François Rouet1, Janin Nouhin1, Du-Ping Zheng2, Benjamin Roche3, Allison Black4, Sophearot Prak1, Marie Leoz5, Catherine Gaudy-Graffin6, Laurent Ferradini7, Chandara Mom8, Sovatha Mam8, Charlotte Gautier1, Gérard Lesage6, Sreymom Ken1, Kerya Phon1, Alexandra Kerleguer1, Chunfu Yang2, William Killam9, Masami Fujita7, Chhivun Mean8, Didier Fontenille1, Francis Barin6, Jean-Christophe Plantier5, Trevor Bedford4, Artur Ramos9, Vonthanak Saphonn10. 1. Unité Virus de l'Immunodéficience Humaine (VIH)/Hépatites, Institut Pasteur du Cambodge, Phnom Penh, Cambodia. 2. International Laboratory Branch, Centers for Disease Control and Prevention, Atlanta, Georgia. 3. Unité Mixte de Recherche Institut de Recherche pour le Développement 224, Centre National de la Recherche Scientifique 5290, Université de Montpellier, Maladies Infectieuses et Vecteurs: Ecologie, Génétique, Evolution et Contrôle, Montpellier, France. 4. Fred Hutchinson Cancer Research Center, Seattle, Washington. 5. Centre National de Référence sur le VIH, Laboratoire Associé, EA2656, Rouen University Hospital, Tours, France. 6. Centre National de Référence sur le VIH and Institut national de la santé et de la recherche médicale, Unité 966, Tours, France. 7. World Health Organization, Phnom Penh, Cambodia. 8. National Center for HIV/AIDS, Dermatology and Sexually Transmitted Diseases, Phnom Penh, Cambodia. 9. Division of Global HIV/AIDS, Centers for Disease Control and Prevention, Phnom Penh, Cambodia. 10. University of Health Sciences, Phnom Penh, Cambodia.
Abstract
Background: In 2014-2015, 242 individuals aged 2-89 years were newly diagnosed with human immunodeficiency virus type 1 (HIV-1) in Roka, a rural commune in Cambodia. A case-control study attributed the outbreak to unsafe injections. We aimed to reconstruct the likely transmission history of the outbreak. Methods: We assessed in 209 (86.4%) HIV-infected cases the presence of hepatitis C virus (HCV) and hepatitis B virus (HBV). We identified recent infections using antibody (Ab) avidity testing for HIV and HCV. We performed amplification, sequencing, and evolutionary phylogenetic analyses of viral strains. Geographical coordinates and parenteral exposure through medical services provided by an unlicensed healthcare practitioner were obtained from 193 cases and 1499 controls during interviews. Results: Cases were coinfected with HCV (78.5%) and HBV (12.9%). We identified 79 (37.8%) recent (<130 days) HIV infections. Phylogeny of 202 HIV env C2V3 sequences showed a 198-sample CRF01_AE strains cluster, with time to most recent common ancestor (tMRCA) in September 2013 (95% highest posterior density, August 2012-July 2014), and a peak of 15 infections/day in September 2014. Three geospatial HIV hotspots were discernible in Roka and correlated with high exposure to the practitioner (P = .04). Fifty-nine of 153 (38.6%) tested cases showed recent (<180 days) HCV infections. Ninety HCV NS5B sequences formed 3 main clades, 1 containing 34 subtypes 1b with tMRCA in 2012, and 2 with 51 subtypes 6e and tMRCAs in 2002-2003. Conclusions: Unsafe injections in Cambodia most likely led to an explosive iatrogenic spreading of HIV, associated with a long-standing and more genetically diverse HCV propagation.
Background: In 2014-2015, 242 individuals aged 2-89 years were newly diagnosed with human immunodeficiency virus type 1 (HIV-1) in Roka, a rural commune in Cambodia. A case-control study attributed the outbreak to unsafe injections. We aimed to reconstruct the likely transmission history of the outbreak. Methods: We assessed in 209 (86.4%) HIV-infected cases the presence of hepatitis C virus (HCV) and hepatitis B virus (HBV). We identified recent infections using antibody (Ab) avidity testing for HIV and HCV. We performed amplification, sequencing, and evolutionary phylogenetic analyses of viral strains. Geographical coordinates and parenteral exposure through medical services provided by an unlicensed healthcare practitioner were obtained from 193 cases and 1499 controls during interviews. Results: Cases were coinfected with HCV (78.5%) and HBV (12.9%). We identified 79 (37.8%) recent (<130 days) HIV infections. Phylogeny of 202 HIV env C2V3 sequences showed a 198-sample CRF01_AE strains cluster, with time to most recent common ancestor (tMRCA) in September 2013 (95% highest posterior density, August 2012-July 2014), and a peak of 15 infections/day in September 2014. Three geospatial HIV hotspots were discernible in Roka and correlated with high exposure to the practitioner (P = .04). Fifty-nine of 153 (38.6%) tested cases showed recent (<180 days) HCV infections. Ninety HCV NS5B sequences formed 3 main clades, 1 containing 34 subtypes 1b with tMRCA in 2012, and 2 with 51 subtypes 6e and tMRCAs in 2002-2003. Conclusions: Unsafe injections in Cambodia most likely led to an explosive iatrogenic spreading of HIV, associated with a long-standing and more genetically diverse HCV propagation.
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