Epidemiological Evidence of Nosocomial and Zoonotic Transmission of Human T-Cell Leukemia Virus-1 in a Large Survey in a Rural Population of Central Africa.

BACKGROUND: Central Africa is one of the largest areas of high endemicity for human T-cell leukemia virus-1 (HTLV-1). However, no preventive measures are yet implemented to reduce its transmission, which can be sexual, from mother-to-child, or through contaminated blood products. Rare zoonotic transmissions from nonhuman primates (NHPs) have also been reported in this region. Here we investigated the HTLV-1 prevalence and associated risk factors in a rural population in Cameroon. METHODS: From 2019 to 2021, we performed a cross-sectional survey in the eastern region of Cameroon. HTLV-1 infection was first screened by ELISA, then tested by western blot and envelope gene targeted polymerase chain reaction. Risk factors associated with HTLV-1 infection were identified by logistic regression in univariable and multivariable analyses. RESULTS: Among 3400 participants, HTLV-1 prevalence was 1.1% (95% confidence interval [CI], .7-1.5). Factors independently associated with HTLV-1 infection were Pygmy ethnicity (adjusted odd ratio [aOR], 2.9; 95% CI, 1.3-6.2), history of surgery (aOR, 6.3; 95% CI, 2.2-17.8), and NHP bite (aOR, 6.6; 95% CI, 2.2-19.8). CONCLUSIONS: These results suggest both iatrogenic and zoonotic transmission of HTLV-1 in Cameroon. Further studies are needed to assess the risk of nosocomial transmission of HTLV-1, to guide public health authorities in implementing preventive measures to control HTLV-1 transmission.

Pneumococcal Carriage in Burkina Faso After 13-Valent Pneumococcal Conjugate Vaccine Introduction: Results From 2 Cross-sectional Population-Based Surveys.

BACKGROUND: Burkina Faso, a country in Africa's meningitis belt, introduced 13-valent pneumococcal conjugate vaccine (PCV13) in October 2013, with 3 primary doses given at 8, 12 and 16 weeks of age. To assess whether the new PCV13 program controlled pneumococcal carriage, we evaluated overall and serotype-specific colonization among children and adults during the first 3 years after introduction. METHODS: We conducted 2 population-based, cross-sectional, age-stratified surveys in 2015 and 2017 in the city of Bobo-Dioulasso. We used standardized questionnaires to collect sociodemographic, epidemiologic, and vaccination data. Consenting eligible participants provided nasopharyngeal (all ages) and oropharyngeal (≥5 years only) swab specimens. Swab specimens were plated onto blood agar either directly (2015) or after broth enrichment (2017). Pneumococci were serotyped by conventional multiplex polymerase chain reaction. We assessed vaccine effect by comparing the proportion of vaccine-type (VT) carriage among colonized individuals from a published baseline survey (2008) with each post-PCV survey. RESULTS: We recruited 992 (2015) and 1005 (2017) participants. Among children aged <5 years, 42.8% (2015) and 74.0% (2017) received ≥2 PCV13 doses. Among pneumococcal carriers aged <1 year, VT carriage declined from 55.8% in 2008 to 36.9% in 2017 (difference, 18.9%; 95% confidence interval, 1.9%-35.9%; P = .03); among carriers aged 1-4 years, VT carriage declined from 55.3% to 31.8% (difference, 23.5%; 6.8%-40.2%; P = .004); and among participants aged ≥5 years, no significant change was observed. CONCLUSION: Within 3 years of PCV13 implementation in Burkina Faso, we documented substantial reductions in the percentage of pneumococcal carriers with a VT among children aged <5 years, but not among persons aged ≥5 years. More time, a change in the PCV13 schedule, or both, may be needed to better control pneumococcal carriage in this setting.

Cost-effectiveness of adding a birth dose of hepatitis B vaccine in the Dafra district of the Hauts-Bassins Region in Burkina Faso (NéoVac Study).

BACKGROUND: The World Health Organization (WHO) recommends a first hepatitis B vaccine dose within 24 h of birth (HepB-BD) to prevent mother-to-child transmission. Evidence for this strategy's economic value in Africa is limited. We assessed the costs and cost-effectiveness of adding HepB-BD to the current three-dose pentavalent schedule (HepB3) in the Dafra district of the Hauts-Bassins Region in Burkina Faso. METHODS: Using a decision tree combined with a Markov model, we estimated the expected number of life-years (LY) and disability-adjusted life-years (DALYs) saved, incremental costs, and incremental cost-effectiveness ratios (ICER) of HepB-BD + HepB3 versus HepB3 alone in Dafra's 2017 birth cohort (n = 11,462). Institutional delivery rates, vaccine coverage, and vaccination costs from a health system perspective were estimated from field-collected data. We estimated the effectiveness of HepB-BD, age-specific transition probabilities, and horizontal transmission risks using data from previous African studies. Costs and health outcomes were discounted at an annual rate of 3%. We conducted one-way and probabilistic sensitivity analyses to assess uncertainty. RESULTS: In the base-case analysis without discounting, HepB-BD + HepB3 yielded a net cost saving of US$18,979 and saved 163 DALYs compared with HepB3 alone. With discounting, HepB-BD + HepB3 compared with HepB3 resulted in an incremental cost of US$554 and 31 DALYs averted, translating into an ICER of US$18/DALY averted. In one-way sensitivity analyses, HepB-BD + HepB3 remained cost-effective (at the cost-effectiveness threshold of US$671 i.e. the Burkina Faso per-capita gross domestic product) for all parameter changes. However, results were very sensitive to variations in HepB-BD unit cost per vaccinated neonate and perinatal transmission risk in mothers carrying the hepatitis B e antigen. The probabilities of HepB-BD + HepB3 being cost-effective were 71.7% and 86.7%, at the cost-effectiveness thresholds of US$335 and US$671, respectively. CONCLUSION: Introducing HepB-BD in Burkina Faso is likely to be cost-effective.

Impact of Introducing Hepatitis B Birth Dose Vaccines into the Infant Immunization Program in Burkina Faso: Study Protocol for a Stepped Wedge Cluster Randomized Trial (NéoVac Study).

To achieve global hepatitis elimination by 2030, it is critical to prevent the mother-to-child transmission (MTCT) of hepatitis B virus (HBV). Since 2009, the WHO has recommended administering hepatitis B vaccine to all neonates within 24 h of birth to prevent MTCT. However, many countries in sub-Saharan Africa only provide hepatitis B immunization at the age of 6, 10, and 14 weeks or 8, 12, and 16 weeks using a combined vaccine. To accelerate the introduction of the hepatitis B birth dose vaccine (HepB-BD) into sub-Saharan Africa, it is critical to establish to what extent the addition of HepB-BD can further reduce HBV transmission in areas where three-dose infant vaccination has been implemented. We therefore designed a study to evaluate the impact, acceptability, and cost-effectiveness of incorporating the HepB-BD into the routine immunization program in a real-life field condition in Burkina Faso, where the hepatitis B vaccination is currently scheduled at 8-12-16 weeks. Through a multidisciplinary approach combining epidemiology, anthropology, and health economics, the Neonatal Vaccination against Hepatitis B in Africa (NéoVac) study conducts a pragmatic stepped wedge cluster randomized controlled trial in rural areas of the Hauts-Bassins Region. The study was registered in ClinicalTrials.gov (identifier: NCT04029454). A health center is designated as a cluster, and the introduction of HepB-BD will be rolled out sequentially in 24 centers. Following an initial period in which no health center administers HepB-BD, one center will be randomly allocated to incorporate HepB-BD. Then, at a regular interval, another center will be randomized to cross from the control to the intervention period, until all 24 centers integrate HepB-BD. Pregnant women attending antenatal care will be systematically invited to participate. Infants born during the control period will follow the conventional immunization schedule (8-12-16 weeks), while those born in the interventional period will receive HepB-BD in addition to the routine vaccines (0-8-12-16 weeks). The primary outcome, the proportion of hepatitis B surface antigen (HBsAg) positivity in infants aged at 9 months, will be compared between children born before and after HepB-BD introduction. The study will generate data that may assist governments and stakeholders in sub-Saharan Africa to make evidence-based decisions about whether to add HepB-BD into the national immunization programs.

Application of a Pneumococcal Serotype-specific Urinary Antigen Detection Test for Identification of Pediatric Pneumonia in Burkina Faso.

BACKGROUND: Serotype-specific diagnosis of pneumococcal community-acquired pneumonia in children under age 5 years would mark a major advancement for understanding pneumococcal epidemiology and supporting vaccine decision-making. METHODS: A Luminex technology-based multiplex urinary antigen detection (UAD) diagnostic assay was developed and subsequently validated in adults, but its applicability to children is unknown. This study aimed to set appropriate cutoffs for use of the UAD in a healthy pediatric population and apply these cutoffs in children with pneumonia in sub-Saharan Africa. The cutoffs were determined by assessing 379 urines obtained from healthy children under age 5 years from the Bobo-Dioulasso area for serotypes included in 13-valent pneumococcal conjugate vaccine (UAD-1) and the 11 other serotypes unique to 23-valent pneumococcal polysaccharide vaccine (UAD-2). RESULTS: Based on the assigned cutoff values, among 108 children who met the World Health Organization consolidation endpoint criteria, UAD-1 and UAD-2 were positive in 23.3% and 8.3%, respectively; among 364 children with clinically suspected pneumonia who did not meet the World Health Organization criteria, UAD-1 and UAD-2 were positive for 6.6% and 3.6%, respectively. Pneumococcal carriage prevalence was similar among pneumonia cases (30%) versus controls (35%) as was semiquantitative carriage density. CONCLUSIONS: UAD-1 and UAD-2 were able to distinguish community controls from children with pneumonia, particularly pneumonia with consolidation. Future studies are needed to confirm these results and more fully assess the contribution of pneumococcal carriage and concurrent viral infection.

Assessment of missed opportunities for vaccination (MOV) in Burkina Faso using the World Health Organization's revised MOV strategy: Findings and strategic considerations to improve routine childhood immunization coverage.

BACKGROUND: Despite the remarkable achievements of the Expanded Programme on Immunization (EPI) in Burkina Faso, numerous challenges remain, including missed opportunities for vaccination (MOV) which occur when people visit a health facility with at least one vaccine due according to the national immunization schedule, are free of contraindications, and leave without receiving all due vaccine doses. In 2016, we used the revised World Health Organization's (WHO) MOV strategy to assess the extent of and reasons for MOV in Burkina Faso. METHODS: We purposively selected 27 primary health facilities (PHFs) from the eight health districts with the highest absolute numbers of children who missed the first dose of measles-rubella (MR1) in 2015. We conducted exit interviews with caregivers of children aged 0-23 months, and requested health workers to complete a self-administered knowledge, attitudes and practices (KAP) questionnaire. RESULTS: A total of 489 caregivers were interviewed, of which 411 were eligible for inclusion in our analysis. Medical consultation (35%) and vaccination (24.5%) were the most frequent reasons for visiting PHFs. Among the 73% of children eligible for vaccination, 76% of vaccination opportunities were missed. Among eligible children, the percentage with MOV was significantly higher in those aged ≥12 months and also in those attending for a reason other than vaccination. A total of 248 health workers completed the KAP questionnaire. Of these, 70% (n = 168/239) considered their knowledge on immunization to be insufficient or outdated; 83% failed to correctly identify valid contraindications to vaccination. CONCLUSION: Addressing MOV offers the potential for substantial increases in vaccine coverage and equity, and ultimately reducing the burden of vaccine-preventable diseases (VPDs). This will require the implementation of a series of interventions aimed at improving community knowledge and practices, raising health workers' awareness, and fostering the integration of immunization with other health services.

Quality and reliability of vaccination documentation in the routine childhood immunization program in Burkina Faso: Results from a cross-sectional survey.

INTRODUCTION: Accurate and timely vaccination data are important to the Expanded Program on Immunization (EPI) to assess individual vaccination status and to monitor performance and vaccine coverage (VC). Since 2013, Burkina Faso introduced several new vaccines into the routine childhood immunization schedule. However, sustained efforts for a timely update and alignment of immunization home-based (HBRs) and health facility-based records (FBRs) with the evolving schedule were not implemented. METHODS: In 2016-17, we conducted a 6-week cross-sectional survey in 30 health facilities (HFs) across 10 health districts (HDs), targeting children aged < 24 months and their caregivers. Data collected included sociodemographics, availability of vaccination recording fields in HBRs, and vaccination dates. We evaluated the characteristics, completion patterns, and concordance of HBRs and FBRs to determine their reliability as data sources in estimating VC. A standard HBR was defined as one that had recording fields for all recommended 17 vaccine doses of the schedule, and discordance between HBR and FBR as having different vaccination dates recorded, or vaccination information missing in one of the records. We computed proportions and concordance statistics, and used logistic regression to explore predictors of discordance. RESULTS: We recruited 619 children, including 74% (n = 458) aged 0-11 months. Half (50.6%) of HBRs were non-standard. About two-thirds (64.6%) of children were concerned with discordant information. Compared to HBRs, FBRs were generally associated with low negative predictive values (median: 0.41; IQR: 0.16-0.70). Multivariate logistic regression model showed that standard HBR was protectively associated with discordant information (OR = 0.46, 95% CI: 0.26-0.81, p = 0.010). CONCLUSION: We documented a lack of standardization of HBRs and frequent information discordance with FBRs. There is a pressing need to update and standardize vaccination recording tools and ensure their continuous availability in HFs to improve data quality in Burkina Faso.

Case-Control Study of the Immune Status of Humans Infected With Zoonotic Gorilla Simian Foamy Viruses.

BACKGROUND: Zoonotic simian foamy viruses (SFVs) establish persistent infections in humans, for whom the long-term consequences for health are poorly described. In this study, we aimed to characterize blood-cell phenotypes and plasma biomarkers associated with gorilla SFV infection in humans. METHODS: We used a case-control design to compare 15 Cameroonian hunters infected with gorilla SFV (cases) to 15 controls matched for age and ethnicity. A flow cytometry-based phenotypic study and quantification of plasma immune biomarkers were carried out on blood samples from all participants. Wilcoxon signed-rank tests were used to compare cases and controls. RESULTS: Cases had a significantly higher percentage of CD8 T lymphocytes than controls (median, 17.6% vs 13.7%; P = .03) but similar levels of B, natural killer, and CD4 T lymphocytes. Cases also had a lower proportion of recent CD4 thymic emigrants (10.9% vs 18.6%, P = .05), a higher proportion of programmed death receptor 1 (PD-1) expressing memory CD4 T lymphocytes (31.7% vs 24.7%, P = .01), and higher plasma levels of the soluble CD163 scavenger receptor (0.84 vs .59 µg/mL, P = .003) than controls. CONCLUSIONS: We show, for the first time, that chronic infection with SFV is associated with T lymphocyte differentiation and monocyte activation.

An Immunodominant and Conserved B-Cell Epitope in the Envelope of Simian Foamy Virus Recognized by Humans Infected with Zoonotic Strains from Apes.

Cross-species transmission of simian foamy viruses (SFVs) from nonhuman primates (NHPs) to humans is currently ongoing. These zoonotic retroviruses establish lifelong persistent infection in their human hosts. SFV are apparently nonpathogenic in vivo, with ubiquitous in vitro tropism. Here, we aimed to identify envelope B-cell epitopes that are recognized following a zoonotic SFV infection. We screened a library of 169 peptides covering the external portion of the envelope from the prototype foamy virus (SFVpsc_huHSRV.13) for recognition by samples from 52 Central African hunters (16 uninfected and 36 infected with chimpanzee, gorilla, or Cercopithecus SFV). We demonstrate the specific recognition of peptide N96-V110 located in the leader peptide, gp18LP Forty-three variant peptides with truncations, alanine substitutions, or amino acid changes found in other SFV species were tested. We mapped the epitope between positions 98 and 108 and defined six amino acids essential for recognition. Most plasma samples from SFV-infected humans cross-reacted with sequences from apes and Old World monkey SFV species. The magnitude of binding to peptide N96-V110 was significantly higher for samples of individuals infected with a chimpanzee or gorilla SFV than those infected with a Cercopithecus SFV. In conclusion, we have been the first to define an immunodominant B-cell epitope recognized by humans following zoonotic SFV infection.IMPORTANCE Foamy viruses are the oldest known retroviruses and have been mostly described to be nonpathogenic in their natural animal hosts. SFVs can be transmitted to humans, in whom they establish persistent infection, like the simian lenti- and deltaviruses that led to the emergence of two major human pathogens, human immunodeficiency virus type 1 and human T-lymphotropic virus type 1. This is the first identification of an SFV-specific B-cell epitope recognized by human plasma samples. The immunodominant epitope lies in gp18LP, probably at the base of the envelope trimers. The NHP species the most genetically related to humans transmitted SFV strains that induced the strongest antibody responses. Importantly, this epitope is well conserved across SFV species that infect African and Asian NHPs.

Potent neutralizing antibodies in humans infected with zoonotic simian foamy viruses target conserved epitopes located in the dimorphic domain of the surface envelope protein.

Human diseases of zoonotic origin are a major public health problem. Simian foamy viruses (SFVs) are complex retroviruses which are currently spilling over to humans. Replication-competent SFVs persist over the lifetime of their human hosts, without spreading to secondary hosts, suggesting the presence of efficient immune control. Accordingly, we aimed to perform an in-depth characterization of neutralizing antibodies raised by humans infected with a zoonotic SFV. We quantified the neutralizing capacity of plasma samples from 58 SFV-infected hunters against primary zoonotic gorilla and chimpanzee SFV strains, and laboratory-adapted chimpanzee SFV. The genotype of the strain infecting each hunter was identified by direct sequencing of the env gene amplified from the buffy coat with genotype-specific primers. Foamy virus vector particles (FVV) enveloped by wild-type and chimeric gorilla SFV were used to map the envelope region targeted by antibodies. Here, we showed high titers of neutralizing antibodies in the plasma of most SFV-infected individuals. Neutralizing antibodies target the dimorphic portion of the envelope protein surface domain. Epitopes recognized by neutralizing antibodies have been conserved during the cospeciation of SFV with their nonhuman primate host. Greater neutralization breadth in plasma samples of SFV-infected humans was statistically associated with smaller SFV-related hematological changes. The neutralization patterns provide evidence for persistent expression of viral proteins and a high prevalence of coinfection. In conclusion, neutralizing antibodies raised against zoonotic SFV target immunodominant and conserved epitopes located in the receptor binding domain. These properties support their potential role in restricting the spread of SFV in the human population.

Clinical Signs and Blood Test Results Among Humans Infected With Zoonotic Simian Foamy Virus: A Case-Control Study.

Background: A spillover of simian foamy virus (SFV) to humans, following bites from infected nonhuman primates (NHPs), is ongoing in exposed populations. These retroviruses establish persistent infections of unknown physiological consequences to the human host. Methods: We performed a case-control study to compare 24 Cameroonian hunters infected with gorilla SFV and 24 controls matched for age and ethnicity. A complete physical examination and blood test were performed for all participants. Logistic regression and Wilcoxon signed rank tests were used to compare cases and controls. Results: The cases had significantly lower levels of hemoglobin than the controls (median, 12.7 vs 14.4 g/dL; P = .01). Basophil levels were also significantly lower in cases than controls, with no differences for other leukocyte subsets. Cases had significantly higher urea, creatinine, protein, creatinine phosphokinase, and lactate dehydrogenase levels and lower bilirubin levels than controls. Cases and controls had similar frequencies of general, cutaneous, gastrointestinal, neurological, and cardiorespiratory signs. Conclusions: The first case-control study of apparently healthy SFV-infected Cameroonian hunters showed the presence of hematological abnormalities. A thorough clinical and laboratory workup is now needed to establish the medical relevance of these observations because more than half of cases had mild or moderate anemia. Clinical Trials Registration: NCT03225794.

Simian Immunodeficiency Virus seroreactivity in inhabitants from rural Cameroon frequently in contact with non-human primates.

Central African tropical forests are home to several species of non-human primates (NHPs), infected by Simian Immunodeficiency Virus (SIV). It is well-known that HIV-1 epidemic is due to cross-transmission and adaptation of SIV to humans. The main goal of this work was to investigate if a NHP bite is a risk factor for SIV acquisition. A cross-sectional study was performed in rural Cameroon on 246 bitten individuals (mostly by adult NHPs), matched, according to sex, age, and ethnicity (Bantus and Pygmies), with an equal number of not-bitten subjects. Following a serological assay for a wide range of SIVs, we observed a high level of indeterminate seroreactivity (25.8%) in the total population, whereas 68.9% were sero-negative and 5.3% HIV-1 positive. Bites do not appear to be a risk factor for SIV seroreactivity, in contrast to Simian Foamy Virus and Simian T-Lymphotropic Virus type 1 in the same studied population.

Correlation of West Nile Virus Incidence in Donated Blood with West Nile Neuroinvasive Disease Rates, United States, 2010-2012.

Over the past decade, West Nile virus (WNV) has spread across the United States. We aggregated blood donor data from 2010-2012 and then calculated the incidence of WNV RNA-positive donations and compared the incidence with neuroinvasive disease (NID) case data from the ArboNET surveillance system. Of 10,107,853 donations, 640 were confirmed positive. The seasonal WNV incidence rate per 100,000 persons was 33.4 (95% CI 22-45) in 2010, 25.7 (95% CI 15-34) in 2011, and 119.9 (95% CI 98-141) in 2012. NID to blood donor ratios were 1 in 164 (95% CI 152-178) in 2010, 1 in 158 (95% CI 145-174) in 2011, and 1 in 131 (95% CI 127-136) in 2012. We updated estimates of the ratio of NID to WNV infection rates, demonstrating stable disease penetrance over the study period. Blood donor WNV RNA screening is a valuable public health tool for WNV surveillance.

Zoonotic Transmission of Two New Strains of Human T-lymphotropic Virus Type 4 in Hunters Bitten by a Gorilla in Central Africa.

Molecular screening of 300 at-risk people from Central Africa identified 2 human T-lymphotropic virus (HTLV)-4-infected individuals. A zoonotic origin of infection was suggested, as both individuals reported being severely bitten by a gorilla during hunting activities. One strain was highly divergent and was designated as the HTLV-4 subtype-b prototype.

The epigenomic landscape of African rainforest hunter-gatherers and farmers.

The genetic history of African populations is increasingly well documented, yet their patterns of epigenomic variation remain uncharacterized. Moreover, the relative impacts of DNA sequence variation and temporal changes in lifestyle and habitat on the human epigenome remain unknown. Here we generate genome-wide genotype and DNA methylation profiles for 362 rainforest hunter-gatherers and sedentary farmers. We find that the current habitat and historical lifestyle of a population have similarly critical impacts on the methylome, but the biological functions affected strongly differ. Specifically, methylation variation associated with recent changes in habitat mostly concerns immune and cellular functions, whereas that associated with historical lifestyle affects developmental processes. Furthermore, methylation variation--particularly that correlated with historical lifestyle--shows strong associations with nearby genetic variants that, moreover, are enriched in signals of natural selection. Our work provides new insight into the genetic and environmental factors affecting the epigenomic landscape of human populations over time.

Cocirculation of Two env Molecular Variants, of Possible Recombinant Origin, in Gorilla and Chimpanzee Simian Foamy Virus Strains from Central Africa.

UNLABELLED: Simian foamy virus (SFV) is a ubiquitous retrovirus in nonhuman primates (NHPs) that can be transmitted to humans, mostly through severe bites. In the past few years, our laboratory has identified more than 50 hunters from central Africa infected with zoonotic SFVs. Analysis of the complete sequences of five SFVs obtained from these individuals revealed that env was the most variable gene. Furthermore, recombinant SFV strains, some of which involve sequences in the env gene, were recently identified. Here, we investigated the variability of the env genes of zoonotic SFV strains and searched for possible recombinants. We sequenced the complete env gene or its surface glycoprotein region (SU) from DNA amplified from the blood of (i) a series of 40 individuals from Cameroon or Gabon infected with a gorilla or chimpanzee foamy virus (FV) strain and (ii) 1 gorilla and 3 infected chimpanzees living in the same areas as these hunters. Phylogenetic analyses revealed the existence of two env variants among both the gorilla and chimpanzee FV strains that were present in zoonotic and NHP strains. These variants differ greatly (>30% variability) in a 753-bp-long region located in the receptor-binding domain of SU, whereas the rest of the gene is very conserved. Although the organizations of the Env protein sequences are similar, the potential glycosylation patterns differ between variants. Analysis of recombination suggests that the variants emerged through recombination between different strains, although all parental strains could not be identified. IMPORTANCE: SFV infection in humans is a great example of a zoonotic retroviral infection that has not spread among human populations, in contrast to human immunodeficiency viruses (HIVs) and human T-lymphotropic viruses (HTLVs). Recombination was a major mechanism leading to the emergence of HIV. Here, we show that two SFV molecular envelope gene variants circulate among ape populations in Central Africa and that both can be transmitted to humans. These variants differ greatly in the SU region that corresponds to the part of the Env protein in contact with the environment. These variants may have emerged through recombination between SFV strains infecting different NHP species.

A Severe Bite From a Nonhuman Primate Is a Major Risk Factor for HTLV-1 Infection in Hunters From Central Africa.

BACKGROUND: HTLV-1 infection is endemic to Central African populations. The risk factors for HTLV-1 acquisition in humans via the interspecies transmission of STLV-1 (its simian counterpart) remain largely unknown. METHODS: We studied 269 individuals (254 men, 15 women) bitten by a nonhuman primate (NHP), mostly during hunting activities. These, Pygmies and Bantus, living in the southern Cameroonian rainforest, were matched for sex, age, and ethnicity with individuals from the same settlements reporting no NHP bites. HTLV-1 serology was performed by Western blot on plasma samples. PCR was carried out for HTLV-1 provirus on buffy-coat DNAs. The amplified products were sequenced and analyzed by phylogenetic analyses. RESULTS: HTLV-1 prevalence was 8.6% (23/269) in individuals with bites, vs 1.5% (4/269) in matched controls (P < .001). Moreover, HTLV-1 infection was linked to bite severity. The 23 HTLV-1-positive bitten individuals reported being bitten by a gorilla (17), chimpanzee (3), or small monkey (3). Thirteen (56%) were coinfected with a simian foamy virus known to be acquired through severe bites. Mother-to-child infection was excluded in 6 HTLV-1-infected bitten individuals. All the HTLV-1-positive hunters bitten by a gorilla or chimpanzee were infected with a subtype B strain similar to that present in apes from the same area. Two hunters bitten by small monkeys (C. agilis in one case) were infected with a HTLV-1 subtype F strain very similar to the STLV-1 strains present in such monkeys. CONCLUSIONS: These results strongly suggest ongoing direct zoonotic acquisition of STLV-1 in humans through severe NHP bites during hunting activities.

In vivo cellular tropism of gorilla simian foamy virus in blood of infected humans.

UNLABELLED: Simian foamy viruses (SFV) are retroviruses that are widespread among nonhuman primates. SFV can be transmitted to humans, giving rise to a persistent infection. Only a few data are available concerning the distribution of SFV in human blood cells. Here we purified blood mononuclear cell subsets from 11 individuals infected with a Gorilla gorilla SFV strain and quantified SFV DNA levels by quantitative PCR. SFV DNA was detected in the majority of the CD8(+), CD4(+), and CD19(+) lymphocyte samples and rarely in CD14(+) monocyte and CD56(+) NK lymphocyte samples. The median (interquartile range [IQR]) SFV DNA counts were 16.0 (11.0 to 49.8), 11.3 (5.9 to 28.3), and 17.2 (2.0 to 25.2) copies/10(5) cells in CD8(+) T lymphocytes, CD4(+) T lymphocytes, and CD19(+) B lymphocytes, respectively. In the CD4 compartment, SFV DNA was detected in both memory and naive CD4(+) T lymphocytes. SFV DNA levels in CD4(+) T cells were positively correlated with the duration of the infection. Our study shows with a quantitative method that CD8(+), CD4(+), and B lymphocytes are major cellular targets of SFV in the blood of infected humans. IMPORTANCE: Investigation of SFV infections in humans is important due to the origin of human immunodeficiency viruses (HIV) and human T cell lymphotropic viruses (HTLV) from cross-species transmission of their simian counterparts to humans. Surprisingly little is known about many aspects of the biology of SFV in infected humans, including quantitative data concerning the cellular targets of SFV in vivo. Here we show that the distribution of SFV DNA among the different leukocyte populations is not homogeneous and that viral load in CD4(+) T lymphocytes is correlated with the duration of infection. These new data will help in understanding the biology of retroviral infections in humans and can be useful in the growing field of SFV-based gene therapy.

Epidemiology and genetic variability of HHV-8/KSHV in Pygmy and Bantu populations in Cameroon.

BACKGROUND: Kaposi's sarcoma associated herpesvirus (KSHV/HHV-8) is the causal agent of all forms of Kaposi sarcoma. Molecular epidemiology of the variable K1 region identified five major subtypes exhibiting a clear geographical clustering. The present study is designed to gain new insights into the KSHV epidemiology and genetic diversity in Cameroon. METHODOLOGY/PRINCIPAL FINDINGS: Bantu and Pygmy populations from remote rural villages were studied. Antibodies directed against latent nuclear antigens (LANA) were detected by indirect immunofluorescence using BC3 cells. Peripheral blood cell DNAs were subjected to a nested PCR amplifying a 737 bp K1 gene fragment. Consensus sequences were phylogenetically analyzed. We studied 2,063 persons (967 females, 1,096 males, mean age 39 years), either Bantus (1,276) or Pygmies (787). The Bantu group was older (42 versus 35 years: P<10(-4)). KSHV anti-LANA seroprevalence was of 37.2% (768/2063), with a significant increase with age (P<10(-4)) but no difference according to sex. Seroprevalence, as well as the anti-LANA antibodies titres, were higher in Bantus (43.2%) than in Pygmies (27.6%) (P<10(-4)), independently of age. We generated 29 K1 sequences, comprising 24 Bantus and five Pygmies. These sequences belonged to A5 (24 cases) or B (five cases) subtypes. They exhibited neither geographical nor ethnic aggregation. A5 strains showed a wide genetic diversity while the B strains were more homogenous and belonged to the B1 subgroup. CONCLUSION: These data demonstrate high KSHV seroprevalence in the two major populations living in Southern and Eastern Cameroon with presence of mostly genetically diverse A5 but also B K1 subtypes.

Molecular epidemiology of merkel cell polyomavirus: evidence for geographically related variant genotypes.

Merkel cell polyomavirus (MCPyV) is linked to a cutaneous cancer mainly occurring in Caucasians. DNA from skin swabs of 255 adults, originating from the 5 continents, were subjected to MCPyV PCRs. Phylogenetic analyses demonstrate the existence of 5 major geographically related MCPyV genotypes (Europe/North America, Africa [sub-Saharan], Oceania, South America, and Asia/Japan).