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Sicilia P, Fantilli AC, Cuba F, Di Cola G, Barbás MG, Poklepovich T, Ré VE, Castro G, Pisano MB. Novel strategy for whole-genome sequencing of hepatitis A virus using NGS illumina technology and phylogenetic comparison with partial VP1/2A genomic region. Sci Rep 2025; 15:6375. [PMID: 39984720 PMCID: PMC11845616 DOI: 10.1038/s41598-025-91116-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/18/2024] [Accepted: 02/18/2025] [Indexed: 02/23/2025] Open
Abstract
Molecular epidemiology of hepatitis A virus (HAV) plays a critical role in identifying outbreak origin and conducting surveillance. Although it is mostly carried out using short partial VP1/2A genomic sequences, utilizing whole-genome sequences (WGS) provides more accurate and robust information. We developed an amplicon-based next-generation sequencing (NGS) strategy to obtain complete HAV genomes utilizing the COVIDSeq Test (Illumina). Twenty-five primer pairs were designed and used to amplify partial genomic fragments (400 bp) that comprise the entire HAV genome sequence from previously HAV positive serum and stool samples from Argentina. The DNA library was prepared using the Illumina COVIDSeq Test and sequenced in a MiSeq equipment. Phylogenetic analyses were performed with IQ-Tree using WGS and VP1/2A partial sequences of 1084pb and 422pb. Eleven samples were amplified and sequenced, with coverage between 79.3 and 100% (> 90% in 9 samples). Although phylogenetic analyses of partial sequences allowed genotype and subgenotype identification, WGS analyses yielded more accurate and reliable results for the phylogeny (phylogenetic definition). The amplicon-based NGS WGS tool developed by adapting the COVIDSeq test to HAV proved to be efficient. The study of partial VP1/2A regions (mainly the 1084 bp fragment) would constitute useful alternatives for outbreak investigation and surveillance when WGS could not be performed.
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Affiliation(s)
- Paola Sicilia
- Departamento Laboratorio Central de la Provincia de Córdoba, Ministerio de Salud, Gobierno de la Provincia de Córdoba. Tránsito Cáceres de Allende 421, X5000HVE, Córdoba, Argentina
| | - Anabella Clara Fantilli
- Instituto de Virología "Dr. J. M. Vanella", CONICET, Facultad de Ciencias Médicas, Universidad Nacional de Córdoba, Enfermera Gordillo Gómez s/n, Ciudad Universitaria, CP5016, Córdoba, Argentina
| | - Facundo Cuba
- Unidad Operativa Centro Nacional de Genómica y Bioinformática - ANLIS "Dr. Carlos G. Malbrán", Av. Vélez Sarsfield 563, C1282 AFF, Ciudad Autónoma de Buenos Aires (CABA), Argentina
| | - Guadalupe Di Cola
- Instituto de Virología "Dr. J. M. Vanella", CONICET, Facultad de Ciencias Médicas, Universidad Nacional de Córdoba, Enfermera Gordillo Gómez s/n, Ciudad Universitaria, CP5016, Córdoba, Argentina
| | - María Gabriela Barbás
- Departamento Laboratorio Central de la Provincia de Córdoba, Ministerio de Salud, Gobierno de la Provincia de Córdoba. Tránsito Cáceres de Allende 421, X5000HVE, Córdoba, Argentina
| | - Tomás Poklepovich
- Unidad Operativa Centro Nacional de Genómica y Bioinformática - ANLIS "Dr. Carlos G. Malbrán", Av. Vélez Sarsfield 563, C1282 AFF, Ciudad Autónoma de Buenos Aires (CABA), Argentina
| | - Viviana Elizabeth Ré
- Instituto de Virología "Dr. J. M. Vanella", CONICET, Facultad de Ciencias Médicas, Universidad Nacional de Córdoba, Enfermera Gordillo Gómez s/n, Ciudad Universitaria, CP5016, Córdoba, Argentina
| | - Gonzalo Castro
- Departamento Laboratorio Central de la Provincia de Córdoba, Ministerio de Salud, Gobierno de la Provincia de Córdoba. Tránsito Cáceres de Allende 421, X5000HVE, Córdoba, Argentina
- Instituto de Virología "Dr. J. M. Vanella", CONICET, Facultad de Ciencias Médicas, Universidad Nacional de Córdoba, Enfermera Gordillo Gómez s/n, Ciudad Universitaria, CP5016, Córdoba, Argentina
| | - María Belén Pisano
- Instituto de Virología "Dr. J. M. Vanella", CONICET, Facultad de Ciencias Médicas, Universidad Nacional de Córdoba, Enfermera Gordillo Gómez s/n, Ciudad Universitaria, CP5016, Córdoba, Argentina.
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Amponsah-Dacosta E, Ratshisusu L, Modise LM, Blose N, Simani OE, Selabe SG, Kagina BM, Muloiwa R. Hepatitis A Seroprevalence Among HIV-Exposed and Unexposed Pediatric Populations in South Africa. Vaccines (Basel) 2024; 12:1276. [PMID: 39591179 PMCID: PMC11598911 DOI: 10.3390/vaccines12111276] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/11/2024] [Revised: 10/30/2024] [Accepted: 11/08/2024] [Indexed: 11/28/2024] Open
Abstract
Background: There is limited evidence comparing hepatitis A seroprevalence among HIV-exposed uninfected (HEU), HIV-infected (HIV), and unexposed uninfected (HUU) children. This compromises rational vaccine decision-making. Methods: This study comprised a retrospective health facility-based population of children aged 1 month-12 years. Archival sera were tested for markers of acute (anti-HAV IgM) or past (total anti-HAV) HAV infection. Subgroup analysis was conducted based on perinatal HIV exposure or infection status. Results: Among 513 children, the median age was 10 (IQR: 4-25) months. The median maternal age was 29 (IQR: 25-34) years. An anti-HAV seropositivity of 95.1% (117/122 [95% CI 90.2-98.4]) was found among those ≤6 months of age, indicative of the rate of transplacental antibody transfer. Among 1-12-year-olds, hepatitis A seroprevalence was 19.3% (37/192 [95% CI 14.1-25.7]), while 1.1% (2/188 [95% CI 0.12-2.76]) had evidence of acute infection. Compared to HIV-exposed subgroups (HIV = 60%, 6/10 [95% CI 27.4-86.3] and HEU = 45%, 9/20 [95% CI 23.8-68]), hepatitis A seroprevalence among HUU children was low (29.2%, 47/161 [95% CI 22.4-37.0]). Conclusions: Natural immunity among HIV-exposed and unexposed children in South Africa is insufficient to protect against severe liver complications associated with HAV infection later in adulthood.
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Affiliation(s)
- Edina Amponsah-Dacosta
- Vaccines for Africa Initiative, School of Public Health, Faculty of Health Sciences, University of Cape Town, Cape Town 7925, South Africa; (B.M.K.); (R.M.)
| | - Lufuno Ratshisusu
- HIV and Hepatitis Research Unit, Department of Virology, Sefako Makgatho Health Sciences University, Pretoria 0208, South Africa; (L.R.); (L.M.M.); (O.E.S.); (S.G.S.)
| | - Lorato M. Modise
- HIV and Hepatitis Research Unit, Department of Virology, Sefako Makgatho Health Sciences University, Pretoria 0208, South Africa; (L.R.); (L.M.M.); (O.E.S.); (S.G.S.)
| | | | - Omphile E. Simani
- HIV and Hepatitis Research Unit, Department of Virology, Sefako Makgatho Health Sciences University, Pretoria 0208, South Africa; (L.R.); (L.M.M.); (O.E.S.); (S.G.S.)
| | - Selokela G. Selabe
- HIV and Hepatitis Research Unit, Department of Virology, Sefako Makgatho Health Sciences University, Pretoria 0208, South Africa; (L.R.); (L.M.M.); (O.E.S.); (S.G.S.)
- National Health Laboratory Service, Sefako Makgatho Health Sciences University, Pretoria 0208, South Africa
| | - Benjamin M. Kagina
- Vaccines for Africa Initiative, School of Public Health, Faculty of Health Sciences, University of Cape Town, Cape Town 7925, South Africa; (B.M.K.); (R.M.)
| | - Rudzani Muloiwa
- Vaccines for Africa Initiative, School of Public Health, Faculty of Health Sciences, University of Cape Town, Cape Town 7925, South Africa; (B.M.K.); (R.M.)
- Department of Paediatrics and Child Health, Faculty of Health Sciences, University of Cape Town, Cape Town 7925, South Africa
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Zufan SE, Mercoulia K, Kwong JC, Judd LM, Howden BP, Seemann T, Stinear TP. High-performance enrichment-based genome sequencing to support the investigation of hepatitis A virus outbreaks. Microbiol Spectr 2024; 12:e0283423. [PMID: 38018979 PMCID: PMC10783085 DOI: 10.1128/spectrum.02834-23] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/24/2023] [Accepted: 10/14/2023] [Indexed: 11/30/2023] Open
Abstract
IMPORTANCE This proof-of-concept study introduces a hybrid capture oligo panel for whole-genome sequencing of all six human pathogenic hepatitis A virus (HAV) subgenotypes, exhibiting a higher sensitivity than some conventional genotyping assays. The ability of hybrid capture to enrich multiple targets allows for a single, streamlined workflow, thus facilitating the potential harmonization of molecular surveillance of HAV with other enteric viruses. Even challenging sample matrices can be accommodated, making them suitable for broad implementation in clinical and public health laboratories. This innovative approach has significant implications for enhancing multijurisdictional outbreak investigations as well as our understanding of the global diversity and transmission dynamics of HAV.
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Affiliation(s)
- Sara E. Zufan
- The Center for Pathogen Genomics, The University of Melbourne, Melbourne, Victoria, Australia
- Department of Microbiology and Immunology, The University of Melbourne at the Peter Doherty Institute for Infection and Immunity, Melbourne, Victoria, Australia
| | - Karolina Mercoulia
- Department of Microbiology and Immunology, The University of Melbourne at the Peter Doherty Institute for Infection and Immunity, Melbourne, Victoria, Australia
- Microbiological Diagnostic Unit Public Health Laboratory, The University of Melbourne at the Peter Doherty Institute for Infection and Immunity, Melbourne, Victoria, Australia
| | - Jason C. Kwong
- Department of Infectious Diseases, Austin Health, Heidelberg, Victoria, Australia
- Department of Infectious Diseases, The University of Melbourne at the Peter Doherty Institute for Infection and Immunity, Melbourne, Victoria, Australia
| | - Louise M. Judd
- Department of Microbiology and Immunology, The University of Melbourne at the Peter Doherty Institute for Infection and Immunity, Melbourne, Victoria, Australia
- Doherty Applied Microbial Genomics, The University of Melbourne at the Peter Doherty Institute for Infection and Immunity, Melbourne, Victoria, Australia
| | - Benjamin P. Howden
- The Center for Pathogen Genomics, The University of Melbourne, Melbourne, Victoria, Australia
- Department of Microbiology and Immunology, The University of Melbourne at the Peter Doherty Institute for Infection and Immunity, Melbourne, Victoria, Australia
- Microbiological Diagnostic Unit Public Health Laboratory, The University of Melbourne at the Peter Doherty Institute for Infection and Immunity, Melbourne, Victoria, Australia
| | - Torsten Seemann
- The Center for Pathogen Genomics, The University of Melbourne, Melbourne, Victoria, Australia
- Department of Microbiology and Immunology, The University of Melbourne at the Peter Doherty Institute for Infection and Immunity, Melbourne, Victoria, Australia
| | - Timothy P. Stinear
- The Center for Pathogen Genomics, The University of Melbourne, Melbourne, Victoria, Australia
- Department of Microbiology and Immunology, The University of Melbourne at the Peter Doherty Institute for Infection and Immunity, Melbourne, Victoria, Australia
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Fallucca A, Restivo V, Sgariglia MC, Roveta M, Trucchi C. Hepatitis a Vaccine as Opportunity of Primary Prevention for Food Handlers: A Narrative Review. Vaccines (Basel) 2023; 11:1271. [PMID: 37515087 PMCID: PMC10383099 DOI: 10.3390/vaccines11071271] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/29/2023] [Revised: 07/17/2023] [Accepted: 07/18/2023] [Indexed: 07/30/2023] Open
Abstract
The hepatitis A virus (HAV) is still a leading cause of viral hepatitis worldwide. After a long incubation period, the clinical manifestations range from asymptomatic infection to acute liver failure. The severity of the disease increases with age and pre-existing liver disease. The transmission is mainly via person-to-person contact or ingestion of contaminated food or water. Food contamination can occur at any step of the food chain, especially when infected people handle not-heated or otherwise-treated food. HAV is endemic in low-income countries because of poor sanitary and sociodemographic conditions. The populations of developed countries are highly susceptible, and large outbreaks occur when HAV is introduced from endemic countries due to globalization, travel, and movement of foodstuffs. HAV prevention includes hygiene practices, immunoglobulins, and vaccination. Safe and effective inactivated and live attenuated vaccines are available and provide long-term protection. The vaccine targets are children and subjects at increased risk of HAV exposure or serious clinical outcomes. This review discusses the critical role of food handlers in the spread of HAV and the opportunity for food industry employers to consider food handler immunization a tool to manage both food safety in compliance with HACCP principles and food operators' biologic risk.
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Affiliation(s)
- Alessandra Fallucca
- Department of Health Promotion, Maternal and Infant Care, Internal Medicine and Medical Specialties (PROMISE) “G. D’Alessandro”, University of Palermo, 90127 Palermo, Italy
| | - Vincenzo Restivo
- Department of Health Promotion, Maternal and Infant Care, Internal Medicine and Medical Specialties (PROMISE) “G. D’Alessandro”, University of Palermo, 90127 Palermo, Italy
| | | | - Marco Roveta
- Food Hygiene and Nutrition Service, Department of Prevention, Local Health Unit 3, 16142 Genoa, Italy
| | - Cecilia Trucchi
- Food Hygiene and Nutrition Service, Department of Prevention, Local Health Unit 3, 16142 Genoa, Italy
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5
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Genotyping and Molecular Diagnosis of Hepatitis A Virus in Human Clinical Samples Using Multiplex PCR-Based Next-Generation Sequencing. Microorganisms 2022; 10:microorganisms10010100. [PMID: 35056549 PMCID: PMC8779169 DOI: 10.3390/microorganisms10010100] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/26/2021] [Revised: 12/17/2021] [Accepted: 12/23/2021] [Indexed: 02/04/2023] Open
Abstract
Hepatitis A virus (HAV) is a serious threat to public health worldwide. We used multiplex polymerase chain reaction (PCR)-based next-generation sequencing (NGS) to derive information on viral genetic diversity and conduct precise phylogenetic analysis. Four HAV genome sequences were obtained using multiplex PCR-based NGS. HAV whole-genome sequence of one sample was obtained by conventional Sanger sequencing. The HAV strains demonstrated a geographic cluster with sub-genotype IA strains in the Republic of Korea. The phylogenetic pattern of HAV viral protein (VP) 3 region showed no phylogenetic conflict between the whole-genome and partial-genome sequences. The VP3 region in serum and stool samples showed sensitive detection of HAV with differences of quantification that did not exceed <10 copies/μL than the consensus VP4 region using quantitative PCR (qPCR). In conclusion, multiplex PCR-based NGS was implemented to define HAV genotypes using nearly whole-genome sequences obtained directly from hepatitis A patients. The VP3 region might be a potential candidate for tracking the genotypic origin of emerging HAV outbreaks. VP3-specific qPCR was developed for the molecular diagnosis of HAV infection. This study may be useful to predict for the disease management and subsequent development of hepatitis A infection at high risk of severe illness.
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Ramachandran S, Xia GL, Dimitrova Z, Lin Y, Montgomery M, Augustine R, Kamili S, Khudyakov Y. Changing Molecular Epidemiology of Hepatitis A Virus Infection, United States, 1996-2019. Emerg Infect Dis 2021; 27:1742-1745. [PMID: 34013865 PMCID: PMC8153864 DOI: 10.3201/eid2706.203036] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/19/2022] Open
Abstract
Hepatitis A virus (HAV) genotype IA was most common among strains tested in US outbreak investigations and surveillance during 1996-2015. However, HAV genotype IB gained prominence during 2016-2019 person-to-person multistate outbreaks. Detection of previously uncommon strains highlights the changing molecular epidemiology of HAV infection in the United States.
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7
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Lee D, Cho S, Chae S, Choi W, Han M. Evaluation of a test method to detect hepatitis A virus in salted shellfish. J Food Saf 2021. [DOI: 10.1111/jfs.12883] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/28/2022]
Affiliation(s)
- Deog‐Yong Lee
- Division of Viral Diseases, Center for Laboratory Control of Infectious Diseases Korea Disease Control and Prevention Agency Cheonhju Republic of Korea
| | - Seung‐Rye Cho
- Division of Viral Diseases, Center for Laboratory Control of Infectious Diseases Korea Disease Control and Prevention Agency Cheonhju Republic of Korea
| | - Su‐Jin Chae
- Division of Viral Diseases, Center for Laboratory Control of Infectious Diseases Korea Disease Control and Prevention Agency Cheonhju Republic of Korea
| | - Wooyoung Choi
- Division of Viral Diseases, Center for Laboratory Control of Infectious Diseases Korea Disease Control and Prevention Agency Cheonhju Republic of Korea
| | - Myung‐Guk Han
- Division of Viral Diseases, Center for Laboratory Control of Infectious Diseases Korea Disease Control and Prevention Agency Cheonhju Republic of Korea
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8
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Nelson NP, Weng MK, Hofmeister MG, Moore KL, Doshani M, Kamili S, Koneru A, Haber P, Hagan L, Romero JR, Schillie S, Harris AM. Prevention of Hepatitis A Virus Infection in the United States: Recommendations of the Advisory Committee on Immunization Practices, 2020. MMWR Recomm Rep 2020; 69:1-38. [PMID: 32614811 PMCID: PMC8631741 DOI: 10.15585/mmwr.rr6905a1] [Citation(s) in RCA: 119] [Impact Index Per Article: 23.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022] Open
Abstract
HEPATITIS A IS A VACCINE-PREVENTABLE, COMMUNICABLE DISEASE OF THE LIVER CAUSED BY THE HEPATITIS A VIRUS (HAV). THE INFECTION IS TRANSMITTED VIA THE FECAL-ORAL ROUTE, USUALLY FROM DIRECT PERSON-TO-PERSON CONTACT OR CONSUMPTION OF CONTAMINATED FOOD OR WATER. HEPATITIS A IS AN ACUTE, SELF-LIMITED DISEASE THAT DOES NOT RESULT IN CHRONIC INFECTION. HAV ANTIBODIES (IMMUNOGLOBULIN G [IGG] ANTI-HAV) PRODUCED IN RESPONSE TO HAV INFECTION PERSIST FOR LIFE AND PROTECT AGAINST REINFECTION; IGG ANTI-HAV PRODUCED AFTER VACCINATION CONFER LONG-TERM IMMUNITY. THIS REPORT SUPPLANTS AND SUMMARIZES PREVIOUSLY PUBLISHED RECOMMENDATIONS FROM THE ADVISORY COMMITTEE ON IMMUNIZATION PRACTICES (ACIP) REGARDING THE PREVENTION OF HAV INFECTION IN THE UNITED STATES. ACIP RECOMMENDS ROUTINE VACCINATION OF CHILDREN AGED 12-23 MONTHS AND CATCH-UP VACCINATION FOR CHILDREN AND ADOLESCENTS AGED 2-18 YEARS WHO HAVE NOT PREVIOUSLY RECEIVED HEPATITIS A (HEPA) VACCINE AT ANY AGE. ACIP RECOMMENDS HEPA VACCINATION FOR ADULTS AT RISK FOR HAV INFECTION OR SEVERE DISEASE FROM HAV INFECTION AND FOR ADULTS REQUESTING PROTECTION AGAINST HAV WITHOUT ACKNOWLEDGMENT OF A RISK FACTOR. THESE RECOMMENDATIONS ALSO PROVIDE GUIDANCE FOR VACCINATION BEFORE TRAVEL, FOR POSTEXPOSURE PROPHYLAXIS, IN SETTINGS PROVIDING SERVICES TO ADULTS, AND DURING OUTBREAKS.
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Probert WS, Gonzalez C, Espinosa A, Hacker JK. Molecular Genotyping of Hepatitis A Virus, California, USA, 2017-2018. Emerg Infect Dis 2019; 25:1594-1596. [PMID: 31310213 PMCID: PMC6649344 DOI: 10.3201/eid2508.181489] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022] Open
Abstract
We implemented subgenomic and whole-genome sequencing to support the investigation of a large hepatitis A virus outbreak among persons experiencing homelessness, users of illicit drugs, or both in California, USA, during 2017-2018. Genotyping data helped confirm case-patients, track chains of transmission, and monitor the effectiveness of public health control measures.
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Ciccozzi M, Lai A, Zehender G, Borsetti A, Cella E, Ciotti M, Sagnelli E, Sagnelli C, Angeletti S. The phylogenetic approach for viral infectious disease evolution and epidemiology: An updating review. J Med Virol 2019; 91:1707-1724. [PMID: 31243773 DOI: 10.1002/jmv.25526] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/13/2019] [Accepted: 06/24/2019] [Indexed: 12/16/2022]
Abstract
In the last decade, the phylogenetic approach is recurrent in molecular evolutionary analysis. On 12 May, 2019, about 2 296 213 papers are found, but typing "phylogeny" or "epidemiology AND phylogeny" only 199 804 and 20 133 are retrieved, respectively. Molecular epidemiology in infectious diseases is widely used to define the source of infection as so as the ancestral relationships of individuals sampled from a population. Coalescent theory and phylogeographic analysis have had scientific application in several, recent pandemic events, and nosocomial outbreaks. Hepatitis viruses and immunodeficiency virus (human immunodeficiency virus) have been largely studied. Phylogenetic analysis has been recently applied on Polyomaviruses so as in the more recent outbreaks due to different arboviruses type as Zika and chikungunya viruses discovering the source of infection and the geographic spread. Data on sequences isolated by the microorganism are essential to apply the phylogenetic tools and research in the field of infectious disease phylodinamics is growing up. There is the need to apply molecular phylogenetic and evolutionary methods in areas out of infectious diseases, as translational genomics and personalized medicine. Lastly, the application of these tools in vaccine strategy so as in antibiotic and antiviral researchers are encouraged.
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Affiliation(s)
- Massimo Ciccozzi
- Unit of Medical Statistics and Molecular Epidemiology, University Campus Bio-Medico of Rome, Rome, Italy
| | - Alessia Lai
- Department of Biomedical and Clinical Sciences 'L. Sacco', University of Milan, Milan, Italy
| | - Gianguglielmo Zehender
- Department of Biomedical and Clinical Sciences 'L. Sacco', University of Milan, Milan, Italy
| | - Alessandra Borsetti
- National HIV/AIDS Research Center, Istituto Superiore di Sanità, Roma, Italy
| | - Eleonora Cella
- Unit of Medical Statistics and Molecular Epidemiology, University Campus Bio-Medico of Rome, Rome, Italy
| | - Marco Ciotti
- Laboratory of Molecular Virology, Polyclinic Tor Vergata Foundation, Rome, Italy
| | - Evangelista Sagnelli
- Department of Mental Health and Public Medicine, Section of Infectious Diseases, University of Campania Luigi Vanvitelli, Naples, Italy
| | - Caterina Sagnelli
- Department of Mental Health and Public Medicine, Section of Infectious Diseases, University of Campania Luigi Vanvitelli, Naples, Italy
| | - Silvia Angeletti
- Unit of Clinical Laboratory Science, University Campus Bio-Medico of Rome, Rome, Italy
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Hofmeister MG, Foster MA, Teshale EH. Epidemiology and Transmission of Hepatitis A Virus and Hepatitis E Virus Infections in the United States. Cold Spring Harb Perspect Med 2019; 9:a033431. [PMID: 29712684 PMCID: PMC6444696 DOI: 10.1101/cshperspect.a033431] [Citation(s) in RCA: 24] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/22/2022]
Abstract
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.
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Affiliation(s)
- Megan G Hofmeister
- Division of Viral Hepatitis, Centers for Disease Control and Prevention, Atlanta, Georgia 30329
- Epidemic Intelligence Service, Centers for Disease Control and Prevention, Atlanta, Georgia 30329
| | - Monique A Foster
- Division of Viral Hepatitis, Centers for Disease Control and Prevention, Atlanta, Georgia 30329
| | - Eyasu H Teshale
- Division of Viral Hepatitis, Centers for Disease Control and Prevention, Atlanta, Georgia 30329
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12
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Foster M, Ramachandran S, Myatt K, Donovan D, Bohm S, Fiedler J, Barbeau B, Collins J, Thoroughman D, McDonald E, Ballard J, Eason J, Jorgensen C. Hepatitis A Virus Outbreaks Associated with Drug Use and Homelessness - California, Kentucky, Michigan, and Utah, 2017. MMWR-MORBIDITY AND MORTALITY WEEKLY REPORT 2018; 67:1208-1210. [PMID: 30383739 PMCID: PMC6319801 DOI: 10.15585/mmwr.mm6743a3] [Citation(s) in RCA: 93] [Impact Index Per Article: 13.3] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Indexed: 12/19/2022]
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Public health investigation and response to a hepatitis A outbreak from imported scallops consumed raw—Hawaii, 2016. Epidemiol Infect 2018; 147:e28. [DOI: 10.1017/s0950268818002844] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/06/2022] Open
Abstract
Abstract
During the summer of 2016, the Hawaii Department of Health responded to the second-largest domestic foodborne hepatitis A virus (HAV) outbreak in the post-vaccine era. The epidemiological investigation included case finding and investigation, sequencing of RNA positive clinical specimens, product trace-back and virologic testing and sequencing of HAV RNA from the product. Additionally, an online survey open to all Hawaii residents was conducted to estimate baseline commercial food consumption. We identified 292 confirmed HAV cases, of whom 11 (4%) were possible secondary cases. Seventy-four (25%) were hospitalised and there were two deaths. Among all cases, 94% reported eating at Oahu or Kauai Island branches of Restaurant Chain A, with 86% of those cases reporting raw scallop consumption. In contrast, a food consumption survey conducted during the outbreak indicated 25% of Oahu residents patronised Restaurant Chain A in the 7 weeks before the survey. Product trace-back revealed a single distributor that supplied scallops imported from the Philippines to Restaurant Chain A. Recovery, amplification and sequence comparison of HAV recovered from scallops revealed viral sequences matching those from case-patients. Removal of product from implicated restaurants and vaccination of those potentially exposed led to the cessation of the outbreak. This outbreak further highlights the need for improved imported food safety.
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Tejada-Strop A, Zafrullah M, Kamili S, Stramer SL, Purdy MA. Distribution of hepatitis A antibodies in US blood donors. Transfusion 2018; 58:2761-2765. [PMID: 30284286 DOI: 10.1111/trf.14916] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/19/2018] [Revised: 06/14/2018] [Accepted: 06/15/2018] [Indexed: 11/28/2022]
Abstract
BACKGROUND Recently, there has been an increase in the number of hepatitis A outbreaks in the United States. Although the presence of hepatitis A virus (HAV) RNA in blood donors is known to be low, HAV antibody prevalence in this population is unknown. STUDY DESIGN AND METHODS Samples from 5001 US blood donors collected primarily in the midwestern United States in 2015 were tested for the presence of HAV IgG antibodies using chemiluminescent microparticle immunoassays on the ARCHITECT platform (Abbott Laboratories). RESULTS The overall prevalence of IgG anti-HAV was 60%. Only one specimen was IgM anti-HAV positive, for an incidence of 0.02%. IgG anti-HAV prevalence among donors aged 16 to 19 years was 67%, decreased to 54% among donors aged 40 to 49 years and increased to 70% among donors aged 80 to 93 years. No differences were seen by sex with overall IgG anti-HAV prevalence of 61% and 60% for males and females, respectively. Among the five states (Illinois, Indiana, Kansas, Kentucky, and Missouri) with the highest number of donors tested, IgG anti-HAV prevalence in Missouri (65%) was significantly higher (p <0.01) than that in Illinois (52%) or Kentucky (59%). No other significant differences between states were noted. CONCLUSION This study demonstrates the overall high rates of IgG anti-HAV in US blood donors, with the low associated risk of HAV transfusion transmission likely the result of low incidence and effective vaccination.
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Affiliation(s)
- Alexandra Tejada-Strop
- Division of Viral Hepatitis, Centers for Disease Control and Prevention, Atlanta, Georgia
| | - Mohammad Zafrullah
- Division of Viral Hepatitis, Centers for Disease Control and Prevention, Atlanta, Georgia
| | - Saleem Kamili
- Division of Viral Hepatitis, Centers for Disease Control and Prevention, Atlanta, Georgia
| | - Susan L Stramer
- Scientific Affairs, American Red Cross, Gaithersburg, Maryland
| | - Michael A Purdy
- Division of Viral Hepatitis, Centers for Disease Control and Prevention, Atlanta, Georgia
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15
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Lin KY, Chen GJ, Lee YL, Huang YC, Cheng A, Sun HY, Chang SY, Liu CE, Hung CC. Hepatitis A virus infection and hepatitis A vaccination in human immunodeficiency virus-positive patients: A review. World J Gastroenterol 2017; 23:3589-3606. [PMID: 28611512 PMCID: PMC5449416 DOI: 10.3748/wjg.v23.i20.3589] [Citation(s) in RCA: 71] [Impact Index Per Article: 8.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/12/2017] [Revised: 03/31/2017] [Accepted: 05/04/2017] [Indexed: 02/06/2023] Open
Abstract
Hepatitis A virus (HAV) is one of the most common infectious etiologies of acute hepatitis worldwide. The virus is known to be transmitted fecal-orally, resulting in symptoms ranging from asymptomatic infection to fulminant hepatitis. HAV can also be transmitted through oral-anal sex. Residents from regions of low endemicity for HAV infection often remain susceptible in their adulthood. Therefore, clustered HAV infections or outbreaks of acute hepatitis A among men who have sex with men and injecting drug users have been reported in countries of low endemicity for HAV infection. The duration of HAV viremia and stool shedding of HAV may be longer in human immunodeficiency virus (HIV)-positive individuals compared to HIV-negative individuals with acute hepatitis A. Current guidelines recommend HAV vaccination for individuals with increased risks of exposure to HAV (such as from injecting drug use, oral-anal sex, travel to or residence in endemic areas, frequent clotting factor or blood transfusions) or with increased risks of fulminant disease (such as those with chronic hepatitis). The seroconversion rates following the recommended standard adult dosing schedule (2 doses of HAVRIX 1440 U or VAQTA 50 U administered 6-12 mo apart) are lower among HIV-positive individuals compared to HIV-negative individuals. While the response rates may be augmented by adding a booster dose at week 4 sandwiched between the first dose and the 6-mo dose, the need of booster vaccination remain less clear among HIV-positive individuals who have lost anti-HAV antibodies.
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16
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Neffatti H, Lebraud P, Hottelet C, Gharbi J, Challouf T, Roque-Afonso AM. Southern Tunisia: A still high endemicity area for hepatitis A. PLoS One 2017; 12:e0175887. [PMID: 28426700 PMCID: PMC5398567 DOI: 10.1371/journal.pone.0175887] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/28/2017] [Accepted: 04/02/2017] [Indexed: 11/29/2022] Open
Abstract
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.
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Affiliation(s)
- Houcine Neffatti
- AP-HP, Hôpital Paul Brousse, Virologie, Villejuif, France
- Université de Monastir, Institut Supérieur de Biotechnologie, Monastir, Tunisia
| | | | | | - Jawher Gharbi
- Université de Monastir, Institut Supérieur de Biotechnologie, Monastir, Tunisia
| | - Taieb Challouf
- Hôpital de Médenine, Médecine interne, Medenine, Tunisia
| | - Anne-Marie Roque-Afonso
- AP-HP, Hôpital Paul Brousse, Virologie, Villejuif, France
- INSERM U1193, Villejuif, France
- * E-mail:
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Fraisse A, Coudray-Meunier C, Martin-Latil S, Hennechart-Collette C, Delannoy S, Fach P, Perelle S. Digital RT-PCR method for hepatitis A virus and norovirus quantification in soft berries. Int J Food Microbiol 2017; 243:36-45. [DOI: 10.1016/j.ijfoodmicro.2016.11.022] [Citation(s) in RCA: 40] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/09/2016] [Revised: 11/18/2016] [Accepted: 11/21/2016] [Indexed: 11/16/2022]
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Tsatsralt-Od B, Baasanjav N, Nyamkhuu D, Ohnishi H, Takahashi M, Kobayashi T, Nagashima S, Nishizawa T, Okamoto H. Molecular analysis of hepatitis A virus strains obtained from patients with acute hepatitis A in Mongolia, 2004-2013. J Med Virol 2015; 88:622-30. [PMID: 26369542 DOI: 10.1002/jmv.24380] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 09/10/2015] [Indexed: 01/22/2023]
Abstract
Despite the high endemicity of hepatitis A virus (HAV) in Mongolia, the genetic information on those HAV strains is limited. Serum samples obtained from 935 patients with acute hepatitis in Ulaanbaatar, Mongolia during 2004-2013 were tested for the presence of HAV RNA using reverse transcription-PCR with primers targeting the VP1-2B region (481 nucleotides, primer sequences at both ends excluded). Overall, 180 patients (19.3%) had detectable HAV RNA. These 180 isolates shared 94.6-100% identity and formed four phylogenetic clusters within subgenotype IA. One or three representative HAV isolates from each cluster exhibited 2.6-3.9% difference between clusters over the entire genome. Cluster 1 accounted for 65.0% of the total, followed by Cluster 2 (30.6%), Cluster 3 (3.3%), and Cluster 4 (1.1%). Clusters 1 and 2 were predominant throughout the observation period, whereas Cluster 3 was undetectable in 2009 and 2013 and Cluster 4 became undetectable after 2009. The Mongolian HAV isolates were closest to those of Chinese or Japanese origin (97.7-98.5% identities over the entire genome), suggesting the evolution from a common ancestor with those circulating in China and Japan. Further molecular epidemiological analyses of HAV infection are necessary to investigate the factors underlying the spread of HAV and to implement appropriate prevention measures in Mongolia.
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Affiliation(s)
- Bira Tsatsralt-Od
- National Institute of Medicine, Ministry of Health and Ministry of Science Education, Ulaanbaatar, Mongolia.,National Center for Communicable Diseases, Ministry of Health, Ulaanbaatar, Mongolia
| | - Nachin Baasanjav
- National Institute of Medicine, Ministry of Health and Ministry of Science Education, Ulaanbaatar, Mongolia
| | - Dulmaa Nyamkhuu
- National Center for Communicable Diseases, Ministry of Health, Ulaanbaatar, Mongolia
| | - Hiroshi Ohnishi
- Division of Virology, Department of Infection and Immunity, Jichi Medical University School of Medicine, Tochigi, Japan
| | - Masaharu Takahashi
- Division of Virology, Department of Infection and Immunity, Jichi Medical University School of Medicine, Tochigi, Japan
| | - Tominari Kobayashi
- Division of Virology, Department of Infection and Immunity, Jichi Medical University School of Medicine, Tochigi, Japan
| | - Shigeo Nagashima
- Division of Virology, Department of Infection and Immunity, Jichi Medical University School of Medicine, Tochigi, Japan
| | - Tsutomu Nishizawa
- Division of Virology, Department of Infection and Immunity, Jichi Medical University School of Medicine, Tochigi, Japan
| | - Hiroaki Okamoto
- Division of Virology, Department of Infection and Immunity, Jichi Medical University School of Medicine, Tochigi, Japan
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Evidence of hepatitis A virus person-to-person transmission in household outbreaks. PLoS One 2014; 9:e102925. [PMID: 25050760 PMCID: PMC4106857 DOI: 10.1371/journal.pone.0102925] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/16/2014] [Accepted: 06/23/2014] [Indexed: 01/11/2023] Open
Abstract
The person-to-person transmission of the hepatitis A virus primarily occurs in enclosed spaces, particularly in the presence of inadequate hygiene conditions and a high proportion of susceptible individuals. Thus, intimate family contact stands out as a risk factor for HAV infection dissemination. The present study aimed to evaluate the occurrence of household HAV transmission. Blood samples were collected from patients with hepatitis A (index cases) and their family members (contacts) that were referred to an ambulatory care clinic specializing in viral hepatitis. A total of 97 samples were collected from 30 families with a confirmed hepatitis A case (index case). Serological and molecular techniques for the diagnosis of hepatitis A were conducted on all samples. HAV infection (anti-HAV IgM + and/or HAV RNA +) was detected in 34.3% (23/67) of the contacts; 34.3% (23/67) of the contacts were immune to HAV, and 31.4% (21/67) were susceptible. In the household contacts, HAV immunity was significantly associated with older age; susceptibility to infection and HAV infection were associated with younger age. Household outbreaks were detected in 16/30 families studied. Co-circulation of subgenotypes IA and IB was found in the household outbreaks, and person-to-person transmission was evidenced in six of the household outbreaks, with 100% homology between the index case and contact strains. The results demonstrated the relevance of HAV household transmission, reaffirming the need for hepatitis A vaccine administration in susceptible contacts and effective infection control procedures to prevent the extension of household outbreaks.
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20
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Environmental persistence and transfer of enteric viruses. Curr Opin Virol 2014; 4:37-43. [DOI: 10.1016/j.coviro.2013.12.003] [Citation(s) in RCA: 104] [Impact Index Per Article: 9.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/08/2013] [Revised: 12/06/2013] [Accepted: 12/12/2013] [Indexed: 11/18/2022]
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21
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Vaughan G, Forbi JC, Xia GL, Fonseca-Ford M, Vazquez R, Khudyakov YE, Montiel S, Waterman S, Alpuche C, Gonçalves Rossi LM, Luna N. Full-length genome characterization and genetic relatedness analysis of hepatitis A virus outbreak strains associated with acute liver failure among children. J Med Virol 2014; 86:202-208. [PMID: 24243548 DOI: 10.1002/jmv.23843] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 10/08/2013] [Indexed: 11/08/2022]
Abstract
Clinical infection by hepatitis A virus (HAV) is generally self-limited but in some cases can progress to liver failure. Here, an HAV outbreak investigation among children with acute liver failure in a highly endemic country is presented. In addition, a sensitive method for HAV whole genome amplification and sequencing suitable for analysis of clinical samples is described. In this setting, two fatal cases attributed to acute liver failure and two asymptomatic cases living in the same household were identified. In a second household, one HAV case was observed with jaundice which resolved spontaneously. Partial molecular characterization showed that both households were infected by HAV subtype IA; however, the infecting strains in the two households were different. The HAV outbreak strains recovered from all cases grouped together within cluster IA1, which contains closely related HAV strains from the United States commonly associated with international travelers. Full-genome HAV sequences obtained from the household with the acute liver failure cases were related (genetic distances ranging from 0.01% to 0.04%), indicating a common-source infection. Interestingly, the strain recovered from the asymptomatic household contact was nearly identical to the strain causing acute liver failure. The whole genome sequence from the case in the second household was distinctly different from the strains associated with acute liver failure. Thus, infection with almost identical HAV strains resulted in drastically different clinical outcomes.
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Affiliation(s)
- Gilberto Vaughan
- Division of Viral Hepatitis, Centers for Diseases Control and Prevention, Atlanta, Georgia
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Schuchat A, Bell BP. Monitoring the impact of vaccines postlicensure: new challenges, new opportunities. Expert Rev Vaccines 2014; 7:437-56. [DOI: 10.1586/14760584.7.4.437] [Citation(s) in RCA: 24] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/08/2022]
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Vaughan G, Goncalves Rossi LM, Forbi JC, de Paula VS, Purdy MA, Xia G, Khudyakov YE. Hepatitis A virus: host interactions, molecular epidemiology and evolution. INFECTION, GENETICS AND EVOLUTION : JOURNAL OF MOLECULAR EPIDEMIOLOGY AND EVOLUTIONARY GENETICS IN INFECTIOUS DISEASES 2014; 21:227-243. [PMID: 24200587 DOI: 10.1016/j.meegid.2013.10.023] [Citation(s) in RCA: 106] [Impact Index Per Article: 9.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 07/28/2013] [Revised: 10/25/2013] [Accepted: 10/26/2013] [Indexed: 12/16/2022]
Abstract
Infection with hepatitis A virus (HAV) is the commonest viral cause of liver disease and presents an important public health problem worldwide. Several unique HAV properties and molecular mechanisms of its interaction with host were recently discovered and should aid in clarifying the pathogenesis of hepatitis A. Genetic characterization of HAV strains have resulted in the identification of different genotypes and subtypes, which exhibit a characteristic worldwide distribution. Shifts in HAV endemicity occurring in different parts of the world, introduction of genetically diverse strains from geographically distant regions, genotype displacement observed in some countries and population expansion detected in the last decades of the 20th century using phylogenetic analysis are important factors contributing to the complex dynamics of HAV infections worldwide. Strong selection pressures, some of which, like usage of deoptimized codons, are unique to HAV, limit genetic variability of the virus. Analysis of subgenomic regions has been proven useful for outbreak investigations. However, sharing short sequences among epidemiologically unrelated strains indicates that specific identification of HAV strains for molecular surveillance can be achieved only using whole-genome sequences. Here, we present up-to-date information on the HAV molecular epidemiology and evolution, and highlight the most relevant features of the HAV-host interactions.
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Affiliation(s)
- Gilberto Vaughan
- Division of Viral Hepatitis, Centers for Disease Control and Prevention, Atlanta, GA, United States.
| | | | - Joseph C Forbi
- Division of Viral Hepatitis, Centers for Disease Control and Prevention, Atlanta, GA, United States
| | - Vanessa S de Paula
- Laboratory of Viral Hepatitis, Oswaldo Cruz Institute, FIOCRUZ, Rio de Janeiro, Brazil
| | - Michael A Purdy
- Division of Viral Hepatitis, Centers for Disease Control and Prevention, Atlanta, GA, United States
| | - Guoliang Xia
- Division of Viral Hepatitis, Centers for Disease Control and Prevention, Atlanta, GA, United States
| | - Yury E Khudyakov
- Division of Viral Hepatitis, Centers for Disease Control and Prevention, Atlanta, GA, United States
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Vaughan G, Xia G, Forbi JC, Purdy MA, Rossi LMG, Spradling PR, Khudyakov YE. Genetic relatedness among hepatitis A virus strains associated with food-borne outbreaks. PLoS One 2013; 8:e74546. [PMID: 24223112 PMCID: PMC3819349 DOI: 10.1371/journal.pone.0074546] [Citation(s) in RCA: 24] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/01/2013] [Accepted: 08/02/2013] [Indexed: 11/19/2022] Open
Abstract
The genetic characterization of hepatitis A virus (HAV) strains is commonly accomplished by sequencing subgenomic regions, such as the VP1/P2B junction. HAV genome is not extensively variable, thus presenting opportunity for sharing sequences of subgenomic regions among genetically unrelated isolates. The degree of misrepresentation of phylogenetic relationships by subgenomic regions is especially important for tracking transmissions. Here, we analyzed whole-genome (WG) sequences of 101 HAV strains identified from 4 major multi-state, food-borne outbreaks of hepatitis A in the Unites States and from 14 non-outbreak-related HAV strains that shared identical VP1/P2B sequences with the outbreak strains. Although HAV strains with an identical VP1/P2B sequence were specific to each outbreak, WG were different, with genetic diversity reaching 0.31% (mean 0.09%). Evaluation of different subgenomic regions did not identify any other section of the HAV genome that could accurately represent phylogenetic relationships observed using WG sequences. The identification of 2-3 dominant HAV strains in 3 out of 4 outbreaks indicates contamination of the implicated food items with a heterogeneous HAV population. However, analysis of intra-host HAV variants from eight patients involved in one outbreak showed that only a single sequence variant established infection in each patient. Four non-outbreak strains were found closely related to strains from 2 outbreaks, whereas ten were genetically different from the outbreak strains. Thus, accurate tracking of HAV strains can be accomplished using HAV WG sequences, while short subgenomic regions are useful for identification of transmissions only among cases with known epidemiological association.
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Affiliation(s)
- Gilberto Vaughan
- Division of Viral Hepatitis, Centers for Diseases Control and Prevention, Atlanta, Georgia, United States of America
| | - Guoliang Xia
- Division of Viral Hepatitis, Centers for Diseases Control and Prevention, Atlanta, Georgia, United States of America
| | - Joseph C. Forbi
- Division of Viral Hepatitis, Centers for Diseases Control and Prevention, Atlanta, Georgia, United States of America
| | - Michael A. Purdy
- Division of Viral Hepatitis, Centers for Diseases Control and Prevention, Atlanta, Georgia, United States of America
| | - Lívia Maria Gonçalves Rossi
- Division of Viral Hepatitis, Centers for Diseases Control and Prevention, Atlanta, Georgia, United States of America
| | - Philip R. Spradling
- Division of Viral Hepatitis, Centers for Diseases Control and Prevention, Atlanta, Georgia, United States of America
| | - Yury E. Khudyakov
- Division of Viral Hepatitis, Centers for Diseases Control and Prevention, Atlanta, Georgia, United States of America
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25
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Jayakumar S, Carbonneau M, Hotte N, Befus AD, St Laurent C, Owen R, McCarthy M, Madsen K, Bailey RJ, Ma M, Bain V, Rioux K, Tandon P. VSL#3 ® probiotic therapy does not reduce portal pressures in patients with decompensated cirrhosis. Liver Int 2013; 33:1470-7. [PMID: 23968203 DOI: 10.1111/liv.12280] [Citation(s) in RCA: 47] [Impact Index Per Article: 3.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/08/2013] [Accepted: 06/20/2013] [Indexed: 12/12/2022]
Abstract
BACKGROUND & AIMS In patients with decompensated cirrhosis, bacterial translocation can contribute to splanchnic vasodilatation, decreased effective circulating volume, and portal hypertension. The primary objective of this randomized, double blind placebo controlled trial was to evaluate the effect of the probiotic VSL#3(®) on the hepatic venous pressure gradient (HVPG). METHODS Seventeen patients with decompensated cirrhosis and an HVPG of ≥ 10 mmHg were randomized to receive 2 months of VSL#3(®) or an identical placebo. HVPG, endotoxin, interleukin (IL)-6, IL-8, IL-10, renin, aldosterone, nitric oxide and stool microbiota were measured at baseline and study end. RESULTS Two of the 17 patients were taken off the trial before completion (one for alcohol abuse and the second for SBP - both in placebo arm). Data were analysed on the remaining 15 patients. The median model for end-stage liver disease score was 12, and 80% of patients had Child Pugh B disease. The treatment arm had a greater decrease in HVPG from baseline to study end than the placebo arm (median change from baseline -11.6% vs +2.8%), although this reduction was not statistically significant in either group. There was a significant reduction in the plasma aldosterone level in the VSL#3(®) group, but no significant changes in the other measured parameters, including the stool microflora analysis. CONCLUSIONS Within the limitations of our sample size, VSL#3(®) therapy does not appear to have a significant impact on portal pressure reduction in patients with decompensated cirrhosis.
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Affiliation(s)
- Saumya Jayakumar
- Department of Medicine, University of Calgary, Calgary, Alberta, Canada; Department of Medicine, University of Alberta, Edmonton, Alberta, Canada
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Genetic diversity of hepatitis A virus in China: VP3-VP1-2A genes and evidence of quasispecies distribution in the isolates. PLoS One 2013; 8:e74752. [PMID: 24069343 PMCID: PMC3775754 DOI: 10.1371/journal.pone.0074752] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/17/2013] [Accepted: 08/07/2013] [Indexed: 12/11/2022] Open
Abstract
Hepatitis A virus (HAV) is the most common cause of infectious hepatitis throughout the world, spread largely by the fecal-oral route. To characterize the genetic diversity of the virus circulating in China where HAV in endemic, we selected the outbreak cases with identical sequences in VP1-2A junction region and compiled a panel of 42 isolates. The VP3-VP1-2A regions of the HAV capsid-coding genes were further sequenced and analyzed. The quasispecies distribution was evaluated by cloning the VP3 and VP1-2A genes in three clinical samples. Phylogenetic analysis demonstrated that the same genotyping results could be obtained whether using the complete VP3, VP1, or partial VP1-2A genes for analysis in this study, although some differences did exist. Most isolates clustered in sub-genotype IA, and fewer in sub-genotype IB. No amino acid mutations were found at the published neutralizing epitope sites, however, several unique amino acid substitutions in the VP3 or VP1 region were identified, with two amino acid variants closely located to the immunodominant site. Quasispecies analysis showed the mutation frequencies were in the range of 7.22x10-4 -2.33x10-3 substitutions per nucleotide for VP3, VP1, or VP1-2A. When compared with the consensus sequences, mutated nucleotide sites represented the minority of all the analyzed sequences sites. HAV replicated as a complex distribution of closely genetically related variants referred to as quasispecies, and were under negative selection. The results indicate that diverse HAV strains and quasispecies inside the viral populations are presented in China, with unique amino acid substitutions detected close to the immunodominant site, and that the possibility of antigenic escaping mutants cannot be ruled out and needs to be further analyzed.
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Waterman S, Cortés Alcalá R, Spradling P. Crossing borders. Viral hepatitis in the United States, Mexico, and the United States–Mexico border region. Clin Infect Dis 2013; 55:v-vi. [PMID: 23136093 DOI: 10.1093/cid/cis821] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/24/2022] Open
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Spradling PR, Xing J, Phippard A, Fonseca-Ford M, Montiel S, Guzmán NL, Campuzano RV, Vaughan G, Xia GL, Drobeniuc J, Kamili S, Cortés-Alcalá R, Waterman SH. Acute viral hepatitis in the United States-Mexico border region: data from the Border Infectious Disease Surveillance (BIDS) Project, 2000-2009. J Immigr Minor Health 2013; 15:390-397. [PMID: 22447176 PMCID: PMC6515900 DOI: 10.1007/s10903-012-9604-8] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/30/2023]
Abstract
Little is known about the characteristics of acute viral hepatitis cases in the United States (US)-Mexico border region. We analyzed characteristics of acute viral hepatitis cases collected from the Border Infectious Disease Surveillance Project from January 2000-December 2009. Over the study period, 1,437 acute hepatitis A, 311 acute hepatitis B, and 362 acute hepatitis C cases were reported from 5 Mexico and 2 US sites. Mexican hepatitis A cases most frequently reported close personal contact with a known case, whereas, US cases most often reported cross-border travel. Injection drug use was common among Mexican and US acute hepatitis B and C cases. Cross-border travel during the incubation period was common among acute viral hepatitis cases in both countries. Assiduous adherence to vaccination and prevention guidelines in the US is needed and strategic implementation of hepatitis vaccination and prevention programs south of the border should be considered.
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Affiliation(s)
- Philip R Spradling
- Division of Viral Hepatitis, National Center for HIV, Hepatitis, STD, and TB Prevention, Centers for Disease Control and Prevention, Mailstop G37, 1600 Clifton Road NE, Atlanta, GA 30333, USA.
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Waterborne Diseases of the Ocean, Enteric Viruses. Infect Dis (Lond) 2013. [DOI: 10.1007/978-1-4614-5719-0_13] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 10/27/2022] Open
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Erhart LM, Ernst KC. The changing epidemiology of hepatitis A in Arizona following intensive immunization programs (1988-2007). Vaccine 2012; 30:6103-10. [PMID: 22835739 DOI: 10.1016/j.vaccine.2012.07.029] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/08/2012] [Revised: 07/09/2012] [Accepted: 07/10/2012] [Indexed: 11/29/2022]
Abstract
INTRODUCTION Arizona had the highest hepatitis A incidence of any U.S. state during 1987-1997. In 1995, the first hepatitis A vaccines became available in the U.S. A series of hepatitis A vaccination policies and recommendations were implemented in 1996-2006. Our objective was to examine the shifting epidemiologic patterns in hepatitis A in Arizona from 1988 to 2007. METHODS Passive surveillance reports to the Arizona Department of Health Services were used to compare hepatitis A rates by age, race/ethnicity and geographic area, before and after widespread vaccination. Reported risk factors and possible sources of infection were compared for two time periods. Age-adjusted incidence during three periods was mapped. RESULTS Overall hepatitis A incidence in Arizona fell from 58 cases per 100,000 in 1988 to 2 per 100,000 in 2007. The proportion of reported cases among children dropped from 62% in 1994-1995 to 32% in 2006-2007. Racial/ethnic disparities between American Indians and non-Hispanic White populations have been eliminated. The geographic distribution of cases within the state has shifted. Earlier cases were likely to report contact with another hepatitis A case or childcare facilities, while later cases indicated recent international travel. CONCLUSION A major shift in the overall burden of hepatitis A and hepatitis A transmission has occurred in Arizona since the widespread implementation of immunization policies and the concomitant rise in vaccination rates in the state. Current transmission has shifted to older age groups and disparities by race/ethnicity are now highest in Hispanic populations. Future strategies to further reduce hepatitis A transmission may require broadening recommendations to include general adult populations without previous vaccination history.
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Affiliation(s)
- Laura M Erhart
- Office of Infectious Disease Services, Arizona Department of Health Services, Phoenix, AZ, USA
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Escobar-Gutiérrez A, Cruz-Rivera M, Ruiz-Tovar K, Vaughan G. Genetic relatedness among Japanese HAV isolates, 2010. J Clin Virol 2012; 54:287-288. [PMID: 22521263 DOI: 10.1016/j.jcv.2012.03.011] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/27/2012] [Accepted: 03/28/2012] [Indexed: 01/19/2023]
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Immunity to hepatitis A when outbreaks of infection in men who have sex with men (MSM) are rare. Vaccine 2012; 30:3430-4. [PMID: 22449421 DOI: 10.1016/j.vaccine.2012.03.024] [Citation(s) in RCA: 19] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/19/2011] [Revised: 03/09/2012] [Accepted: 03/12/2012] [Indexed: 01/13/2023]
Abstract
BACKGROUND Epidemics of hepatitis A among men who have sex with men (MSM) have decreased significantly in recent years although the level of immunity that is required to prevent epidemics has not been studied. Our aim was to determine the level of immunity to hepatitis A among MSM. METHODS This was a retrospective study conducted using notifications of Hepatitis A in Victoria from 1991 to 2010, serological testing for hepatitis A among MSM attending Melbourne Sexual Health Centre (MSHC), and vaccination records among MSM attending MSHC. RESULTS Hepatitis A notifications declined from 370 to 47 and the male to female ratio declined from 4.2 to 0.9 in Victoria between 1991 to 2010. Between 2002 and 2011, there were 12,064 individuals MSM seen at MSHC of whom 3055 (25%) were tested for hepatitis A antibodies and 1180 (39%) had antibodies. The proportion of MSM who were tested for hepatitis A rose significantly over time (P<0.01), but the proportion of these with hepatitis A antibodies did not (P=0.28). Hepatitis A antibodies were more common in MSM over 30 (54%) compared to those 30 or less (32%), (Crude Odds Ratio 2.5 (95% confidence interval 2.1-2.9)) and were uncommon in MSM under 20 (19%). Vaccination against hepatitis A was recorded in 49% of 660 clinical files of MSM who attended the centre between 2003 and 2011 and did not change over time (P=0.42) but was significantly more common in those over 30 years of age (P<0.005). CONCLUSION Hepatitis A is rare in MSM in Victoria where levels of immunity are about 40-50%. As outbreaks have occurred when levels of immunity were around 30%, maintaining vaccination levels over 40-50% is important if outbreaks are to be prevented. The lower levels of immunity in younger MSM create the potential for outbreaks in this sub-group.
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Genetic analysis of hepatitis A virus strains that induced epidemics in Korea during 2007-2009. J Clin Microbiol 2012; 50:1252-7. [PMID: 22238447 DOI: 10.1128/jcm.01114-11] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/21/2023] Open
Abstract
Hepatitis A virus is one of the most prominent causes of fecally transmitted acute hepatitis worldwide. In order to characterize the viral agents causing an outbreak in Korea (comprising North and South Korea) from June 2007 to May 2009, we collected specimens and performed genotyping of the VP1/P2A and VP3/VP1 regions of hepatitis A virus. We then used a multiple-alignment algorithm to compare the nucleotide sequences of the 2 regions with those of reference strains. Hepatitis A virus antibodies were detected in 64 patients from 5 reported outbreaks (North Korea, June 2007 [n = 11]; Jeonnam, April 2008 [n = 15]; Daegu, May 2008 [n = 13]; Seoul, May 2009 [n = 22]; and Incheon, May 2009 [n = 3]). We found 100% homology between strains isolated from the Kaesong Industrial Region and Jeonnam. While those strains were classified as genotype IA strains, strains from Seoul and Incheon were identified as genotype IIIA strains and showed 98.9 to 100% homology. Genotype IIIA was also dominant in Daegu, where strains were 95.7 to 100% homologous. All hepatitis A virus strains isolated from the Kaesong Industrial Region, Jeonnam, Seoul, and Incheon belonged to a single cluster. However, strains from Daegu could be classified into 2 clusters, suggesting that the outbreak had multiple sources. This study indicates that hepatitis A virus strains of 2 different genotypes are currently cocirculating in Korea. Moreover, it documents an increasing prevalence of genotype IIIA strains in the country.
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Teshale EH, Ramachandran S, Xia GL, Roberts H, Groeger J, Barry V, Hu DJ, Holmberg SD, Holtzman D, Ward JW, Teo CG, Khudyakov Y. Genotypic distribution of hepatitis B virus (HBV) among acute cases of HBV infection, selected United States counties, 1999-2005. Clin Infect Dis 2011; 53:751-6. [PMID: 21860013 DOI: 10.1093/cid/cir495] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/23/2022] Open
Abstract
BACKGROUND Knowledge of the genotypic distribution of hepatitis B virus (HBV) facilitates epidemiologic tracking and surveillance of HBV infection as well as prediction of its disease burden. In the United States, HBV genotyping studies have been conducted for chronic but not acute hepatitis B. METHODS Serum samples were collected from patients with acute hepatitis B cases reported from the 6 counties that participated in the Sentinel Counties Study of Acute Viral Hepatitis from 1999 through 2005. Polymerase chain reaction followed by nucleotide sequencing of a 435-base pair segment of the HBV S gene was performed, and the sequences were phylogenetically analyzed. RESULTS Of 614 patients identified with available serum samples, 75% were infected with genotype A HBV and 18% were infected with genotype D HBV. Thirty-two percent of genotype A sequences constituted a single subgenotype A2 cluster. The odds of infection with genotype A (vs with genotype D) were 5 times greater among black individuals than among Hispanic individuals (odds ratio [OR], 5; 95% confidence interval [CI], 2.3-10.7). The odds of infection with genotype A were 49, 8, and 4 times greater among patients from Jefferson County (Alabama), Pinellas County (Florida), and San Francisco (California), respectively, than among those living in Denver County (Colorado). Genotype A was less common among recent injection drug users than it was among non-injection drug users (OR, 0.2; 95% CI, 0.1-0.4). CONCLUSIONS HBV genotype distribution was significantly associated with ethnicity, place of residence, and risk behavior.
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Affiliation(s)
- Eyasu H Teshale
- Division of Viral Hepatitis, National Center for HIV, Hepatitis, TB and STD Prevention, Centers for Disease Control and Prevention, Atlanta, Georgia, USA.
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Amado LA, Villar LM, de Paula VS, Pinto MA, Gaspar AMC. Exposure to multiple subgenotypes of hepatitis A virus during an outbreak using matched serum and saliva specimens. J Med Virol 2011; 83:768-75. [PMID: 21412786 DOI: 10.1002/jmv.22045] [Citation(s) in RCA: 13] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/08/2022]
Abstract
Matched serum and saliva samples were collected simultaneously from 124 subjects exposed during a hepatitis A virus (HAV) outbreak at a daycare center in Rio de Janeiro, Brazil. All samples were tested for IgM and total anti-HAV antibodies by enzyme immunoassay (EIA). HAV was detected by nested PCR in serum, saliva, and water samples employing primers for the VP1/2A region of the viral RNA; all positive products were then sequenced. The viral load of the matched samples was determined by real-time PCR using the TaqMan system. HAV-RNA was identified by nested PCR in 37.7% of the saliva samples, 29% of the serum samples, and one drinking water sample. The mean HAV viral load was similar in the serum and saliva specimens (10(3) copies/ml). HAV genotypes IA and IB were detected in both specimen types, and the water sample isolate was classified as genotype IB, indicating the existence of more than one source of infection at the daycare center. In six infected patients, a different HAV subgenotype was found in their serum than in their saliva, and this unusual pattern of mixed HAV infection was investigated further by molecular cloning followed by nucleotide sequencing. All clones derived from the saliva samples belonged to subgenotype IB and shared 96.5-100% identity. However, clones derived from their corresponding serum sample belonged to subgenotype IA and shared 90.5-100% identity. This study showed the important role that non-invasive saliva samples can play in the molecular epidemiological analysis of a hepatitis A outbreak.
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Affiliation(s)
- Luciane Almeida Amado
- Laboratory of Technological Development in Virology, Oswaldo Cruz Institute - FIOCRUZ, Rio de Janeiro/RJ, Brazil.
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Ajmera V, Xia G, Vaughan G, Forbi JC, Ganova-Raeva LM, Khudyakov Y, Opio CK, Taylor R, Restrepo R, Munoz S, Fontana RJ, Lee WM. What factors determine the severity of hepatitis A-related acute liver failure? J Viral Hepat 2011; 18:e167-e174. [PMID: 21143345 PMCID: PMC4931904 DOI: 10.1111/j.1365-2893.2010.01410.x] [Citation(s) in RCA: 43] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
The reason(s) that hepatitis A virus (HAV) infection may progress infrequently to acute liver failure are poorly understood. We examined host and viral factors in 29 consecutive adult patients with HAV-associated acute liver failure enrolled at 10 sites participating in the US ALF Study Group. Eighteen of twenty-four acute liver failure sera were PCR positive while six had no detectable virus. HAV genotype was determined using phylogenetic analysis and the full-length genome sequences of the HAV from a cute liver failure sera were compared to those from self-limited acute HAV cases selected from the CDC database. We found that rates of nucleotide substitution did not vary significantly between the liver failure and non-liver failure cases and there was no significant variation in amino acid sequences between the two groups. Four of 18 HAV isolates were sub-genotype IB, acquired from the same study site over a 3.5-year period. Sub-genotype IB was found more frequently among acute liver failure cases compared to the non-liver failure cases (chi-square test, P < 0.01). At another centre, a mother and her son presented with HAV and liver failure within 1 month of each other. Predictors of spontaneous survival included detectable serum HAV RNA, while age, gender, HAV genotype and nucleotide substitutions were not associated with outcome. The more frequent appearance of rapid viral clearance and its association with poor outcomes in acute liver failure as well as the finding of familial cases imply a possible host genetic predisposition that contributes to a fulminant course. Recurrent cases of the rare sub-genotype IB over several years at a single centre imply a community reservoir of infection and possible increased pathogenicity of certain infrequent viral genotypes.
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Affiliation(s)
- V Ajmera
- Digestive and Liver Diseases Division, UT Southwestern Medical Center, Dallas, TX 75390-8887, USA
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Cao J, Bi S, Meng Q, Shen L, Zheng H, Zhang Y. Genotyping of acute hepatitis a virus isolates from China, 2003-2008. J Med Virol 2011; 83:1134-41. [PMID: 21520140 DOI: 10.1002/jmv.22086] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 01/28/2011] [Indexed: 11/12/2022]
Abstract
Hepatitis A virus (HAV) is usually transmitted by an oral-fecal route and is prevalent not only in developing countries but also in developed countries. In the present study, the phylogenetic characterization of the VP1/2A junction region (321 nucleotides) of China HAV isolates was examined. Anti-HAV IgM-positive serum samples were collected from 8 provinces, including 20 cities or counties in China from 2003 to 2008; 337 isolates from 406 HAV patients' serum samples were amplified by RT-PCR, sequenced at the VP1/2A junction region and aligned with the published sequences from GenBank to establish phylogenetic analysis. All China HAV isolates in this study belonged to genotype I, with 98.8% (333/337) of samples clustering in sub-genotype IA and 1.2% (4/337) in sub-genotype IB. In addition, sub-genotype IA isolates clustered into four groups (92.7-100% nucleotide identity), and the samples collected from all China HAV isolates in this investigation showed 87.5-100% nucleotide identity, but the amino acids in this region were more conserved (95.2-100% identity). Few unique amino acid changes could be deduced (VP1-253: Glu → Gly; 2A-34: Pro → Ala; 2A-33: Leu → Phe). Genetically identical or similar HAV strains existed in some investigated areas in China during different years, suggesting that an indigenous strain has been circulating in those regions. This report provides new data on the genetic relatedness and molecular epidemiology of HAV isolates from China as well as the distribution of sub-genotype IA and IB in this part of the world.
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Affiliation(s)
- Jingyuan Cao
- State Key Laboratory for Molecular Virology & Genetic Engineering, National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Changping Qu, Beijing, PR China.
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Roque-Afonso AM, Desbois D, Dussaix E. Hepatitis A virus: serology and molecular diagnostics. Future Virol 2010. [DOI: 10.2217/fvl.10.9] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/10/2023]
Abstract
The diagnosis of hepatitis A virus (HAV) infection is based on the detection of anti-HAV IgM. Shortcomings of this serological approach include the persistence of IgM after normalization of liver enzymes or its detection during polyclonal activation of the immune system due to unrelated viral infection or autoimmune diseases. Molecular diagnosis of HAV along with anti-HAV IgG avidity measurement are helpful in case of positive IgM where laboratory evidence of acute hepatitis is absent and there is no epidemiologic link to other cases. Molecular epidemiology allows us to determine whether viruses from different locations are related to each other and provides further understanding of viral epidemiology by identifying sources and transmission modes. It has been demonstrated that the rapid turnover of HAV strains in low-endemicity countries is caused by their introduction by travelers. Growing sequence databases allow for the identification of geographic origin of viral strains. Collaboration between surveillance laboratories, including database sharing, should be promoted for deeper investigation of outbreaks and improved prevention approaches.
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Affiliation(s)
- Anne Marie Roque-Afonso
- Centre National de Référence pour les Virus à Transmission Entérique, AP-HP, Hôpital Paul Brousse, Laboratoire de Virologie, Villejuif, 94804, France
| | - Delphine Desbois
- Centre National de Référence pour les Virus à Transmission Entérique, AP-HP, Hôpital Paul Brousse, Laboratoire de Virologie, Villejuif, 94804, France
| | - Elisabeth Dussaix
- Centre National de Référence pour les Virus à Transmission Entérique, AP-HP, Hôpital Paul Brousse, Laboratoire de Virologie, Villejuif, 94804, France
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An outbreak of hepatitis A in recently vaccinated students from ice snacks made from contaminated well water. Epidemiol Infect 2009; 137:428-33. [PMID: 18817585 DOI: 10.1017/s0950268808001337] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/05/2022] Open
Abstract
On 30 May 2006, township S in Sichuan Province, China, reported an outbreak of hepatitis A (HA) in students who had recently received HA vaccine. The concern was raised that the vaccine had caused the outbreak. We attempted to identify the source of infection and mode of transmission. A HA case was defined as onset of jaundice or anorexia since 1 April 2006 with a twofold elevation of alanine aminotransferase (ALT) and anti-HA virus-IgM in a resident of or visitor to the township. Exposures to vaccine and snacks of 90 case-students to those of 107 control-students were compared. Thirty-four per cent of cases ate ice slush compared to 4.7% of controls (OR 4.1), and 51% of cases ate snow cones compared to 17% of controls (OR 8.3). The ice snacks were made with well water. HA virus RNA was detected by reverse transcription-polymerase chain reaction from patients' blood and well water. Untreated well water poses important dangers to the public in areas where piped, potable water is available.
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Villar LM, de Melo MMM, Calado IA, de Almeida AJ, Lampe E, Gaspar AMC. Should Brazilian patients with chronic hepatitis C virus infection be vaccinated against hepatitis A virus? J Gastroenterol Hepatol 2009; 24:238-42. [PMID: 19215334 DOI: 10.1111/j.1440-1746.2008.05575.x] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/09/2022]
Abstract
BACKGROUND AND AIM Hepatitis A virus (HAV) superinfection is associated with a high risk of liver failure and death in patients with hepatitis C virus (HCV) infection. The aim of this study was to investigate the presence of serological and molecular HAV markers in a population of HCV-infected patients in order to determine a cost-effective strategy to vaccinate against HAV. METHODS The presence of total and immunoglobulin (Ig)M anti-HAV antibodies was investigated in 399 patients (median age, 50 years; range, 4-81) referred to the Public Health Central Laboratory of Pernambuco State who tested positive for anti-HCV antibodies and HCV RNA. HAV RNA was investigated by reverse transcription-nested polymerase chain reaction in these patients. RESULTS Three hundred and eighty-four (96%) patients were positive for anti-HAV total and negative for IgM anti-HAV antibodies (immune patients). Three patients had IgM (and total) anti-HAV antibodies, showing an acute infection, and two of them had HAV RNA detected in serum samples. HAV RNA was also found in another patient in the absence of detectable anti-HAV antibodies. By nucleotide sequencing, it was demonstrated that the HAV isolates infecting these patients belonged to subgenotype 1B. CONCLUSION This study provides valuable new data on anti-HAV prevalence among HCV carriers in Brazil. In the present study, we found a high proportion of patients with anti-HAV positivity, indicating that anti-HAV testing of HCV-infected patients is a cost-effective strategy and should be carried out before vaccination against HAV in these patients, particularly in regions such as our geographical area with high total anti-HAV prevalence.
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Affiliation(s)
- Livia M Villar
- Viral Hepatitis Laboratory, Oswaldo Cruz Institute, FIOCRUZ, Rio de Janeiro, Brazil.
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Hepatitis viruses and emerging viruses. FOODBORNE PATHOGENS 2009. [PMCID: PMC7152215 DOI: 10.1533/9781845696337.3.891] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Indexed: 11/15/2022]
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Evaluation of genomic regions of hepatitis A virus for phylogenetic analysis: Suitability of the 2C region for genotyping. J Virol Methods 2008; 153:36-42. [DOI: 10.1016/j.jviromet.2008.06.014] [Citation(s) in RCA: 18] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/20/2008] [Revised: 06/10/2008] [Accepted: 06/12/2008] [Indexed: 11/20/2022]
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Mohler-Kuo M, Steffen R, Bopp M, Jacobs RJ, Mutsch M. Prevalence of hepatitis A virus risk factors in a very low endemic country, Switzerland. Vaccine 2007; 25:8718-25. [DOI: 10.1016/j.vaccine.2007.10.033] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/23/2007] [Revised: 10/12/2007] [Accepted: 10/15/2007] [Indexed: 10/22/2022]
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Craig AS, Watson B, Zink TK, Davis JP, Yu C, Schaffner W. Hepatitis A Outbreak Activity in the United States: Responding to a Vaccine-Preventable Disease. Am J Med Sci 2007; 334:180-3. [PMID: 17873531 DOI: 10.1097/maj.0b013e3181425411] [Citation(s) in RCA: 22] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
Abstract
BACKGROUND The occurrence of hepatitis A in the United States is heterogeneous because of disease cycles with substantial variation in incidence among states and involvement of numerous behavioral risk factors. In spite of the Advisory Committee on Immunization Practices' (ACIP) 1999 recommendation for routine hepatitis A immunization in states with high rates of disease and the fact that disease rates are at a historic low, outbreaks continue to occur. METHODS We reviewed outbreaks of hepatitis A in the United States occurring from 1994 through 2004. We searched PubMed, ProMed, Google, and the CDC Foodborne Disease Outbreak and Epi-X Internet sites to ascertain the number and type of hepatitis A outbreaks. The CDC's MMWR publication and the Hepatitis Control Report were also searched. RESULTS A total of 256 hepatitis A outbreaks were identified from 1994 through 2004. The mean number of outbreaks was 23 per year (median 25). The number of outbreaks in states with traditionally low/intermediate endemic rates of hepatitis A remained relatively constant during the study period. Outbreaks declined significantly (P = 0.01) in states with previously high rates of disease--most of which have implemented hepatitis A vaccination programs. CONCLUSIONS Outbreaks of hepatitis A continue to occur in the United States despite the licensure of two safe and effective vaccines in 1995 and the apparent decline in the number of outbreaks in states with previously high rates of hepatitis A. The recent ACIP recommendation for universal hepatitis A vaccination at age 1 year in all states will contribute to a further reduction in hepatitis A outbreaks.
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Affiliation(s)
- Allen S Craig
- Tennessee Department of Health, Nashville, Tennessee 37247, USA.
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Munné MS, Vladimirsky S, Otegui L, Soto S, Brajterman L, Castro R, Velasco MCC, Bonnano A, Fernández E, Remondegui C, Passeggi C, Rodríguez C, Pizarro M, Fabre A, Moreiro R, Quarleri J, González JE. Molecular characterization of hepatitis A virus isolates from Argentina. J Med Virol 2007; 79:887-894. [PMID: 17516519 DOI: 10.1002/jmv.20818] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/08/2022]
Abstract
Hepatitis A, a vaccine preventable disease, is now of transitional or intermediate endemicity in Argentina, as the epidemiologic pattern of the disease has shifted with improvements in living conditions in some parts of the country. Increase in the susceptibility of older children and adults has led to increasing disease incidence. Molecular epidemiology has played an important role in the understanding of HAV infection by identifying modes of spreading and by permitting the monitoring of changes in circulating virus brought about by prevention programs. South American isolates characterized are limited. Eighty-two sporadic and outbreak isolates from Argentina were sequenced in the VP1/2A region of HAV genome over a 9-year period. All the isolates belonged to subgenotype IA. All our sequences grouped into two big clusters. Apparently, at least two lineages have been co-circulating in the same place at the same time. Despite great genetic variability, few point amino acid changes could be deduced. Four sequences showed an Arg --> Lys substitution at 1-297 which characterized the genotype IB at the amino acid level. Many isolates carried a conservative amino acid substitution Leu --> Ile at position 42 of the 2A domain, previously described as a possible fingerprint of HAV sequences in Brazil. The other rare changes have been found before, except for a 1-277 Asn --> Ser substitution displayed in two isolates that has not been previously reported. Argentina recently implemented universal vaccination in 1-year-old children. Molecular tools would be useful in an active surveillance program.
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Affiliation(s)
- María S Munné
- Lab. Nac.de Referencia Hepatitis Virales, Instituto Nacional de Enfermedades Infecciosas, ANLIS Dr. C.G. Malbrán, Ciudad Autónoma de Buenos Aires, Argentina.
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Rizzetto M, Zoulim F. Viral Hepatitis. TEXTBOOK OF HEPATOLOGY 2007:819-956. [DOI: 10.1002/9780470691861.ch9a] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/03/2025]
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Frank C, Walter J, Muehlen M, Jansen A, van Treeck U, Hauri AM, Zoellner I, Rakha M, Hoehne M, Hamouda O, Schreier E, Stark K. Major outbreak of hepatitis A associated with orange juice among tourists, Egypt, 2004. Emerg Infect Dis 2007; 13:156-8. [PMID: 17370535 PMCID: PMC2725821 DOI: 10.3201/eid1301.060487] [Citation(s) in RCA: 56] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/25/2022] Open
Abstract
In 2004, a major outbreak of hepatitis A among tourists returning from Egypt involved 351 case-patients from 9 European countries who were infected with a single strain (genotype 1b). The case-control study identified orange juice as the most likely infection vehicle. Vaccination against hepatitis A virus is strongly recommended before travel to disease-endemic areas.
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Cristina J, Costa-Mattioli M. Genetic variability and molecular evolution of hepatitis A virus. Virus Res 2007; 127:151-7. [PMID: 17328982 DOI: 10.1016/j.virusres.2007.01.005] [Citation(s) in RCA: 58] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/05/2006] [Accepted: 01/08/2007] [Indexed: 02/08/2023]
Abstract
Hepatitis A virus (HAV), the causative agent of type A viral hepatitis, was first identified about three decades ago. Recent findings have shown that HAV possess several characteristics that make it unique among the family Picornaviridae, particularly in terms of its mechanisms of polyprotein processing and virion morphogenesis. HAV circulates in vivo as distributions of closely genetically related variants referred to as quasispecies. HAV exploits all known mechanisms of genetic variation to ensure its survival, including mutation and recombination. Only one serotype and six different genetic groups (three humans and three simian) have been described. HAV mutation rate is significantly lower as compared to other members of the family Picornaviridae. The mode of evolution appears, at least in part, to contribute to the presence of only one known serotype.
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Affiliation(s)
- Juan Cristina
- Laboratorio de Virología Molecular, Centro de Investigaciones Nucleares, Facultad de Ciencias, Iguá 4225, 11400 Montevideo, Uruguay.
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Endo K, Inoue J, Takahashi M, Mitsui T, Masuko K, Akahane Y, Okamoto H. Analysis of the full-length genome of a subgenotype IIIB hepatitis A virus isolate: primers for broadly reactive PCR and genotypic analysis. J Med Virol 2007; 79:8-17. [PMID: 17133545 DOI: 10.1002/jmv.20757] [Citation(s) in RCA: 24] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/10/2022]
Abstract
Among six known subgenotypes (IA, IB, IIA, IIB, IIIA, and IIIB) of human hepatitis A virus (HAV), the complete genomic sequence has not been determined for IIIB. In this study, the full-length genomic sequence of a IIIB HAV isolate (HA-JNG06-90F) recovered from a Japanese patient who contracted sporadic hepatitis A in 1990, was determined. The HA-JNG06-90F genome, which comprised 7462 nt excluding the poly(A) tail, was related most closely to NOR-21 of subgenotype IIIA with an identity of 89.1%, and was only 82.6-83.4% similar to human HAV isolates of genotypes I and II over the entire genome. Comparison of full-length genomic sequences of 20 reported isolates and HA-JNG06-90F generated optimal results for separation of different levels: the nucleotide identities were 80.7-86.6% at the genotype level, 89.1-91.9% at the subgenotype level, and 94.6-99.7% at the isolate level. Similar ranges of nucleotide identity were observed when comparing partial nucleotide sequences of the VP1-2B (481 nt; primer sequences at both ends excluded) and 3C/3D (590 nt) regions, which were amplifiable by PCR with primers designed from well-conserved areas of the HAV genome. All 66 samples with IgM-class HAV antibodies tested positive for HAV RNA by both VP1-2B (481 nt)-PCR and 3C/3D (590 nt)-PCR: subgenotype assignment was concordant in all samples tested (IA [n = 61], IB [n = 1], IIIA [n = 2] and IIIB [n = 2]). These results suggest that two broadly reactive PCRs using primers derived from the VP1-2B and 3C/3D regions, respectively, may be applicable to universal detection and phylogenetic analysis of various HAV strains.
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Affiliation(s)
- Kazunori Endo
- Division of Virology, Department of Infection and Immunity, Jichi Medical University School of Medicine, Tochigi-Ken, Japan
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Taylor RM, Davern T, Munoz S, Han SH, McGuire B, Larson AM, Hynan L, Lee WM, Fontana RJ. Fulminant hepatitis A virus infection in the United States: Incidence, prognosis, and outcomes. Hepatology 2006; 44:1589-97. [PMID: 17133489 PMCID: PMC3505613 DOI: 10.1002/hep.21439] [Citation(s) in RCA: 120] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
Acute liver failure (ALF) due to hepatitis A virus (HAV) infection is an uncommon but potentially lethal illness. The aim of this study was to identify readily available laboratory and clinical features associated with a poor prognosis among ALF patients with HAV infection. The presenting features of 29 adults with anti-HAV IgM positive ALF enrolled in the ALFSG_between 1998 and 2005 were reviewed. The HAV patients listed for transplantation by UNOS were also reviewed. Acute HAV accounted for 3.1% of patients enrolled in the ALFSG. At 3 weeks follow-up, 16 had spontaneously recovered (55%), 9 underwent transplantation (31%), and 4 had died (14%). A prognostic model incorporating 4 presenting features (serum ALT <2,600 IU/L, creatinine >2.0 mg/dL, intubation, pressors) had an AUROC for transplant/death of 0.899 which was significantly better than the King's College criteria (0.623, P = .018) and MELD scores (0.707, P = .0503). Between 1988 and 2005, the frequency of patients requiring liver transplantation for HAV in the UNOS database significantly decreased from 0.7 % to 0.1% (P < .001). In addition, the proportion of HAV cases enrolled in the ALFSG significantly decreased from 5% to 0.8% (P = .007). In conclusion, the frequency of HAV patients enrolling in the ALFSG and being listed for liver transplantation in the United States has declined in parallel. A prognostic index consisting of 4 clinical and laboratory features predicted the likelihood of transplant/death significantly better than other published models suggesting that disease specific prognostic models may be of value in non-acetaminophen ALF.
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Affiliation(s)
- Ryan M. Taylor
- Department of Internal Medicine, University of Michigan, Ann Arbor, MI
| | - Timothy Davern
- University of California at San Francisco, San Francisco, CA
| | | | | | | | | | - Linda Hynan
- University of Texas Southwestern Medical Center, Dallas, TX
| | - William M. Lee
- University of Texas Southwestern Medical Center, Dallas, TX
| | - Robert J. Fontana
- Department of Internal Medicine, University of Michigan, Ann Arbor, MI
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