Phylogeography, Risk Factors and Genetic History of Hepatitis C Virus in Gabon, Central Africa

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

Dynamic Interaction between STLV-1 Proviral Load and T-Cell Response during Chronic Infection and after Immunosuppression in Non-Human Primates

We used mandrills (Mandrillus sphinx) naturally infected with simian T-cell leukemia virus type 1 (STLV-1) as a model for evaluating the influence of natural STLV-1 infection on the dynamics and evolution of the immune system during chronic infection. Furthermore, in order to evaluate the role of the immune system in controlling the infection during latency, we induced immunosuppression in the infected monkeys. We first showed that the STLV-1 proviral load was higher in males than in females and increased significantly with the duration of infection: mandrills infected for 10–6 years had a significantly higher proviral load than those infected for 2–4 years. Curiously, this observation was associated with a clear reduction in CD4+ T-cell number with age. We also found that the percentage of CD4+ T cells co-expressing the activation marker HLA-DR and the mean percentage of CD25+ in CD4+ and CD8+ T cells were significantly higher in infected than in uninfected animals. Furthermore, the STLV-1 proviral load correlated positively with T-cell activation but not with the frequency of T cells secreting interferon γ in response to Tax peptides. Lastly, we showed that, during immunosuppression in infected monkeys, the percentages of CD8+ T cells expressing HLA-DR+ and of CD4+ T cells expressing the proliferation marker Ki67 decreased significantly, although the percentage of CD8+ T cells expressing HLA-DR+ and Ki67 increased significantly by the end of treatment. Interestingly, the proviral load increased significantly after immunosuppression in the monkey with the highest load. Our study demonstrates that mandrills naturally infected with STLV-1 could be a suitable model for studying the relations between host and virus. Further studies are needed to determine whether the different compartments of the immune response during infection induce the long latency by controlling viral replication over time. Such studies would provide important information for the development of immune-based therapeutic strategies

Prevalence, genetic diversity and antiretroviral drugs resistance-associated mutations among untreated HIV-1-infected pregnant women in Gabon, central Africa

BACKGROUND: In Africa, the wide genetic diversity of HIV has resulted in emergence of new strains, rapid spread of this virus in sub-Saharan populations and therefore spread of the HIV epidemic throughout the continent. METHODS: To determine the prevalence of antibodies to HIV among a high-risk population in Gabon, 1098 and 2916 samples were collected from pregnant women in 2005 and 2008, respectively. HIV genotypes were evaluated in 107 HIV-1-positive samples to determine the circulating subtypes of strains and their resistance to antiretroviral drugs (ARVs). RESULTS: The seroprevalences were 6.3% in 2005 and 6.0% in 2008. The main subtype was recombinant CRF02_AG (46.7%), followed by the subtypes A (19.6%), G (10.3%), F (4.7%), H (1.9%) and D (0.9%) and the complex recombinants CRF06_cpx (1.9%) and CRF11_cpx (1.9%); 12.1% of subtypes could not be characterized. Analysis of ARVs resistance to the protease and reverse transcriptase coding regions showed mutations associated with extensive subtype polymorphism. In the present study, the HIV strains showed reduced susceptibility to ARVs (2.8%), particularly to protease inhibitors (1.9%) and nucleoside reverse transcriptase inhibitors (0.9%). CONCLUSIONS: The evolving genetic diversity of HIV calls for continuous monitoring of its molecular epidemiology in Gabon and in other central African countries

Correction: Correction: A Novel Rhabdovirus Associated with Acute Hemorrhagic Fever in Central Africa.

[This corrects the article DOI: 10.1371/journal.ppat.1002924.]

Hepatitis C Virus Infection May Lead to Slower Emergence of P. falciparum in Blood

International audienceBACKGROUND: Areas endemic for Plasmodium falciparum, hepatitis B virus (HBV) and hepatitis C virus (HCV) overlap in many parts of sub-Saharan Africa. HBV and HCV infections develop in the liver, where takes place the first development stage of P. falciparum before its further spread in blood. The complex mechanisms involved in the development of hepatitis may potentially influence the development of the liver stage of malaria parasites. Understanding the molecular mechanisms of these interactions could provide new pathophysiological insights for treatment strategies in Malaria. METHODOLOGY: We studied a cohort of 319 individuals living in a village where the three infections are prevalent. The patients were initially given a curative antimalarial treatment and were then monitored for the emergence of asexual P. falciparum forms in blood, fortnightly for one year, by microscopy and polymerase chain reaction. PRINCIPAL FINDINGS: At inclusion, 65 (20.4%) subjects had detectable malaria parasites in blood, 36 (11.3%) were HBV chronic carriers, and 61 (18.9%) were HCV chronic carriers. During follow-up, asexual P. falciparum forms were detected in the blood of 203 patients. The median time to P. falciparum emergence in blood was respectively 140 and 120 days in HBV- and HBV+ individuals, and 135 and 224 days in HCV- and HCV+ individuals. HCV carriage was associated with delayed emergence of asexual P. falciparum forms in blood relative to patients without HCV infection. CONCLUSIONS: This pilot study represents first tentative evidence of a potential epidemiological interaction between HBV, HCV and P. falciparum infections. Age is an important confounding factor in this setting however multivariate analysis points to an interaction between P. falciparum and HCV at the hepatic level with a slower emergence of P. falciparum in HCV chronic carriers. More in depth analysis are necessary to unravel the basis of hepatic interactions between these two pathogens, which could help in identifying new therapeutic approaches against malaria

Socializing One Health: an innovative strategy to investigate social and behavioral risks of emerging viral threats

In an effort to strengthen global capacity to prevent, detect, and control infectious diseases in animals and people, the United States Agency for International Development’s (USAID) Emerging Pandemic Threats (EPT) PREDICT project funded development of regional, national, and local One Health capacities for early disease detection, rapid response, disease control, and risk reduction. From the outset, the EPT approach was inclusive of social science research methods designed to understand the contexts and behaviors of communities living and working at human-animal-environment interfaces considered high-risk for virus emergence. Using qualitative and quantitative approaches, PREDICT behavioral research aimed to identify and assess a range of socio-cultural behaviors that could be influential in zoonotic disease emergence, amplification, and transmission. This broad approach to behavioral risk characterization enabled us to identify and characterize human activities that could be linked to the transmission dynamics of new and emerging viruses. This paper provides a discussion of implementation of a social science approach within a zoonotic surveillance framework. We conducted in-depth ethnographic interviews and focus groups to better understand the individual- and community-level knowledge, attitudes, and practices that potentially put participants at risk for zoonotic disease transmission from the animals they live and work with, across 6 interface domains. When we asked highly-exposed individuals (ie. bushmeat hunters, wildlife or guano farmers) about the risk they perceived in their occupational activities, most did not perceive it to be risky, whether because it was normalized by years (or generations) of doing such an activity, or due to lack of information about potential risks. Integrating the social sciences allows investigations of the specific human activities that are hypothesized to drive disease emergence, amplification, and transmission, in order to better substantiate behavioral disease drivers, along with the social dimensions of infection and transmission dynamics. Understanding these dynamics is critical to achieving health security--the protection from threats to health-- which requires investments in both collective and individual health security. Involving behavioral sciences into zoonotic disease surveillance allowed us to push toward fuller community integration and engagement and toward dialogue and implementation of recommendations for disease prevention and improved health security

Diversity plot of SIVcpz-Gab4 with SIVcpz-Gab1 and SIVcpz-Gab2 sequences.

<p>Regions with uncertain aligment or sites with a gap in any sequence were excluded (8261 nucleotides after de-gapping). The nucleotide sequence difference is plotted for windows of 450 nucleotides and a 20-nucleotide step increment.</p