaminases, INR and bilirubin levels compared to autochthonous cases and (iii) imported HAV infections tend to be associated with higher transaminases in comparison to autochthonous cases. © Georg Thieme Verlag KG Stuttgart · New York.

Hepatitis E Virus Infection in Dromedaries, North and East Africa, United Arab Emirates, and Pakistan, 1983–2015

PubMed Central

Rasche, Andrea; Saqib, Muhammad; Liljander, Anne M.; Bornstein, Set; Zohaib, Ali; Renneker, Stefanie; Steinhagen, Katja; Wernery, Renate; Younan, Mario; Gluecks, Ilona; Hilali, Mosaad; Musa, Bakri E.; Jores, Joerg; Wernery, Ulrich; Drexer, Jan Felix; Corman, Victor Max

2016-01-01

A new hepatitis E virus (HEV-7) was recently found in dromedaries and 1 human from the United Arab Emirates. We screened 2,438 dromedary samples from Pakistan, the United Arab Emirates, and 4 African countries. HEV-7 is long established, diversified and geographically widespread. Dromedaries may constitute a neglected source of zoonotic HEV infections. PMID:27315454

Transfusion-Transmitted Hepatitis E: NAT Screening of Blood Donations and Infectious Dose.

PubMed

Dreier, Jens; Knabbe, Cornelius; Vollmer, Tanja

2018-01-01

The risk and importance of transfusion-transmitted hepatitis E virus (TT-HEV) infections by contaminated blood products is currently a controversial discussed topic in transfusion medicine. The infectious dose, in particular, remains an unknown quantity. In the present study, we illuminate and review this aspect seen from the viewpoint of a blood donation service with more than 2 years of experience in routine HEV blood donor screening. We systematically review the actual status of presently known cases of TT-HEV infections and available routine NAT-screening assays. The review of the literature revealed a significant variation regarding the infectious dose causing hepatitis E. We also present the outcome of six cases confronted with HEV-contaminated blood products, identified by routine HEV RNA screening of minipools using the highly sensitive RealStar HEV RT-PCR Kit (95% LOD: 4.7 IU/mL). Finally, the distribution of viral RNA in different blood components [plasma, red blood cell concentrate (RBC), platelet concentrates (PC)] was quantified using the first WHO international standard for HEV RNA for NAT-based assays. None of the six patients receiving an HEV-contaminated blood product from five different donors (donor 1: RBC, donor 2-5: APC) developed an acute hepatitis E infection, most likely due to low viral load in donor plasma (<100 IU/mL). Of note, the distribution of viral RNA in blood components depends on the plasma content of the component; nonetheless, HEV RNA could be detected in RBCs even when low viral plasma loads of 100-1,000 IU/mL are present. Comprehensive retrospective studies of TT-HEV infection offered further insights into the infectivity of HEV RNA-positive blood products. Minipool HEV NAT screening (96 samples) of blood donations should be adequate as a routine screening assay to identify high viremic donors and will cover at least a large part of viremic phases.

[Typing and identification of non-polio enterovirus from acute flaccid paralysis cases in Ningxia, 1997-2011].

PubMed

Ma, Jiang-tao; Chen, Hui; Yuan, Fang; Ma, Xue-min; Guan, Guang-yu; Zhan, Jun

2012-11-01

To identify the serotype of 73 non-polio enterovirus (NPEV) strains from acute flaccid paralysis (AFP) cases in Ningxia province, during 1997 - 2011. Partial sequencing of the VP1 region was amplified by RT-PCR with degenerate primers and sequenced while sequences were compared with the database of GenBank by the BLAST algorithm. Evolution was analyzed by constructing phylogenetic tree using Mega 5.1. In this study, a total of 73 NPEVs were analyzed, including 4 strains un-typed, 69 strains typed by RT-PCR. A total of 27 serotypes were identified, including 8 serotypes of human enterovirus (HEV)-A, 19 serotypes of HEV-B. The HEV-B group (46/69, 66.7%) constituted the largest proportion of isolates, followed by HEV-A (23/69, 33.3%), but no strains were found that belonged to HEV-C or HEV-D group. In the 69 strains, enterovirus 71 was the most frequently seen isolates, followed by coxsackie-virus A4, 16, 9 and echovirus 24, 6. HEV-B was the most predominant (46/69, 66.7%) serotype of NPEV in Ningxia during the AFP surveillance, in 1997 - 2011.

Hepatitis E Virus: Foodborne, Waterborne and Zoonotic Transmission

PubMed Central

Yugo, Danielle M.; Meng, Xiang-Jin

2013-01-01

Hepatitis E virus (HEV) is responsible for epidemics and endemics of acute hepatitis in humans, mainly through waterborne, foodborne, and zoonotic transmission routes. HEV is a single-stranded, positive-sense RNA virus classified in the family Hepeviridae and encompasses four known Genotypes (1–4), at least two new putative genotypes of mammalian HEV, and one floating genus of avian HEV. Genotypes 1 and 2 HEVs only affect humans, while Genotypes 3 and 4 are zoonotic and responsible for sporadic and autochthonous infections in both humans and several other animal species worldwide. HEV has an ever-expanding host range and has been identified in numerous animal species. Swine serve as a reservoir species for HEV transmission to humans; however, it is likely that other animal species may also act as reservoirs. HEV poses an important public health concern with cases of the disease definitively linked to handling of infected pigs, consumption of raw and undercooked animal meats, and animal manure contamination of drinking or irrigation water. Infectious HEV has been identified in numerous sources of concern including animal feces, sewage water, inadequately-treated water, contaminated shellfish and produce, as well as animal meats. Many aspects of HEV pathogenesis, replication, and immunological responses remain unknown, as HEV is an extremely understudied but important human pathogen. This article reviews the current understanding of HEV transmission routes with emphasis on food and environmental sources and the prevalence of HEV in animal species with zoonotic potential in humans. PMID:24071919

Kocuria kristinae infection associated with acute cholecystitis

PubMed Central

Ma, Edmond SK; Wong, Chris LP; Lai, Kristi TW; Chan, Edmond CH; Yam, WC; Chan, Angus CW

2005-01-01

Background Kocuria, previously classified into the genus of Micrococcus, is commonly found on human skin. Two species, K. rosea and K. kristinae, are etiologically associated with catheter-related bacteremia. Case presentation We describe the first case of K. kristinae infection associated with acute cholecystitis. The microorganism was isolated from the bile of a 56-year old Chinese man who underwent laparoscopic cholecystectomy. He developed post-operative fever that resolved readily after levofloxacin treatment. Conclusion Our report of K. kristinae infection associated with acute cholecystitis expands the clinical spectrum of infections caused by this group of bacteria. With increasing number of recent reports describing the association between Kocuria spp. and infectious diseases, the significance of their isolation from clinical specimens cannot be underestimated. A complete picture of infections related to Kocuria spp. will have to await the documentation of more clinical cases. PMID:16029488

Kocuria kristinae infection associated with acute cholecystitis.

PubMed

Ma, Edmond S K; Wong, Chris L P; Lai, Kristi T W; Chan, Edmond C H; Yam, W C; Chan, Angus C W

2005-07-19

Kocuria, previously classified into the genus of Micrococcus, is commonly found on human skin. Two species, K. rosea and K. kristinae, are etiologically associated with catheter-related bacteremia. We describe the first case of K. kristinae infection associated with acute cholecystitis. The microorganism was isolated from the bile of a 56-year old Chinese man who underwent laparoscopic cholecystectomy. He developed post-operative fever that resolved readily after levofloxacin treatment. Our report of K. kristinae infection associated with acute cholecystitis expands the clinical spectrum of infections caused by this group of bacteria. With increasing number of recent reports describing the association between Kocuria spp. and infectious diseases, the significance of their isolation from clinical specimens cannot be underestimated. A complete picture of infections related to Kocuria spp. will have to await the documentation of more clinical cases.

Estimating Acute Viral Hepatitis Infections From Nationally Reported Cases

PubMed Central

Liu, Stephen; Roberts, Henry; Jiles, Ruth B.; Holmberg, Scott D.

2014-01-01

Objectives. Because only a fraction of patients with acute viral hepatitis A, B, and C are reported through national surveillance to the Centers for Disease Control and Prevention, we estimated the true numbers. Methods. We applied a simple probabilistic model to estimate the fraction of patients with acute hepatitis A, hepatitis B, and hepatitis C who would have been symptomatic, would have sought health care tests, and would have been reported to health officials in 2011. Results. For hepatitis A, the frequencies of symptoms (85%), care seeking (88%), and reporting (69%) yielded an estimate of 2730 infections (2.0 infections per reported case). For hepatitis B, the frequencies of symptoms (39%), care seeking (88%), and reporting (45%) indicated 18 730 infections (6.5 infections per reported case). For hepatitis C, the frequency of symptoms among injection drug users (13%) and those infected otherwise (48%), proportion seeking care (88%), and percentage reported (53%) indicated 17 100 infections (12.3 infections per reported case). Conclusions. These adjustment factors will allow state and local health authorities to estimate acute hepatitis infections locally and plan prevention activities accordingly. PMID:24432918

Echovirus 6 Infects Human Exocrine and Endocrine Pancreatic Cells and Induces Pro-Inflammatory Innate Immune Response

PubMed Central

Sarmiento, Luis; Frisk, Gun; Anagandula, Mahesh; Hodik, Monika; Barchetta, Ilaria; Netanyah, Eitan; Cabrera-Rode, Eduardo; Cilio, Corrado M.

2017-01-01

Human enteroviruses (HEV), especially coxsackievirus serotype B (CVB) and echovirus (E), have been associated with diseases of both the exocrine and endocrine pancreas, but so far evidence on HEV infection in human pancreas has been reported only in islets and ductal cells. This study aimed to investigate the capability of echovirus strains to infect human exocrine and endocrine pancreatic cells. Infection of explanted human islets and exocrine cells with seven field strains of E6 caused cytopathic effect, virus titer increase and production of HEV protein VP1 in both cell types. Virus particles were found in islets and acinar cells infected with E6. No cytopathic effect or infectious progeny production was observed in exocrine cells exposed to the beta cell-tropic strains of E16 and E30. Endocrine cells responded to E6, E16 and E30 by upregulating the transcription of interferon-induced with helicase C domain 1 (IF1H1), 2′-5′-oligoadenylate synthetase 1 (OAS1), interferon-β (IFN-β), chemokine (C–X–C motif) ligand 10 (CXCL10) and chemokine (C–C motif) ligand 5 (CCL5). Echovirus 6, but not E16 or E30, led to increased transcription of these genes in exocrine cells. These data demonstrate for the first time that human exocrine cells represent a target for E6 infection and suggest that certain HEV serotypes can replicate in human pancreatic exocrine cells, while the pancreatic endocrine cells are permissive to a wider range of HEV. PMID:28146100

Development of nickel/metal-hydride batteries for EVs and HEVs

NASA Astrophysics Data System (ADS)

Taniguchi, Akihiro; Fujioka, Noriyuki; Ikoma, Munehisa; Ohta, Akira

This paper is to introduce the nickel/metal-hydride (Ni/MH) batteries for electric vehicles (EVs) and hybrid electric vehicles (HEVs) developed and mass-produced by our company. EV-95 for EVs enables a vehicle to drive approximately 200 km per charge. As the specific power is extremely high, more than 200 W/kg at 80% depth of discharge (DOD), the acceleration performance is equivalent to that of gasoline fuel automobiles. The life characteristic is also superior. This battery gives the satisfactory result of more than 1000 cycles in bench tests and approximately 4-year on-board driving. EV-28 developed for small EVs comprises of a compact and light battery module with high specific power of 300 W/kg at 80% DOD by introducing a new technology for internal cell connection. Meanwhile, our cylindrical battery for the HEV was adopted into the first generation Toyota Prius in 1997 which is the world's first mass-product HEV, and has a high specific power of 600 W/kg. Its life characteristic was found to be equivalent to more than 100,000 km driving. Furthermore, a new prismatic module in which six cells are connected internally was used for the second generation Prius in 2000. The prismatic battery comprises of a compact and light battery pack with a high specific power of 1000 W/kg, which is approximately 1.7 times that of conventional cylindrical batteries, as a consequence of the development of a new internal cell connection and a new current collection structure.

Acute Sleep Deprivation Enhances Post-Infection Sleep and Promotes Survival during Bacterial Infection in Drosophila

PubMed Central

Kuo, Tzu-Hsing; Williams, Julie A.

2014-01-01

Study Objectives: Sleep is known to increase as an acute response to infection. However, the function of this behavioral response in host defense is not well understood. To address this problem, we evaluated the effect of acute sleep deprivation on post-infection sleep and immune function in Drosophila. Setting: Laboratory. Participants: Drosophila melanogaster. Methods and Results: Flies were subjected to sleep deprivation before (early DEP) or after (late DEP) bacterial infection. Relative to a non-deprived control, flies subjected to early DEP had enhanced sleep after infection as well as increased bacterial clearance and survival outcome. Flies subjected to late DEP experienced enhanced sleep following the deprivation period, and showed a modest improvement in survival outcome. Continuous DEP (early and late DEP) throughout infection also enhanced sleep later during infection and improved survival. However, improved survival in flies subjected to late or continuous DEP did not occur until after flies had experienced sleep. During infection, both early and late DEP enhanced NFκB transcriptional activity as measured by a luciferase reporter (κB-luc) in living flies. Early DEP also increased NFκB activity prior to infection. Flies that were deficient in expression of either the Relish or Dif NFκB transcription factors showed normal responses to early DEP. However, the effect of early DEP on post-infection sleep and survival was abolished in double mutants, which indicates that Relish and Dif have redundant roles in this process. Conclusions: Acute sleep deprivation elevated NFκB-dependent activity, increased post-infection sleep, and improved survival during bacterial infection. Citation: Kuo TH, Williams JA. Acute sleep deprivation enhances post-infection sleep and promotes survival during bacterial infection in Drosophila. SLEEP 2014;37(5):859-869. PMID:24790264

[Antibiotic prescribing in acute respiratory tract infections in general practice].

PubMed

Malo, S; Bjerrum, L; Feja, C; Lallana, M J; Poncel, A; Rabanaque, M J

2015-06-01

Antimicrobial resistance is a worldwide threat to public health. Acute respiratory tract infections are the main reason for antibiotic prescribing in the Spanish paediatric population. The aim of the study was to describe the frequency of antibiotic prescription and their pattern of use in acute respiratory tract infections diagnosed in children in Primary Care in Aragón (Spain). A study was conducted over a 1-year period on children between 0 and 14 years-old, recording all episodes of acute otitis, acute pharyngotonsillitis, non-specific upper respiratory infection, and acute bronchitis. The proportion of episodes within each diagnosis receiving an antibiotic prescription was calculated, and the prescribing pattern was determined. Half (50%) of the children in Aragón were diagnosed with a respiratory tract infection during the study period. Non-specific upper respiratory infection was the most frequent diagnosis. An antibiotic was prescribed in 75% of pharyngotonsillitis episodes, 72% of otitis, 27% of bronchitis, and 16% of non-specific upper respiratory infections. Broad spectrum antibiotics, mainly amoxicillin and amoxicillin-clavulanic, were predominantly prescribed. Antibiotic prescribing in respiratory tract infections in children was generally high, and the choice of antibiotics was probably inappropriate in a high percentage of cases. Therefore an improvement in antibiotic prescribing in children appears to be needed. Copyright © 2014 Asociación Española de Pediatría. Published by Elsevier España, S.L.U. All rights reserved.

Molecular cloning and immunoglobulin E reactivity of a natural rubber latex lecithinase homologue, the major allergenic component of Hev b 4.

PubMed

Sunderasan, E; Bahari, A; Arif, S A M; Zainal, Z; Hamilton, R G; Yeang, H Y

2005-11-01

Hev b 4 is an allergenic natural rubber latex (NRL) protein complex that is reactive in skin prick tests and in vitro immunoassays. On SDS-polyacrylamide gel electrophoresis (SDS-PAGE), Hev b 4 is discerned predominantly at 53-55 kDa together with a 57 kDa minor component previously identified as a cyanogenic glucosidase. Of the 13 NRL allergens recognized by the International Union of Immunological Societies, the 53-55 kDa Hev b 4 major protein is the only candidate that lacks complete cDNA and protein sequence information. We sought to clone the transcript encoding the Hev b 4 major protein, and characterize the native protein and its recombinant form in relation to IgE binding. The 5'/3' rapid amplification of cDNA ends method was employed to obtain the complete cDNA of the Hev b 4 major protein. A recombinant form of the protein was over-expressed in Escherichia coli. The native Hev b 4 major protein was deglycosylated by trifluoromethane sulphonic acid. Western immunoblots of the native, deglycosylated and recombinant proteins were performed using both polyclonal antibodies and sera from latex-allergic patients. The cDNA encoding the Hev b 4 major protein was cloned. Its open reading frame matched lecithinases in the conserved domain database and contained 10 predicted glycosylation sites. Detection of glycans on the Hev b 4 lecithinase homologue confirmed it to be a glycoprotein. The deglycosylated lecithinase homologue was discerned at 40 kDa on SDS-PAGE, this being comparable to the 38.53 kDa mass predicted by its cDNA. Deglycosylation of the lecithinase homologue resulted in the loss of IgE recognition, although reactivity to polyclonal rabbit anti-Hev b 4 was retained. IgE from latex-allergic patients also failed to recognize the non-glycosylated E. coli recombinant lecithinase homologue. The IgE epitopes of the Hev b 4 lecithinase homologue reside mainly in its carbohydrate moiety, which also account for the discrepancy between the observed molecular

Current Knowledge on Hepatitis E.

PubMed

Pérez-Gracia, María Teresa; García, Mario; Suay, Beatriz; Mateos-Lindemann, María Luisa

2015-06-28

Although only a single serotype of hepatitis E virus (HEV), the causative agent of hepatitis E, has been identified, there is great genetic variation among the different HEV isolates reported. There are at least four major recognized genotypes of HEV: genotypes 1 and 2 are mainly restricted to humans and linked to epidemic outbreaks in nonindustrialized countries, whereas genotypes 3 and 4 are zoonotic in both developing and industrialized countries. Besides human strains, genotype 3 and 4 strains of HEV have been genetically characterized from swine, sika deer, mongooses, sheep, and rabbits. Currently, there are approximately 11,000 human and animal sequences of HEV available at the International Nucleotide Sequence Database Collaboration. HEV is the major cause of waterborne outbreaks of hepatitis in areas of poor sanitation. Additionally, it is responsible for sporadic cases of viral hepatitis in not only endemic but industrialized countries as well. Transmission of HEV occurs predominantly by the fecal-oral route, although parenteral and perinatal routes have been reported. HEV infection develops in most individuals as a self-limiting, acute, icteric hepatitis; with mortality rates around 1%. However, some affected individuals will develop fulminant hepatic failure, a serious condition that is frequently fatal without a liver transplant. This complication is particularly common when the infection occurs in pregnant women, where mortality rates rise dramatically to up to 25%. Among the preventive measures available to avoid HEV infection, two separate subunit vaccines containing recombinant truncated capsid proteins of HEV have been shown to be highly effective in the prevention of disease. One of them, HEV 239, was approved in China, and its commercialization by Innovax began in November 2012 under the name Hecolin(®).

Multiplex Hydrolysis Probe Real-Time PCR for Simultaneous Detection of Hepatitis A Virus and Hepatitis E Virus

PubMed Central

Qiu, Feng; Cao, Jingyuan; Su, Qiudong; Yi, Yao; Bi, Shengli

2014-01-01

Detection of hepatitis viral infections has traditionally relied on the circulating antibody test using the enzyme-linked immunosorbent assay. However, multiplex real-time PCR has been increasingly used for a variety of viral nucleic acid detections and has proven to be superior to traditional methods. Hepatitis A virus (HAV) and hepatitis E virus (HEV) are the major causes of acute hepatitis worldwide; both HAV and HEV infection are a main public health problem. In the present study, a one-step multiplex reverse transcriptase quantitative polymerase chain reaction assay using hydrolysis probes was developed for simultaneously detecting HAV and HEV. This novel detection system proved specific to the target viruses, to be highly sensitive and to be applicable to clinical sera samples, making it useful for rapid, accurate and feasible identification of HAV and HEV. PMID:24886818

Hepatitis E in Qatar imported by expatriate workers from Nepal: epidemiological characteristics and clinical manifestations.

PubMed

Ibrahim, Abdulsalam Saif; Alkhal, Abdulatif; Jacob, Joyal; Ghadban, Wisam; Almarri, Ajayeb

2009-06-01

Prompted by cases of acute hepatitis in expatriate workers presenting at Alkhor Hospital, Qatar, a limited prospective observational study was conducted from July 2005 to June 2006 to determine the epidemiological and clinical features of patients (predominantly Nepalese) presenting with acute hepatitis. Countrywide during that period samples from 86 Nepalese presenting at different centers were found to be anti-HEV IgG positive and 50 of these were also positive for anti-HEV IgM. Fifty-eight of those Nepalese were seen and treated at Alkhor Hospital and of them 43 were confirmed as cases of acute HEV, being positive for both anti-HEV IgM and IgG. The remaining 15 were diagnosed as probable cases of acute HEV on the basis of clinical and epidemiological similarity. It seems likely that transit in Kathmandu in reportedly unsanitary conditions was the focus of infection. In some of those examined at Alkhor, ultrasound detected a thickened gallbladder wall in 30 of 39 (76.9%) with two cases having clinical acalcular cholecystitis. Higher levels of alanine aminotransferase and aspartate aminotransferase were associated with severe disease and derangement in coagulation. On the available evidence hepatitis E was imported by expatriate workers and it is clear that medical screening of these workers pre- and post-arrival must be improved to prevent further outbreaks. It is also essential that health care workers in Qatar are made aware of this ongoing problem of imported HEV and understand the variable presentation of the condition.

Community-Based Seroepidemiological Survey of Hepatitis E Virus Infection in Catalonia, Spain▿

PubMed Central

Buti, Maria; Domínguez, Àngela; Plans, Pere; Jardí, Rossend; Schaper, Mélani; Espuñes, Jordi; Cardeñosa, Neus; Rodríguez-Frías, Francisco; Esteban, Rafael; Plasència, Antoni; Salleras, Luis

2006-01-01

The objective of the study was to investigate the prevalence of immunoglobulin G (IgG) antibodies to hepatitis E virus (HEV) infection in a population sample from Catalonia and to analyze the demographic and clinical variables associated with the presence of these antibodies. A total of 1,280 subjects between 15 and 74 years of age were selected randomly from urban and rural areas. Data for sociodemographic and clinical variables were collected by using a questionnaire. IgG antibodies to HEV were determined by an immunoenzymatic method. The odds ratios (ORs) and 95% confidence intervals (95% CIs) were calculated for studied variables. Multiple logistic regression analysis was used to determine which variables were independently associated with the prevalence of HEV infection. Anti-HEV antibodies were detected in 96 (7.3%) of the 1,280 samples analyzed. The prevalence of antibodies was greater among males (7.8%) than among women (7%) and increased with age for both sexes, from 3% among subjects 15 to 24 years of age to 12% among subjects ≥65 years of age. Bivariate analysis of the sociodemographic and clinical variables showed an association between the prevalence of hepatitis E virus infection and minor surgery (OR, 1.96; 95% CI, 1.24 to 3.11), abdominal surgery (OR, 1.74; 95% CI, 1.12 to 2.73), and, for women, being uniparous or multiparous (OR, 2.84; 95% CI, 1.19 to 6.79). The multivariate analysis showed an association with minor surgery only (OR, 1.68; 95% CI, 1.03 to 2.70). In conclusion, anti-HEV antibodies were detected in 7.3% of the Catalan population. The seroprevalence of anti-HEV antibodies increased with age and was associated with previous minor surgery. PMID:17050741

Severe acute malnutrition and infection

PubMed Central

Jones, Kelsey D J; Berkley, James A

2014-01-01

Severe acute malnutrition (SAM) is associated with increased severity of common infectious diseases, and death amongst children with SAM is almost always as a result of infection. The diagnosis and management of infection are often different in malnourished versus well-nourished children. The objectives of this brief are to outline the evidence underpinning important practical questions relating to the management of infectious diseases in children with SAM and to highlight research gaps. Overall, the evidence base for many aspects covered in this brief is very poor. The brief addresses antimicrobials; antipyretics; tuberculosis; HIV; malaria; pneumonia; diarrhoea; sepsis; measles; urinary tract infection; nosocomial Infections; soil transmitted helminths; skin infections and pharmacology in the context of SAM. The brief is structured into sets of clinical questions, which we hope will maximise the relevance to contemporary practice. PMID:25475887

High clinical manifestation rate in an imported outbreak of hepatitis E genotype 1 infection in a German group of travellers returning from India.

PubMed

Pischke, Sven; Schulze-Zur-Wiesch, Julian; Lütgehetmann, Marc; Kreuels, Benno; Lueth, Stefan; Kapaun, Petra; Benten, Daniel; Schmiedel, Stefan; Sterneck, Martina; Lohse, Ansgar W; Polywka, Susanne

2017-01-01

Background. There are only few reports about travel-associated, imported tropical hepatitis E virus (HEV) genotype 1 infections within Western travellers. We describe the clinical course of a single outbreak of hepatitis E in a German travellers group returning from India and compare the results of two commercial HEV-seroassays. After identifying hepatitis E in an index patient returning from a journey to India all 24 members of this journey were tested for anti-HEV-IgG and IgM using two commercial seroassays (Wantai and Mikrogen), for HEV-RNA by PCR and HEV-Ag by an antigen-assay (Wantai). 5/24 (21%) individuals were viraemic with viral loads between 580-4,800,000 IU/mL. Bilirubin and ALT levels in these patients ranged from 1.3-14.9 mg/dL (mean 7.3 mg/dL, SD 5.6 mg/dL) and 151-4,820 U/L (mean 1,832U/L, SD 1842U/L), respectively and showed significant correlations with viral loads (r = 0.863, p < 0.001; r = 0.890, p < 0.001). No risk factor for food-borne HEV-transmission was identified. All viraemic patients (5/5) tested positive for anti-HEV-IgG and IgM in the Wantai-assay but only 4/5 in the Mikrogen-assay. Wantai-HEV-antigen-assay was negative in all patients. Six months later all previously viraemic patients tested positive for anti-HEV-IgG and negative for IgM in both assays. However, two non-viremic individuals who initially tested Wantai-IgM-positive stayed positive indicating false positive results. Despite the exact number of exposed individuals could not be determined HEV genotype 1 infections have a high manifestation rate of more than 20%.The Wantai-antigen-test failed, the Wantai-IgMrapid- test and the Mikrogen-IgM-recomblot showed a better performance but still they cannot replace real-time PCR for diagnosing ongoing HEV-infections.

Seroprevalence of Hepatitis E Virus in Roma Settlements: A Comparison with the General Population in Slovakia.

PubMed

Halánová, Monika; Veseliny, Eduard; Kalinová, Zuzana; Jarčuška, Peter; Janičko, Martin; Urbančíková, Ingrid; Pella, Daniel; Dražilová, Sylvia; Babinská, Ingrid

2018-05-03

Hepatitis E infection is one of the most frequent causes of acute hepatitis in the world. Currently five human genotypes with different geographical distributions and distinct epidemiologic patterns are identified. In Slovakia, only rare cases of hepatitis E have been reported in past years. Because the most important risk factors associated with HEV infection include consumption of contaminated pork meat and poor hygienic standards, the aim of the study was to evaluate the prevalence of anti-HEV total antibodies and the main risk factors for HEV in the population living in separated and segregated Roma settlements ( n = 195), which represent places with increased risk of infection in Slovakia and to compare it with the prevalence in the general population ( n = 69). Of 264 respondents included in the study, 47 (17.8%) showed positivity for anti-HEV antibodies, 42 of whom were Roma (21.5%, n = 195) and 5 (7.2%, n = 69) non-Roma. The population living in Roma settlements lives in poorer conditions and are at higher risk of HEV in comparison to the general population. However, differences in living conditions within the settlements do not contributed to lower risk of HEV antibody prevalence between Roma living in settlements.

Seroprevalence of Hepatitis E Virus in Roma Settlements: A Comparison with the General Population in Slovakia

PubMed Central

Veseliny, Eduard; Kalinová, Zuzana; Jarčuška, Peter; Urbančíková, Ingrid; Pella, Daniel; Dražilová, Sylvia; Babinská, Ingrid

2018-01-01

Hepatitis E infection is one of the most frequent causes of acute hepatitis in the world. Currently five human genotypes with different geographical distributions and distinct epidemiologic patterns are identified. In Slovakia, only rare cases of hepatitis E have been reported in past years. Because the most important risk factors associated with HEV infection include consumption of contaminated pork meat and poor hygienic standards, the aim of the study was to evaluate the prevalence of anti-HEV total antibodies and the main risk factors for HEV in the population living in separated and segregated Roma settlements (n = 195), which represent places with increased risk of infection in Slovakia and to compare it with the prevalence in the general population (n = 69). Of 264 respondents included in the study, 47 (17.8%) showed positivity for anti-HEV antibodies, 42 of whom were Roma (21.5%, n = 195) and 5 (7.2%, n = 69) non-Roma. The population living in Roma settlements lives in poorer conditions and are at higher risk of HEV in comparison to the general population. However, differences in living conditions within the settlements do not contributed to lower risk of HEV antibody prevalence between Roma living in settlements. PMID:29751522

Neutrophil Kinetics in Acute Infection*

PubMed Central

Marsh, J. C.; Boggs, D. R.; Cartwright, G. E.; Wintrobe, M. M.

1967-01-01

Neutrophil kinetics of acute experimental infection were studied with diisopropylfluorophosphate-32P labeling in 31 dogs inoculated intrabronchially with pneumococci. In vitro neutrophil labeling indicated a rapid transit time through the blood in early infections, with an elevated marginal granulocyte pool sometimes preceding an elevation of the circulating granulocyte pool. 13 hr after infection, the circulating and total blood granulocyte pools were increased but the rate of neutrophil transit through the blood was normal. During the recovery from infection there was a marked prolongation of neutrophil blood transit time, suggesting virtually complete cessation of bone marrow release of neutrophils into the blood. Labeling of neutrophils in vivo indicated an increased rate of emptying of the bone marrow storage pool proportional to the severity of infection as measured by the fever index. The change in the blood ratio of nonsegmented to segmented neutrophils was a much more accurate index of the severity of infection than the blood granulocyte concentration, correlating significantly with the fever index. PMID:6073999

Restricted Enzooticity of Hepatitis E Virus Genotypes 1 to 4 in the United States ▿

PubMed Central

Dong, Chen; Meng, Jihong; Dai, Xing; Liang, Jiu-Hong; Feagins, Alicia R.; Meng, Xiang-Jin; Belfiore, Natalia M.; Bradford, Carol; Corn, Joseph L.; Cray, Carolyn; Glass, Gregory E.; Gordon, Melvin L.; Hesse, Richard A.; Montgomery, Donald L.; Nicholson, William L.; Pilny, Anthony A.; Ramamoorthy, Sheela; Shaver, Douglas D.; Drobeniuc, Jan; Purdy, Michael A.; Fields, Howard A.; Kamili, Saleem; Teo, Chong-Gee

2011-01-01

Hepatitis E is recognized as a zoonosis, and swine are known reservoirs, but how broadly enzootic its causative agent, hepatitis E virus (HEV), is remains controversial. To determine the prevalence of HEV infection in animals, a serological assay with capability to detect anti-HEV-antibody across a wide variety of animal species was devised. Recombinant antigens comprising truncated capsid proteins generated from HEV-subgenomic constructs that represent all four viral genotypes were used to capture anti-HEV in the test sample and as an analyte reporter. To facilitate development and validation of the assay, serum samples were assembled from blood donors (n = 372), acute hepatitis E patients (n = 94), five laboratory animals (rhesus monkey, pig, New Zealand rabbit, Wistar rat, and BALB/c mouse) immunized with HEV antigens, and four pigs experimentally infected with HEV. The assay was then applied to 4,936 sera collected from 35 genera of animals that were wild, feral, domesticated, or otherwise held captive in the United States. Test positivity was determined in 457 samples (9.3%). These originated from: bison (3/65, 4.6%), cattle (174/1,156, 15%), dogs (2/212, 0.9%), Norway rats (2/318, 0.6%), farmed swine (267/648, 41.2%), and feral swine (9/306, 2.9%). Only the porcine samples yielded the highest reactivities. HEV RNA was amplified from one farmed pig and two feral pigs and characterized by nucleotide sequencing to belong to genotype 3. HEV infected farmed swine primarily, and the role of other animals as reservoirs of its zoonotic spread appears to be limited. PMID:21998412

Human bocavirus in children with acute respiratory infections in Vietnam.

PubMed

Tran, Dinh Nguyen; Nguyen, Tran Quynh Nhu; Nguyen, Tuan Anh; Hayakawa, Satoshi; Mizuguchi, Masashi; Ushijima, Hiroshi

2014-06-01

Acute respiratory infections are the major cause of morbidity and mortality globally. Human bocavirus (HBoV), a novel virus, is recognized to increasingly associate with previously unknown etiology respiratory infections in young children. In this study, the epidemiological, clinical, and molecular characteristics of HBoV infections were described in hospitalized Vietnamese pediatric patients. From April 2010 to May 2011, 1,082 nasopharyngeal swab samples were obtained from patients with acute respiratory infections at the Children's Hospital 2, Ho Chi Minh City, Vietnam. Samples were screened for HBoV by PCR and further molecularly characterized by sequencing. HBoV was found in 78 (7.2%) children. Co-infection with other viruses was observed in 66.7% of patients infected with HBoV. Children 12-24 months old were the most affected age group. Infections with HBoV were found year-round, though most cases occurred in the dry season (December-April). HBoV was possible to cause severe diseases as determined by higher rates of hypoxia, pneumonia, and longer hospitalization duration in patients with HBoV infection than in those without (P-value <0.05). Co-infection with HBoV did not affect the disease severity. The phylogenetic analysis of partial VP1 gene showed minor variations and all HBoV sequences belonged to species 1 (HBoV1). In conclusion, HBoV1 was circulating in Vietnam and detected frequently in young children during dry season. Acute respiratory infections caused by HBoV1 were severe enough for hospitalization, which implied that HBoV1 may have an important role in acute respiratory infections among children. © 2013 Wiley Periodicals, Inc.

Hepatitis E risks: pigs or blood-that is the question.

PubMed

Tedder, Richard S; Ijaz, Samreen; Kitchen, Alan; Ushiro-Lumb, Ines; Tettmar, Kate I; Hewitt, Patricia; Andrews, Nick

2017-02-01

Infection with hepatitis E virus (HEV) Genotype 3 is recognized as a food-borne zoonosis in developed countries where it usually causes a mild self-limited acute hepatitis. It may cause a persistent infection in the immunosuppressed human that can progress to cirrhosis. To protect the patient from transfusion-acquired HEV infection, steps have been taken in the United Kingdom to provide for at-risk patients only components from donors screened for HEV viremia. This strategy does not protect from dietary exposure and calls into question estimation of relative risk between blood transfusion and diet. Using data on HEV viremia, component exposure, residual plasma volume, and resulting transmission, the dose of virus administered and subsequent transmission rates were determined and used to populate a model that can infer the relationship between blood and dietary exposure. The annual attack rate of a population, defined as seroconversion, provides an estimate of the risk of receiving a component containing HEV from a viremic donor. The lowest viral dose that resulted in infection was 2 × 10 4 IUs and 55% of components containing this dose transmitted infection. The transfusion risk of infection only exceeds the annual dietary risk when more than 13 individual donor components are transfused. For many solid organ transplant patients dietary exposure far exceeds the risk of transfusion from unscreened donors. It is only in the immunosuppressed patient requiring extensive blood component support that transfusion risk dominates. This understanding should inform policy decisions on HEV RNA screening of blood donations. © 2017 AABB.

Epidemiology of Hepatitis E Virus in an Urban Community in Dhaka City

PubMed Central

Rahman, Salimur; Jahan, Munira; Tabassum, Shahina; Fazle Akbar, Sheikh Mohammad

2014-01-01

ABSTRACT Introduction Hepatitis E virus (HEV) is endemic in Bangladesh and sporadic and epidemic outbreaks of acute hepatitis E occur in this country almost regularly. Although the real magnitude of HEV prevalence has not been documented in Bangladesh, HEV infections and HEV-related acute hepatitis of Bangladeshi origin have been reported from different parts of the world. Methods The study was conducted in Mirpur area of Dhaka city, which is a major residential area of the capital of Bangladesh. Three hundred adults were randomly included in the study. None had any history of jaundice or complains of liver diseases. Results The study revealed 30% prevalence of HEV in this population. The prevalence increased with age, but there was no gender difference. Conclusion HEV is a highly prevalent disease in Bangladesh as elsewhere in the developing world. Since there is no specific treatment for HEV, improvement of personal hygiene and ensuring supply of safe food and drinking water remain most important approach to sustain the virus. How to cite this article: Rahman S, Mahtab MA, Jahan M, Tabassum S, Akbar SMF. Epidemiology of Hepatitis E Virus in an Urban Community in Dhaka City. Euroasian J Hepato-Gastroenterol 2014; 4(1):4-6. PMID:29264310

Estimating the Burden of Maternal and Neonatal Deaths Associated With Jaundice in Bangladesh: Possible Role of Hepatitis E Infection

PubMed Central

Halder, Amal K.; Streatfield, Peter K.; Sazzad, Hossain M.S.; Nurul Huda, Tarique M.; Hossain, M. Jahangir; Luby, Stephen P.

2012-01-01

Objectives. We estimated the population-based incidence of maternal and neonatal mortality associated with hepatitis E virus (HEV) in Bangladesh. Methods. We analyzed verbal autopsy data from 4 population-based studies in Bangladesh to calculate the maternal and neonatal mortality ratios associated with jaundice during pregnancy. We then reviewed the published literature to estimate the proportion of maternal deaths associated with liver disease during pregnancy that were the result of HEV in hospitals. Results. We found that 19% to 25% of all maternal deaths and 7% to 13% of all neonatal deaths in Bangladesh were associated with jaundice in pregnant women. In the published literature, 58% of deaths in pregnant women with acute liver disease in hospitals were associated with HEV. Conclusions. Jaundice is frequently associated with maternal and neonatal deaths in Bangladesh, and the published literature suggests that HEV may cause many of these deaths. HEV is preventable, and studies to estimate the burden of HEV in endemic countries are urgently needed. PMID:23078501

Cytokine responses in acute and persistent human parvovirus B19 infection

PubMed Central

Isa, A; Lundqvist, A; Lindblom, A; Tolfvenstam, T; Broliden, K

2007-01-01

The aim of this study was to characterize the proinflammatory and T helper (Th)1/Th2 cytokine responses during acute parvovirus B19 (B19) infection and determine whether an imbalance of the Th1/Th2 cytokine pattern is related to persistent B19 infection. Cytokines were quantified by multiplex beads immunoassay in serum from B19-infected patients and controls. The cytokine responses were correlated with B19 serology, quantitative B19 DNA levels and clinical symptoms. In addition to a proinflammatory response, elevated levels of the Th1 type of cytokines interleukin (IL)-2, IL-12 and IL-15 were evident at time of the initial peak of B19 viral load in a few patients during acute infection. This pattern was seen in the absence of an interferon (IFN)-γ response. During follow-up (20–130 weeks post-acute infection) some of these patients had a sustained Th1 cytokine response. The Th1 cytokine response correlated with the previously identified sustained CD8+ T cell response and viraemia. A cross-sectional study on patients with persistent B19 infection showed no apparent imbalance of their cytokine pattern, except for an elevated level of IFN-γ response. No general immunodeficiency was diagnosed as an explanation for the viral persistence in this later group. Neither the acutely infected nor the persistently infected patients demonstrated a Th2 cytokine response. In conclusion, the acutely infected patients demonstrated a sustained Th1 cytokine response whereas the persistently infected patients did not exhibit an apparent imbalance of their cytokine pattern except for an elevated IFN-γ response. PMID:17302890

Current Knowledge on Hepatitis E

PubMed Central

Pérez-Gracia, María Teresa; García, Mario; Suay, Beatriz; Mateos-Lindemann, María Luisa

2015-01-01

Although only a single serotype of hepatitis E virus (HEV), the causative agent of hepatitis E, has been identified, there is great genetic variation among the different HEV isolates reported. There are at least four major recognized genotypes of HEV: genotypes 1 and 2 are mainly restricted to humans and linked to epidemic outbreaks in nonindustrialized countries, whereas genotypes 3 and 4 are zoonotic in both developing and industrialized countries. Besides human strains, genotype 3 and 4 strains of HEV have been genetically characterized from swine, sika deer, mongooses, sheep, and rabbits. Currently, there are approximately 11,000 human and animal sequences of HEV available at the International Nucleotide Sequence Database Collaboration. HEV is the major cause of waterborne outbreaks of hepatitis in areas of poor sanitation. Additionally, it is responsible for sporadic cases of viral hepatitis in not only endemic but industrialized countries as well. Transmission of HEV occurs predominantly by the fecal-oral route, although parenteral and perinatal routes have been reported. HEV infection develops in most individuals as a self-limiting, acute, icteric hepatitis; with mortality rates around 1%. However, some affected individuals will develop fulminant hepatic failure, a serious condition that is frequently fatal without a liver transplant. This complication is particularly common when the infection occurs in pregnant women, where mortality rates rise dramatically to up to 25%. Among the preventive measures available to avoid HEV infection, two separate subunit vaccines containing recombinant truncated capsid proteins of HEV have been shown to be highly effective in the prevention of disease. One of them, HEV 239, was approved in China, and its commercialization by Innovax began in November 2012 under the name Hecolin®. PMID:26355220

Risk factors for acute surgical site infections after lumbar surgery: a retrospective study.

PubMed

Lai, Qi; Song, Quanwei; Guo, Runsheng; Bi, Haidi; Liu, Xuqiang; Yu, Xiaolong; Zhu, Jianghao; Dai, Min; Zhang, Bin

2017-07-19

Currently, many scholars are concerned about the treatment of postoperative infection; however, few have completed multivariate analyses to determine factors that contribute to the risk of infection. Therefore, we conducted a multivariate analysis of a retrospectively collected database to analyze the risk factors for acute surgical site infection following lumbar surgery, including fracture fixation, lumbar fusion, and minimally invasive lumbar surgery. We retrospectively reviewed data from patients who underwent lumbar surgery between 2014 and 2016, including lumbar fusion, internal fracture fixation, and minimally invasive surgery in our hospital's spinal surgery unit. Patient demographics, procedures, and wound infection rates were analyzed using descriptive statistics, and risk factors were analyzed using logistic regression analyses. Twenty-six patients (2.81%) experienced acute surgical site infection following lumbar surgery in our study. The patients' mean body mass index, smoking history, operative time, blood loss, draining time, and drainage volume in the acute surgical site infection group were significantly different from those in the non-acute surgical site infection group (p < 0.05). Additionally, diabetes mellitus, chronic obstructive pulmonary disease, osteoporosis, preoperative antibiotics, type of disease, and operative type in the acute surgical site infection group were significantly different than those in the non-acute surgical site infection group (p < 0.05). Using binary logistic regression analyses, body mass index, smoking, diabetes mellitus, osteoporosis, preoperative antibiotics, fracture, operative type, operative time, blood loss, and drainage time were independent predictors of acute surgical site infection following lumbar surgery. In order to reduce the risk of infection following lumbar surgery, patients should be evaluated for the risk factors noted above.

Serological evidence of hepatitis E virus infection in pigs and jaundice among pig handlers in Bangladesh.

PubMed

Haider, N; Khan, M S U; Hossain, M B; Sazzad, H M S; Rahman, M Z; Ahmed, F; Zeidner, N S

2017-11-01

Hepatitis E virus (HEV) is the most common cause of viral hepatitis in humans. Pigs may act as a reservoir of HEV, and pig handlers were frequently identified with a higher prevalence of antibodies to HEV. The objectives of this study were to identify evidence of HEV infection in pigs and compare the history of jaundice between pig handlers and people not exposed to pigs and pork. Blood and faecal samples were collected from 100 pigs derived from three slaughterhouses in the Gazipur district of Bangladesh from January to June, 2011. We also interviewed 200 pig handlers and 250 non-exposed people who did not eat pork or handled pigs in the past 2 years. We tested the pig sera for HEV-specific antibodies using a competitive ELISA and pig faecal samples for HEV RNA using real-time RT-PCR. Of 100 pig sera, 82% (n = 82) had detectable antibody against HEV. Of the 200 pig handlers, 28% (56/200) demonstrated jaundice within the past 2 years, whereas only 17% (43/250) of controls had a history of jaundice (p < .05). Compared to non-exposed people, those who slaughtered pigs (31% versus 15%, p < .001), reared pigs (37% versus 20%, p < .001), butchered pigs (35% versus 19%, p < .001) or involved in pork transportation (28% versus 13%, p < .001) were more likely to be affected with jaundice in the preceding 2 years. In multivariate logistic regression analysis, exposure to pigs (odds ratio [OR]: 2.2, 95% CI: 1.2-3.9) and age (OR: 0.97, 95% CI: 0.95-0.99) was significantly associated with jaundice in the past 2 years. Pigs in Bangladesh demonstrated evidence of HEV infection, and a history of jaundice was significantly more frequent in pig handlers. Identifying and genotyping HEV in pigs and pig handlers may provide further evidence of the pig's role in zoonotic HEV transmission in Bangladesh. © 2017 Blackwell Verlag GmbH.

Swine is a possible source of hepatitis E virus infection by comparative study of hepatitis A and E seroprevalence in Thailand.

PubMed

Sa-nguanmoo, Pattaratida; Posuwan, Nawarat; Vichaiwattana, Preeyaporn; Wutthiratkowit, Norra; Owatanapanich, Somchai; Wasitthankasem, Rujipat; Thongmee, Thanunrat; Poovorawan, Kittiyod; Theamboonlers, Apiradee; Vongpunsawad, Sompong; Poovorawan, Yong

2015-01-01

Hepatitis A virus (HAV) and hepatitis E virus (HEV) infection in developing countries are associated with contaminated food or water. Although Thailand is non-endemic for HEV, sporadic infections may occur from zoonotic transmission. Individuals between 7 months to 69 years (mean age = 32.8) from predominantly Islamic Narathiwat (n = 305) and swine farm-dense Lop Buri (n = 416) provinces were screened for anti-HEV and anti-HAV antibodies by commercial enzyme-linked immunosorbent assay and automated chemiluminescent microparticle immunoassay, respectively. Seroprevalence and relative antibody titers were analyzed according to age groups. HAV IgG antibody positive rates in Lop Buri and Narathiwat residents were 39.9% and 58%, respectively (p < 0.001). Greater than 90% of individuals >50 years old in both provinces possessed anti-HAV IgG. In contrast, seroprevalence for anti-HEV IgG was much higher in Lop Buri (37.3%) than in Narathiwat (8.9%) (p < 0.001). Highest anti-HEV IgG prevalence was found among 21-30 year-olds (50%) in Lop Buri and 41-50 year-olds (14.1%) in Narathiwat. In summary, fewer individuals possessed anti-HEV IgG in Narathiwat where most residents abstained from pork and fewer swine farms are present. Therefore, an increased anti-HEV IgG seroprevalence was associated with the density of swine farm and possibly pork consumption. Adults were more likely than children to have antibodies to both HEV and HAV.

Swine Is a Possible Source of Hepatitis E Virus Infection by Comparative Study of Hepatitis A and E Seroprevalence in Thailand

PubMed Central

Sa-nguanmoo, Pattaratida; Posuwan, Nawarat; Vichaiwattana, Preeyaporn; Wutthiratkowit, Norra; Owatanapanich, Somchai; Wasitthankasem, Rujipat; Thongmee, Thanunrat; Poovorawan, Kittiyod; Theamboonlers, Apiradee; Vongpunsawad, Sompong; Poovorawan, Yong

2015-01-01

Hepatitis A virus (HAV) and hepatitis E virus (HEV) infection in developing countries are associated with contaminated food or water. Although Thailand is non-endemic for HEV, sporadic infections may occur from zoonotic transmission. Individuals between 7 months to 69 years (mean age = 32.8) from predominantly Islamic Narathiwat (n = 305) and swine farm-dense Lop Buri (n = 416) provinces were screened for anti-HEV and anti-HAV antibodies by commercial enzyme-linked immunosorbent assay and automated chemiluminescent microparticle immunoassay, respectively. Seroprevalence and relative antibody titers were analyzed according to age groups. HAV IgG antibody positive rates in Lop Buri and Narathiwat residents were 39.9% and 58%, respectively (p < 0.001). Greater than 90% of individuals >50 years old in both provinces possessed anti-HAV IgG. In contrast, seroprevalence for anti-HEV IgG was much higher in Lop Buri (37.3%) than in Narathiwat (8.9%) (p < 0.001). Highest anti-HEV IgG prevalence was found among 21-30 year-olds (50%) in Lop Buri and 41-50 year-olds (14.1%) in Narathiwat. In summary, fewer individuals possessed anti-HEV IgG in Narathiwat where most residents abstained from pork and fewer swine farms are present. Therefore, an increased anti-HEV IgG seroprevalence was associated with the density of swine farm and possibly pork consumption. Adults were more likely than children to have antibodies to both HEV and HAV. PMID:25927925

Acute sleep deprivation enhances post-infection sleep and promotes survival during bacterial infection in Drosophila.

PubMed

Kuo, Tzu-Hsing; Williams, Julie A

2014-05-01

Sleep is known to increase as an acute response to infection. However, the function of this behavioral response in host defense is not well understood. To address this problem, we evaluated the effect of acute sleep deprivation on post-infection sleep and immune function in Drosophila. Laboratory. Drosophila melanogaster. Flies were subjected to sleep deprivation before (early DEP) or after (late DEP) bacterial infection. Relative to a non-deprived control, flies subjected to early DEP had enhanced sleep after infection as well as increased bacterial clearance and survival outcome. Flies subjected to late DEP experienced enhanced sleep following the deprivation period, and showed a modest improvement in survival outcome. Continuous DEP (early and late DEP) throughout infection also enhanced sleep later during infection and improved survival. However, improved survival in flies subjected to late or continuous DEP did not occur until after flies had experienced sleep. During infection, both early and late DEP enhanced NFκB transcriptional activity as measured by a luciferase reporter (κB-luc) in living flies. Early DEP also increased NFκB activity prior to infection. Flies that were deficient in expression of either the Relish or Dif NFκB transcription factors showed normal responses to early DEP. However, the effect of early DEP on post-infection sleep and survival was abolished in double mutants, which indicates that Relish and Dif have redundant roles in this process. Acute sleep deprivation elevated NFκB-dependent activity, increased post-infection sleep, and improved survival during bacterial infection.

Preliminary evidence of mitochondrial dysfunction associated with post-infective fatigue after acute infection with Epstein Barr virus.

PubMed

Vernon, Suzanne D; Whistler, Toni; Cameron, Barbara; Hickie, Ian B; Reeves, William C; Lloyd, Andrew

2006-01-31

Acute infectious diseases are typically accompanied by non-specific symptoms including fever, malaise, irritability and somnolence that usually resolve on recovery. However, in some individuals these symptoms persist in what is commonly termed post-infective fatigue. The objective of this pilot study was to determine the gene expression correlates of post-infective fatigue following acute Epstein Barr virus (EBV) infection. We followed 5 people with acute mononucleosis who developed post-infective fatigue of more than 6 months duration and 5 HLA-matched control subjects who recovered within 3 months. Subjects had peripheral blood mononuclear cell (PBMC) samples collected at varying time points including at diagnosis, then every 2 weeks for 3 months, then every 3 months for a year. Total RNA was extracted from the PBMC samples and hybridized to microarrays spotted with 3,800 oligonucleotides. Those who developed post-infective fatigue had gene expression profiles indicative of an altered host response during acute mononucleosis compared to those who recovered uneventfully. Several genes including ISG20 (interferon stimulated gene), DNAJB2 (DnaJ [Hsp40] homolog and CD99), CDK8 (cyclin-dependent kinase 8), E2F2 (E2F transcription factor 2), CDK8 (cyclin-dependent kinase 8), and ACTN2 (actinin, alpha 2), known to be regulated during EBV infection, were differentially expressed in post-infective fatigue cases. Several of the differentially expressed genes affect mitochondrial functions including fatty acid metabolism and the cell cycle. These preliminary data provide insights into alterations in gene transcripts associated with the varied clinical outcomes from acute infectious mononucleosis.

[Acute dacryocystitis complicating primary mononucleosis infection].

PubMed

Delbet, C; PhamDang, N; Mondie, J-M; Barthelemy, I

2010-01-01

Infectious mononucleosis may lead to numerous complications. Tonsillar hyperplasia with risk of airway obstruction is well known. Dacryocystitis is a rare but potentially severe complication. A 6-year-old child with primary mononucleosis infectious diagnosed 8 days before, developed acute dacryocystitis, with rapid evolution to orbital cellulitis, despite adequate antibiotherapy. Emergency surgical drainage was required. Dacryocystitis is a rare and little documented complication of EBV infection. Its acute evolution to orbital cellulitis is possible and potentially severe. Its physiopathology is specific. Patients are initially free of chronic stenosis and epiphora, which express acute obstruction of the lachrymal sac due to general lymphoid hyperplasia. Copyright © 2010 Elsevier Masson SAS. All rights reserved.

Hepatitis E Virus (Genotype 3) in Slurry Samples from Swine Farming Activities in Italy.

PubMed

La Rosa, G; Della Libera, S; Brambilla, M; Bisaglia, C; Pisani, G; Ciccaglione, A R; Bruni, R; Taffon, S; Equestre, M; Iaconelli, M

2017-06-01

Hepatitis E virus (HEV) is an emergent causative agent of acute hepatitis, transmitted by fecal-oral route. Infection with HEV is a global cause for morbidity and mortality throughout the world: it mainly causes large outbreaks in endemic areas and sporadic autochthonous cases in industrialized countries where HEV infections seem to be an emergent zoonotic disease. Infection of porcine livestock and its relationship with the human cases have been demonstrated. The present study describes an investigation on the prevalence and diversity of HEV in pig slurry in Italy. Slurry samples (24) were collected from ten farms located in North Italy during 2015 and analyzed for HEV, using four broad-range nested PCR assays targeting ORF1 (MTase), ORF2 (capsid) genes, and ORF2/3 regions. Overall, 18 samples (75%) were positive for HEV RNA, and characterized as genotype 3. Nine samples could be subtyped by ORF2 sequencing: Eight belonged to subtype 3f, while one sequence could not be characterized by blast analysis and phylogenetic analysis and may actually represent a new subtype. Furthermore, similarity of 99% was found between 3f Italian HEV sequences of human and swine origins. Real-Time PCR assay was also performed, in order to obtain quantitative data on positive samples. Two swine slurry samples were positive, containing 600 and 1000 UI per mL of sewage. The results of this study show that HEV strains belonging to zoonotic genotype 3 are widely present in swine excreta, and have high degree of identity with strains detected in autochthonous HEV cases. Improving swine farming operations safety and increasing operators' awareness of the zoonotic potential connected with the handling of swine effluents turn out to be key points in order to reduce the environmental and sanitary problem represented by the possible dissemination of HEV to water bodies.

Longevity of T-cell memory following acute viral infection.

PubMed

Walker, Joshua M; Slifka, Mark K

2010-01-01

Investigation of T-cell-mediated immunity following acute viral infection represents an area of research with broad implications for both fundamental immunology research as well as vaccine development. Here, we review techniques that are used to assess T-cell memory including limiting dilution analysis, enzyme-linked immunospot (ELISPOT) assays, intracellular cytokine staining (ICCS) and peptide-MHC Class I tetramer staining. The durability of T-cell memory is explored in the context of several acute viral infections including vaccinia virus (VV), measles virus (MV) and yellow fever virus (YFV). Following acute infection, different virus-specific T-cell subpopulations exhibit distinct cytokine profiles and these profiles change over the course of infection. Differential regulation of the cytotoxic proteins, granzyme A, granzyme B and perforin are also observed in virus-specific T cells following infection. As a result of this work, we have gained a broader understanding of the kinetics and magnitude of antiviral T-cell immunity as well as new insight into the patterns of immunodominance and differential regulation of cytokines and cytotoxicity-associated molecules. This information may eventually lead to the generation of more effective vaccines that elicit T-cell memory with the optimal combination of functional characteristics required for providing protective immunity against infectious disease.

A cross-sectional study of hepatitis E virus infection in healthy people directly exposed and unexposed to pigs in a rural community in northern Thailand.

PubMed

Hinjoy, S; Nelson, K E; Gibbons, R V; Jarman, R G; Mongkolsirichaikul, D; Smithsuwan, P; Fernandez, S; Labrique, A B; Patchanee, P

2013-12-01

A cross-sectional study of the association between occupational pig exposure and hepatitis E virus (HEV) infection in adult pig farmers and the general population who were not directly exposed to pigs was conducted in Nan Province, Thailand, from November 2010 to April 2011. All participants were interviewed to provide information on their job history, eating habits and other potential confounders. The prevalence of anti-HEV immunoglobulin G antibodies (IgG) among 513 subjects was 23.0%. Hand washing with water and soap was associated with a lower seroprevalence of HEV infection, whereas living in an area with frequent flooding (OR 1.64, 95% CI: 1.00-2.68) and consuming internal pig organs more than twice per week (OR 3.23, 95%CI: 1.15-9.01) were both associated with a higher seroprevalence of anti-HEV IgG. There was no association between HEV seroprevalence and frequent, direct occupational pig contact. © 2012 Blackwell Verlag GmbH.

Preliminary evidence of mitochondrial dysfunction associated with post-infective fatigue after acute infection with Epstein Barr Virus

PubMed Central

Vernon, Suzanne D; Whistler, Toni; Cameron, Barbara; Hickie, Ian B; Reeves, William C; Lloyd, Andrew

2006-01-01

Background Acute infectious diseases are typically accompanied by non-specific symptoms including fever, malaise, irritability and somnolence that usually resolve on recovery. However, in some individuals these symptoms persist in what is commonly termed post-infective fatigue. The objective of this pilot study was to determine the gene expression correlates of post-infective fatigue following acute Epstein Barr virus (EBV) infection. Methods We followed 5 people with acute mononucleosis who developed post-infective fatigue of more than 6 months duration and 5 HLA-matched control subjects who recovered within 3 months. Subjects had peripheral blood mononuclear cell (PBMC) samples collected at varying time points including at diagnosis, then every 2 weeks for 3 months, then every 3 months for a year. Total RNA was extracted from the PBMC samples and hybridized to microarrays spotted with 3,800 oligonucleotides. Results Those who developed post-infective fatigue had gene expression profiles indicative of an altered host response during acute mononucleosis compared to those who recovered uneventfully. Several genes including ISG20 (interferon stimulated gene), DNAJB2 (DnaJ [Hsp40] homolog and CD99), CDK8 (cyclin-dependent kinase 8), E2F2 (E2F transcription factor 2), CDK8 (cyclin-dependent kinase 8), and ACTN2 (actinin, alpha 2), known to be regulated during EBV infection, were differentially expressed in post-infective fatigue cases. Several of the differentially expressed genes affect mitochondrial functions including fatty acid metabolism and the cell cycle. Conclusion These preliminary data provide insights into alterations in gene transcripts associated with the varied clinical outcomes from acute infectious mononucleosis. PMID:16448567

High-Temperature High-Power Packaging Techniques for HEV Traction Applications

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

Barlow, F.D.; Elshabini, A.

A key issue associated with the wider adoption of hybrid-electric vehicles (HEV) and plug in hybrid-electric vehicles (PHEV) is the implementation of the power electronic systems that are required in these products [1]. To date, many consumers find the adoption of these technologies problematic based on a financial analysis of the initial cost versus the savings available from reduced fuel consumption. Therefore, one of the primary industry goals is the reduction in the price of these vehicles relative to the cost of traditional gasoline powered vehicles. Part of this cost reduction must come through optimization of the power electronics requiredmore » by these vehicles. In addition, the efficiency of the systems must be optimized in order to provide the greatest range possible. For some drivers, any reduction in the range associated with a potential HEV or PHEV solution in comparison to a gasoline powered vehicle represents a significant barrier to adoption and the efficiency of the power electronics plays an important role in this range. Likewise, high efficiencies are also important since lost power further complicates the thermal management of these systems. Reliability is also an important concern since most drivers have a high level of comfort with gasoline powered vehicles and are somewhat reluctant to switch to a less proven technology. Reliability problems in the power electronics or associated components could not only cause a high warranty cost to the manufacturer, but may also taint these technologies in the consumer's eyes. A larger vehicle offering in HEVs is another important consideration from a power electronics point of view. A larger vehicle will need more horsepower, or a larger rated drive. In some ways this will be more difficult to implement from a cost and size point of view. Both the packaging of these modules and the thermal management of these systems at competitive price points create significant challenges. One way in which

Fundamental modeling the performance and degradation of HEV Lithium-ion battery

NASA Astrophysics Data System (ADS)

Fang, Weifang

Li-ion battery is now replacing nickel-metal hydride (NiMH) for hybrid electric vehicles (HEV). The advantages of Li-ion battery over NiMH are that it can provide longer life, higher cell voltage and higher energy density, etc. However, there are still some issues unsolved for Li-ion battery to fully satisfy the HEV requirement. At high temperature, thermal runaway may cause safety issues. At low temperature, however, its performance is dramatically reduced and also Li deposition may occur. Furthermore, degradation due to side reactions in the electrodes during cycling and storage results in capacity loss and impedance rise. An electrochemical-thermal coupled model is first used to predict performance of individual electrodes of Li-ion cells under HEV conditions that encompass a wide range of ambient temperatures. The model is validated against experimental data of not only the full cell but also individual electrodes and then used to study lithium deposition on the negative electrode during charging Li-ion battery at subzero temperature. The simulated property evolution, e.g. Li concentrations in electrode and electrolyte, shows that either low temperature or high charge rate may force Li insertion (into the negative carbon electrode) to occur in a narrow region near the separator. Therefore, Li deposition is mostly like to happen in this location. Modeling simulation shows that reduction of the negative electrode particle size can reduce Li deposition, which has same effect as improvement of the Li diffusion coefficient in the negative electrode. The model is also used to study charge protocols at subzero temperature. Model simulation shows that employing pulse current can improve cell temperature by the heat generated inside the cell, thus this designed charge protocol is able to reduce Li deposition and improve the charge efficiency as well. Individual aging mechanism is then implemented into each electrode to study Li-ion battery degradation during accelerated

Household Air Pollution and Acute Lower Respiratory Infections in Adults: A Systematic Review.

PubMed

Jary, Hannah; Simpson, Hope; Havens, Deborah; Manda, Geoffrey; Pope, Daniel; Bruce, Nigel; Mortimer, Kevin

2016-01-01

Household air pollution from solid fuel burning kills over 4 million people every year including half a million children from acute lower respiratory infections. Although biologically plausible, it is not clear whether household air pollution is also associated with acute lower respiratory infections in adults. We systematically reviewed the literature on household air pollution and acute lower respiratory infection in adults to identify knowledge gaps and research opportunities. Ten bibliographic databases were searched to identify studies of household air pollution and adult acute lower respiratory infection. Data were extracted from eligible studies using standardised forms. From 4617 titles, 513 abstracts and 72 full-text articles were reviewed. Eight studies met the inclusion criteria of which 2 found a significant adjusted increased risk of acute lower respiratory infection, 2 identified a univariate association whilst 4 found no significant association. Study quality was generally limited. Heterogeneity in methods and findings precluded meta-analysis. A systematic review of the literature found limited evidence for an association between household air pollution and risk of acute lower respiratory infection in adults. Additional research, with carefully defined exposure and outcome measures, is required to complete the risk profile caused by household air pollution in adults. CRD42015028042.

Severe asthma exacerbation: role of acute Chlamydophila pneumoniae and Mycoplasma pneumoniae infection.

PubMed

Cosentini, Roberto; Tarsia, Paolo; Canetta, Ciro; Graziadei, Giovanna; Brambilla, Anna Maria; Aliberti, Stefano; Pappalettera, Maria; Tantardini, Francesca; Blasi, Francesco

2008-05-30

Chlamydophila pneumoniae and Mycoplasma pneumoniae are associated with acute exacerbation of bronchial asthma (AEBA). The aim of this study was to evaluate the correlation between these acute bacterial infections and the severity of AEBA. We prospectively analysed consecutive patients admitted to the Emergency Department with acute asthma exacerbation. In every patient peak expiratory flow (PEF) measurement was performed on admission, and spirometry during follow-up. Serology for Chlamydophila and Mycoplasma pneumoniae was performed on admission and after 4-8 weeks. Fifty-eight patients completed the study. Acute atypical infections (AAI) was observed in 22/58 cases; we found single acute C. pneumoniae in 19 cases, single acute M. pneumoniae in 2 cases, and double acute infection in one case. Functional impairment on admission was greater in patients with AAI than in patients without AAI (PEF 205 +/- 104 L/min vs 276 +/- 117 p = 0.02) and persisted until visit 2 (FEV1% 76.30 +/- 24.54 vs FEV1% 92.91 +/- 13.89, p = 0.002). Moreover, the proportion of patients who presented with severe AEBA was significantly greater in the group with AAI than in the group without AAI (15/22 vs 12/36, p = 0.01; OR 4.29, 95% CI 1.38-13.32). Our data suggest an association between acute atypical infection and a more severe AEBA.

Acute Rubella Virus Infection among Women with Spontaneous Abortion in Mwanza City, Tanzania.

PubMed

Lulandala, Lukombodzo; Mirambo, Mariam M; Matovelo, Dismas; Gumodoka, Balthazar; Mshana, Stephen E

2017-03-01

Acute rubella virus infection in early pregnancy has been associated with poor pregnancy outcome ranging from spontaneous abortion, stillbirth and multiple birth defects known as Congenital Rubella Syndrome (CRS). Despite its importance the prevalence of acute rubella virus infections is not known among women with spontaneous abortion in most centres in developing countries. The present study was aimed to determine the seroprevalence of acute rubella infection among women with spontaneous abortion in Mwanza city. A total of 268 women with spontaneous abortion were enrolled from four different hospitals in Mwanza city between November 2015 and April 2016. Blood samples were collected; sera were extracted and stored at -80°C until processing. Acute rubella virus infection was diagnosed by the detection of rubella specific IgM antibodies using indirect Enzyme Linked Immunosorbent Assay (ELISA) as per manufacturer's instructions. Data were analysed by using STATA version 11. The mean age of enrolled women was 26.3±5.6 years. The prevalence of acute rubella virus infection was found to be 9/268 (3.7%, 95% CI: 1-5). Only women residing in urban areas (AOR: 5.65, 95% CI: 1.15-27.77, p=0.035) were found to predict acute rubella virus infection among cases with spontaneous abortion in Mwanza city. About four out of hundred women residing in urban areas with spontaneous abortion in Mwanza are acutely infected with rubella virus highlighting the potential of this virus in contributing to poor pregnancy outcome in this setting.

Acute Rubella Virus Infection among Women with Spontaneous Abortion in Mwanza City, Tanzania

PubMed Central

Lulandala, Lukombodzo; Matovelo, Dismas; Gumodoka, Balthazar; Mshana, Stephen E

2017-01-01

Introduction Acute rubella virus infection in early pregnancy has been associated with poor pregnancy outcome ranging from spontaneous abortion, stillbirth and multiple birth defects known as Congenital Rubella Syndrome (CRS). Despite its importance the prevalence of acute rubella virus infections is not known among women with spontaneous abortion in most centres in developing countries. Aim The present study was aimed to determine the seroprevalence of acute rubella infection among women with spontaneous abortion in Mwanza city. Materials and Methods A total of 268 women with spontaneous abortion were enrolled from four different hospitals in Mwanza city between November 2015 and April 2016. Blood samples were collected; sera were extracted and stored at -80°C until processing. Acute rubella virus infection was diagnosed by the detection of rubella specific IgM antibodies using indirect Enzyme Linked Immunosorbent Assay (ELISA) as per manufacturer’s instructions. Data were analysed by using STATA version 11. Results The mean age of enrolled women was 26.3±5.6 years. The prevalence of acute rubella virus infection was found to be 9/268 (3.7%, 95% CI: 1-5). Only women residing in urban areas (AOR: 5.65, 95% CI: 1.15-27.77, p=0.035) were found to predict acute rubella virus infection among cases with spontaneous abortion in Mwanza city. Conclusion About four out of hundred women residing in urban areas with spontaneous abortion in Mwanza are acutely infected with rubella virus highlighting the potential of this virus in contributing to poor pregnancy outcome in this setting. PMID:28511456

Hepatitis A and E seroprevalence and associated risk factors: a community-based cross-sectional survey in rural Amazonia.

PubMed

Vitral, Claudia Lamarca; da Silva-Nunes, Mônica; Pinto, Marcelo Alves; de Oliveira, Jaqueline Mendes; Gaspar, Ana Maria Coimbra; Pereira, Rebeca Cristina Costa; Ferreira, Marcelo Urbano

2014-08-23

Hepatitis A virus (HAV) and hepatitis E virus (HEV) are both transmitted by the faecal-oral route, and represent common causes of acute hepatitis in developing countries. The endemicity of HAV infection has shifted from high to moderate in Brazil. Human cases of HEV infection seem to be rare, although the virus has been detected in swine livestock and effluents of slaughterhouses. This study was to determine the epidemiology of hepatitis A and E in one of the largest agricultural settlements in the Amazon Basin of Brazil. Serum samples collected from 397 individuals aged between 5 and 90 years during a population-based cross-sectional survey were tested for anti-HAV and anti-HEV antibodies. Associated risk factors and spatial clustering of HAV and HEV seropositivity were also analyzed. The overall rate of HAV seropositivity was 82.9% (95% confidence interval (CI), 79.2-86.6%). Multilevel logistic regression analysis identified increasing age (in years; odds ratio (OR), 1.097; 95% CI, 1.050-1.147; P < 0.001) and crowding (OR, 1.603; 95% CI, 1.054-2.440; P = 0.028) as significant risk factors for HAV seropositivity. Anti-HEV IgG was detected in 50/388 settlers (12.9%, 95% CI, 9.5-16.2%). Anti-HEV IgM was detected in 7/43 (16.3%) anti-IgG positive samples, and 4 of them had a confirmed result by immunoblot. Increasing age was the only significant determinant of HEV seropositivity (OR, 1.033; 95% CI, 1.016-1.050; P < 0.001). No significant spatial clustering of HAV and HEV seropositivity was detected in the area. Both HAV and HEV are endemic, with differing rates of infection in children and adults in this rural setting of the Brazilian Amazon. Anti-HEV prevalence was considerably higher than those previously reported in Brazil. The detection of HEV- specific IgM antibodies in four asymptomatic individuals is highly suggestive of the circulation of HEV in this rural population.

cDNA encoding a polypeptide including a hev ein sequence

DOEpatents

Raikhel, Natasha V.; Broekaert, Willem F.; Chua, Nam-Hai; Kush, Anil

2000-07-04

A cDNA clone (HEV1) encoding hevein was isolated via polymerase chain reaction (PCR) using mixed oligonucleotides corresponding to two regions of hevein as primers and a Hevea brasiliensis latex cDNA library as a template. HEV1 is 1018 nucleotides long and includes an open reading frame of 204 amino acids. The deduced amino acid sequence contains a putative signal sequence of 17 amino acid residues followed by a 187 amino acid polypeptide. The amino-terminal region (43 amino acids) is identical to hevein and shows homology to several chitin-binding proteins and to the amino-termini of wound-induced genes in potato and poplar. The carboxyl-terminal portion of the polypeptide (144 amino acids) is 74-79% homologous to the carboxyl-terminal region of wound-inducible genes of potato. Wounding, as well as application of the plant hormones abscisic acid and ethylene, resulted in accumulation of hevein transcripts in leaves, stems and latex, but not in roots, as shown by using the cDNA as a probe. A fusion protein was produced in E. coli from the protein of the present invention and maltose binding protein produced by the E. coli.

The Diagnosis, Evaluation and Treatment of Acute and Recurrent Pediatric Urinary Tract Infections

PubMed Central

Becknell, Brian; Schober, Megan; Korbel, Lindsey; Spencer, John David

2015-01-01

Urinary tract infection is one of the most common bacterial infections encountered by pediatricians. Currently, the diagnosis and management of acute urinary tract infection and recurrent urinary tract infection in children remains controversial. Recently published guidelines and large clinical trials have attempted to clarify UTI diagnostic and management strategies. In this manuscript, we review the diagnosis and management of acute and recurrent urinary tract infection in the pediatric population. PMID:25421102

Acute Infection in Total Knee Arthroplasty: Diagnosis and Treatment

PubMed Central

Martínez-Pastor, Juan Carlos; Maculé-Beneyto, Francisco; Suso-Vergara, Santiago

2013-01-01

Infection is one of the most serious complications after total knee arthroplasty (TKA). The current incidence of prosthetic knee infection is 1-3%, depending on the series. For treatment and control to be more cost effective, multidisciplinary groups made up of professionals from different specialities who can work together to eradicate these kinds of infections need to be assembled. About the microbiology, Staphylococcus aureus and coagulase-negative staphylococcus were among the most frequent microorganisms involved (74%). Anamnesis and clinical examination are of primary importance in order to determine whether the problem may point to a possible acute septic complication. The first diagnosis may then be supported by increased CRP and ESR levels. The surgical treatment for a chronic prosthetic knee infection has been perfectly defined and standardized, and consists in a two-stage implant revision process. In contrast, the treatment for acute prosthetic knee infection is currently under debate. Considering the different surgical techniques that already exist, surgical debridement with conservation of the prosthesis and polythene revision appears to be an attractive option for both surgeon and patient, as it is less aggressive than the two-stage revision process and has lower initial costs. The different results obtained from this technique, along with prognosis factors and conclusions to keep in mind when it is indicated for an acute prosthetic infection, whether post-operative or haematogenous, will be analysed by the authors. PMID:23919094

Severe thrombocytopenia as a complication of acute Epstein-Barr virus infection.

PubMed

Likic, Robert; Kuzmanic, Dusko

2004-01-31

Severe thrombocytopenia is an extremely rare complication of acute Epstein-Barr virus (EBV) infection. EBV infection usually causes hematological abnormalities, mainly atypical lymphocytosis, which is a feature of infectious mononucleosis, and uncomplicated cases often present with mild decreases in platelet counts. Our otherwise healthy, 21-year-old male Caucasian patient had thrombocytopenia and bleeding diathesis with platelet counts of 8 x 10(9)/L without other signs and symptoms of infectious mononucleosis. We commenced treatment with intravenous methylprednisolone before the acute EBV infection was serologically confirmed. Platelet counts initially rose and then fell after we stopped administrating corticosteroids. Repeated administration of methylprednisolone was followed by full recovery of the platelet count and normalization of formerly elevated transaminases. EBV infection may happen in children, adolescents and adults and this differential diagnosis should be considered in every patient presenting with acute thrombocytopenia.

High mortality associated with an outbreak of hepatitis E among displaced persons in Darfur, Sudan.

PubMed

Boccia, Delia; Guthmann, Jean-Paul; Klovstad, Hilde; Hamid, Nuha; Tatay, Mercedes; Ciglenecki, Iza; Nizou, Jacques-Yves; Nicand, Elisabeth; Guerin, Philippe Jean

2006-06-15

Hepatitis E virus (HEV) causes acute onset of jaundice and a high case-fatality ratio in pregnant women. We provide a clinical description of hospitalized case patients and assess the specific impact on pregnant women during a large epidemic of HEV infection in a displaced population in Mornay camp (78,800 inhabitants), western Darfur, Sudan. We reviewed hospital records. A sample of 20 clinical cases underwent laboratory confirmation. These patients were tested for immunoglobulin G (IgG) and immunoglobulin M (IgM) antibody to HEV (serum) and for amplification of the HEV genome (serum and stool). We performed a cross-sectional survey in the community to determine the attack rate and case-fatality ratio in pregnant women. Over 6 months, 253 HEV cases were recorded at the hospital, of which 61 (24.1%) were in pregnant women. A total of 72 cases (39.1% of those for whom clinical records were available) had a diagnosis of hepatic encephalopathy. Of the 45 who died (case-fatality ratio, 17.8%), 19 were pregnant women (specific case-fatality ratio, 31.1%). Acute hepatitis E was confirmed in 95% (19/20) of cases sampled; 18 case-patients were positive for IgG (optical density ratio > or =3), for IgM (optical density ratio >2 ), or for both, whereas 1 was negative for IgG and IgM but positive for HEV RNA in serum. The survey identified 220 jaundiced women among the 1133 pregnant women recorded over 3 months (attack rate, 19.4%). A total of 18 deaths were recorded among these jaundiced pregnant women (specific case-fatality ratio, 8.2%). This large epidemic of HEV infection illustrates the dramatic impact of this disease on pregnant women. Timely interventions and a vaccine are urgently needed to prevent mortality in this special group.

Characterisation of three novel giant viruses reveals huge diversity among viruses infecting Prymnesiales (Haptophyta).

PubMed

Johannessen, Torill Vik; Bratbak, Gunnar; Larsen, Aud; Ogata, Hiroyuki; Egge, Elianne S; Edvardsen, Bente; Eikrem, Wenche; Sandaa, Ruth-Anne

2015-02-01

We have isolated three novel lytic dsDNA-viruses from Raunefjorden (Norway) that are putative members of the Mimiviridae family, namely Haptolina ericina virus RF02 (HeV RF02), Prymnesium kappa virus RF01 (PkV RF01), and Prymnesium kappa virus RF02 (PkV RF02). Each of the novel haptophyte viruses challenges the common conceptions of algal viruses with respect to host range, phylogenetic affiliation and size. PkV RF01 has a capsid of ~310 nm and is the largest algal virus particle ever reported while PkV RF01 and HeV RF02 were able to infect different species, even belonging to different genera. Moreover, PkV RF01 and HeV RF02 infected the same hosts, but phylogenetic analysis placed them in different groups. Our results reveal large variation among viruses infecting closely related microalgae, and challenge the common conception that algal viruses have narrow host range, and phylogeny reflecting their host affiliation. Copyright © 2014 Elsevier Inc. All rights reserved.

A Comprehensive Study of Neutralizing Antigenic Sites on the Hepatitis E Virus (HEV) Capsid by Constructing, Clustering, and Characterizing a Tool Box*

PubMed Central

Zhao, Min; Li, Xiao-Jing; Tang, Zi-Min; Yang, Fan; Wang, Si-Ling; Cai, Wei; Zhang, Ke; Xia, Ning-Shao; Zheng, Zi-Zheng

2015-01-01

The hepatitis E virus (HEV) ORF2 encodes a single structural capsid protein. The E2s domain (amino acids 459–606) of the capsid protein has been identified as the major immune target. All identified neutralizing epitopes are located on this domain; however, a comprehensive characterization of antigenic sites on the domain is lacking due to its high degree of conformation dependence. Here, we used the statistical software SPSS to analyze cELISA (competitive ELISA) data to classify monoclonal antibodies (mAbs), which recognized conformational epitopes on E2s domain. Using this novel analysis method, we identified various conformational mAbs that recognized the E2s domain. These mAbs were distributed into 6 independent groups, suggesting the presence of at least 6 epitopes. Twelve representative mAbs covering the six groups were selected as a tool box to further map functional antigenic sites on the E2s domain. By combining functional and location information of the 12 representative mAbs, this study provided a complete picture of potential neutralizing epitope regions and immune-dominant determinants on E2s domain. One epitope region is located on top of the E2s domain close to the monomer interface; the other is located on the monomer side of the E2s dimer around the groove zone. Besides, two non-neutralizing epitopes were also identified on E2s domain that did not stimulate neutralizing antibodies. Our results help further the understanding of protective mechanisms induced by the HEV vaccine. Furthermore, the tool box with 12 representative mAbs will be useful for studying the HEV infection process. PMID:26085097

Genomic Circuitry Underlying Immunological Response to Pediatric Acute Respiratory Infection.

PubMed

Henrickson, Sarah E; Manne, Sasikanth; Dolfi, Douglas V; Mansfield, Kathleen D; Parkhouse, Kaela; Mistry, Rakesh D; Alpern, Elizabeth R; Hensley, Scott E; Sullivan, Kathleen E; Coffin, Susan E; Wherry, E John

2018-01-09

Acute respiratory tract viral infections (ARTIs) cause significant morbidity and mortality. CD8 T cells are fundamental to host responses, but transcriptional alterations underlying anti-viral mechanisms and links to clinical characteristics remain unclear. CD8 T cell transcriptional circuitry in acutely ill pediatric patients with influenza-like illness was distinct for different viral pathogens. Although changes included expected upregulation of interferon-stimulated genes (ISGs), transcriptional downregulation was prominent upon exposure to innate immune signals in early IFV infection. Network analysis linked changes to severity of infection, asthma, sex, and age. An influenza pediatric signature (IPS) distinguished acute influenza from other ARTIs and outperformed other influenza prediction gene lists. The IPS allowed a deeper investigation of the connection between transcriptional alterations and clinical characteristics of acute illness, including age-based differences in circuits connecting the STAT1/2 pathway to ISGs. A CD8 T cell-focused systems immunology approach in pediatrics identified age-based alterations in ARTI host response pathways. Copyright © 2017 The Author(s). Published by Elsevier Inc. All rights reserved.

World Health Organization International Standard to harmonize assays for detection of hepatitis E virus RNA.

PubMed

Baylis, Sally A; Blümel, Johannes; Mizusawa, Saeko; Matsubayashi, Keiji; Sakata, Hidekatsu; Okada, Yoshiaki; Nübling, C Micha; Hanschmann, Kay-Martin O

2013-05-01

Nucleic acid amplification technique-based assays are a primary method for the detection of acute hepatitis E virus (HEV) infection, but assay sensitivity can vary widely. To improve interlaboratory results for the detection and quantification of HEV RNA, a candidate World Health Organization (WHO) International Standard (IS) strain was evaluated in a collaborative study involving 23 laboratories from 10 countries. The IS, code number 6329/10, was formulated by using a genotype 3a HEV strain from a blood donation, diluted in pooled human plasma and lyophilized. A Japanese national standard, representing a genotype 3b HEV strain, was prepared and evaluated in parallel. The potencies of the standards were determined by qualitative and quantitative assays. Assay variability was substantially reduced when HEV RNA concentrations were expressed relative to the IS. Thus, WHO has established 6329/10 as the IS for HEV RNA, with a unitage of 250,000 International Units per milliliter.

Transmitted drug resistance in patients with acute/recent HIV infection in Brazil.

PubMed

Ferreira, Ana Cristina G; Coelho, Lara E; Grinsztejn, Eduarda; Jesus, Carlos S de; Guimarães, Monick L; Veloso, Valdiléa G; Grinsztejn, Beatriz; Cardoso, Sandra W

The widespread use of antiretroviral therapy increased the transmission of antiretroviral resistant HIV strains. Antiretroviral therapy initiation during acute/recent HIV infection limits HIV reservoirs and improves immune response in HIV infected individuals. Transmitted drug resistance may jeopardize the early goals of early antiretroviral treatment among acute/recent HIV infected patients. Patients with acute/recent HIV infection who underwent resistance test before antiretroviral treatment initiation were included in this analysis. HIV-1 sequences were obtained using an in house protease/reverse transcriptase genotyping assay. Transmitted drug resistance was identified according to the Stanford HIV Database for Transmitted Drug Resistance Mutations, based on WHO 2009 surveillance list, and HIV-1 subtyping according to Rega HIV-1 subtyping tool. Comparison between patients with and without transmitted drug resistance was made using Kruskal-Wallis and Chi-square tests. Forty-three patients were included, 13 with acute HIV infection and 30 with recent HIV infection. The overall transmitted drug resistance prevalence was 16.3% (95% confidence interval [CI]: 8.1-30.0%). The highest prevalence of resistance (11.6%, 95% CI: 8.1-24.5) was against non-nucleoside reverse transcriptase inhibitors, and K103N was the most frequently identified mutation. The high prevalence of nonnucleoside reverse transcriptase inhibitors resistance indicates that efavirenz-based regimen without prior resistance testing is not ideal for acutely/recently HIV-infected individuals in our setting. In this context, the recent proposal of including integrase inhibitors as a first line regimen in Brazil could be an advantage for the treatment of newly HIV infected individuals. However, it also poses a new challenge, since integrase resistance test is not routinely performed for antiretroviral naive individuals. Further studies on transmitted drug resistance among acutely/recently HIV-infected are

Hendra Virus and Nipah Virus Animal Vaccines

PubMed Central

Weir, Dawn L.; Reid, Peter A.

2016-01-01

Hendra virus (HeV) and Nipah virus (NiV) are zoonotic viruses that emerged in the mid to late 1990s causing disease outbreaks in livestock and people. HeV appeared in Queensland, Australia in 1994 causing a severe respiratory disease in horses along with a human case fatality. NiV emerged a few years later in Malaysia and Singapore in 1998-99 causing a large outbreak of encephalitis with high mortality in people and also respiratory disease in pigs which served as amplifying hosts. The key pathological elements of HeV and NiV infection in several species of mammals, and also in people, are a severe systemic and often fatal neurologic and/or respiratory disease. In people, both HeV and NiV are also capable of causing relapsed encephalitis following recovery from an acute infection. The known reservoir hosts of HeV and NiV are several species of pteropid fruit bats. Spillovers of HeV into horses continue to occur in Australia and NiV has caused outbreaks in people in Bangladesh and India nearly annually since 2001, making HeV and NiV important transboundary biological threats. NiV in particular possesses several features that underscore its potential as a pandemic threat, including its ability to infect humans directly from natural reservoirs or indirectly from other susceptible animals, along with a capacity of limited human-to-human transmission. Several HeV and NiV animal challenge models have been developed which have facilitated an understanding of pathogenesis and allowed for the successful development of both active and passive immunization countermeasures. PMID:27154393

Hendra virus and Nipah virus animal vaccines.

PubMed

Broder, Christopher C; Weir, Dawn L; Reid, Peter A

2016-06-24

Hendra virus (HeV) and Nipah virus (NiV) are zoonotic viruses that emerged in the mid to late 1990s causing disease outbreaks in livestock and people. HeV appeared in Queensland, Australia in 1994 causing a severe respiratory disease in horses along with a human case fatality. NiV emerged a few years later in Malaysia and Singapore in 1998-1999 causing a large outbreak of encephalitis with high mortality in people and also respiratory disease in pigs which served as amplifying hosts. The key pathological elements of HeV and NiV infection in several species of mammals, and also in people, are a severe systemic and often fatal neurologic and/or respiratory disease. In people, both HeV and NiV are also capable of causing relapsed encephalitis following recovery from an acute infection. The known reservoir hosts of HeV and NiV are several species of pteropid fruit bats. Spillovers of HeV into horses continue to occur in Australia and NiV has caused outbreaks in people in Bangladesh and India nearly annually since 2001, making HeV and NiV important transboundary biological threats. NiV in particular possesses several features that underscore its potential as a pandemic threat, including its ability to infect humans directly from natural reservoirs or indirectly from other susceptible animals, along with a capacity of limited human-to-human transmission. Several HeV and NiV animal challenge models have been developed which have facilitated an understanding of pathogenesis and allowed for the successful development of both active and passive immunization countermeasures. Published by Elsevier Ltd.

Hepatitis E virus in South America: the current scenario.

PubMed

Pisano, María Belén; Martínez Wassaf, Maribel; Mirazo, Santiago; Fantilli, Anabella; Arbiza, Juan; Debes, José; Ré, Viviana E

2018-05-22

Hepatitis E virus (HEV) is one of the most frequent causes of acute viral hepatitis of enteric transmission worldwide. In South America the overall epidemiology has been little studied, and the burden of the disease remains largely unknown. A research of all scientific articles about HEV circulation in South America until November 2017 was carried out. Human seroprevalences of HEV varied according to the studied population: blood donors presented prevalence rates ranging from 1.8 to 9.8%, while reports from HIV-infected individuals, transplant recipients and patients on hemodialysis showed higher prevalence rates. Only two cases of chronic hepatitis in solid-organ transplant patients from Argentina and Brazil have been described. Detection of HEV in the swine population is widely prevalent in the region. Anti-HEV antibodies have also been detected in other animal species; among them, antibody detection was recently documented in wild boars from Uruguay. Although scarce, studies focused on environmental and food HEV detection have shown viral presence in these kind of samples, highlighting possible transmission sources of HEV in the continent. HEV genotype 3 was the most frequently detected in the region, with HEV genotype 1 detected only in Venezuela and Uruguay. HEV is widely distributed throughout South America, producing sporadic cases of acute hepatitis, but as a possible agent of chronic hepatitis. Finding the virus in humans, animals, environmental samples and food, show that it can be transmitted through many sources, alerting local governments and health systems to improve diagnosis and for the implementation of preventive measures. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

Severe asthma exacerbation: role of acute Chlamydophila pneumoniae and Mycoplasma pneumoniae infection

PubMed Central

Cosentini, Roberto; Tarsia, Paolo; Canetta, Ciro; Graziadei, Giovanna; Brambilla, Anna Maria; Aliberti, Stefano; Pappalettera, Maria; Tantardini, Francesca; Blasi, Francesco

2008-01-01

Background Chlamydophila pneumoniae and Mycoplasma pneumoniae are associated with acute exacerbation of bronchial asthma (AEBA). The aim of this study was to evaluate the correlation between these acute bacterial infections and the severity of AEBA. Methods We prospectively analysed consecutive patients admitted to the Emergency Department with acute asthma exacerbation. In every patient peak expiratory flow (PEF) measurement was performed on admission, and spirometry during follow-up. Serology for Chlamydophila and Mycoplasma pneumoniae was performed on admission and after 4–8 weeks. Results Fifty-eight patients completed the study. Acute atypical infections (AAI) was observed in 22/58 cases; we found single acute C. pneumoniae in 19 cases, single acute M. pneumoniae in 2 cases, and double acute infection in one case. Functional impairment on admission was greater in patients with AAI than in patients without AAI (PEF 205 ± 104 L/min vs 276 ± 117 p = 0.02) and persisted until visit 2 (FEV1% 76.30 ± 24.54 vs FEV1% 92.91 ± 13.89, p = 0.002). Moreover, the proportion of patients who presented with severe AEBA was significantly greater in the group with AAI than in the group without AAI (15/22 vs 12/36, p = 0.01; OR 4.29, 95% CI 1.38–13.32). Conclusion Our data suggest an association between acute atypical infection and a more severe AEBA. PMID:18513407

Seroprevalence of Hepatitis E Virus infection among volunteer blood donors in central province of Iran in 2012

PubMed Central

Ehteram, Hassan; Ramezani, Amitis; Eslamifar, Ali; Sofian, Masoomeh; Banifazl, Mohammad; Ghassemi, Shahin; Aghakhani, Arezoo; Mashayekhi, Parisa

2013-01-01

Background and Objectives Hepatitis E virus (HEV) is a major public health concern in developing countries. HEV transmission occurs primarily by the fecal-oral route. It has also been reported that blood donors are potentially able to cause transfusion-associated hepatitis E in endemic areas. This study aimed to determine the seroprevalence of HEV infection among volunteer blood donors in Central province of Iran in 2012. Material and Methods A total of 530 consecutive blood donor samples collected from Blood Transfusion Organization, Central Province of Iran. All samples were tested for the presence of IgG Hepatitis E antibody (anti-HEV) using enzyme-linked immunosorbent assay (ELISA). Results From 530 blood donors, 91.9% were male and 8.1% were female. Overall, anti-HEV was found in 76 of 530 samples (14.3%). There was no significant difference in HEV seropositivity between the subjects regarding gender and area of residence (urban vs. rural). Anti-HEV was distributed among all age groups. Although people aged 31-50 years had the highest prevalence, but there was no statistical difference between the age groups. Conclusion This study shows a relatively high prevalence of anti-HEV in the blood donors of Central province of Iran. More investigations are needed to assess the potential benefit of adding HEV screening of blood products to the current blood donor selection criteria. PMID:23825737

High-Temperature High-Power Packaging Techniques for HEV Traction Applications

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

Elshabini, Aicha; Barlow, Fred D.

A key issue associated with the wider adoption of hybrid-electric vehicles (HEV) and plug in hybrid-electric vehicles (PHEV) is the implementation of the power electronic systems that are required in these products. One of the primary industry goals is the reduction in the price of these vehicles relative to the cost of traditional gasoline powered vehicles. Today these systems, such as the Prius, utilize one coolant loop for the engine at approximately 100 C coolant temperatures, and a second coolant loop for the inverter at 65 C. One way in which significant cost reduction of these systems could be achievedmore » is through the use of a single coolant loop for both the power electronics as well as the internal combustion engine (ICE). This change in coolant temperature significantly increases the junction temperatures of the devices and creates a number of challenges for both device fabrication and the assembly of these devices into inverters and converters for HEV and PHEV applications. Traditional power modules and the state-of-the-art inverters in the current HEV products, are based on chip and wire assembly and direct bond copper (DBC) on ceramic substrates. While a shift to silicon carbide (SiC) devices from silicon (Si) devices would allow the higher operating temperatures required for a single coolant loop, it also creates a number of challenges for the assembly of these devices into power inverters. While this traditional packaging technology can be extended to higher temperatures, the key issues are the substrate material and conductor stability, die bonding material, wire bonds, and bond metallurgy reliability as well as encapsulation materials that are stable at high operating temperatures. The larger temperature differential during power cycling, which would be created by higher coolant temperatures, places tremendous stress on traditional aluminum wire bonds that are used to interconnect power devices. Selection of the bond metallurgy and wire bond

Prospective Study of Acute HIV-1 Infection in Adults in East Africa and Thailand.

PubMed

Robb, Merlin L; Eller, Leigh A; Kibuuka, Hannah; Rono, Kathleen; Maganga, Lucas; Nitayaphan, Sorachai; Kroon, Eugene; Sawe, Fred K; Sinei, Samuel; Sriplienchan, Somchai; Jagodzinski, Linda L; Malia, Jennifer; Manak, Mark; de Souza, Mark S; Tovanabutra, Sodsai; Sanders-Buell, Eric; Rolland, Morgane; Dorsey-Spitz, Julie; Eller, Michael A; Milazzo, Mark; Li, Qun; Lewandowski, Andrew; Wu, Hao; Swann, Edith; O'Connell, Robert J; Peel, Sheila; Dawson, Peter; Kim, Jerome H; Michael, Nelson L

2016-06-02

Acute human immunodeficiency virus type 1 (HIV-1) infection is a major contributor to transmission of HIV-1. An understanding of acute HIV-1 infection may be important in the development of treatment strategies to eradicate HIV-1 or achieve a functional cure. We performed twice-weekly qualitative plasma HIV-1 RNA nucleic acid testing in 2276 volunteers who were at high risk for HIV-1 infection. For participants in whom acute HIV-1 infection was detected, clinical observations, quantitative measurements of plasma HIV-1 RNA levels (to assess viremia) and HIV antibodies, and results of immunophenotyping of lymphocytes were obtained twice weekly. Fifty of 112 volunteers with acute HIV-1 infection had two or more blood samples collected before HIV-1 antibodies were detected. The median peak viremia (6.7 log10 copies per milliliter) occurred 13 days after the first sample showed reactivity on nucleic acid testing. Reactivity on an enzyme immunoassay occurred at a median of 14 days. The nadir of viremia (4.3 log10 copies per milliliter) occurred at a median of 31 days and was nearly equivalent to the viral-load set point, the steady-state viremia that persists durably after resolution of acute viremia (median plasma HIV-1 RNA level, 4.4 log10 copies per milliliter). The peak viremia and downslope were correlated with the viral-load set point. Clinical manifestations of acute HIV-1 infection were most common just before and at the time of peak viremia. A median of one symptom of acute HIV-1 infection was recorded at a median of two study visits, and a median of one sign of acute HIV-1 infection was recorded at a median of three visits. The viral-load set point occurred at a median of 31 days after the first detection of plasma viremia and correlated with peak viremia. Few symptoms and signs were observed during acute HIV-1 infection, and they were most common before peak viremia. (Funded by the Department of Defense and the National Institute of Allergy and Infectious

Decreased egg production in laying hens associated with infection with genotype 3 avian hepatitis E virus strain from China.

PubMed

Zhao, Qin; Liu, Baoyuan; Sun, Yani; Du, Taofeng; Chen, Yiyang; Wang, Xinjie; Li, Huixia; Nan, Yuchen; Zhang, Gaiping; Zhou, En-Min

2017-05-01

To determine the relationship between decreased egg production and avian HEV infection, thirty healthy 23-week-old Hy-Line Variety Brown layer hens were randomly divided into 3 groups with 10 hens per group. Next, a genotype 3 avian HEV strain from China was used to inoculate laying hens via oronasal or intravenous routes using a 50% chicken infectious dose of 500. All hens were necropsied at 14 weeks postinoculation (wpi). Fecal virus shedding, viremia, seroconversion, serum alanine aminotransferase (ALT) increases and liver lesions showed that after intravenous (i.v.) and oronasal inoculation, the laying hens were successfully infected. Compared with the uninoculated group, the i.v. and oronasally inoculated groups exhibited egg production decreases at 1wpi and 2wpi, reaching peak production at 3wpi and 8wpi, respectively. In both groups, decreased production was evident for 12 weeks and overall decreases ranged from 10% to 30%. In addition, in the 7 field layer farms exhibiting decreased egg production, vaccination regimens had been completed against Newcastle disease, infectious bronchitis, avian influenza H9N2 and H5N1 and egg drop syndrome virus. However, circulating avian HEV was confirmed on these farms using tests to detect avian HEV IgG antibodies and RNA. Therefore, the experimental and field data indicate that avian HEV infection acting alone could account for observed decreases in egg production in laying hens. Copyright © 2017 Elsevier B.V. All rights reserved.

Exposure to hepatitis E virus, hepatitis A virus and Borrelia spp. infections in forest rangers from a single forest district in western Poland.

PubMed

Bura, Maciej; Bukowska, Alicja; Michalak, Michał; Bura, Aleksandra; Nawrocki, Mariusz J; Karczewski, Marek; Mozer-Lisewska, Iwona

2018-03-13

Hepatitis E virus (HEV) infection is an emerging problem in developed countries. At least 2 zoonotic genotypes of the virus (HEV-3 and HEV-4) infect human beings. There are some data suggesting that forest rangers (FRs) can be at a higher risk of contact with HEV. The aim of this study was to assess the prevalence of HEV exposure markers in FRs from a single forest district in Greater Poland in relation to anti-HAV (hepatitis A virus) IgG, and anti-Borrelia spp. IgM and IgG antibodies. In total, 138 participants (48 FRs and 90 blood donors - BDs) were tested for anti-HEV IgM and IgG (EUROIMMUN Medizinische Labordiagnostika AG, Luebeck, Germany) and 96 individuals (48 FRs and 48 BDs) were tested for anti-HAV IgG (ARCHITECT immunoassays, Abbott Laboratories, Wiesbaden, Germany); anti-Borrelia IgM and IgG (EUROIMMUN kits) were assessed in FRs only. Anti-HEV markers were detected in 3 participants (2.2%; IgM in 1 FR, IgG in 2 BDs), less frequently than anti-HAV (16 out of 96 individuals, about 17%; FRs 19% vs BDs 15%) or anti-Borrelia antibodies (18 out of 48 individuals, 37.5%) (p < 0.0001 for both). Older study participants (≥45 years of age) were more frequently HAV-seropositive (29% vs 4% of the younger individuals; p = 0.0012). We failed to unequivocally prove HEV exposure in FRs. The HAV seroprevalence in this study paralleled the situation in the general population. Exposure to Borrelia spp. in FRs was common.

Anomaly Detection in Host Signaling Pathways for the Early Prognosis of Acute Infection.

PubMed

Wang, Kun; Langevin, Stanley; O'Hern, Corey S; Shattuck, Mark D; Ogle, Serenity; Forero, Adriana; Morrison, Juliet; Slayden, Richard; Katze, Michael G; Kirby, Michael

2016-01-01

Clinical diagnosis of acute infectious diseases during the early stages of infection is critical to administering the appropriate treatment to improve the disease outcome. We present a data driven analysis of the human cellular response to respiratory viruses including influenza, respiratory syncytia virus, and human rhinovirus, and compared this with the response to the bacterial endotoxin, Lipopolysaccharides (LPS). Using an anomaly detection framework we identified pathways that clearly distinguish between asymptomatic and symptomatic patients infected with the four different respiratory viruses and that accurately diagnosed patients exposed to a bacterial infection. Connectivity pathway analysis comparing the viral and bacterial diagnostic signatures identified host cellular pathways that were unique to patients exposed to LPS endotoxin indicating this type of analysis could be used to identify host biomarkers that can differentiate clinical etiologies of acute infection. We applied the Multivariate State Estimation Technique (MSET) on two human influenza (H1N1 and H3N2) gene expression data sets to define host networks perturbed in the asymptomatic phase of infection. Our analysis identified pathways in the respiratory virus diagnostic signature as prognostic biomarkers that triggered prior to clinical presentation of acute symptoms. These early warning pathways correctly predicted that almost half of the subjects would become symptomatic in less than forty hours post-infection and that three of the 18 subjects would become symptomatic after only 8 hours. These results provide a proof-of-concept for utility of anomaly detection algorithms to classify host pathway signatures that can identify presymptomatic signatures of acute diseases and differentiate between etiologies of infection. On a global scale, acute respiratory infections cause a significant proportion of human co-morbidities and account for 4.25 million deaths annually. The development of clinical

Anomaly Detection in Host Signaling Pathways for the Early Prognosis of Acute Infection

PubMed Central

O’Hern, Corey S.; Shattuck, Mark D.; Ogle, Serenity; Forero, Adriana; Morrison, Juliet; Slayden, Richard; Katze, Michael G.

2016-01-01

Clinical diagnosis of acute infectious diseases during the early stages of infection is critical to administering the appropriate treatment to improve the disease outcome. We present a data driven analysis of the human cellular response to respiratory viruses including influenza, respiratory syncytia virus, and human rhinovirus, and compared this with the response to the bacterial endotoxin, Lipopolysaccharides (LPS). Using an anomaly detection framework we identified pathways that clearly distinguish between asymptomatic and symptomatic patients infected with the four different respiratory viruses and that accurately diagnosed patients exposed to a bacterial infection. Connectivity pathway analysis comparing the viral and bacterial diagnostic signatures identified host cellular pathways that were unique to patients exposed to LPS endotoxin indicating this type of analysis could be used to identify host biomarkers that can differentiate clinical etiologies of acute infection. We applied the Multivariate State Estimation Technique (MSET) on two human influenza (H1N1 and H3N2) gene expression data sets to define host networks perturbed in the asymptomatic phase of infection. Our analysis identified pathways in the respiratory virus diagnostic signature as prognostic biomarkers that triggered prior to clinical presentation of acute symptoms. These early warning pathways correctly predicted that almost half of the subjects would become symptomatic in less than forty hours post-infection and that three of the 18 subjects would become symptomatic after only 8 hours. These results provide a proof-of-concept for utility of anomaly detection algorithms to classify host pathway signatures that can identify presymptomatic signatures of acute diseases and differentiate between etiologies of infection. On a global scale, acute respiratory infections cause a significant proportion of human co-morbidities and account for 4.25 million deaths annually. The development of clinical

Differential cellular targets of Epstein-Barr virus (EBV) infection between acute EBV-associated hemophagocytic lymphohistiocytosis and chronic active EBV infection.

PubMed

Kasahara, Y; Yachie, A; Takei, K; Kanegane, C; Okada, K; Ohta, K; Seki, H; Igarashi, N; Maruhashi, K; Katayama, K; Katoh, E; Terao, G; Sakiyama, Y; Koizumi, S

2001-09-15

Unusual Epstein-Barr virus (EBV) infection into T or natural killer cells plays a pivotal role in the pathogenesis of acute EBV-associated hemophagocytic lymphohistiocytosis (EBV-HLH) and chronic active EBV infection (CAEBV). The precise frequency and localization of EBV genome in lymphocyte subpopulations especially within T-cell subpopulations are unclear in these EBV-related disorders. This study analyzed the frequency of EBV-infected cells in circulating lymphocyte subpopulations from 4 patients with acute EBV-HLH and 4 with CAEBV. EBV- encoded small RNA-1 in situ hybridization examination of peripheral blood lymphocytes showed a significantly higher frequency of EBV-infected cells of 1.0% to 13.4% in EBV-HLH and 1.6% to 25.6% in CAEBV, respectively. The patterns of EBV infection in lymphocyte subpopulations were quite different between acute EBV-HLH and CAEBV. EBV infection was predominant in CD8(+) T cells in all EBV-HLH patients, whereas the dominant EBV-infected cell populations were non-CD8(+) lymphocyte subpopulations in CAEBV patients. Phenotypical analysis revealed that EBV-infected cell populations from both EBV-HLH and CAEBV were activated. There was no predominance of any EBV substrain of latent membrane protein-1, EBV-associated nuclear antigen (EBNA)-1, and EBNA-2 genes between the 2 abnormal EBV-associated disorders, and self-limited acute infectious mononucleosis. These results showing differential virus-cell interactions between acute EBV-HLH and CAEBV indicated different pathogenic mechanisms against EBV infection between the 2 EBV-associated diseases, which accounts for the difference in clinical manifestations between the 2 diseases.

Acute disseminated encephalomyelitis in dengue viral infection.

PubMed

Wan Sulaiman, Wan Aliaa; Inche Mat, Liyana Najwa; Hashim, Hasnur Zaman; Hoo, Fan Kee; Ching, Siew Mooi; Vasudevan, Ramachandran; Mohamed, Mohd Hazmi; Basri, Hamidon

2017-09-01

Dengue is the most common arboviral disease affecting many countries worldwide. An RNA virus from the flaviviridae family, dengue has four antigenically distinct serotypes (DEN-1-DEN-4). Neurological involvement in dengue can be classified into dengue encephalopathy immune-mediated syndromes, encephalitis, neuromuscular or dengue muscle dysfunction and neuro-ophthalmic involvement. Acute disseminated encephalomyelitis (ADEM) is an immune mediated acute demyelinating disorder of the central nervous system following recent infection or vaccination. This monophasic illness is characterised by multifocal white matter involvement. Many dengue studies and case reports have linked ADEM with dengue virus infection but the association is still not clear. Therefore, this article is to review and discuss concerning ADEM in dengue as an immune-medicated neurological complication; and the management strategy required based on recent literature. Copyright © 2017 Elsevier Ltd. All rights reserved.

Herpes zoster infection: a rare cause of acute urinary retention.

PubMed

Chan, Jonathan E; Kapoor, Anil

2003-06-01

Herpes zoster (HZ) infection has been reported as a rare cause of acute urinary retention. HZ infection involving sacral, thoracolumbar, and rarely high thoracic dermatomes is believed to occasionally cause motor and sensory neuropathy of the bladder. This is specifically achieved by the interruption of the detrusor reflex causing subsequent bladder atonia. As the course and management of this entity is quite benign, HZ should remain a diagnostic consideration in the management of urinary retention. We report a case of acute urinary retention of approximately 2.5 liters associated with HZ infection and review the proposed pathogenesis and therapeutic considerations in the management of this entity.

Non-invasive detection of infection in acute pancreatic and acute necrotic collections with diffusion-weighted magnetic resonance imaging: preliminary findings.

PubMed

Islim, Filiz; Salik, Aysun Erbahceci; Bayramoglu, Sibel; Guven, Koray; Alis, Halil; Turhan, Ahmet Nuray

2014-06-01

The purpose of this study was to evaluate the contribution of diffusion-weighted magnetic resonance imaging (DW-MRI) to the detection of infection in acute pancreatitis-related collections. A total of 21 DW-MRI, and computed tomography (CT) were performed on 20 patients diagnosed as acute pancreatitis with acute peri-pancreatic fluid or necrotic collections. Collections were classified as infected or sterile according to the culture and follow-up results. Collections with gas bubbles on CT images were considered to be infected. Collections with peripheral bright signals on DW-MRI images were considered to be positive, whereas those without signals were considered to be negative. Apparent diffusion coefficient (ADC) values of the peripheral and central parts of the collections were measured. Student's t test was used to compare the means of ADC values of independent groups. Apart from one false positive result, the presence of infection was detected by DW-MRI with 95.2% accuracy. The sensitivity and accuracy of DW-MRI were higher than CT for the detection of infection. The ADC values in the central parts of the collections were significantly different between the infected and sterile groups. DW-MRI can be used as a non-invasive technique for the detection of infection in acute pancreatitis-associated collections.

Preoperative Anemia Is Associated With Failure of Open Debridement Polyethylene Exchange in Acute and Acute Hematogenous Prosthetic Joint Infection.

PubMed

Swenson, Richard D; Butterfield, James A; Irwin, Timothy J; Zurlo, John J; Davis, Charles M

2018-06-01

Acute and acute hematogenous prosthetic joint infections (PJIs) are often treated with open debridement and polyethylene exchange (ODPE) in an effort to save the prosthesis, decrease morbidity, and reduce costs. However, failure of ODPE may compromise a subsequent 2-stage treatment. The purpose of this study is to identify patient factors that impact the success of ODPE for acute and acute hematogenous PJIs. A retrospective review examined comorbidities, preoperative laboratory values, and patient history for patients with successful and failed ODPE treatment for acute perioperative or acute hematogenous periprosthetic hip or knee joint infections. Successful treatment was defined as retaining a well-fixed implant without the need for additional surgery for a minimum of 6-month follow-up with or without lifelong oral maintenance antibiotics. Fifty-three of 72 patients (73.6%) underwent successful ODPE. Of the 19 failures, 14 completed 2-stage revision with one subsequent known failure for recurrent infection. Patients with a Staphylococcus aureus infection were more likely to fail ODPE (48.3% vs 11.6%, P = .0012, odds ratio 7.1, 95% confidence interval 2.3-25.3). Patients with a preoperative hematocrit ≤32.1 were also more likely to fail ODPE (55% vs 16%, P = .0013, odds ratio 6.7, 95% confidence interval 2.2-22.4). When neither risk factor was present, 97.1% of PJIs were successfully treated with ODPE. S aureus infection and preoperative hematocrit ≤32.1 are independent risk factors for ODPE failure. ODPE is a safe alternative to 2-stage revision in patients without preoperative anemia and without S aureus infection. Two-thirds of patients with a failed ODPE were successfully treated with a 2-stage reimplantation. Copyright © 2018 Elsevier Inc. All rights reserved.

75 FR 52755 - Draft Guidance for Industry on Acute Bacterial Skin and Skin Structure Infections: Developing...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-08-27

...] Draft Guidance for Industry on Acute Bacterial Skin and Skin Structure Infections: Developing Drugs for... ``Acute Bacterial Skin and Skin Structure Infections: Developing Drugs for Treatment.'' The purpose of... antimicrobial drugs for the treatment of acute bacterial skin and skin structure infections (ABSSSI), impetigo...

First evidence of the Hepatitis E virus in environmental waters in Colombia

PubMed Central

Baez, Paula A.; Lopez, Maria Camila; Duque-Jaramillo, Alejandra; Pelaez, Dioselina; Molina, Francisco; Navas, Maria-Cristina

2017-01-01

Hepatitis E virus (HEV) is one of the main causes of acute viral hepatitis of enteric transmission. HEV has been detected in environmental samples in several countries from Europe and Asia, constituting a risk factor for waterborne infection. In Colombia, HEV has been identified in samples obtained from patients as well as from swine, but no environmental studies have been carried out. To determine if HEV is present in environmental waters, samples from the main source of drinking water plant and of wastewater system of eight municipalities and two villages of Antioquia state (North West Colombia), were collected between December 2012 and April 2014. The HEV genome was detected by RT-PCR in 23.3% (7/30) of the samples from the main source of drinking water plants and in 16.7% (5/30) from sewage. Viral concentrates obtained from three positive sewage samples were used to inoculate HepG2 cell cultures that were followed for one month; however, the viral genome was not detected in any cell culture. This study demonstrates the circulation of HEV in both source of drinking water plants and wastewater in Antioquia state, Colombia. The presence of HEV in environmental waters could be a risk for waterborne transmission in this population. The findings of the present study, together with the evidence of HEV circulation in human and swine in Colombia, should be consider by public health authorities for the development of surveillance programs and the inclusion of HEV infection diagnosis in the guidelines of viral hepatitis in the country. This is the first report of HEV in environmental samples in Colombia and the second one in Latin America. PMID:28520759

First evidence of the Hepatitis E virus in environmental waters in Colombia.

PubMed

Baez, Paula A; Lopez, Maria Camila; Duque-Jaramillo, Alejandra; Pelaez, Dioselina; Molina, Francisco; Navas, Maria-Cristina

2017-01-01

Hepatitis E virus (HEV) is one of the main causes of acute viral hepatitis of enteric transmission. HEV has been detected in environmental samples in several countries from Europe and Asia, constituting a risk factor for waterborne infection. In Colombia, HEV has been identified in samples obtained from patients as well as from swine, but no environmental studies have been carried out. To determine if HEV is present in environmental waters, samples from the main source of drinking water plant and of wastewater system of eight municipalities and two villages of Antioquia state (North West Colombia), were collected between December 2012 and April 2014. The HEV genome was detected by RT-PCR in 23.3% (7/30) of the samples from the main source of drinking water plants and in 16.7% (5/30) from sewage. Viral concentrates obtained from three positive sewage samples were used to inoculate HepG2 cell cultures that were followed for one month; however, the viral genome was not detected in any cell culture. This study demonstrates the circulation of HEV in both source of drinking water plants and wastewater in Antioquia state, Colombia. The presence of HEV in environmental waters could be a risk for waterborne transmission in this population. The findings of the present study, together with the evidence of HEV circulation in human and swine in Colombia, should be consider by public health authorities for the development of surveillance programs and the inclusion of HEV infection diagnosis in the guidelines of viral hepatitis in the country. This is the first report of HEV in environmental samples in Colombia and the second one in Latin America.

Infection prevention and control measures for acute respiratory infections in healthcare settings: an update.

PubMed

Seto, W H; Conly, J M; Pessoa-Silva, C L; Malik, M; Eremin, S

2013-01-01

Viruses account for the majority of the acute respiratory tract infections (ARIs) globally with a mortality exceeding 4 million deaths per year. The most commonly encountered viruses, in order of frequency, include influenza, respiratory syncytial virus, parainfluenza and adenovirus. Current evidence suggests that the major mode of transmission of ARls is through large droplets, but transmission through contact (including hand contamination with subsequent self-inoculation) and infectious respiratory aerosols of various sizes and at short range (coined as "opportunistic" airborne transmission) may also occur for some pathogens. Opportunistic airborne transmission may occur when conducting highrisk aerosol generating procedures and airborne precautions will be required in this setting. General infection control measures effective for all respiratory viral infections are reviewed and followed by discussion on some of the common viruses, including severe acute respiratory syndrome (SARS) coronavirus and the recently discovered novel coronavirus.

Prospective Study of Acute HIV-1 Infection in Adults in East Africa and Thailand

PubMed Central

Robb, Merlin L.; Eller, Leigh A.; Kibuuka, Hannah; Rono, Kathleen; Maganga, Lucas; Nitayaphan, Sorachai; Kroon, Eugene; Sawe, Fred K.; Sinei, Samuel; Sriplienchan, Somchai; Jagodzinski, Linda L.; Malia, Jennifer; Manak, Mark; de Souza, Mark S.; Tovanabutra, Sodsai; Sanders-Buell, Eric; Rolland, Morgane; Dorsey-Spitz, Julie; Eller, Michael A.; Milazzo, Mark; Li, Qun; Lewandowski, Andrew; Wu, Hao; Swann, Edith; O'Connell, Robert J.; Peel, Sheila; Dawson, Peter; Kim, Jerome H.; Michael, Nelson L.

2016-01-01

Background Acute human immunodeficiency virus type 1 (HIV-1) infection is a major contributor to transmission of HIV-1. An understanding of acute HIV-1 infection may be important in the development of treatment strategies to eradicate HIV-1 or achieve a functional cure. Methods We performed twice-weekly qualitative plasma HIV-1 RNA nucleic acid testing in 2276 volunteers who were at high risk for HIV-1 infection. For participants in whom acute HIV-1 infection was detected, clinical observations, quantitative measurements of plasma HIV-1 RNA levels (to assess viremia) and HIV antibodies, and results of immunophenotyping of lymphocytes were obtained twice weekly. Results Fifty of 112 volunteers with acute HIV-1 infection had two or more blood samples collected before HIV-1 antibodies were detected. The median peak viremia (6.7 log10 copies per milliliter) occurred 13 days after the first sample showed reactivity on nucleic acid testing. Reactivity on an enzyme immunoassay occurred at a median of 14 days. The nadir of viremia (4.3 log10 copies per milliliter) occurred at a median of 31 days and was nearly equivalent to the viral-load set point, the steady-state viremia that persists durably after resolution of acute viremia (median plasma HIV-1 RNA level, 4.4 log10 copies per milliliter). The peak viremia and downslope were correlated with the viral-load set point. Clinical manifestations of acute HIV-1 infection were most common just before and at the time of peak viremia. A median of one symptom of acute HIV-1 infection was recorded at a median of two study visits, and a median of one sign of acute HIV-1 infection was recorded at a median of three visits. Conclusions The viral-load set point occurred at a median of 31 days after the first detection of plasma viremia and correlated with peak viremia. Few symptoms and signs were observed during acute HIV-1 infection, and they were most common before peak viremia. (Funded by the Department of Defense and the National

Acute infectious mononucleosis and coincidental measles virus infection.

PubMed

Atrasheuskaya, A V; Kameneva, S N; Neverov, A A; Ignatyev, G M

2004-10-01

Both Epstein-Barr and measles viruses (MV) cause immune suppression, and the association of the two viruses is evaluated as life threatening. The cell immune impairment caused by simultaneous Epstein-Barr and measles viral infections was responsible for the complicated course of the disease in all described previously reports and for unfavorable outcomes in most of the cases. Timely diagnosis of coincidental viral infections could be a useful predictor for the clinical course and complications. Diagnosis must be based on an accurate assessment of clinical, hematologic, serologic manifestations and supported by appropriate laboratory methods. Recognizing the infectious etiology of concomitant infections is important for both clinicians and epidemiologists. To describe a case report of a 20-year-old woman previously vaccinated against measles infected with acute mononucleosis and coincidental measles virus infection. The clinical, routine laboratory, as well as serological and virologic findings of this patient were scrutinized. Special emphasis was placed on the use of RT-PCR/PCR for confirming the involvement of both measles virus and Epstein-Barr virus (EBV) in this patient's illness. Infectious mononucleosis was not suspected at admission to the hospital. The final diagnosis of a concomitant measles virus infection and acute infectious mononucleosis was facilitated using viral serology to detect virus-specific IgG and IgM antibodies and by RT-PCR for the detection of measles virus RNA and EBV DNA from peripheral blood monocyte cells (PBMC). The present report highlights the difficulty of diagnosing two coincidental virus infections on clinical grounds. Serological and molecular laboratory methods, specifically the PCR (RT-PCR) analysis, are found to be useful for confirming the concomitant viral infections and proper identification of the infecting pathogens.

Levofloxacin in Preventing Infection in Young Patients With Acute Leukemia Receiving Chemotherapy or Undergoing Stem Cell Transplantation

ClinicalTrials.gov

2018-05-07

Acute Leukemias of Ambiguous Lineage; Bacterial Infection; Diarrhea; Fungal Infection; Musculoskeletal Complications; Neutropenia; Recurrent Childhood Acute Lymphoblastic Leukemia; Recurrent Childhood Acute Myeloid Leukemia; Secondary Acute Myeloid Leukemia; Untreated Childhood Acute Myeloid Leukemia and Other Myeloid Malignancies

Acute parvovirus B19 infection in adults: a retrospective study of 49 cases.

PubMed

Rodríguez Bandera, A I; Mayor Arenal, M; Vorlicka, K; Ruiz Bravo-Burguilllos, E; Montero Vega, D; Vidaurrázaga Díaz-Arcaya, C

2015-01-01

Our aim was to describe the epidemiologic, clinical, and laboratory characteristics of acute parvovirus B19 infection in adults. This study describes all cases of acute parvovirus B19 infection in patients older than 18 years of age who were treated at Hospital Universitario La Paz in Madrid, Spain, in 2012. Forty-nine adults were treated for acute parvovirus B19 infection. Most were young women who were infected in the spring or early summer. In over half the cases skin lesions were key diagnostic signs.We saw the full range of types of rash of purplish exanthems that were fairly generalized; vasculitis was relatively common (in >18%). Mild or moderate abnormalities in blood counts and indicators of liver dysfunction resolved spontaneously in all but 2 immunocompromised patients, who developed chronic anemia. This is the largest case series of acute parvovirus B19 infection published to date. This infection should be suspected on observing signs of purplish skin rashes, no matter the location or pattern of distribution, or vasculitis, especially if accompanied by fever and joint pain in young women in the spring. Measures to avoid infection should be recommended to individuals at risk. Copyright © 2014 Elsevier España, S.L.U. and AEDV. All rights reserved.

Sulfation-dependent recognition of high endothelial venules (HEV)- ligands by L-selectin and MECA 79, and adhesion-blocking monoclonal antibody

PubMed Central

1994-01-01

L-selectin is a lectin-like receptor that mediates the attachment of lymphocytes to high endothelial venules (HEV) of lymph nodes during the process of lymphocyte recirculation. Two sulfated, mucin-like glycoproteins known as Sgp50/GlyCAM-1 and Sgp90/CD34 have previously been identified as HEV-associated ligands for L-selectin. These proteins were originally detected with an L-selectin/Ig chimera called LEC-IgG. GlyCAM-1 and CD34 are also recognized by an antiperipheral node addressin (PNAd) mAb called MECA 79, which blocks L-selectin- dependent adhesion and selectively stains lymph node HEV. The present study compares the requirements for the binding of MECA 79 and LEC-IgG to HEV-ligands. Whereas desialylation of GlyCAM-1 and CD34 drastically reduced binding to LEC-IgG, this treatment enhanced the binding of GlyCAM-1 to MECA 79. In contrast, the binding of both MECA 79 and LEC- IgG to GlyCAM-1 and CD34 was greatly decreased when the sulfation of these ligands was reduced with chlorate, a metabolic inhibitor of sulfation. Because MECA 79 stains HEV-like vessels at various sites of inflammation, recognition by L-selectin of ligands outside of secondary lymphoid organs may depend on sulfation. In addition to their reactivity with GlyCAM-1 and CD34, both MECA 79 and LEC-IgG recognize an independent molecule of approximately 200 kD in a sulfate-dependent manner. Thus, this molecule, which we designate Sgp200, is an additional ligand for L-selectin. PMID:7525849

Pathology during acute infections: contributions of intracellular pathogens and the CTL response.

PubMed

Ganusov, Vitaly V; Antia, Rustom

2005-06-22

Previous work has shown how, in the case of cytotoxic T-lymphocyte (CTL) responses to persistent viral infections, pathology may arise as a consequence of cell destruction directly by the virus or indirectly due to the CTL response, leading to maximum pathology at intermediate efficacy of the immune response. We expand these studies to consider pathology arising during acute infections with intracellular pathogens controlled by the CTL response. We show that, in contrast to persistent infections, pathology during acute infections is minimized with increasing efficacy of the immune response. The implications of these results for vaccination are discussed.

Viral Co-Infections in Pediatric Patients Hospitalized with Lower Tract Acute Respiratory Infections.

PubMed

Cebey-López, Miriam; Herberg, Jethro; Pardo-Seco, Jacobo; Gómez-Carballa, Alberto; Martinón-Torres, Nazareth; Salas, Antonio; Martinón-Sánchez, José María; Gormley, Stuart; Sumner, Edward; Fink, Colin; Martinón-Torres, Federico

2015-01-01

Molecular techniques can often reveal a broader range of pathogens in respiratory infections. We aim to investigate the prevalence and age pattern of viral co-infection in children hospitalized with lower tract acute respiratory infection (LT-ARI), using molecular techniques. A nested polymerase chain reaction approach was used to detect Influenza (A, B), metapneumovirus, respiratory syncytial virus (RSV), parainfluenza (1-4), rhinovirus, adenovirus (A-F), bocavirus and coronaviruses (NL63, 229E, OC43) in respiratory samples of children with acute respiratory infection prospectively admitted to any of the GENDRES network hospitals between 2011-2013. The results were corroborated in an independent cohort collected in the UK. A total of 204 and 97 nasopharyngeal samples were collected in the GENDRES and UK cohorts, respectively. In both cohorts, RSV was the most frequent pathogen (52.9% and 36.1% of the cohorts, respectively). Co-infection with multiple viruses was found in 92 samples (45.1%) and 29 samples (29.9%), respectively; this was most frequent in the 12-24 months age group. The most frequently observed co-infection patterns were RSV-Rhinovirus (23 patients, 11.3%, GENDRES cohort) and RSV-bocavirus / bocavirus-influenza (5 patients, 5.2%, UK cohort). The presence of more than one virus in pediatric patients admitted to hospital with LT-ARI is very frequent and seems to peak at 12-24 months of age. The clinical significance of these findings is unclear but should warrant further analysis.

Occurrence of water-borne enteric viruses in two settlements based in Eastern Chad: analysis of hepatitis E virus, hepatitis A virus and human adenovirus in water sources.

PubMed

Guerrero-Latorre, Laura; Carratala, Anna; Rodriguez-Manzano, Jesus; Calgua, Byron; Hundesa, Ayalkibet; Girones, Rosina

2011-09-01

Hepatitis E virus (HEV) is a common cause of water-borne acute hepatitis in areas with poor sanitation. In 2004 an outbreak of HEV infection affected around 2,000 people in Eastern Chad (Dar Sila). This paper describes the decrease in the incidence of acute jaundice syndrome (AJS) from 2004 until 2009 when a mean incidence of 0.48 cases/1,000 people/year was recorded in the region. Outbreaks of AJS were identified in some of the camps in 2007 and 2008. Moreover, water samples from drinking water sources were screened for human adenoviruses considered as viral indicators and for hepatitis A virus and HEV. Screening of faecal samples from donkeys for HEV gave negative results. Some of the samples were also analysed for faecal coliforms showing values before disinfection treatment between 3 and >50 colony forming units per 100 mL. All water samples tested were negative for HEV and HAV; however, the presence of low levels of human adenoviruses in 4 out of 16 samples analysed indicates possible human faecal contamination of groundwater. Consequently, breakdowns in the treatment of drinking water and/or increased excretion of hepatitis viruses, which could be related to the arrival of a new population, could spread future outbreaks through drinking water.

Severe Acute Respiratory Syndrome–associated Coronavirus Infection

PubMed Central

Ip, Margaret; Ng, KC; Wu, Alan; Lee, Nelson; Rainer, Timothy H.; Joynt, Gavin M.; Sung, Joseph J. Y.; Tam, John S.

2003-01-01

Whether severe acute respiratory syndrome–associated coronavirus (SARS-CoV) infection can be asymptomatic is unclear. We examined the seroprevalence of SARS-CoV among 674 healthcare workers from a hospital in which a SARS outbreak had occurred. A total of 353 (52%) experienced mild self-limiting illnesses, and 321 (48%) were asymptomatic throughout the course of these observations. None of these healthcare workers had antibody to SARS CoV, indicating that subclinical or mild infection attributable to SARS CoV in adults is rare. PMID:14718090

Endoplasmic Reticulum Stress Induced Synthesis of a Novel Viral Factor Mediates Efficient Replication of Genotype-1 Hepatitis E Virus.

PubMed

Nair, Vidya P; Anang, Saumya; Subramani, Chandru; Madhvi, Abhilasha; Bakshi, Karishma; Srivastava, Akriti; Shalimar; Nayak, Baibaswata; Ranjith Kumar, C T; Surjit, Milan

2016-04-01

Hepatitis E virus (HEV) causes acute hepatitis in many parts of the world including Asia, Africa and Latin America. Though self-limiting in normal individuals, it results in ~30% mortality in infected pregnant women. It has also been reported to cause acute and chronic hepatitis in organ transplant patients. Of the seven viral genotypes, genotype-1 virus infects humans and is a major public health concern in South Asian countries. Sporadic cases of genotype-3 and 4 infection in human and animals such as pigs, deer, mongeese have been reported primarily from industrialized countries. Genotype-5, 6 and 7 viruses are known to infect animals such as wild boar and camel, respectively. Genotype-3 and 4 viruses have been successfully propagated in the laboratory in mammalian cell culture. However, genotype-1 virus replicates poorly in mammalian cell culture and no other efficient model exists to study its life cycle. Here, we report that endoplasmic reticulum (ER) stress promotes genotype-1 HEV replication by inducing cap-independent, internal initiation mediated translation of a novel viral protein (named ORF4). Importantly, ORF4 expression and stimulatory effect of ER stress inducers on viral replication is specific to genotype-1. ORF4 protein sequence is mostly conserved among genotype-1 HEV isolates and ORF4 specific antibodies were detected in genotype-1 HEV patient serum. ORF4 interacted with multiple viral and host proteins and assembled a protein complex consisting of viral helicase, RNA dependent RNA polymerase (RdRp), X, host eEF1α1 (eukaryotic elongation factor 1 isoform-1) and tubulinβ. In association with eEF1α1, ORF4 stimulated viral RdRp activity. Furthermore, human hepatoma cells that stably express ORF4 or engineered proteasome resistant ORF4 mutant genome permitted enhanced viral replication. These findings reveal a positive role of ER stress in promoting genotype-1 HEV replication and pave the way towards development of an efficient model of the

Change in brain magnetic resonance spectroscopy after treatment during acute HIV infection.

PubMed

Sailasuta, Napapon; Ross, William; Ananworanich, Jintanat; Chalermchai, Thep; DeGruttola, Victor; Lerdlum, Sukalaya; Pothisri, Mantana; Busovaca, Edgar; Ratto-Kim, Silvia; Jagodzinski, Linda; Spudich, Serena; Michael, Nelson; Kim, Jerome H; Valcour, Victor

2012-01-01

Single voxel proton magnetic resonance spectroscopy (MRS) can be used to monitor changes in brain inflammation and neuronal integrity associated with HIV infection and its treatments. We used MRS to measure brain changes during the first weeks following HIV infection and in response to antiretroviral therapy (ART). Brain metabolite levels of N-acetyl aspartate (NAA), choline (tCHO), creatine (CR), myoinositol (MI), and glutamate and glutamine (GLX) were measured in acute HIV subjects (n = 31) and compared to chronic HIV+individuals (n = 26) and HIV negative control subjects (n = 10) from Bangkok, Thailand. Metabolites were measured in frontal gray matter (FGM), frontal white matter (FWM), occipital gray matter (OGM), and basal ganglia (BG). Repeat measures were obtained in 17 acute subjects 1, 3 and 6 months following initiation of ART. After adjustment for age we identified elevated BG tCHO/CR in acute HIV cases at baseline (median 14 days after HIV infection) compared to control (p = 0.0014), as well as chronic subjects (p = 0.0023). A similar tCHO/CR elevation was noted in OGM; no other metabolite abnormalities were seen between acute and control subjects. Mixed longitudinal models revealed resolution of BG tCHO/CR elevation after ART (p = 0.022) with tCHO/CR similar to control subjects at 6 months. We detected cellular inflammation in the absence of measurable neuronal injury within the first month of HIV infection, and normalization of this inflammation following acutely administered ART. Our findings suggest that early ART may be neuroprotective in HIV infection by mitigating processes leading to CNS injury.

Incidence of respiratory viruses in Peruvian children with acute respiratory infections.

PubMed

del Valle Mendoza, Juana; Cornejo-Tapia, Angela; Weilg, Pablo; Verne, Eduardo; Nazario-Fuertes, Ronald; Ugarte, Claudia; del Valle, Luis J; Pumarola, Tomás

2015-06-01

Acute respiratory infections are responsible for high morbi-mortality in Peruvian children. However, the etiological agents are poorly identified. This study, conducted during the pandemic outbreak of H1N1 influenza in 2009, aims to determine the main etiological agents responsible for acute respiratory infections in children from Lima, Peru. Nasopharyngeal swabs collected from 717 children with acute respiratory infections between January 2009 and December 2010 were analyzed by multiplex RT-PCR for 13 respiratory viruses: influenza A, B, and C virus; parainfluenza virus (PIV) 1, 2, 3, and 4; and human respiratory syncytial virus (RSV) A and B, among others. Samples were also tested with direct fluorescent-antibodies (DFA) for six respiratory viruses. RT-PCR and DFA detected respiratory viruses in 240 (33.5%) and 85 (11.9%) cases, respectively. The most common etiological agents were RSV-A (15.3%), followed by influenza A (4.6%), PIV-1 (3.6%), and PIV-2 (1.8%). The viruses identified by DFA corresponded to RSV (5.9%) and influenza A (1.8%). Therefore, respiratory syncytial viruses (RSV) were found to be the most common etiology of acute respiratory infections. The authors suggest that active surveillance be conducted to identify the causative agents and improve clinical management, especially in the context of possible circulation of pandemic viruses. © 2015 Wiley Periodicals, Inc.

In Vivo Administration of a JAK3 Inhibitor during Acute SIV Infection Leads to Significant Increases in Viral Load during Chronic Infection

PubMed Central

Takahashi, Yoshiaki; Byrareddy, Siddappa N.; Albrecht, Christina; Brameier, Markus; Walter, Lutz; Mayne, Ann E.; Dunbar, Paul; Russo, Robert; Little, Dawn M.; Villinger, Tara; Khowawisetsut, Ladawan; Pattanapanyasat, Kovit; Villinger, Francois; Ansari, Aftab A.

2014-01-01

The studies reported herein are the first to document the effect of the in vivo administration of a JAK3 inhibitor for defining the potential role of NK cells during acute SIV infection of a group of 15 rhesus macaques (RM). An additional group of 16 MHC/KIR typed RM was included as controls. The previously optimized in vivo dose regimen (20 mg/kg daily for 35 days) led to a marked depletion of each of the major NK cell subsets both in the blood and gastro-intestinal tissues (GIT) during acute infection. While such depletion had no detectable effects on plasma viral loads during acute infection, there was a significant sustained increase in plasma viral loads during chronic infection. While the potential mechanisms that lead to such increased plasma viral loads during chronic infection remain unclear, several correlates were documented. Thus, during acute infection, the administration of the JAK3 inhibitor besides depleting all NK cell subsets also decreased some CD8+ T cells and inhibited the mobilization of the plasmacytoid dendritic cells in the blood and their localization to the GIT. Of interest is the finding that the administration of the JAK3 inhibitor during acute infection also resulted in the sustained maintenance during chronic infection of a high number of naïve and central memory CD4+ T cells, increases in B cells in the blood, but decreases in the frequencies and function of NKG2a+ NK cells within the GIT and blood, respectively. These data identify a unique role for JAK3 inhibitor sensitive cells, that includes NK cells during acute infection that in concert lead to high viral loads in SIV infected RM during chronic infection without affecting detectable changes in antiviral humoral/cellular responses. Identifying the precise mechanisms by which JAK3 sensitive cells exert their influence is critical with important implications for vaccine design against lentiviruses. PMID:24603870

Viral Infection in Adults with Severe Acute Respiratory Infection in Colombia

PubMed Central

Remolina, Yuly Andrea; Ulloa, María Mercedes; Vargas, Hernán; Díaz, Liliana; Gómez, Sandra Liliana; Saavedra, Alfredo; Sánchez, Edgar; Cortés, Jorge Alberto

2015-01-01

Objectives To identify the viral aetiology in adult patients with severe acute respiratory infection (SARI) admitted to sentinel surveillance institutions in Bogotá in 2012. Design A cross-sectional study was conducted in which microarray molecular techniques for viral identification were used on nasopharyngeal samples of adult patients submitted to the surveillance system, and further descriptions of clinical features and relevant clinical outcomes, such as mortality, need for critical care, use of mechanical ventilation and hospital stay, were obtained. Setting Respiratory infections requiring hospital admission in surveillance centres in Bogotá, Colombia. Participants Ninety-one adult patients with acute respiratory infection (55% were female). Measurements Viral identification, intensive care unit admission, hospital stay, and mortality. Results Viral identification was achieved for 63 patients (69.2%). Comorbidity was frequently identified and mainly involved chronic pulmonary disease or pregnancy. Influenza, Bocavirus and Adenovirus were identified in 30.8%, 28.6% and 18.7% of the cases, respectively. Admission to the intensive care unit occurred in 42.9% of the cases, while mechanical ventilation was required for 36.3%. The average hospital stay was 9.9 days, and mortality was 15.4%. Antibiotics were empirically used in 90.1% of patients. Conclusions The prevalence of viral aetiology of SARI in this study was high, with adverse clinical outcomes, intensive care requirements and high mortality. PMID:26576054

[Acute skin infections and their imitators in children : A photo quiz].

PubMed

Theiler, M; Schwieger-Briel, A; Weibel, L

2017-10-01

Skin infections account for 40% of emergency visits in pediatric dermatology. It is important to promptly recognize skin infections with potential complications and initiate treatment. However some characteristic skin findings may imitate skin infections and are often misdiagnosed. To illustrate frequent pediatric skin infections and pitfalls in view of imitators and differential diagnoses. A photo quiz is presented with the discussion of a selection of acute pediatric skin infections in comparison to their infectious or noninfectious differential diagnoses. The following infectious skin conditions and imitators are described and clinical clues for differentiation highlighted: eczema herpeticum and bacterial superinfection of atopic dermatitis; exanthematous hand, foot and mouth disease and varicella infection; erythema chronicum multilocularis and anular urticaria; Gianotti-Crosti syndrome and Gianotti-Crosti-like reaction; bacterial folliculitis of the scalp and kerion celsi and eosinophilic pustular folliculitis of the scalp; cutaneous Leishmaniasis and idiopathic facial aseptic granuloma; allergic and bacterial lymphangitis; bullous impetigo contagiosa and nonaccidental scalding. Careful anamnesis and skin examination with attention to the here illustrated differential diagnoses are essential to avoid pitfalls in the evaluation of acute pediatric skin infections.

An unusual case of infective endocarditis presenting as acute myocardial infarction.

PubMed

Chen, Zhong; Ng, Francesca; Nageh, Thuraia

2007-06-01

A 39-year-old Zimbabwean man presented with a 1 week history of fever, general malaise and acute-onset chest pain. He had a urethral stricture, which had been managed with an indwelling supra-pubic catheter. The electrocardiography on admission showed inferior ST-T segments elevation. His chest pain and electrocardiography changes resolved subsequent to thrombolysis, and he remained haemodynamically stable. The 12-h troponin I was increased at 10.5 microg/l (NR <0.04 microg/l). Echocardiography confirmed severe mitral regurgitation and a flail anterior mitral valve leaflet with an independently oscillating mobile vegetation. Enterococci faecalis were grown on blood cultures. A diagnosis of enterococci infective endocarditis with concomitant acute myocardial infarction due to possible septic emboli was made. Despite the successful outcome from thrombolysis in the setting of acute myocardial infarction with infective endocarditis, the case highlights the current lack of definitive data on the optimal acute management of such an unusual clinical scenario. Although there is serious concern that thrombolytic treatment for myocardial infarction in the setting of infective endocarditis may be associated with higher risk of cerebral haemorrhage, there is little documented evidence supporting the safety of primary percutaneous coronary intervention with these patients.

Viral Co-Infections in Pediatric Patients Hospitalized with Lower Tract Acute Respiratory Infections

PubMed Central

Cebey-López, Miriam; Herberg, Jethro; Pardo-Seco, Jacobo; Gómez-Carballa, Alberto; Martinón-Torres, Nazareth; Salas, Antonio; Martinón-Sánchez, José María; Gormley, Stuart; Sumner, Edward; Fink, Colin; Martinón-Torres, Federico

2015-01-01

Background Molecular techniques can often reveal a broader range of pathogens in respiratory infections. We aim to investigate the prevalence and age pattern of viral co-infection in children hospitalized with lower tract acute respiratory infection (LT-ARI), using molecular techniques. Methods A nested polymerase chain reaction approach was used to detect Influenza (A, B), metapneumovirus, respiratory syncytial virus (RSV), parainfluenza (1–4), rhinovirus, adenovirus (A—F), bocavirus and coronaviruses (NL63, 229E, OC43) in respiratory samples of children with acute respiratory infection prospectively admitted to any of the GENDRES network hospitals between 2011–2013. The results were corroborated in an independent cohort collected in the UK. Results A total of 204 and 97 nasopharyngeal samples were collected in the GENDRES and UK cohorts, respectively. In both cohorts, RSV was the most frequent pathogen (52.9% and 36.1% of the cohorts, respectively). Co-infection with multiple viruses was found in 92 samples (45.1%) and 29 samples (29.9%), respectively; this was most frequent in the 12–24 months age group. The most frequently observed co-infection patterns were RSV—Rhinovirus (23 patients, 11.3%, GENDRES cohort) and RSV—bocavirus / bocavirus—influenza (5 patients, 5.2%, UK cohort). Conclusion The presence of more than one virus in pediatric patients admitted to hospital with LT-ARI is very frequent and seems to peak at 12–24 months of age. The clinical significance of these findings is unclear but should warrant further analysis. PMID:26332375

Tetherin/BST-2 promotes dendritic cell activation and function during acute retrovirus infection

PubMed Central

Li, Sam X.; Barrett, Bradley S.; Guo, Kejun; Kassiotis, George; Hasenkrug, Kim J.; Dittmer, Ulf; Gibbert, Kathrin; Santiago, Mario L.

2016-01-01

Tetherin/BST-2 is a host restriction factor that inhibits retrovirus release from infected cells in vitro by tethering nascent virions to the plasma membrane. However, contradictory data exists on whether Tetherin inhibits acute retrovirus infection in vivo. Previously, we reported that Tetherin-mediated inhibition of Friend retrovirus (FV) replication at 2 weeks post-infection correlated with stronger natural killer, CD4+ T and CD8+ T cell responses. Here, we further investigated the role of Tetherin in counteracting retrovirus replication in vivo. FV infection levels were similar between wild-type (WT) and Tetherin KO mice at 3 to 7 days post-infection despite removal of a potent restriction factor, Apobec3/Rfv3. However, during this phase of acute infection, Tetherin enhanced myeloid dendritic cell (DC) function. DCs from infected, but not uninfected, WT mice expressed significantly higher MHC class II and the co-stimulatory molecule CD80 compared to Tetherin KO DCs. Tetherin-associated DC activation during acute FV infection correlated with stronger NK cell responses. Furthermore, Tetherin+ DCs from FV-infected mice more strongly stimulated FV-specific CD4+ T cells ex vivo compared to Tetherin KO DCs. The results link the antiretroviral and immunomodulatory activity of Tetherin in vivo to improved DC activation and MHC class II antigen presentation. PMID:26846717

Tetherin/BST-2 promotes dendritic cell activation and function during acute retrovirus infection.

PubMed

Li, Sam X; Barrett, Bradley S; Guo, Kejun; Kassiotis, George; Hasenkrug, Kim J; Dittmer, Ulf; Gibbert, Kathrin; Santiago, Mario L

2016-02-05

Tetherin/BST-2 is a host restriction factor that inhibits retrovirus release from infected cells in vitro by tethering nascent virions to the plasma membrane. However, contradictory data exists on whether Tetherin inhibits acute retrovirus infection in vivo. Previously, we reported that Tetherin-mediated inhibition of Friend retrovirus (FV) replication at 2 weeks post-infection correlated with stronger natural killer, CD4+ T and CD8+ T cell responses. Here, we further investigated the role of Tetherin in counteracting retrovirus replication in vivo. FV infection levels were similar between wild-type (WT) and Tetherin KO mice at 3 to 7 days post-infection despite removal of a potent restriction factor, Apobec3/Rfv3. However, during this phase of acute infection, Tetherin enhanced myeloid dendritic cell (DC) function. DCs from infected, but not uninfected, WT mice expressed significantly higher MHC class II and the co-stimulatory molecule CD80 compared to Tetherin KO DCs. Tetherin-associated DC activation during acute FV infection correlated with stronger NK cell responses. Furthermore, Tetherin+ DCs from FV-infected mice more strongly stimulated FV-specific CD4+ T cells ex vivo compared to Tetherin KO DCs. The results link the antiretroviral and immunomodulatory activity of Tetherin in vivo to improved DC activation and MHC class II antigen presentation.

Sequential Bottlenecks Drive Viral Evolution in Early Acute Hepatitis C Virus Infection

PubMed Central

McElroy, Kerensa; Gaudieri, Silvana; Pham, Son T.; Chopra, Abha; Cameron, Barbara; Maher, Lisa; Dore, Gregory J.; White, Peter A.; Lloyd, Andrew R.

2011-01-01

Hepatitis C is a pandemic human RNA virus, which commonly causes chronic infection and liver disease. The characterization of viral populations that successfully initiate infection, and also those that drive progression to chronicity is instrumental for understanding pathogenesis and vaccine design. A comprehensive and longitudinal analysis of the viral population was conducted in four subjects followed from very early acute infection to resolution of disease outcome. By means of next generation sequencing (NGS) and standard cloning/Sanger sequencing, genetic diversity and viral variants were quantified over the course of the infection at frequencies as low as 0.1%. Phylogenetic analysis of reassembled viral variants revealed acute infection was dominated by two sequential bottleneck events, irrespective of subsequent chronicity or clearance. The first bottleneck was associated with transmission, with one to two viral variants successfully establishing infection. The second occurred approximately 100 days post-infection, and was characterized by a decline in viral diversity. In the two subjects who developed chronic infection, this second bottleneck was followed by the emergence of a new viral population, which evolved from the founder variants via a selective sweep with fixation in a small number of mutated sites. The diversity at sites with non-synonymous mutation was higher in predicted cytotoxic T cell epitopes, suggesting immune-driven evolution. These results provide the first detailed analysis of early within-host evolution of HCV, indicating strong selective forces limit viral evolution in the acute phase of infection. PMID:21912520

Structural analysis of the endogenous glycoallergen Hev b 2 (endo-β-1,3-glucanase) from Hevea brasiliensis and its recognition by human basophils

PubMed Central

Rodríguez-Romero, Adela; Hernández-Santoyo, Alejandra; Fuentes-Silva, Deyanira; Palomares, Laura A.; Muñoz-Cruz, Samira; Yépez-Mulia, Lilian; Orozco-Martínez, Socorro

2014-01-01

Endogenous glycosylated Hev b 2 (endo-β-1,3-glucanase) from Hevea brasiliensis is an important latex allergen that is recognized by IgE antibodies from patients who suffer from latex allergy. The carbohydrate moieties of Hev b 2 constitute a potentially important IgE-binding epitope that could be responsible for its cross-reactivity. Here, the structure of the endogenous isoform II of Hev b 2 that exhibits three post-translational modifications, including an N-terminal pyro­glutamate and two glycosylation sites at Asn27 and at Asn314, is reported from two crystal polymorphs. These modifications form a patch on the surface of the molecule that is proposed to be one of the binding sites for IgE. A structure is also proposed for the most important N-glycan present in this protein as determined by digestion with specific enzymes. To analyze the role of the carbohydrate moieties in IgE antibody binding and in human basophil activation, the glycoallergen was enzymatically deglycosylated and evaluated. Time-lapse automated video microscopy of basophils stimulated with glycosylated Hev b 2 revealed basophil activation and degranulation. Immunological studies suggested that carbohydrates on Hev b 2 represent an allergenic IgE epitope. In addition, a dimer was found in each asymmetric unit that may reflect a regulatory mechanism of this plant defence protein. PMID:24531467

Prevalence and correlates of acute respiratory infections in children less than two years of age.

PubMed

Saeed, A A; Bani, I A

2000-12-01

To study acute respiratory infections of children less than 2 years of age in Riyadh City and their sociodemographic and anthropometric correlates. Study subjects included 250 mothers selected by systematic random sampling from mothers attending 5 Primary Health Care Centers selected by simple random sampling from the 5 geographical zones (one from each zone) in Riyadh during a one month period. Data was collected via a structured pilot tested modified questionnaire filled in by trained research assistants who interviewed mothers regarding acute respiratory infections during the past 2 weeks in their children aged less than 2 years. Heights and weights of both children and mothers were measured and the necessary sociodemographic characteristics of the mothers, and children were collected by the research assistants in addition to mothers' practices concerning their child's acute respiratory infections. The prevalence of acute respiratory infection in children was 24%, mostly in children whose mothers are less educated, aged 35 years or more, married at age 25 years or more and whose relatives take care of their children while working outside the home. The children affected were mostly 7 - 12 months of age, lighter in weight, not vaccinated, with no follow up cards and not weighed during the last 4 months. About 3 quarters of the mothers consulted somebody about acute respiratory infections, mostly at modern health facilities particularly government Primary Health Care Centers. Tachypnea, or diarrhea or both were the most important symptoms urging mothers to seek medical advice. Working mothers whose children are taken care of by relatives is the only significant predictor of acute respiratory infections, and children with a follow up card is the only significant predictor for consulting somebody about acute respiratory infections. Intervention strategies to control acute respiratory infections in children less than 2 years of age should target working mothers, less

[Prevention of virus hepatitis A to E].

PubMed

Cornberg, M; Manns, M P

2011-03-01

Infection with hepatitis viruses can lead to acute hepatitis with the risk of developing liver failure. Chronic viral hepatitis may evolve into liver cirrhosis and hepatocellular carcinoma. Thus, prevention of viral hepatitis and its sequels is essential. Vaccination against hepatitis A is successful in almost all individuals. Protective antibodies maintain for at least 20 years. Booster vaccinations are not necessary. Since the introduction of hepatitis A vaccines, the incidence of new HAV-infections has declined significantly. Hepatitis B vaccines are safe and highly effective. Special populations such as dialysis patients or immunocompromised patients require special vaccine schedules. New vaccines with improved adjuvants are currently being tested in clinical trials. So far there is no hepatitis C vaccine on the horizon. Prophylaxis of HCV-infections relies primarily on hygiene measures. Early therapy of acute hepatitis C can prevent chronic hepatitis C. HDV-infection can only be established if HBsAg is present. Thus, prevention of hepatitis B or elimination of HBsAg means prevention of hepatitis delta. Hepatitis E vaccines have been evaluated in phase III studies. The development of HEV vaccines becomes more relevant since chronic HEV infections have been reported in immunosuppressed individuals.

Change in Brain Magnetic Resonance Spectroscopy after Treatment during Acute HIV Infection

PubMed Central

Sailasuta, Napapon; Ross, William; Ananworanich, Jintanat; Chalermchai, Thep; DeGruttola, Victor; Lerdlum, Sukalaya; Pothisri, Mantana; Busovaca, Edgar; Ratto-Kim, Silvia; Jagodzinski, Linda; Spudich, Serena; Michael, Nelson; Kim, Jerome H.; Valcour, Victor

2012-01-01

Objective Single voxel proton magnetic resonance spectroscopy (MRS) can be used to monitor changes in brain inflammation and neuronal integrity associated with HIV infection and its treatments. We used MRS to measure brain changes during the first weeks following HIV infection and in response to antiretroviral therapy (ART). Methods Brain metabolite levels of N-acetyl aspartate (NAA), choline (tCHO), creatine (CR), myoinositol (MI), and glutamate and glutamine (GLX) were measured in acute HIV subjects (n = 31) and compared to chronic HIV+individuals (n = 26) and HIV negative control subjects (n = 10) from Bangkok, Thailand. Metabolites were measured in frontal gray matter (FGM), frontal white matter (FWM), occipital gray matter (OGM), and basal ganglia (BG). Repeat measures were obtained in 17 acute subjects 1, 3 and 6 months following initiation of ART. Results After adjustment for age we identified elevated BG tCHO/CR in acute HIV cases at baseline (median 14 days after HIV infection) compared to control (p = 0.0014), as well as chronic subjects (p = 0.0023). A similar tCHO/CR elevation was noted in OGM; no other metabolite abnormalities were seen between acute and control subjects. Mixed longitudinal models revealed resolution of BG tCHO/CR elevation after ART (p = 0.022) with tCHO/CR similar to control subjects at 6 months. Interpretation We detected cellular inflammation in the absence of measurable neuronal injury within the first month of HIV infection, and normalization of this inflammation following acutely administered ART. Our findings suggest that early ART may be neuroprotective in HIV infection by mitigating processes leading to CNS injury. PMID:23229129

Impact of Infection Prevention and Control Initiatives on Acute Respiratory Infections in a Pediatric Long-Term Care Facility.

PubMed

Murray, Meghan T; Jackson, Olivia; Cohen, Bevin; Hutcheon, Gordon; Saiman, Lisa; Larson, Elaine; Neu, Natalie

2016-07-01

We evaluated the collective impact of several infection prevention and control initiatives aimed at reducing acute respiratory infections (ARIs) in a pediatric long-term care facility. ARIs did not decrease overall, though the proportion of infections associated with outbreaks and average number of cases per outbreak decreased. Influenza rates decreased significantly. Infect Control Hosp Epidemiol 2016;37:859-862.

Transmission of Hepatitis E Virus in Developing Countries

PubMed Central

Khuroo, Mohammad S.; Khuroo, Mehnaaz S.; Khuroo, Naira S.

2016-01-01

Hepatitis E virus (HEV), an RNA virus of the Hepeviridae family, has marked heterogeneity. While all five HEV genotypes can cause human infections, genotypes HEV-1 and -2 infect humans alone, genotypes HEV-3 and -4 primarily infect pigs, boars and deer, and genotype HEV-7 primarily infects dromedaries. The global distribution of HEV has distinct epidemiological patterns based on ecology and socioeconomic factors. In resource-poor countries, disease presents as large-scale waterborne epidemics, and few epidemics have spread through person-to-person contact; however, endemic diseases within these countries can potentially spread through person-to-person contact or fecally contaminated water and foods. Vertical transmission of HEV from infected mother to fetus causes high fetal and perinatal mortality. Other means of transmission, such as zoonotic transmission, can fluctuate depending upon the region and strain of the virus. For instance, zoonotic transmission can sometimes play an insignificant role in human infections, such as in India, where human and pig HEV infections are unrelated. However, recently China and Southeast Asia have experienced a zoonotic spread of HEV-4 from pigs to humans and this has become the dominant mode of transmission of hepatitis E in eastern China. Zoonotic HEV infections in humans occur by eating undercooked pig flesh, raw liver, and sausages; through vocational contact; or via pig slurry, which leads to environmental contamination of agricultural products and seafood. Lastly, blood transfusion-associated HEV infections occur in many countries and screening of donors for HEV RNA is currently under serious consideration. To summarize, HEV genotypes 1 and 2 cause epidemic and endemic diseases in resource poor countries, primarily spreading through contaminated drinking water. HEV genotypes 3 and 4 on the other hand, cause autochthonous infections in developed, and many developing countries, by means of a unique zoonotic food

Hippocampal protection in mice with an attenuated inflammatory monocyte response to acute CNS picornavirus infection

PubMed Central

Howe, Charles L.; LaFrance-Corey, Reghann G.; Sundsbak, Rhianna S.; Sauer, Brian M.; LaFrance, Stephanie J.; Buenz, Eric J.; Schmalstieg, William F.

2012-01-01

Neuronal injury during acute viral infection of the brain is associated with the development of persistent cognitive deficits and seizures in humans. In C57BL/6 mice acutely infected with the Theiler's murine encephalomyelitis virus, hippocampal CA1 neurons are injured by a rapid innate immune response, resulting in profound memory deficits. In contrast, infected SJL and B6xSJL F1 hybrid mice exhibit essentially complete hippocampal and memory preservation. Analysis of brain-infiltrating leukocytes revealed that SJL mice mount a sharply attenuated inflammatory monocyte response as compared to B6 mice. Bone marrow transplantation experiments isolated the attenuation to the SJL immune system. Adoptive transfer of B6 inflammatory monocytes into acutely infected B6xSJL hosts converted these mice to a hippocampal damage phenotype and induced a cognitive deficit marked by failure to recognize a novel object. These findings show that inflammatory monocytes are the critical cellular mediator of hippocampal injury during acute picornavirus infection of the brain. PMID:22848791

[Different species of human rhinovirus infection in children with acute respiratory tract infections in Beijing].

PubMed

Song, Ming-hui; Zhao, Lin-qing; Qian, Yuan; Zhu, Ru-nan; Deng, Jie; Wang, Fang; Sun, Yu; Tian, Run

2013-12-01

To understand the clinical characteristics of different groups human rhinovirus (HRV)-A, B and C infection in children with acute respiratory tract infections (ARI) in Beijing. Respiratory tract specimens (n = 1412) collected from children with ARI during Jan. 2011 to Dec. 2012 were tested for HRV by using semi-nested PCR. Gene fragments of VP4/VP2 capsid protein amplified from HRV positive specimens were sequenced for HRV genotype confirmation. Then epidemiological characteristics of these HRV-positive cases were analyzed. Among these 1412 specimens tested, 103 (7.3%) were HRV positive, including 54 (52.4%) positive for HRV-A, 14 (13.6%) for HRV-B, 35 (34.0%) for HRV-C determined by sequence analysis. The positive rates of HRV-A, B and C (2.5%, 16/638; 0.3%, 2/638 and 1.3%, 8/638) in children with acute upper respiratory tract infections (URI) were lower than those (5.8%, 36/623; 1.8%, 11/623 and 3.9%, 24/623) in children with acute lower respiratory tract infections (LRI) (P = 0.003, 0.011, 0.003). In children with LRI, the positive rates of HRV-A, C were similar to each other (P = 0.112), and both were higher than that of HRV-B (P = 0.000, P = 0.026). The severity of ARI among children positive for different groups HRV showed no significant difference evaluated by Kruskal-Wallis H test (Hc = 0.044, P > 0.05), as well as that between children co-infected with HRV and other viruses and those infected with HRV only evaluated by Wilcoxon rank sum test (Zc = 0.872, P > 0.05). HRV is one of important pathogens for children with ARI, especially LRI in Beijing. The positive rates of HRV-A and HRV-C are similar to each other, and both are higher than that of HRV-B. No significant difference was shown among children with different HRV genotypes by evaluation of the severity of ARI, and co-infections of HRV with other viruses do not significantly increase the severity of ARI.

Pericardial Tamponade in an Adult Suffering from Acute Mumps Infection

PubMed Central

Flieger, Robert Rainer; Mankertz, Annette; Yilmaz, Kadir; Roepke, Torsten Kai

2016-01-01

Here, we report a case of a 51-year-old man with acute pericardial tamponade requiring emergency pericardiocentesis after he suffered from sore throat, headache, malaise, and sweats for two weeks. Serological analyses revealed increased mumps IgM and IgG indicating an acute mumps infection whereas other bacterial and viral infections were excluded. In addition, MRI revealed atypical swelling of the left submandibular gland. Whereas mumps has become a rare entity in children due to comprehensive vaccination regimens in western civilizations, our case highlights mumps as an important differential diagnosis also in adults, where the virus can induce life-threatening complications such as pericardial tamponade. PMID:27818687

Acute Parasitic Infections as a Cause of Fever of Unknown Origin in Egypt

DTIC Science & Technology

1993-10-01

series and included 10 with acute and biliary system (Bassily et al., 1989). fascioliasis , 9 with schistosomiasis and I Diagnosing these patients...Farid et al., 1989). Acute Ilosp., Postal Code 11517, Cairo. Egpt. fascioliasis is treated with bithionol, 88 Table: Diagnostic categories of fcver of...diagnosis Infections 80 57 Tuberculosis (32), Salmonellosis (10), Fascioliasis (10), Schistosomiasis (9). Infective Endocarditis (5), Brucellosis (4

Differences in Risk Behavior and Demographic Factors between Men who have Sex with Men with Acute and Non-Acute Human Immunodeficiency Virus Infection in a Community-Based Testing Program in Los Angeles

PubMed Central

Davey, Dvora Joseph; Beymer, Matthew; Roberts, Chelsea P; Bolan, Robert K; Klausner, Jeffrey D

2016-01-01

Introduction High viremia combined with HIV-infection status unawareness and increased sexual risk behavior contributes to a disproportionate amount of new HIV infections. Methods From August 2011-July 2015, the Los Angeles LGBT Center conducted 66,546 HIV tests. We compared factors including the presence of concomitant sexually transmitted infections, number of recent sex partners and reported condomless anal intercourse between men who have sex with men (MSM) diagnosed with an acute HIV infection and a non-acute HIV infection using multivariable logistic regression. Results Of 1,082 unique MSM who tested HIV-infected for the first time, 165 (15%) had an acute infection and 917 had a non-acute infection. HIV rapid antibody testing was 84.8% sensitive for detecting HIV infection (95% CI=82.9%-87.1%). Median HIV viral load among acutely infected MSM was 842,000 copies/ml (interquartile range=98,200-4,897,318). MSM with acute infection had twice the number of sex partners in the prior 30-days (median=2), and prior 3-months (median=4) before diagnosis compared to those diagnosed with non-acute infection (p=<0.0001). The odds of acute HIV infection were increased with the numbers of recent sex partners after controlling for age and race/ethnicity (aOR >5 partners in past 30-days=2.74; 95%CI=1.46-5.14; aOR >10 partners in past 3-months=2.41; 95%CI=1.36-4.25). Non-African American MSM had almost double the odds of being diagnosed with an acute HIV infection compared with African-American MSM (aOR=1.97; 95% CI=1.10-3.52). Conclusion MSM with acute HIV infection had nearly twice as many sex partners in the past 30-days and 3-months compared with MSM with newly diagnosed non-acute HIV infection. Those diagnosed with acute HIV infection had decreased odds of being African American MSM. PMID:27861243

Reassessment of HIV-1 acute phase infectivity: accounting for heterogeneity and study design with simulated cohorts.

PubMed

Bellan, Steve E; Dushoff, Jonathan; Galvani, Alison P; Meyers, Lauren Ancel

2015-03-01

The infectivity of the HIV-1 acute phase has been directly measured only once, from a retrospectively identified cohort of serodiscordant heterosexual couples in Rakai, Uganda. Analyses of this cohort underlie the widespread view that the acute phase is highly infectious, even more so than would be predicted from its elevated viral load, and that transmission occurring shortly after infection may therefore compromise interventions that rely on diagnosis and treatment, such as antiretroviral treatment as prevention (TasP). Here, we re-estimate the duration and relative infectivity of the acute phase, while accounting for several possible sources of bias in published estimates, including the retrospective cohort exclusion criteria and unmeasured heterogeneity in risk. We estimated acute phase infectivity using two approaches. First, we combined viral load trajectories and viral load-infectivity relationships to estimate infectivity trajectories over the course of infection, under the assumption that elevated acute phase infectivity is caused by elevated viral load alone. Second, we estimated the relative hazard of transmission during the acute phase versus the chronic phase (RHacute) and the acute phase duration (dacute) by fitting a couples transmission model to the Rakai retrospective cohort using approximate Bayesian computation. Our model fit the data well and accounted for characteristics overlooked by previous analyses, including individual heterogeneity in infectiousness and susceptibility and the retrospective cohort's exclusion of couples that were recorded as serodiscordant only once before being censored by loss to follow-up, couple dissolution, or study termination. Finally, we replicated two highly cited analyses of the Rakai data on simulated data to identify biases underlying the discrepancies between previous estimates and our own. From the Rakai data, we estimated RHacute = 5.3 (95% credibility interval [95% CrI]: 0.79-57) and dacute = 1.7 mo (95% Cr

Seroepidemiology and molecular characterization of hepatitis E virus infection in swine and occupationally exposed workers in Punjab, India.

PubMed

Bansal, M; Kaur, S; Deka, D; Singh, R; Gill, J P S

2017-12-01

Hepatitis E virus (HEV) has two discrete epidemiological patterns: waterborne epidemics in developing countries only, caused by HEV genotype I, and sporadic zoonotic outbreaks in developing and developed countries caused by genotypes III and IV. This study was designed to investigate seroprevalence, molecular detection and the characterization of HEV by nested RT-PCR in swine as well as the occupational risk to exposed human population in Punjab state of north-western India. The occupational risk-exposed group comprised of swine farmers (organized - mixed feed feeders and unorganized - swill feeders), slaughterhouse workers, sewage workers and veterinary internes. During the study period, blood and faecal samples were collected from 320 swine and 360 humans with both high and low occupational exposure risks. The overall seroprevalence of swine HEV was 65.00%, with a significantly higher seropositivity in growing pigs (2-8 months of age). The prevalence of HEV RNA in swine faecal samples by nRT-PCR was 8.75% with a significantly higher detection in swill-fed pigs. With humans in the high occupational exposure risk population, significantly higher anti-HEV IgG seropositivity was observed (60.48%) as compared to control population (10.71%). Strong evidence of association between human anti-HEV IgG seropositivity and certain occupational exposure risk groups was observed (p < 0.05). This indicates that unorganized swine farmers, slaughterhouse workers and sewage workers have higher odds of HEV infection in this study region. Percentage of nucleotide similarity between swine and human HEV isolates was less than that found in countries with zoonotic HEV outbreaks. Molecular characterization revealed the circulation of G IV and G I genotypes among swine and human population in Punjab state, respectively. © 2017 Blackwell Verlag GmbH.

Reassessment of HIV-1 Acute Phase Infectivity: Accounting for Heterogeneity and Study Design with Simulated Cohorts

PubMed Central

Bellan, Steve E.; Dushoff, Jonathan; Galvani, Alison P.; Meyers, Lauren Ancel

2015-01-01

Background The infectivity of the HIV-1 acute phase has been directly measured only once, from a retrospectively identified cohort of serodiscordant heterosexual couples in Rakai, Uganda. Analyses of this cohort underlie the widespread view that the acute phase is highly infectious, even more so than would be predicted from its elevated viral load, and that transmission occurring shortly after infection may therefore compromise interventions that rely on diagnosis and treatment, such as antiretroviral treatment as prevention (TasP). Here, we re-estimate the duration and relative infectivity of the acute phase, while accounting for several possible sources of bias in published estimates, including the retrospective cohort exclusion criteria and unmeasured heterogeneity in risk. Methods and Findings We estimated acute phase infectivity using two approaches. First, we combined viral load trajectories and viral load-infectivity relationships to estimate infectivity trajectories over the course of infection, under the assumption that elevated acute phase infectivity is caused by elevated viral load alone. Second, we estimated the relative hazard of transmission during the acute phase versus the chronic phase (RHacute) and the acute phase duration (d acute) by fitting a couples transmission model to the Rakai retrospective cohort using approximate Bayesian computation. Our model fit the data well and accounted for characteristics overlooked by previous analyses, including individual heterogeneity in infectiousness and susceptibility and the retrospective cohort's exclusion of couples that were recorded as serodiscordant only once before being censored by loss to follow-up, couple dissolution, or study termination. Finally, we replicated two highly cited analyses of the Rakai data on simulated data to identify biases underlying the discrepancies between previous estimates and our own. From the Rakai data, we estimated RHacute = 5.3 (95% credibility interval [95% CrI]: 0

Current Perspectives of Prophylaxis and Management of Acute Infective Endophthalmitis.

PubMed

Tranos, Paris; Dervenis, Nikolaos; Vakalis, Athanasios N; Asteriadis, Solon; Stavrakas, Panagiotis; Konstas, Anastasios G P

2016-05-01

Endophthalmitis is an intraocular inflammatory condition which may or may not be caused by infective agents. Noninfectious (sterile) endophthalmitis may be attributable to various causes including postoperative retained soft lens matter or toxicity following introduction of other agents into the eye. Infectious endophthalmitis is further subdivided into endogenous and exogenous. In endogenous endophthalmitis there is hematogenous spread of organisms from a distant source of infection whereas in exogenous endophthalmitis direct microbial inoculation may occur usually following ocular surgery or penetrating eye injury with or without intraocular foreign bodies. Acute infective endophthalmitis is usually exogenous induced by inoculation of pathogens following ocular surgery, open-globe injury and intravitreal injections. More infrequently the infective source is internal and septicemia spreads to the eye resulting in endogenous endophthalmitis. Several risk factors have been implicated including immunosuppression, ocular surface abnormalities, poor surgical wound construction, complicated cataract surgery with vitreous loss and certain types of intraocular lens. Comprehensive guidelines and recommendations on prophylaxis and monitoring of surgical cases have been proposed to minimize the risk of acute endophthalmitis. Early diagnosis and prompt management of infective endophthalmitis employing appropriately selected intravitreal antibiotics are essential to optimize visual outcome.

Systematic review of mixed cryoglobulinemia associated with hepatitis E virus infection: association or causation?

PubMed

Bazerbachi, Fateh; Leise, Michael D; Watt, Kymberly D; Murad, M Hassan; Prokop, Larry J; Haffar, Samir

2017-08-01

Background and aim: Mixed cryoglobulinemia (MC) has been associated with several viral infections, and chronic hepatitis C is recognized as a major cause. MC associated with hepatitis E virus (HEV) has been described and little is known about this rare association. The aim of this study is to perform a systematic review of MC associated with HEV, and examine the presence of a causal relationship. Methods: An experienced librarian conducted a search of databases from each database's inception to 12 December 2016 based on a priori criteria. The risk of bias was assessed, and Hill's criteria were applied to determine causality. Results: Five publications met inclusion criteria, with a total of 15 cases. Three studies had low, one low to moderate and one moderate risk of bias. Median age was 43 years, and all patients came from Western Europe. Two patients were immunocompetent, while 13 were immunosuppressed, post solid organ transplant and had chronic hepatitis E. Renal involvement was observed in seven patients, mild to moderately severe cryoglobulinemic disease in one patient and severe cryoglobulinemic disease in three patients. One patient improved spontaneously, and another was treated with immunosuppressant reduction leading to viral clearance. Ten patients treated with peg-interferon or ribavirin for 3 months achieved loss of cryoglobulinemia and end-of-treatment response, but sustained virologic response was reported and achieved in two. Immunosuppressant achieved loss of cryoglobulinemia in three patients. One case of chronic renal failure, three cases of end-stage renal disease and one death were observed. Five of the nine Hill's criteria were fulfilled. Conclusion: MC has been described with HEV infection. A causal relationship between HEV infection and cryoglobulinemia is highly probable.

Alcohol during pregnancy worsens acute respiratory infections in children.

PubMed

Libster, Romina; Ferolla, Fausto M; Hijano, Diego R; Acosta, Patricio L; Erviti, Anabella; Polack, Fernando P

2015-11-01

This study explored whether alcohol consumption during pregnancy increased the risk of life-threatening respiratory infections in children. We prospectively evaluated children under the age of two years admitted to hospitals in Buenos Aires, Argentina, with severe acute respiratory infections during the winters of 2011 and 2012. Information on maternal alcohol consumption during the third trimester of pregnancy was collected using standardised questionnaires and categorised as never, low if it was once a week and high if it was equal or more than once a week. Of the 3423 children hospitalised with acute respiratory infection, 2089 (63.7%) had respiratory syncytial virus (RSV). Alcohol consumption during the last trimester was reported by 398 mothers (12.4%) and categorised as low (n = 210, 6.5%) or high (n = 188, 5.9%). A greater effect on life-threatening respiratory infection, defined as oxygen saturation of or up to 87%, was observed with higher alcohol intake due to all viruses and specifically RSV in the logistic regression analyses. Alcohol consumption was strongly associated with life-threatening disease, particularly in boys whose adjusted odds ratio rose from 3.67 to 13.52 when their mothers drank alcohol. Alcohol consumption during pregnancy was associated with life-threatening respiratory infections in boys. ©2015 Foundation Acta Paediatrica. Published by John Wiley & Sons Ltd.

Absence of Cerebrospinal Fluid Signs of Neuronal Injury Before and After Immediate Antiretroviral Therapy in Acute HIV Infection

PubMed Central

Peluso, Michael J.; Valcour, Victor; Ananworanich, Jintanat; Sithinamsuwan, Pasiri; Chalermchai, Thep; Fletcher, James L. K.; Lerdlum, Sukalya; Chomchey, Nitiya; Slike, Bonnie; Sailasuta, Napapon; Gisslén, Magnus; Zetterberg, Henrik; Spudich, Serena

2015-01-01

Background. It is unknown whether neuronal injury begins during acute human immunodeficiency virus (HIV) infection, and whether immediate initiation of combination antiretroviral therapy (cART) prevents neuronal injury. Methods. Cerebrospinal fluid (CSF) neurofilament light chain (NFL), a measure of axonal injury, was assessed before and after cART initiation in individuals starting treatment during acute or chronic HIV infection. Nonparametric statistics examined relationships between NFL and disease progression, neuroinflammation, and cognitive performance. Results. Before treatment, subjects with acute infection had lower CSF NFL levels, with elevations for their age in 1 of 32 subjects with acute infection (3.1%) and 10 of 32 with chronic infection (31%) (P = .006). This persisted after cART initiation, with 1 of 25 acute (4%) and 4 of 9 chronic subjects (44%) showing elevated NFL levels (P = .01). In acute infection, pre-cART NFL levels were inversely correlated with proton magnetic resonance spectroscopic findings of N-acetylaspartate/creatine in frontal gray matter (r = −0.40; P = .03), frontal white matter (r = −0.46; P = .01), and parietal gray matter (r = −0.47; P = .01); correlations persisted after treatment in the frontal white matter (r = −0.51; P = .02) and parietal gray matter (r = −0.46; P = .04). Conclusions. CSF NFL levels are not elevated in untreated acute HIV infection or after 6 months of immediately initiated cART but are abnormal in chronic HIV infection before and after treatment. In acute HIV infection, CSF NFL levels are inversely associated with neuroimaging markers of neuronal health. PMID:25995196

Platelet Activating Factor Contributes to Vascular Leak in Acute Dengue Infection

PubMed Central

Jeewandara, Chandima; Gomes, Laksiri; Wickramasinghe, N.; Gutowska-Owsiak, Danuta; Waithe, Dominic; Paranavitane, S. A.; Shyamali, N. L. A.; Ogg, Graham S.; Malavige, Gathsaurie Neelika

2015-01-01

Background Although plasma leakage is the hallmark of severe dengue infections, the factors that cause increased vascular permeability have not been identified. As platelet activating factor (PAF) is associated with an increase in vascular permeability in other diseases, we set out to investigate its role in acute dengue infection. Materials and Methods PAF levels were initially assessed in 25 patients with acute dengue infection to determine if they were increased in acute dengue. For investigation of the kinetics of PAF, serial PAF values were assessed in 36 patients. The effect of dengue serum on tight junction protein ZO-1 was determined by using human endothelial cell lines (HUVECs). The effect of dengue serum on and trans-endothelial resistance (TEER) was also measured on HUVECs. Results PAF levels were significantly higher in patients with acute dengue (n = 25; p = 0.001) when compared to healthy individuals (n = 12). In further investigation of the kinetics of PAF in serial blood samples of patients (n = 36), PAF levels rose just before the onset of the critical phase. PAF levels were significantly higher in patients with evidence of vascular leak throughout the course of the illness when compared to those with milder disease. Serum from patients with dengue significantly down-regulated expression of tight junction protein, ZO-1 (p = 0.004), HUVECs. This was significantly inhibited (p = 0.004) by use of a PAF receptor (PAFR) blocker. Serum from dengue patients also significantly reduced TEER and this reduction was also significantly (p = 0.02) inhibited by prior incubation with the PAFR blocker. Conclusion Our results suggest the PAF is likely to be playing a significant role in inducing vascular leak in acute dengue infection which offers a potential target for therapeutic intervention. PMID:25646838

Acute Viral Respiratory Infection Rapidly Induces a CD8+ T Cell Exhaustion-like Phenotype.

PubMed

Erickson, John J; Lu, Pengcheng; Wen, Sherry; Hastings, Andrew K; Gilchuk, Pavlo; Joyce, Sebastian; Shyr, Yu; Williams, John V

2015-11-01

Acute viral infections typically generate functional effector CD8(+) T cells (TCD8) that aid in pathogen clearance. However, during acute viral lower respiratory infection, lung TCD8 are functionally impaired and do not optimally control viral replication. T cells also become unresponsive to Ag during chronic infections and cancer via signaling by inhibitory receptors such as programmed cell death-1 (PD-1). PD-1 also contributes to TCD8 impairment during viral lower respiratory infection, but how it regulates TCD8 impairment and the connection between this state and T cell exhaustion during chronic infections are unknown. In this study, we show that PD-1 operates in a cell-intrinsic manner to impair lung TCD8. In light of this, we compared global gene expression profiles of impaired epitope-specific lung TCD8 to functional spleen TCD8 in the same human metapneumovirus-infected mice. These two populations differentially regulate hundreds of genes, including the upregulation of numerous inhibitory receptors by lung TCD8. We then compared the gene expression of TCD8 during human metapneumovirus infection to those in acute or chronic lymphocytic choriomeningitis virus infection. We find that the immunophenotype of lung TCD8 more closely resembles T cell exhaustion late into chronic infection than do functional effector T cells arising early in acute infection. Finally, we demonstrate that trafficking to the infected lung alone is insufficient for TCD8 impairment or inhibitory receptor upregulation, but that viral Ag-induced TCR signaling is also required. Our results indicate that viral Ag in infected lungs rapidly induces an exhaustion-like state in lung TCD8 characterized by progressive functional impairment and upregulation of numerous inhibitory receptors. Copyright © 2015 by The American Association of Immunologists, Inc.

The diagnosis, evaluation and treatment of acute and recurrent pediatric urinary tract infections.

PubMed

Becknell, Brian; Schober, Megan; Korbel, Lindsey; Spencer, John David

2015-01-01

Urinary tract infection (UTI) is one of the most common bacterial infections encountered by pediatricians. Currently, the diagnosis and management of acute UTI and recurrent UTI in children remain controversial. Recently published guidelines and large clinical trials have attempted to clarify UTI diagnostic and management strategies. In this manuscript, we review the diagnosis and management of acute and recurrent UTI in the pediatric population.

Impact of Infection Prevention and Control Initiatives on Acute Respiratory Infections in a Pediatric Long-Term Care Facility

PubMed Central

Murray, Meghan T.; Jackson, Olivia; Cohen, Bevin; Hutcheon, Gordon; Saiman, Lisa; Larson, Elaine; Neu, Natalie

2016-01-01

We evaluated the collective impact of several infection prevention and control initiatives aimed at reducing acute respiratory infections (ARIs) in a pediatric long-term care facility. ARIs did not decrease overall, though the proportion of infections associated with outbreaks and average number of cases per outbreak decreased. Influenza rates decreased significantly. PMID:27053088

Does virus-bacteria coinfection increase the clinical severity of acute respiratory infection?

PubMed

Damasio, Guilherme A C; Pereira, Luciane A; Moreira, Suzana D R; Duarte dos Santos, Claudia N; Dalla-Costa, Libera M; Raboni, Sonia M

2015-09-01

This retrospective cohort study investigated the presence of bacteria in respiratory secretions of patients hospitalized with acute respiratory infections and analyzed the impact of viral and bacterial coinfection on severity and the mortality rate. A total of 169 patients with acute respiratory infections were included, viruses and bacteria in respiratory samples were detected using molecular methods. Among all samples, 73.3% and 59.7% were positive for viruses and bacteria, respectively; 45% contained both virus and bacteria. Bacterial coinfection was more frequent in patients infected by community respiratory viruses than influenza A H1N1pdm (83.3% vs. 40.6%). The most frequently bacteria detected were Streptococcus pneumoniae and Haemophilus influenzae. Both species were co-detected in 54 patients and identified alone in 22 and 21 patients, respectively. Overall, there were no significant differences in the period of hospitalization, severity, or mortality rate between patients infected with respiratory viruses alone and those coinfected by viruses and bacteria. The detection of mixed respiratory pathogens is frequent in hospitalized patients with acute respiratory infections, but its impact on the clinical outcome does not appear substantial. However, it should be noted that most of the patients received broad-spectrum antibiotic therapy, which may have contributed to this favorable outcome. © 2015 Wiley Periodicals, Inc.

Acute Sin Nombre hantavirus infection without pulmonary syndrome, United States.

PubMed Central

Kitsutani, P. T.; Denton, R. W.; Fritz, C. L.; Murray, R. A.; Todd, R. L.; Pape, W. J.; Wyatt Frampton, J.; Young, J. C.; Khan, A. S.; Peters, C. J.; Ksiazek, T. G.

1999-01-01

Hantavirus pulmonary syndrome (HPS) occurs in most infections with Sin Nombre virus and other North American hantaviruses. We report five cases of acute hantavirus infection that did not fit the HPS case definition. The patients had characteristic prodromal symptoms without severe pulmonary involvement. These cases suggest that surveillance for HPS may need to be expanded. PMID:10511527

Susceptibility of Pigs to Zoonotic Hepatitis E Virus Genotype 3 Isolated from a Wild Boar.

PubMed

Thiry, D; Rose, N; Mauroy, A; Paboeuf, F; Dams, L; Roels, S; Pavio, N; Thiry, E

2017-10-01

In Europe, zoonotic hepatitis E virus (HEV) genotype 3 strains mainly circulate in humans, swine and wild boar. The aim of this study was to investigate the potential transmission of a wild boar originating HEV strain (WbHEV) to swine by intravenous or oral inoculation and to study the consequences of infection of a WbHEV strain, a WbHEV strain previously passaged in a pig and a swine HEV strain after oral inoculation. Firstly, an intravenous infection was performed for which five piglets were divided into two groups with three pigs inoculated with a WbHEV field strain and two pigs inoculated with a HEV-negative swine liver homogenate. All pigs were necropsied 8, 9 and 10 days post-inoculation. Secondly, an oral infection of 56 days was performed on 12 piglets divided into four groups inoculated with a WbHEV strain, a WbHEV strain previously passaged in swine, a swine HEV strain or a HEV-negative swine liver homogenate. After intravenous inoculation, HEV RNA was detected in serum, bile, liver, spleen, duodenum, jejunum, colon, lung, gastro-hepatic lymph nodes and faeces in all infected piglets. After oral inoculation, HEV RNA was detected in serum, bile, liver, gastro-hepatic lymph nodes and faeces. Most of HEV-inoculated pigs became seropositive at day 15. This study provides experimental evidence of early viral spread throughout the organism after intravenous infection with a WbHEV strain and supports the notion that such a zoonotic strain could be transmitted via the natural faecal-oral route of infection between wild boar and pigs but also between pigs. © 2016 Blackwell Verlag GmbH.

Capgras-like syndrome in a patient with an acute urinary tract infection

PubMed Central

Salviati, Massimo; Bersani, Francesco Saverio; Macrì, Francesco; Fojanesi, Marta; Minichino, Amedeo; Gallo, Mariana; De Michele, Francesco; Chiaie, Roberto Delle; Biondi, Massimo

2013-01-01

Delusional misidentification syndromes are a group of delusional phenomena in which patients misidentify familiar persons, objects, or themselves, believing that they have been replaced or transformed. In 25%–40% of cases, misidentification syndromes have been reported in association with organic illness. We report an acute episode of Capgras-like delusion lasting 8 days, focused on the idea that people were robots with human bodies, in association with an acute urinary infection. To our knowledge, this is the first case report associating urinary tract infection with Capgras-like syndrome. Awareness of the prevalence of delusional misidentification syndromes associated with acute medical illness should promote diligence on the part of clinicians in recognizing this disorder. PMID:23355784

Electrodiagnostic features of acute paralytic poliomyelitis associated with West Nile virus infection.

PubMed

Al-Shekhlee, Amer; Katirji, Bashar

2004-03-01

West Nile virus (WNV) infection is a potentially fatal disease, with meningoencephalitis being its most common neurological manifestation. Guillain-Barré syndrome (GBS) has also been described, but acute paralytic poliomyelitis has only recently been recognized. We report the clinical and electrodiagnostic findings of five patients with WNV infection, who presented with acute paralytic poliomyelitis. Three patients manifested focal asymmetrical weakness, and two had rapid ascending quadriplegia mimicking GBS. Electrodiagnostic studies during the acute illness showed normal sensory nerve action potentials, compound motor action potentials of normal or reduced amplitude, and no slowing of nerve conduction velocities. Depending on the timing of the examination, fibrillation potentials were widespread, including in those with focal weakness. Cervical magnetic resonance imaging in one patient showed abnormal T2-weighted signals in the spinal cord gray matter. On follow-up, signs of clinical improvement were seen in one patient, whereas two remained quadriplegic and ventilator-dependent 5 months after the onset. This report highlights the value of the electrodiagnostic studies in the diagnosis and prognosis of focal or generalized weakness due to acute paralytic poliomyelitis associated with WNV infection.

Respiratory infections and acute lung injury in systemic illness.

PubMed

Skerrett, S J; Niederman, M S; Fein, A M

1989-12-01

We have discussed the relationship between systemic illness, infection, and lung disease. As we have seen, patients with a wide variety of disease states, including advanced age, diabetes mellitus, alcoholism, collagen vascular disease, cancer, heart failure, and organ transplantation are potentially at increased risk for pneumonia because of disease-related impairments in host defenses. In addition, two virtually ubiquitous conditions in hospitalized patients, malnutrition and therapeutic interventions (especially with common medications), frequently add to the risk of airway invasion by bacterial pathogens. Systemic illness not only makes lung infection more common, but may adversely affect outcome and resolution, as well as determine the clinical presentation of pneumonia. In one particular population, the intubated and mechanically ventilated patient, the risk of infection is particularly high, and nosocomial pneumonia is a major cause of mortality. To the extent that the host response itself leads to the symptoms and signs of infection, systemically ill individuals may have subtle clinical features when serious bacterial invasion is present. Many components of the host defense system can become abnormal with serious illness, but a common mechanism that ties many systemic diseases to pneumonia is an alteration in airway epithelial cell receptivity for bacteria, namely, bacterial adherence, a process that mediates airway colonization, the first pathogenetic step on the road to pneumonia. The impetus for understanding how serious illness promotes lung infection is that once these mechanisms are identified, potential preventative strategies to minimize infection risk in the individual with systemic disease may be developed. The relationship among systemic illness, the lung, and infection also exists in a different direction: infection of a systemic nature (the septic syndrome) can lead to disease in the lung (ARDS). We have described the features of the septic

Prevalence of antibodies to hepatitis E virus among apparently healthy humans and pigs in Bali, Indonesia: Identification of a pig infected with a genotype 4 hepatitis E virus.

PubMed

Wibawa, I Dewa Nyoman; Muljono, David H; Mulyanto; Suryadarma, I G A; Tsuda, Fumio; Takahashi, Masaharu; Nishizawa, Tsutomu; Okamoto, Hiroaki

2004-05-01

In Indonesia where hepatitis E virus (HEV) is believed to be highly endemic, only three outbreaks of HEV transmission have been documented to date in restricted areas (West Kalimantan and East Java). A total of 1,115 serum samples collected from apparently healthy individuals in Bali, Lombok, and Surabaya in Indonesia in 1996 where epidemic HEV transmissions have never been reported, were tested for IgG class antibodies to HEV (anti-HEV). In Bali, anti-HEV was detected in 20% (54/276) of the tested population, in remarkable contrast with 4% (17/446) in Lombok and 0.5% (2/393) in Surabaya. On the other hand, antibodies to hepatitis A virus were highly prevalent in all three regions (95% in Bali, 90% in Lombok, and 89% in Surabaya). Although the majority of the population in Indonesia is Moslem, Balinese people are mostly Hindu and have a habit of consuming pork. Therefore, serum samples were obtained from the 99 farm pigs in Bali and tested for anti-HEV and HEV RNA. The sera from 71 pigs (72%) were positive for anti-HEV and a 2-month-old pig had detectable HEV RNA. The swine HEV isolate recovered from the viremic pig was named SB66-Bali. The SB66-Bali isolate was most closely related to the genotype 4 isolates from China, India, Japan, and Taiwan, but shared only 82.6-90.0% identity in the common 241-412 nucleotides within open reading frame 2 (ORF2). These results indicate that a presumably indigenous HEV strain(s) is circulating in Bali, Indonesia and that HEV infection may occur via zoonosis even in developing countries. Copyright 2004 Wiley-Liss, Inc.

Absence of Cerebrospinal Fluid Signs of Neuronal Injury Before and After Immediate Antiretroviral Therapy in Acute HIV Infection.

PubMed

Peluso, Michael J; Valcour, Victor; Ananworanich, Jintanat; Sithinamsuwan, Pasiri; Chalermchai, Thep; Fletcher, James L K; Lerdlum, Sukalya; Chomchey, Nitiya; Slike, Bonnie; Sailasuta, Napapon; Gisslén, Magnus; Zetterberg, Henrik; Spudich, Serena

2015-12-01

It is unknown whether neuronal injury begins during acute human immunodeficiency virus (HIV) infection, and whether immediate initiation of combination antiretroviral therapy (cART) prevents neuronal injury. Cerebrospinal fluid (CSF) neurofilament light chain (NFL), a measure of axonal injury, was assessed before and after cART initiation in individuals starting treatment during acute or chronic HIV infection. Nonparametric statistics examined relationships between NFL and disease progression, neuroinflammation, and cognitive performance. Before treatment, subjects with acute infection had lower CSF NFL levels, with elevations for their age in 1 of 32 subjects with acute infection (3.1%) and 10 of 32 with chronic infection (31%) (P = .006). This persisted after cART initiation, with 1 of 25 acute (4%) and 4 of 9 chronic subjects (44%) showing elevated NFL levels (P = .01). In acute infection, pre-cART NFL levels were inversely correlated with proton magnetic resonance spectroscopic findings of N-acetylaspartate/creatine in frontal gray matter (r = -0.40; P = .03), frontal white matter (r = -0.46; P = .01), and parietal gray matter (r = -0.47; P = .01); correlations persisted after treatment in the frontal white matter (r = -0.51; P = .02) and parietal gray matter (r = -0.46; P = .04). CSF NFL levels are not elevated in untreated acute HIV infection or after 6 months of immediately initiated cART but are abnormal in chronic HIV infection before and after treatment. In acute HIV infection, CSF NFL levels are inversely associated with neuroimaging markers of neuronal health. © The Author 2015. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Deriving temperature and age appropriate heart rate centiles for children with acute infections.

PubMed

Thompson, M; Harnden, A; Perera, R; Mayon-White, R; Smith, L; McLeod, D; Mant, D

2009-05-01

To describe the reference range for heart rate in children aged 3 months-10 years presenting to primary care with self-limiting infections. Cross-sectional study of children presenting to primary care with suspected acute infection. Heart rate was measured using a pulse oximeter and axillary temperature using an electronic thermometer. Centile charts of heart rates expected at given temperatures for children with self-limiting infections were calculated. Ten general practice surgeries and two out-of-hours centres in England. 1933 children presenting with suspected acute infections were recruited from in-hours general practice surgeries (1050 or 54.3%) or out-of-hours centres (883 or 45.7%). After excluding children who subsequently attended hospital and those without a final diagnosis of acute infection, 1589 children were used to create the centile charts of whom (859 or 54.1%) had upper respiratory tract infections and (215 or 13.5%) non-specific viral illness. Median, 75th, 90th and 97th centiles of heart rate at each temperature level. Heart rate increased by 9.9-14.1 bpm with each 1 degrees C increment in temperature. The 50th, 75th, 90th and 97th centiles of heart rate at each temperature level are presented graphically. Age-specific centile charts of heart rates expected at different temperatures should be used by clinicians in the initial assessment of children with acute infections. The charts will identify children who have a heart rate higher than expected for a given temperature and facilitate the interpretation of changes in heart rate on reassessment. Further research on the predictive value of the centile charts is needed to optimise their diagnostic utility.

Parvovirus B19 infection as a cause of acute myositis in an adult.

PubMed

Cakirca, Mustafa; Karatoprak, Cumali; Ugurlu, Serdal; Zorlu, Mehmet; Kıskaç, Muharrem; Çetin, Güven

2015-01-01

Parvovirus B19 infection is often asymptomatic, but clinical expressions may include transient aplastic crisis, erythema infectiosum, non-immune hydrops fetalis, and chronic red cell aplasia. This virus has also been associated with rheumatoid arthritis and other autoimmune connective tissue diseases; however, we could not identify any acute adult myositis case developed after a Parvovirus B19 infection in the literature. For this reason, we would like to present a rare case of acute myositis developed after Parvovirus B19 infection. In patients presenting with symptoms of fever, rash on the legs and myositis, viral infections such as Parvovirus B19 should be kept in mind. Copyright © 2013 Elsevier Editora Ltda. All rights reserved.

Acute and regressive scleroderma concomitant to an acute CMV primary infection.

PubMed

Goulabchand, Radjiv; Khellaf, Lakhdar; Forestier, Amandine; Costes, Valerie; Foulongne, Vincent; le Quellec, Alain; Guilpain, Philippe

2014-12-01

To describe the pathophysiological mechanisms involving cytomegalovirus (CMV) primary infection and natural killer (NK) cell expansion in the development of localized scleroderma. A 43-year-old woman presented acute erythematous discoloration and skin thickening concerning face, neck, trunk, abdomen, and the four limbs, predominantly in proximal areas. Our case did not respond to systemic sclerosis criteria diagnosis. However, skin and muscle biopsy revealed early scleroderma associated with capillary thrombi, and tissue infiltration with NK cells (CD56+/Granzyme B). Scleroderma was attributed to CMV primary infection responsible for cytolytic hepatitis (7-fold over the limit) and circulating NK cell excess. After 6 months of prednisone and a 2-year follow-up, a complete resolution of symptoms was observed. Our observation suggests a potential triggering role of CMV primary infection in the development of scleroderma. Histological features from our observation addresses the role of CMV and NK cells in the development of endothelial damage and fibrotic process. Copyright © 2014 Elsevier B.V. All rights reserved.

Clustering behavior in microbial communities from acute endodontic infections.

PubMed

Montagner, Francisco; Jacinto, Rogério C; Signoretti, Fernanda G C; Sanches, Paula F; Gomes, Brenda P F A

2012-02-01

Acute endodontic infections harbor heterogeneous microbial communities in both the root canal (RC) system and apical tissues. Data comparing the microbial structure and diversity in endodontic infections in related ecosystems, such as RC with necrotic pulp and acute apical abscess (AAA), are scarce in the literature. The aim of this study was to examine the presence of selected endodontic pathogens in paired samples from necrotic RC and AAA using polymerase chain reaction (PCR) followed by the construction of cluster profiles. Paired samples of RC and AAA exudates were collected from 20 subjects and analyzed by PCR for the presence of selected strict and facultative anaerobic strains. The frequency of species was compared between the RC and the AAA samples. A stringent neighboring clustering algorithm was applied to investigate the existence of similar high-order groups of samples. A dendrogram was constructed to show the arrangement of the sample groups produced by the hierarchical clustering. All samples harbored bacterial DNA. Porphyromonas endodontalis, Prevotella nigrescens, Filifactor alocis, and Tannerela forsythia were frequently detected in both RC and AAA samples. The selected anaerobic species were distributed in diverse small bacteria consortia. The samples of RC and AAA that presented at least one of the targeted microorganisms were grouped in small clusters. Anaerobic species were frequently detected in acute endodontic infections and heterogeneous microbial communities with low clustering behavior were observed in paired samples of RC and AAA. Copyright © 2012. Published by Elsevier Inc.

Procalcitonin cannot be used as a biomarker of infection in heart surgery patients with acute kidney injury.

PubMed

Heredia-Rodríguez, María; Bustamante-Munguira, Juan; Fierro, Inmaculada; Lorenzo, Mario; Jorge-Monjas, Pablo; Gómez-Sánchez, Esther; Álvarez, Francisco J; Bergese, Sergio D; Eiros, José María; Bermejo-Martin, Jesús F; Gómez-Herreras, José I; Tamayo, Eduardo

2016-06-01

We intended to assess how acute kidney injuy impacts on procalcitonin levels in cardiac surgery patients, with or without infection, and whether procalcitonin might be used as a biomarker of infection in acute kidney injuy. A case-control study was designed which included patients that had had cardiac surgery between January 2011 and January 2015. Every patient developing severe sepsis or septic shock (n = 122; 5.5%) was enrolled. In addition, consecutive cardiac surgery patients during 2013 developing systemic inflammatory response syndrome (n = 318) were enrolled. Those recruited 440 patients were divided into 2 groups, according to renal function. Median procalcitonin levels were significantly higher during the 10 postoperative days in the acute kidney injury patients. Regression analysis showed that postoperatory day, creatinine, white blood cells and infection were significantly (P < .0001) associated to serum procalcitonin level. In patients with creatinine ≥2, median procalcitonin levels were similar in infected and non-infected patients. Only when creatinine was less than 2 mg/L, the median procalcitonin levels were significantly higher in patients with infection, as compared to those with no infection. In acute kidney injuy patients, high procalcitonin levels are a marker of acute kidney injuy but will not be able to differentiate infected from non-infected patients. Copyright © 2016 Elsevier Inc. All rights reserved.

Common Cold - an Umbrella Term for Acute Infections of Nose, Throat, Larynx and Bronchi.

PubMed

Kardos, P; Malek, F A

2017-04-01

Acute respiratory tract infections, i. e. rhinitis, sinusitis, pharyngitis, laryngitis, bronchitis, belong to the most common medical conditions with a high economic burden. Nonetheless, there is little agreement concerning their differential diagnosis.This paper will discuss to what extent different anatomical sites of acute respiratory tract infections can be uniquely identified or whether the overlap and consecutive development in signs and symptoms renders these distinctions meaningless.Acute respiratory tract infections are variable but definition of diagnostic categories based on the anatomical sites of the dominant complaints shows that signs and symptoms both overlap to a great extent and/or emerge successively. Thus, in common cold distinguishing between acute symptom-based diagnoses arising from different anatomical sites of the aerodigestive system remains elusive. Therefore, preferred symptomatic treatments should foster a resolution of all possible symptoms as opposed to an isolated treatment of a single symptom (e. g. mucus hypersecretion) according to the presumed anatomical site (i. e. acute bronchitis). © Georg Thieme Verlag KG Stuttgart · New York.

Sputum colour for diagnosis of a bacterial infection in patients with acute cough.

PubMed

Altiner, Attila; Wilm, Stefan; Däubener, Walter; Bormann, Christiane; Pentzek, Michael; Abholz, Heinz-Harald; Scherer, Martin

2009-01-01

Sputum colour plays an important role in the disease concepts for acute cough, both in the patients' and the doctors' view. However, it is unclear whether the sputum colour can be used for diagnosis of a bacterial infection. Cross-sectional study. A total of 42 GP practices in Dusseldorf, Germany. Sputum samples obtained from 241 patients suffering from an episode of acute cough seeing their doctor within a routine consultation. Relation of sputum colour and microbiological proof of bacterial infection defined as positive culture and at least a moderate number of leucocytes per low magnification field. In 28 samples (12%) a bacterial infection was proven. Yellowish or greenish colour of the sputum sample and bacterial infection showed a significant correlation (p = 0.014, Fisher's exact test). The sensitivity of yellowish or greenish sputum used as a test for a bacterial infection was 0.79 (95% CI 0.63-0.94); the specificity was 0.46 (95% CI 0.038-0.53). The positive likelihood-ratio (+LR) was 1.46 (95% CI 1.17-1.85). The sputum colour of patients with acute cough and no underlying chronic lung disease does not imply therapeutic consequences such as prescription of antibiotics.

Serum Metabolic Profiling of Oocyst-Induced Toxoplasma gondii Acute and Chronic Infections in Mice Using Mass-Spectrometry

PubMed Central

Zhou, Chun-Xue; Cong, Wei; Chen, Xiao-Qing; He, Shen-Yi; Elsheikha, Hany M.; Zhu, Xing-Quan

2018-01-01

Toxoplasma gondii is an obligate intracellular parasite causing severe diseases in immunocompromised individuals and congenitally infected neonates, such as encephalitis and chorioretinitis. This study aimed to determine whether serum metabolic profiling can (i) identify metabolites associated with oocyst-induced T. gondii infection and (ii) detect systemic metabolic differences between T. gondii-infected mice and controls. We performed the first global metabolomics analysis of mice serum challenged with 100 sporulated T. gondii Pru oocysts (Genotype II). Sera from acutely infected mice (11 days post-infection, dpi), chronically infected mice (33 dpi) and control mice were collected and analyzed using LC-MS/MS platform. Following False Discovery Rate filtering, we identified 3871 and 2825 ions in ESI+ or ESI− mode, respectively. Principal Component Analysis (PCA) and Partial Least Squares Discriminant Analysis (PLS-DA) identified metabolomic profiles that clearly differentiated T. gondii-infected and -uninfected serum samples. Acute infection significantly influenced the serum metabolome. Our results identified common and uniquely perturbed metabolites and pathways. Acutely infected mice showed perturbations in metabolites associated with glycerophospholipid metabolism, biosynthesis of amino acid, and tyrosine metabolism. These findings demonstrated that acute T. gondii infection induces a global perturbation of mice serum metabolome, providing new insights into the mechanisms underlying systemic metabolic changes during early stage of T. gondii infection. PMID:29354104

Parents' Expectations and Experiences of Antibiotics for Acute Respiratory Infections in Primary Care.

PubMed

Coxeter, Peter D; Mar, Chris Del; Hoffmann, Tammy C

2017-03-01

Primary care visits for children with acute respiratory infections frequently result in antibiotic prescriptions, although antibiotics have limited benefits for common acute respiratory infections and can cause harms, including antibiotic resistance. Parental demands are often blamed for antibiotic prescription. We aimed to explore parents' beliefs about antibiotic necessity, quantify their expectations of antibiotic benefit, and report experiences of other management options and exposure to and preferences for shared decision making. We conducted computer-assisted telephone interviews in an Australia-wide community sample of primary caregivers, hereafter referred to as parents, of children aged 1 to 12 years, using random digit dialing of household landline telephones. Of the 14,505 telephone numbers called, 10,340 were eligible numbers; 589 potentially eligible parents were reached, of whom 401 were interviewed. Most believed antibiotics provide benefits for common acute respiratory infections, especially for acute otitis media (92%), although not using them, particularly for acute cough and sore throat, was sometimes acceptable. Parents grossly overestimated the mean benefit of antibiotics on illness symptom duration by 5 to 10 times, and believed they reduce the likelihood of complications. The majority, 78%, recognized antibiotics may cause harm. Recalling the most recent relevant doctor visit, 44% of parents reported at least some discussion about why antibiotics might be used; shared decision making about antibiotic use was inconsistent, while 75% wanted more involvement in future decisions. Some parents have misperceptions about antibiotic use for acute respiratory infections, highlighting the need for improved communication during visits, including shared decision making to address overoptimistic expectations of antibiotics. Such communication should be one of several strategies that is used to reduce antibiotic use. © 2017 Annals of Family Medicine, Inc.

Parents’ Expectations and Experiences of Antibiotics for Acute Respiratory Infections in Primary Care

PubMed Central

Coxeter, Peter D.; Mar, Chris Del; Hoffmann, Tammy C.

2017-01-01

PURPOSE Primary care visits for children with acute respiratory infections frequently result in antibiotic prescriptions, although antibiotics have limited benefits for common acute respiratory infections and can cause harms, including antibiotic resistance. Parental demands are often blamed for antibiotic prescription. We aimed to explore parents’ beliefs about antibiotic necessity, quantify their expectations of antibiotic benefit, and report experiences of other management options and exposure to and preferences for shared decision making. METHODS We conducted computer-assisted telephone interviews in an Australia-wide community sample of primary caregivers, hereafter referred to as parents, of children aged 1 to 12 years, using random digit dialing of household landline telephones. RESULTS Of the 14,505 telephone numbers called, 10,340 were eligible numbers; 589 potentially eligible parents were reached, of whom 401 were interviewed. Most believed antibiotics provide benefits for common acute respiratory infections, especially for acute otitis media (92%), although not using them, particularly for acute cough and sore throat, was sometimes acceptable. Parents grossly overestimated the mean benefit of antibiotics on illness symptom duration by 5 to 10 times, and believed they reduce the likelihood of complications. The majority, 78%, recognized antibiotics may cause harm. Recalling the most recent relevant doctor visit, 44% of parents reported at least some discussion about why antibiotics might be used; shared decision making about antibiotic use was inconsistent, while 75% wanted more involvement in future decisions. CONCLUSIONS Some parents have misperceptions about antibiotic use for acute respiratory infections, highlighting the need for improved communication during visits, including shared decision making to address overoptimistic expectations of antibiotics. Such communication should be one of several strategies that is used to reduce antibiotic use

Procalcitonin Testing to Guide Antibiotic Therapy in Acute Upper and Lower Respiratory Tract Infections.

PubMed

Schuetz, Philipp; Wirz, Yannick; Mueller, Beat

2018-03-06

Is the use of procalcitonin for guiding antibiotic decisions in patients with acute upper and lower respiratory tract infections associated with improved clinical outcomes compared with usual care? Among patients with varying types and severity of acute respiratory infection, using procalcitonin to guide decisions about antibiotics is associated with lower rates of antibiotic exposure, antibiotic-related adverse effects, and mortality.

Presentation and antimicrobial treatment of acute orofacial infections in general dental practice.

PubMed

Lewis, M A; Meechan, C; MacFarlane, T W; Lamey, P J; Kay, E

1989-01-21

Information on the presentation of orofacial infections and the use of antimicrobial agents in general dental practice in the United Kingdom was obtained using a postal questionnaire. Six hundred dentists were randomly selected and a total of 340 replies were received, giving a response rate of 57%. The dental practitioners estimated that acute infection was present in only a minority (approximately 5%) of patients. A total of seven different antibiotics were prescribed, in a variety of regimens, for the treatment of bacterial infection. However, the majority of dentists (46-62%) preferred a 5-day course of penicillin (250 mg, qid) for bacterial conditions other than acute ulcerative gingivitis, for which most practitioners (89%) prescribed 3 days of metronidazole (200 mg, tid). Nystatin was the most frequently selected anticandidal agent and topical acyclovir the most popular therapy for Herpes simplex infection.