[en] BACKGROUND: The epidemiological and molecular characteristics of hepatitis C virus (HCV) infection in the general population have been poorly investigated in Africa. The aim of this study was to determine the prevalence, genotype distribution and epidemic history of HCV in the Gabonese general population. METHODS/PRINCIPAL FINDINGS: A total of 4042 sera collected from adults in 220 villages in all nine administrative areas of the country were screened for antibodies to HCV. HCV NS5B region sequencing was performed for molecular characterization and population genetic analyses. Of 4042 tested sera, 455 (11.2%) were positive. The seroprevalence of HCV varied significantly by administrative area, with the highest rate in Ogooue-Lolo province (20.4%) and the lowest in Ogooue-Maritine province (3.7%). History of parenteral injections, past hospital admission and age over 55 years were independent risk factors for HCV infection (p<0.0001). Phylogenetic analyses showed that 91.9% of the strains were genotype 4 (HCV-4), 5.7% genotype 1 and 2.2% genotype 2. HCV-4 strains were highly heterogeneous, with more than eight subtypes; subtype 4e predominated (57.3%). Coalescence analyses indicated that subtype 4e was the oldest, with an estimated most recent common ancestor of 1702 [95% CI, 1418-1884]. The epidemic profile indicated that it spread exponentially during the first part of the 20th century, probably by iatrogenic transmission. CONCLUSIONS/SIGNIFICANCE: These results confirm the endemicity of HCV subtype 4e in Gabon and show that its spread is due to a cohort effect, with previous, possibly iatrogenic events. More extensive epidemiological studies are needed to better characterize the route of transmission and the dissemination of HCV in Gabon.
Shepard C, Finelli I, Alter M, (2005) Global epidemiology of hepatitis C virus infection. Lancet Infect Dis 5: 558-567.
World Health Organization (2010) The global burden of diseases: 2004 update. Annex A. Deaths and DALYs 2004. Geneva. Available: http://www.who.int/healthinfo/global_burden_disease/GBD_report_2004update_Annex A.pdf. Accessed 2010 Dec 14.
Frank C, Mohamed M, Strickland G, Lavanchy D, Arthur R, et al. (2000) The role of parenteral antischistosomal therapy in the spread of hepatitis C virus in Egypt. Lancet 355: 887-891.
Madhava V, Burgess C, Drucker E, (2002) Epidemiology of chronic hepatitis C virus infection in sub-Saharan Africa. Lancet Infect Dis 2: 293-302.
Cantaloube J, Gallian P, Bokilo A, Jordier F, Biagini P, et al. (2010) Analysis of hepatitis C virus strains circulating in Republic of the Congo. J Med Virol 82: 562-567.
Ndong-Atome G, Makuwa M, Ouwe-Missi-Oukem-Boyer O, Pybus O, Branger M, et al. (2008) High prevalence of hepatitis C virus infection and predominance of genotype 4 in rural Gabon. J Med Virol 80: 1581-1587.
Nerrienet E, Pouillot R, Lachenal G, Njouom R, Mfoupouendoun J, et al. (2005) Hepatitis C virus infection in Cameroon: A cohort-effect. J Med Virol 76: 208-214.
Njouom R, Pasquier C, Ayouba A, Gessain A, Froment A, et al. (2003) High rate of hepatitis C virus infection and predominance of genotype 4 among elderly inhabitants of a remote village of the rain forest of South Cameroon. J Med Virol 71: 219-225.
Pépin J, Labbé A, Mamadou-Yaya F, Mbélesso P, Mbadingaï S, et al. (2010) Iatrogenic transmission of human T cell lymphotropic virus type 1 and hepatitis C virus through parenteral treatment and chemoprophylaxis of sleeping sickness in colonial Equatorial Africa. Clin Infect Dis 51: 777-784.
Pépin J, Lavoie M, Pybus O, Pouillot R, Foupouapouognigni Y, et al. (2010) Risk factors for hepatitis C virus transmission in colonial Cameroon. Clin Infect Dis 51: 768-776.
Simmonds P, Bukh J, Combet C, Deléage G, Enomoto N, et al. (2005) Consensus proposals for a unified system of nomenclature of hepatitis C virus genotypes. Hepatology 42: 962-973.
Pybus O, Barnes E, Taggart R, Lemey P, Markov P, et al. (2009) Genetic history of hepatitis C virus in East Asia. J Virol 83: 1071-1082.
Markov P, Pepin J, Frost E, Deslandes S, Labbé A, et al. (2009) Phylogeography and molecular epidemiology of hepatitis C virus genotype 2 in Africa. J Gen Virol 90: 2086-2096.
Njouom R, Frost E, Deslandes S, Mamadou-Yaya F, Labbé A, et al. (2009) Predominance of hepatitis C virus genotype 4 infection and rapid transmission between 1935 and 1965 in the Central African Republic. J Gen Virol 90: 2452-2456.
Njouom R, Nerrienet E, Dubois M, Lachenal G, Rousset D, et al. (2007) The hepatitis C virus epidemic in Cameroon: Genetic evidence for rapid transmission between 1920 and 1960. Infect Genet Evol 7: 361-367.
Pouillot R, Lachenal G, Pybus O, Rousset D, Njouom R, (2008) Variable epidemic histories of hepatitis C virus genotype 2 infection in West Africa and Cameroon. Infect Genet Evol 8: 676-681.
Simmonds P, (2004) Genetic diversity and evolution of hepatitis C virus-15 years on. J Gen Virol 85: 3173-3188.
Khan A, Tanaka Y, Azam Z, Abbas Z, Kurbanov F, et al. (2009) Epidemic spread of hepatitis C virus genotype 3a and relation to high incidence of hepatocellular carcinoma in Pakistan. J Med Virol 81: 1189-1197.
Magiorkinis G, Magiorkinis E, Paraskevis D, Ho S, Shapiro B, et al. (2009) The global spread of hepatitis C virus 1a and 1b: a phylodynamic and phylogeographic analysis. PLoS Med 6: e1000198.
Matheï C, Van Dooren S, Lemey P, Van Damme P, Buntinx F, et al. (2008) The epidemic history of hepatitis C among injecting drug users in Flanders, Belgium. J Viral Hepat 15: 399-408.
Nakano T, Lu L, Liu P, Pybus O, (2004) Viral gene sequences reveal the variable history of hepatitis C virus infection among countries. J Infect Dis 190: 1098-1108.
Pybus O, Charleston M, Gupta S, Rambaut A, Holmes E, et al. (2001) The epidemic behavior of the hepatitis C virus. Science 292: 2323-2325.
Pybus O, Cochrane A, Holmes E, Simmonds P, (2005) The hepatitis C virus epidemic among injecting drug users. Infect Genet Evol 5: 131-139.
Tanaka Y, Hanada K, Mizokami M, Yeo A, Shih J, et al. (2002) A comparison of the molecular clock of hepatitis C virus in the United States and Japan predicts that hepatocellular carcinoma incidence in the United States will increase over the next two decades. Proc Natl Acad Sci USA 99: 15584-15589.
Hauri A, Armstrong G, Hutin Y, (2004) The global burden of disease attributable to contaminated injections given in health care settings. Int J STD AIDS 15: 7-16.
Tanaka Y, Hanada K, Orito E, Akahane Y, Chayama K, et al. (2005) Molecular evolutionary analyses implicate injection treatment for schistosomiasis in the initial hepatitis C epidemics in Japan. J Hepatol 42: 47-53.
Delaporte E, Thiers V, Dazza M, Romeo R, Mlika-Cabanne N, et al. (1993) High level of hepatitis C endemicity in Gabon, equatorial Africa. Trans R Soc Trop Med Hyg 87: 636-637.
Xu L, Larzul D, Delaporte E, Bréchot C, Kremsdorf D, (1994) Hepatitis C virus genotype 4 is highly prevalent in central Africa (Gabon). J Gen Virol 75: 2393-2398.
Becquart P, Wauquier N, Mahlakõiv T, Nkoghe D, Padilla C, et al. (2010) High prevalence of both humoral and cellular immunity to Zaire ebolavirus among rural populations in Gabon. PLoS One 5: e9126.
Njouom R, Pasquier C, Ayouba A, Sandres-Sauné K, Mfoupouendoun J, et al. (2003) Hepatitis C virus infection among pregnant women in Yaounde, Cameroon: prevalence, viremia, and genotypes. J Med Virol 69: 384-390.
Pasquier C, Njouom R, Ayouba A, Dubois M, Sartre M, et al. (2005) Distribution and heterogeneity of hepatitis C genotypes in hepatitis patients in Cameroon. J Med Virol 77: 390-398.
Thompson J, Gibson T, Plewniak F, Jeanmougin F, Higgins D, (1997) The CLUSTAL_X windows interface: flexible strategies for multiple sequence alignment aided by quality analysis tools. Nucleic Acids Res 25: 4876-4882.
Tamura K, Peterson D, Peterson N, Stecher G, Nei M, et al. (2011) MEGA5: molecular evolutionary genetics analysis using maximum likelihood, evolutionary distance, and maximum parsimony methods. Mol Biol Evol 28: 2731-2739.
Simmonds P, Smith D, McOmish F, Yap P, Kolberg J, et al. (1994) Identification of genotypes of hepatitis C virus by sequence comparisons in the core, E1 and NS-5 regions. J Gen Virol 75: 1053-1061.
Drummond A, Ho S, Phillips M, Rambaut A, (2006) Relaxed phylogenetics and dating with confidence. PLoS Biol 4: e88.
Hibbs R, Corwin A, Hassan N, Kamel M, Darwish M, et al. (1993) The epidemiology of antibody to hepatitis C in Egypt. J Infect Dis 168: 789-790.
Noguchi S, Sata M, Suzuki H, Mizokami M, Tanikawa K, (1997) Routes of transmission of hepatitis C virus in an endemic rural area of Japan. Molecular epidemiologic study of hepatitis C virus infection. Scand J Infect Dis 29: 23-28.
Shin H, Kim J, Ohno T, Cao K, Mizokami M, et al. (2000) Prevalence and risk factors of hepatitis C virus infection among Koreans in rural area of Korea. Hepatol Res 17: 185-196.
Tawaraya H, Ohkoshi S, Kuwana K, Watanabe M, Kamimura T, et al. (1995) Epidemiologic survey and genetic analysis of endemic hepatitis C virus infection in a Japanese town with a high prevalence of hepatitis B virus carriers. J Med Virol 45: 367-372.
Yoshii E, Shinzawa H, Saito T, Shao L, Kuboki M, et al. (1999) Molecular epidemiology of hepatitis C virus infection in an area endemic for community-acquired acute hepatitis C. Tohoku J Exp Med. 188: 311-316.
Alter M, Margolis H, Krawczynski K, Judson F, Mares A, et al. (1992) The natural history of community-acquired hepatitis C in the United States. The Sentinel Counties Chronic non-A, non-B Hepatitis Study Team. N Engl J Med 327: 1899-1905.
Shobokshi O, Serebour F, Al-Drees A, Mitwalli A, Qahtani A, et al. (2003) Hepatitis C virus seroprevalence rate among Saudis. Saudi Med J 24: S81-86.
Van Damme P, Thyssen A, Van Loock F, (2002) Epidemiology of hepatitis C in Belgium: present and future. Acta Gastroenterol Belg 65: 78-79.
Ndjomou J, Pybus O, Matz B, (2003) Phylogenetic analysis of hepatitis C virus isolates indicates a unique pattern of endemic infection in Cameroon. J Gen Virol 84: 2333-2341.
Bhattacharya D, Accola M, Ansari I, Striker R, Rehrauer W, (2011) Naturally occurring genotype 2b/1a hepatitis C virus in the United States. Virol J 8: 458.
Colina R, Casane D, Vasquez S, García-Aguirre L, Chunga A, et al. (2004) Evidence of intratypic recombination in natural populations of hepatitis C virus. J Gen Virol 85: 31-37.
González-Candelas F, López-Labrador F, Bracho M, (2011) Recombination in hepatitis C virus. Viruses 3: 2006-2024.
Kageyama S, Agdamag D, Alesna E, Leaño P, Heredia A, et al. (2006) A natural inter-genotypic (2b/1b) recombinant of hepatitis C virus in the Philippines. J Med Virol 78: 1423-1428.
Kalinina O, Norder H, Mukomolov S, Magnius L, (2002) A natural intergenotypic recombinant of hepatitis C virus identified in St Petersburg. J Virol 76: 4034-4043.
Kurbanov F, Tanaka Y, Avazova D, Khan A, Sugauchi F, et al. (2008) Detection of hepatitis C virus natural recombinant RF1_2k/1b strain among intravenous drug users in Uzbekistan. Hepatol Res 38: 457-464.
Legrand-Abravanel F, Claudinon J, Nicot F, Dubois M, Chapuy-Regaud S, et al. (2007) New natural intergenotypic (2/5) recombinant of hepatitis C virus. J Virol 81: 4357-4362.
Noppornpanth S, Lien T, Poovorawan Y, Smits S, Osterhaus A, et al. (2006) Identification of a naturally occurring recombinant genotype 2/6 hepatitis C virus. J Virol 80: 7569-7577.
Viazov S, Ross S, Kyuregyan K, Timm J, Neumann-Haefelin C, et al. (2010) Hepatitis C virus recombinants are rare even among intravenous drug users. J Med Virol 82: 232-238.
Zhou Y, Wang X, Hong G, Tan Z, Zhu Y, et al. (2010) Natural intragenotypic and intergenotypic HCV recombinants are rare in southwest China even among patients with multiple exposures. J Clin Virol 49: 272-276.