Neutralization of zoonotic retroviruses by human antibodies: Genotype-specific epitopes within the receptor-binding domain from simian foamy virus.

Infection with viruses of animal origin pose a significant threat to human populations. Simian foamy viruses (SFVs) are frequently transmitted to humans, in which they establish a life-long infection, with the persistence of replication-competent virus. However, zoonotic SFVs do not induce severe disease nor are they transmitted between humans. Thus, SFVs represent a model of zoonotic retroviruses that lead to a chronic infection successfully controlled by the human immune system. We previously showed that infected humans develop potent neutralizing antibodies (nAbs). Within the viral envelope (Env), the surface protein (SU) carries a variable region that defines two genotypes, overlaps with the receptor binding domain (RBD), and is the exclusive target of nAbs. However, its antigenic determinants are not understood. Here, we characterized nAbs present in plasma samples from SFV-infected individuals living in Central Africa. Neutralization assays were carried out in the presence of recombinant SU that compete with SU at the surface of viral vector particles. We defined the regions targeted by the nAbs using mutant SU proteins modified at the glycosylation sites, RBD functional subregions, and genotype-specific sequences that present properties of B-cell epitopes. We observed that nAbs target conformational epitopes. We identified three major epitopic regions: the loops at the apex of the RBD, which likely mediate interactions between Env protomers to form Env trimers, a loop located in the vicinity of the heparan binding site, and a region proximal to the highly conserved glycosylation site N8. We provide information on how nAbs specific for each of the two viral genotypes target different epitopes. Two common immune escape mechanisms, sequence variation and glycan shielding, were not observed. We propose a model according to which the neutralization mechanisms rely on the nAbs to block the Env conformational change and/or interfere with binding to susceptible cells. As the SFV RBD is structurally different from known retroviral RBDs, our data provide fundamental knowledge on the structural basis for the inhibition of viruses by nAbs. Trial registration: The study was registered at www.clinicaltrials.gov: https://clinicaltrials.gov/ct2/show/NCT03225794/.

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.

Plasma antibodies from humans infected with zoonotic simian foamy virus do not inhibit cell-to-cell transmission of the virus despite binding to the surface of infected cells.

Zoonotic simian foamy viruses (SFV) establish lifelong infection in their human hosts. Despite repeated transmission of SFV from nonhuman primates to humans, neither transmission between human hosts nor severe clinical manifestations have been reported. We aim to study the immune responses elicited by chronic infection with this retrovirus and previously reported that SFV-infected individuals generate potent neutralizing antibodies that block cell infection by viral particles. Here, we assessed whether human plasma antibodies block SFV cell-to-cell transmission and present the first description of cell-to-cell spreading of zoonotic gorilla SFV. We set-up a microtitration assay to quantify the ability of plasma samples from 20 Central African individuals infected with gorilla SFV and 9 uninfected controls to block cell-associated transmission of zoonotic gorilla SFV strains. We used flow-based cell cytometry and fluorescence microscopy to study envelope protein (Env) localization and the capacity of plasma antibodies to bind to infected cells. We visualized the cell-to-cell spread of SFV by real-time live imaging of a GFP-expressing prototype foamy virus (CI-PFV) strain. None of the samples neutralized cell-associated SFV infection, despite the inhibition of cell-free virus. We detected gorilla SFV Env in the perinuclear region, cytoplasmic vesicles and at the cell surface. We found that plasma antibodies bind to Env located at the surface of cells infected with primary gorilla SFV strains. Extracellular labeling of SFV proteins by human plasma samples showed patchy staining at the base of the cell and dense continuous staining at the cell apex, as well as staining in the intercellular connections that formed when previously connected cells separated from each other. In conclusion, SFV-specific antibodies from infected humans do not block cell-to-cell transmission, at least in vitro, despite their capacity to bind to the surface of infected cells. Trial registration: Clinical trial registration: www.clinicaltrials.gov, https://clinicaltrials.gov/ct2/show/NCT03225794/.

A structured approach to effective mentoring of women health researchers in Africa.

Objectives: To formatively evaluate the HIGHER Women consortium's Mentor Protégée Program (MPP) and derive lessons for successful African women scientist mentorship. Design: Desk review of program documents and cross-sectional surveys of mentors and protégées. Setting: All 10 regions of Cameroon. Participants: Women working in health research participating in the MPP. Interventions: Building health research skills and providing support for women to cope within the African psycho-social environment using a holistic approach. Main outcome measures: Formed mentor-protégés duos applying the MPP with measurable accomplishments. Results: The consortium counted 121 members with 103 protégées and 18 mentors. Of 103 protégées, 35 responded to the 2018 survey, while 77 responded to the 2022 survey. Mentioned benefits of the program included an increase in scientific peer-reviewed journal publications and presentations at national and international conferences. In the 2022 survey, a Pearson correlation showed an r of 0.41, which, although not statistically significant (p = .592), suggests a positive correlation between the increased number of peer-reviewed articles and increased number of years as HIGHER Women protégées. Conclusions: Mentorship programs can help over time to bridge the gender gaps within Africa as well as the gaps between African-led research and the rest of the world while making a meaningful contribution to enhancing the quality, diversity, and productivity of researchers. A mentoring program such as the HIGHER Women MPP can be improved by leveraging local and international partners to foster the mentoring program's sustainability, scalability, and expanded reach. Funding: World Health Organization's Special Programme for Research and Training in Tropical Diseases (WHO/TDR) and Canada's International Development Research Centre (IDRC Canada).

A structured approach to effective mentoring of women health researchers in Africa

Objectives: To formatively evaluate the HIGHER Women consortium's Mentor Protégée Program (MPP) and derive lessons for successful African women scientist mentorship. Design: Desk review of program documents and cross-sectional surveys of mentors and protégées. Setting: All 10 regions of Cameroon Participants: Women working in health research participating in the MPP. Interventions: Building health research skills and providing support for women to cope within the African psychosocial environment using a holistic approach. Main outcome measures: Formed mentor-protégés duos applying the MPP with measurable accomplishments. Results: The consortium counted 121 members with 103 protégées and 18 mentors. Of 103 protégées, 35 responded to the 2018 survey, while 77 responded to the 2022 survey. Mentioned benefits of the program included an increase in scientific peer-reviewed journal publications and presentations at national and international conferences. In the 2022 survey, a Pearson correlation showed an r of 0.41, which, although not statistically significant (p = .592), suggests a positive correlation between the increased number of peer-reviewed articles and increased number of years as HIGHER Women protégées. Conclusions: Mentorship programs can help over time to bridge the gender gaps within Africa as well as the gaps between African-led research and the rest of the world while making a meaningful contribution to enhancing the quality, diversity, and productivity of researchers. A mentoring program such as the HIGHER Women MPP can be improved by leveraging local and international partners to foster the mentoring program's sustainability, scalability, and expanded reach.

Factors associated with the performance of routine health information system in Yaoundé-Cameroon: a cross-sectional survey.

BACKGROUND: Routine Health Information Systems (RHIS) of low-income countries function below the globally expected standard, characterised by the production and use of poor-quality data, or the non-use of good quality data for informed decision making. This has negatively influenced the health service delivery and uptake. This study focuses on identifying the factors associated with the performance of RHIS of the health facilities (HF) in Yaoundé, so as to guide targeted RHIS strengthening. METHODS: A HF-based cross-sectional study in the 6 health districts (HDs) of Yaoundé was conducted. HFs were chosen using stratified sampling with probability proportional to size per HD. Data were collected, entered into Microsoft Excel 2013 and analysed with IBM- SPSS version 25. Consistency of the questionnaire was measured using Cronbach's alpha coefficient. Pearson's chi-square (and Fisher exact where relevant) tests were used to establish relationships between qualitative variables. Associations were further quantified using unadjusted Odd ratio (OR) for univariable analysis and adjusted odds ratio (aOR) for multivariable analysis with 95% confidence interval (CI). A p-value of less than 0.05 was considered statistically significant. RESULTS: Of 111 selected HFs; 16 (14.4%) were public and 95 (85.6%) private. Respondents aged 24-60 years with an average of 38.3 ± 9.3 years; 58 (52.3%) males and 53(47.7%) females. Cronbach's alpha was 0.96 (95%CI: 0.95-0.98, p < 0.001), proving that the questionnaire was reliable in measuring RHIS performances. At univariable level, the following factors were positively associated with good performances: supportive supervision (OR = 3.03 (1.1, 8.3); p = 0.02), receiving feedback from hierarchy (OR = 3.6 (0.99, 13.2); p = 0.05), having received training on health information (OR = 5.0 (1.6, 16.0); p = 0.003), and presence of a performance evaluation plan (OR = 3.3 (1.4, 8.2), p = 0.007). At multivariable level, the only significantly associated factor was having received training on health information (aOR = 3.3 (1.01, 11.1), p = 0.04). CONCLUSION: Training of health staff in the RHIS favors RHIS good performance. Hence, emphasis should be laid on training and empowering staff, frequent and regular RHIS supervision, and frequent and regular feedback, for an efficient RHIS strengthening in Yaoundé.

Routine health information system in the health facilities in Yaoundé-Cameroon: assessing the gaps for strengthening.

BACKGROUND: Management of health data and its use for informed-decision making is a challenging health sector aspect in developing countries. Monitoring and evaluation of health interventions for meeting health-related Sustainable Development Goals (SDGs), and Cameroon Health Sector Strategy (HSS) targets is facilitated through evidence-based decision-making and public health action. Thus, a routine health information system (RHIS) producing quality data is imperative. The objective of this study was to assess the RHIS in the health facilities (HFs) in Yaoundé in order to identify gaps and weaknesses and to propose measures for strengthening. METHODS: A health facility-based cross-sectional descriptive study was carried out in the six health districts (HDs) of Yaoundé; followed by a qualitative aspect consisting of in-depth interviews of key informants at the Regional Health Office. HFs were selected using a stratified sampling method with probability proportional to the size of each HD. Data were collected (one respondent per HF) using the World Health Organization and MEASURE Evaluation RHIS rapid assessment tool. Data were entered into Microsoft Excel 2013 and analyzed with IBM-SPSS version 20. RESULTS: A total of 111 HFs were selected for the study. Respondents aged 24-60 years with an average of 38.3 ± 9.3 years; 58 (52.3%) male and 53(47.7%) female. Heads of HFs and persons in charge of statistics/data management were most represented with 45.0% and 21.6% respectively. All the twelve subdomains of the RHIS were adequately functioning at between 7 and 30%. These included Human Resources (7%), Data Analysis (10%), Information and Communication Technology (11%), Standards and System Design (15%), Policies and Planning (15%), Information Dissemination (16%), Data Demand and Use (16%), Management (18%), Data Needs (18%), Data Quality Assurance (20%), Collection and Management of Individual Client Data (26%), Collection, Management, and Reporting of Aggregated Facility Data (30%). CONCLUSIONS: The level of functioning of subdomains of the RHIS in Yaoundé was low; thus, immediate and district-specific strengthening actions should be implemented if health-related SDGs and HSS targets are to be met. A nation-wide assessment should be carried out in order to understand the determinants of these poor performances and to strengthen the RHIS.

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.

Prevalence and vaccination coverage of Hepatitis B among healthcare workers in Cameroon: A national seroprevalence survey.

Hepatitis B virus (HBV) infection is hyperendemic in Cameroon, and healthcare workers (HCWs) are at high risk of infection. We aimed to assess prevalence, risk factors and vaccine coverage of HBV infection among HCWs in Cameroon. We conducted a cross-sectional study in 16 hospitals across all regions of Cameroon. HCWs were tested for HBV using rapid diagnostic tests (RDT). We collected data on socio-demographics and HBV vaccination status. We estimated prevalence of HBV and used Poisson regression models with robust standard errors to model the prevalence ratios of HBV positivity between covariates. We enrolled 1824 of 1836 eligible HCWs (97.5%). The mean age was 34 (SD: 10) years, 65.3% (n = 1787) were women, and 11.4% (n = 1747) had three or more doses of the HBV vaccine. Overall, we found a HBV prevalence of 8.7% (95% CI: 5.2%-14.3%). Patient transporters had the highest crude prevalence (14.3%; 95%CI: 5.4%-32.9%), whereas medical doctors had the lowest (3.2%; 95%CI: 0.8%-12.1%). The Far North Region had the highest prevalence of HBV (24.0%; 95%CI: 18.3%-30.8%). HBV prevalence decreased with increasing doses of the HBV vaccine (10.3% for no doses vs 3.5% for three or more doses; P < 0.001). In conclusion, approximately 1 in 12 HCWs in Cameroon have evidence of HBV infection, yet fewer than 1 in 6 have been fully vaccinated. Our results illustrate the urgent need to scale up systematic HBV screening and targeted vaccination of HCWs in the region.

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.