Young women who sell sex in Bangui, Central African Republic: a neglected group highly vulnerable to HIV.

BACKGROUND: The objectives of this study were to determine the association between the vulnerability factors linked to human immunodeficiency virus (HIV) and other sexually transmitted infection among the young women who sell sex (YWSS) group (15-24 years) and adult sex workers, engaged in consensual sex for money (AFSW). METHODS: A cross-sectional study was conducted among AFSW involved in commercial sex transactions. Prevalence ratios (PR) analysis was carried out using log-binomial regression model. RESULTS: The prevalence of HIV-1 was 29.4% among YWSS compared to 19.6% among female sex worker (PR = 1.43 [1.07-1.91]). Consistent condoms use last 3 months were very low at 22.3% and 41.2%, respectively (PR = 0.52 [0.37-0.74]), the low education level among YWSS versus AFSW (PR = 0.55 [0.40-0.76]); YWSS having been a victim of sexual violence in the last 12 months (PR = 2.00 [1.52-2.63]), were also more likely to be HIV positive. CONCLUSIONS: The YWSS had a high prevalence of HIV, experienced other socioeconomic vulnerabilities and remain a key population for comprehensive HIV programs. To reach all YWSS, programs need to consider many outreach programs and address the shared determinants of HIV risk.

Unexpected high frequency of unspecific reactivities by testing pre-epidemic blood specimens from Europe and Africa with SARS-CoV-2 IgG-IgM antibody rapid tests points to IgM as the Achilles heel.

We aimed to evaluate the rates of false-positive test results of three rapid diagnostic tests (RDTs) for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-specific immunoglobulin G (IgG) and IgM detection. Two serum panels from patients hospitalized in Paris, France, and from patients living in Bangui, Central African Republic, acquired before the 2019 COVID-19 outbreak, were tested by 3 CE IVD-labeled RDTs for SARS-CoV-2 serology (BIOSYNEX® COVID-19 BSS [IgG/IgM]; SIENNA™ COVID-19 IgG/IgM Rapid Test Cassette; NG-Test® IgG-IgM COVID-19). Detectable IgG or IgM reactivities could be observed in 31 (3.43%) of the 902 IgG and IgM bands of the 3 RDTs used with all pre-epidemic sera. The frequencies of IgG/IgM reactivities were similar for European (3.20%) and African (3.55%) sera. IgM reactivities were observed in 9 European and 14 African sera, while IgG reactivity was observed in only 1 African serum (15.1% vs. 0.66%). The test NG-Test® IgG-IgM COVID-19 showed the highest rates of IgG or IgM reactivities (6.12% [18/294]), while the test BIOSYNEX® COVID-19 BSS (IgG/IgM) showed the lowest rate (1.36% [4/294]). Some combinations of 2 RDTs in series allowed decreasing significantly the risk of false-positive test results. Our observations point to the risk of false-positive reactivities when using currently available RDT for SARS-CoV-2 serological screening, especially for the IgM band, even if the test is CE IVD-labeled and approved by national health authorities, and provide the rational basis for confirmatory testing by another RDT in case of positive initial screening.

High predictive efficacy of integrase strand transfer inhibitors in perinatally HIV-1-infected African children in therapeutic failure of first- and second-line antiretroviral drug regimens recommended by the WHO.

OBJECTIVES: The predictive efficacy of integrase (IN) strand transfer inhibitors (INSTIs) was investigated in HIV-infected children born to HIV-infected mothers in Africa. METHODS: Plasma was collected at the Complexe Pédiatrique of Bangui, Central African Republic, from INSTI-naive children (n = 8) and adolescents (n = 10) in virological failure (viral load >1000 copies/mL) after 5 years of first- and/or second-line combination ART (cART). IN, reverse transcriptase (RT) and protease (P) genes were genotyped and drug resistance mutations (DRMs) to INSTIs, NRTIs, NNRTIs and PIs were interpreted using the Stanford algorithm. RESULTS: Successful IN, RT and P genotypes were obtained for 18, 13 and 15 children (median age 11 years, range 5-18; 8 were female), respectively. Two (2/18; 11.1%) viruses from children treated with a first-line regimen had INSTI DRMs at codon 138 (E138K and E138T), which is known to harbour major resistance mutations, and also had the accessory mutations L74I, G140K, G140R and G163R. The majority (16/18; 88.9%) of HIV-1 IN sequences demonstrated full susceptibility to all major INSTIs with a high frequency of natural polymorphic mutations. Most (12/15; 80%) genotyped viruses harboured at least one major DRM conferring resistance to at least one of the WHO-recommended antiretroviral drugs (NNRTIs, NRTIs and PIs) prescribed in first- and second-line regimens. CONCLUSIONS: INSTIs could be proposed in first-line regimens in the majority of African children or adolescents and may constitute relevant therapeutic alternatives as second- and third-line cART regimens in HIV-infected children and adolescents living in sub-Saharan Africa.

Usefulness of simultaneous screening for HIV-specific and HCV-specific antibodies and HBsAg by a capillary-based multiplex rapid diagnostic test to strengthen linkage-to-care in sub-Saharan patients attending sexually transmitted infection clinic.

Adult outpatients attending the main sexually transmitted infection clinic of Bangui, Central African Republic, were prospectively subjected to a multiplex rapid diagnostic test for human immunodeficiency virus (HIV), hepatitis B virus (HBV), and hepatitis C virus (HCV). In group I (n = 208) of patients already followed for HIV, 6 (2.9%) were unexpectedly negative, thus corresponding to false positive for HIV by the national HIV algorithm; hepatitis B surface antigen and HCV positivities were high (18.7% and 4.3%, respectively). In group II (n = 71) of patients with unknown HIV status, at least 1 chronic viral disease was diagnosed in 26 (36.6%) patients, including 5 (7.1%) HIV, 17 (23.9%) HBV, and 3 (4.2%) HCV infections.

Performance evaluation of the touchscreen-based Muse™ Auto CD4/CD4% single-platform system for CD4 T cell numeration in absolute number and in percentage using blood samples from children and adult patients living in the Central African Republic.

BACKGROUND: The new microcapillary and fluorescence-based EC IVD-qualified Muse™ Auto CD4/CD4% single-platform assay (EMD Millipore Corporation, Merck Life Sciences, KGaA, Darmstadt, Germany) for CD4 T cell numeration in absolute number and in percentage was evaluated using Central African patients' samples compared against the reference EC IVD-qualified BD FACSCount (Becton-Dickinson, USA) flow cytometer. METHODS: EDTA-blood samples from 124 adults, 10 adolescents, 13 children and 3 infants were tested in parallel at 2 reference laboratories in Bangui. RESULTS: The Muse™ technique was highly reproducible, with low intra- and inter-run variabilities less than 15%. CD4 T cell counts of Muse™ and BD FACSCount in absolute number and percentage were highly correlated (r2 = 0.99 and 0.98, respectively). The mean absolute bias between Muse™ and BD FACSCount cells in absolute number and percentage were -5.91 cells/µl (95% CI -20.90 to 9.08) with limits of agreement from -77.50 to 202.40 cells/µl, and +1.69 %CD4 (95% CI ±1.29 to +2.09), respectively. The percentages of outliers outside the limits of agreement were nearly similar in absolute number (8%) and percentage (10%). CD4 T cell counting by Muse™ allowed identifying the majority of individuals with CD4 T cell <200, <350 or <750 cells/µl corresponding to the relevant thresholds of therapeutic care, with sensitivities of 95.5-100% and specificities of 83.9-100%. CONCLUSIONS: The Muse™ Auto CD4/CD4% Assay analyzer is a reliable alternative flow cytometer for CD4 T lymphocyte enumeration to be used in routine immunological monitoring according to World Health Organization recommendations in HIV-infected adults as well as children living in resource-constrained settings.

Genetic diversity of HPV35 in Chad and the Central African Republic, two landlocked countries of Central Africa: A cross-sectional study.

Human Papillomavirus (HPV)-35 accounts for up 10% of cervical cancers in Sub-Saharan Africa. We herein assessed the genetic diversity of HPV35 in HIV-negative women from Chad (identified as #CHAD) and HIV-infected men having sex with men (MSM) in the Central African Republic (CAR), identified as #CAR. Ten HPV35 DNA from self-collected genital secretions (n = 5) and anal margin samples (n = 5) obtained from women and MSM, respectively, were sequenced using the ABI PRISM® BigDye Sequencing technology. All but one HPV35 strains belonged to the A2 sublineage, and only #CAR5 belonged to A1. HPV35 from #CAR had higher L1 variability compared to #CHAD (mean number of mutations: 16 versus 6). L1 of #CAR5 showed a significant variability (2.29%), suggesting a possible intra-type divergence from HPV35H. Three (BC, DE, and EF) out of the 5 capsid loops domains remained totally conserved, while FG- and HI- loops of #CAR exhibited amino acid variations. #CAR5 also showed the highest LCR variability with a 16bp insertion at binding sites of the YY1. HPV35 from #CHAD exhibited the highest variability in E2 gene (P<0.05). E6 and E7 oncoproteins remained well conserved. There is a relative maintenance of a well conserved HPV35 A2 sublineage within heterosexual women in Chad and MSM with HIV in the Central African Republic.

Risk factors for multidrug-resistant tuberculosis in the Central African Republic: A case-control study.

BACKGROUND: The emergence and spread of multidrug-resistant tuberculosis (MDR-TB) presents a challenge to the "End TB by 2035" strategy. This study aimed to identify the risk factors associated with MDR-TB in patients admitted to the pneumo-physiology clinic of the National University Hospital of Bangui in Central African Republic. METHODS: This was a "retrospective" chart review study. Cases were represented by patients more than 18 years of age treated for MDR-TB and controls were patients with "at least rifampicin-susceptible" TB treated "with first-line anti-TB regimen" and who at the end of treatment were declared cured. The status of "cured" was exclusively applicable to non-MDR TB. Risk factors associated with MDR-TB were identified by multivariate analysis. RESULTS: We included 70 cases and 140 controls. The median age was 35 years, IQR (22;46 years). The main factors associated with the occurrence of MDR-TB in multivariate analysis were male gender (0 R = 3.02 [1.89-3.99], p = 0.001), residence in a peri-urban/urban area (0 R = 3.06 [2.21-4.01], p = 0.002), history of previous TB treatment (0 R= 3.99 [2.77-4.25], p < 0.001) and the presence of multidrug-resistant TB in the family (0 R=1.86 [1.27-2.45], p = 0.021). CONCLUSION: The emergence of MDR-TB can be reduced by implementing appropriate strategies, such as preventive therapy in contacts of MDR-TB patients and detecting and appropriately treating MDR-TB patients to prevent further spread of infection.

Prospecting for yaws in the Mbaïki Health District in the Central African Republic.

Introduction: yaws is endemic in the Central African Republic. The last cases of yaws notified by CAR to WHO date back to 2012. The objective of this study was to measure the prevalence of yaws in the health district of Mbaïki and to describe its clinical and epidemiological characteristics. Methods: this is a descriptive cross-sectional study, conducted from April 10 to 18, 2020 in the Mbaïki health district. Yaws cases were sought in 570 households in the 38 selected villages of the district. Any consenting individual over the age of one year with yaws-like skin lesions was a suspected case of yaws and included in the study. Blood was taken from suspected cases for serological testing (TDR, RPR and TPHA). Any suspected case of yaws with positive RPR and TPHA was considered a confirmed case. Results: a total of 1967 people were examined, of whom 113 were considered suspected cases of yaws. All suspected cases were RPR-positive, 41 TPHA-positive and 13 RDT-positive. Forty-one cases of yaws were confirmed in 18 (47.37%) villages. The prevalence of yaws in the Mbaïki health district was 2.08%. Among the cases, 38.94% were children aged 1 to 14. The sex ratio was 1.69. Lesions clinically suggestive of yaws were papilloma-like in 77.00% of cases, followed by micropapules (8.00%) and ulcerations (5.00%). Conclusion: eight of the nine communes in the Mbaïki health district are yaws-endemic. This result suggests the need to implement the Morges strategy in the Mbaïki health district.

Sero-prevalence of anti-SARS-CoV-2 antibodies among communities between July and August 2022 in Bangui, Central African Republic.

Background: Large-scale population-based seroprevalence studies of SARS-CoV-2 are essential to characterize the cumulative incidence of SARS-CoV-2 infection and to extrapolate the prevalence of presumptive immunity at the population level. Objective. The objective of our survey was to estimate the cumulative population immunity for COVID-19 and to identify individual characteristics associated with positive serostatus. Materials and Methods: This was a clustered cross-sectional study conducted from July 12 to August 20, 2021, in households in the city of Bangui, the capital of the Central African Republic. Information regarding demographic characteristics (age, gender, and place of residence), and comorbidities (chronic diseases) was collected. A venous blood sample was obtained from each participant to determine the level of total anti-SARS-CoV-2 antibodies using a WANTAI SARS-CoV-2 Ab ELISA kit. Results: All up, 799 participants were surveyed. The average age was 27 years, and 45.8% of the respondents were male (sex ratio: 0.8). The overall proportion of respondents with positive serostatus was 74.1%. Participants over 20 years of age were twice as likely to have positive serostatus, with an OR of 2.2 [95% CI: (1.6, 3.1)]. Conclusions: The results of this survey revealed a high cumulative level of immunity in Bangui, thus indicating a significant degree of spread of SARS-CoV-2 in the population. The public health implications of this immunity to SARS-CoV-2 such as the post-vaccination total antibody kinetics remain to be determined.

Seroprevalence of anti-SARS-CoV-2 antibodies before and after implementation of anti-COVID-19 vaccination among hospital staff in Bangui, Central African Republic.

Healthcare workers (HCWs) are at high to very high risk for SARS-CoV-2 infection. The persistence of this pandemic worldwide has instigated the need for an investigation of the level of prevention through immunization and vaccination against SARS-CoV-2 among HCWs. The objective of our study was to evaluate any changes in anti-COVID-19 serological status before and after the vaccination campaign of health personnel in the Central African Republic. We carried out a repeated cross-sectional serological study on HCWs at the university hospital centers of Bangui. Blood samples were collected and tested for anti-SARS-CoV-2 IgM and IgG using the ELISA technique on blood samples. A total of 179 and 141 HCWs were included in the first and second surveys, respectively. Of these staff, 31.8% of HCWs were positive for anti-SARS-CoV-2 IgG in the first survey, whereas 95.7% were positive for anti-SARS-CoV-2 IgG in the second survey. However, the proportion of HCWs positive for SARS-CoV-2 IgM antibodies was low (9.7% in the first survey and 3.6% in the second survey). These findings showed a sharp increase in seroprevalence over a one-year period. This increase is primarily due to the synergistic effect of the infection and the implementation of vaccines against COVID-19. Further studies to assess the persistence of anti-SARS-CoV-2 antibodies are needed.

Five successive waves of SARS-CoV-2 infection in the Central African Republic: a prospective observational study from 2020-2022.

Introduction: the National Laboratory of Clinical Biology and Public Health (NLBPH) in Bangui in the Central African Republic (CAR) carries out the vast majority of molecular screening tests for SARS-CoV-2 infection nationwide. This study aimed to show the contribution of molecular diagnosis and genomic surveillance in monitoring the evolution of longitudinal variations of the SARS-CoV-2 infection epidemic in CAR between 2020 and the end of 2022. Methods: this is an observational study on the variations in the prevalence of detection of SARS-CoV-2 by RT-PCR at the NLCBPH from nasopharyngeal samples taken prospectively over a period of 3 years since the beginning of the COVID-19 epidemic. A subgroup of SARS-CoV-2 positive samples was selected for molecular sequencing performed by Illumina® and MinIon® at the National Institute for Biomedical Research in Kinshasa, Democratic Republic of the Congo. Results: from March 2020 to December 31th, 2022, 88,442 RT-PCR tests were carried out (4/5 of the country) and detected 9,156 cases of SARS-CoV-2 infection in 5 successive waves. The average age of the patients was 39.8 years (extremes ranging from to 92 years). Age(P=0.001), sex(P=0.001) and symptom presentation(P=0.001) were significantly associated with RT-PCR test positivity. Among the different variants identified during successive waves, the Omicron variant predominated during the last two waves. Conclusion: this prospective study over a period of 3 years, marked by 5 successive waves, made it possible to report that age, sex and the presence of clinical symptoms are associated with RT-PCR positivity. Among the different variants identified during successive waves, the Omicron variant predominated during the last two waves.

[Incidence of snakebites in rural communities living in the Paoua savannah and Mbaïki forest areas in Central African Republic]. / Incidence de morsures de serpent dans les communautés rurales de savane de Paoua et de forêt de Mbaïki en République Centrafricaine.

Introduction: Snakebite is one of the most deadly neglected tropical diseases in Africa with more than 20,000 deaths reported each year. According to recent data from hospital in Central African Republic studies, the Paoua health district reports between 300 and 400 cases of ophidian envenomation each year. However, no epidemiological study on snakebites has been conducted at national level, nor a control strategy developed. The objective of this study is to describe the epidemiological aspects of snakebites in two rural communities, one located in savannah zone and the other in forest zone (both secondary and primary forest) in order to ensure adequate management of snakebites in these regions. Method: Prospective community-based study in two health districts in the Central African Republic, the health district of Paoua in savannah area and the health district of Mbaïki in forest area, from December 2019 to January 2021. Snakebites were investigated in the community by selected trained people in charge of reporting data regarding all known cases of snakebites occurring during the study period. The data were actively notified either by health personal or community health workers in order to determine the circumstances and severity of the bite, its management and the clinical course in case of envenomation. Results: A total of 412 snakebite cases were recorded during the study period, of which 198 cases occurred in the rural community of the forest zone and 214 in the community of the savannah zone. Case fatality rate was 5% in the forest zone and 1% in the savanna zone. The incidence rate of snakebite was significantly higher in savannah children compared to those in the forest (98/100,000 vs. 25.1/100,000; p<0.00001) while this incidence rate was significantly lower from age 45 onwards in the savannah area compared to the forest area (167/100,000 vs. 200/100,000; p=0.02). The case fatality rate of children and adults up to 44 years of age appeared to be significantly higher in the forest zone (7 deaths vs 1 death). Snakebites occurred significantly more frequently during field activities in the savannah zone than in the forest zone (51% vs 26%; p<0.0001). The symptomatology of bites was dominated by edema of the bitten limb and bleeding in the two study areas, compatible with cytotoxic and hemorrhagic syndromes due to viper bites. Conclusion: With an incidence rate of more than 160 cases per 100,000 inhabitants in the active population aged 15-44 years in rural communities of the forest and savannah zone, snakebites remain a public health problem in Central African Republic. A study on the toxicity of snakebites in Central African Republic is recommended. Besides, it is urgent to make anti-venomous serums available in health facilities in order to reduce the mortality related to the envenomation.

Incidence and risk factors for tuberculosis among people living with HIV in Bangui: A cohort study.

Objectives: The objectives of this study were to determine the incidence and risk factors of tuberculosis (TB) among people living with HIV (PLHIV). Methods: A cohort study was carried out in an HIV infection management centre in Bangui. PLHIV aged 18 or older, with no history of TB, enrolled between January 1, 2017 and December 31, 2018 were included in the study. The chi-square test was used only to compare the proportions at the 5% significance level. To determine the risk factors, we used the Cox regression adjusted hazard ratio, using Epi Info 7 software. Results: A total of 677 patients including 618 (91.28%) on antiretroviral therapy were included in the study. The median age was 34 with extremes ranging from 18 to 57. Of the patients followed, 104 developed TB. The overall incidence of TB was 15.37 (104/677) cases per 100 PLHIV-years. This incidence was 13.10 (81/618) cases per 100 in patients on ART-years and 38.99 (23/59) cases per 100 patients on pre-ART-years. In pre-ART patients the incidence of TB was therefore almost 3 times higher than that of PLHIV on ART (p = 0.03). WHO clinical stages III and IV (p = 0.02), absence of ART (p = 0.03), poor adherence (p = 0.004) and low functional capacity (p = 0.04) were the risk factors associated with the occurrence of TB among PLHIV in Bangui. Conclusions: The high incidence of TB in our context is essentially linked to delay in diagnosis and the quality of care. Early initiation of antiretroviral therapy, systematic screening for TB in PLHIV upon entry into the active queue and better monitoring of patients on ART are strongly recommended.

Analytical performances of Exacto® HIV self-test in the Central African Republic.

We herein evaluated the analytical performances of the CE-IVD capillary blood Exacto® HIV self-test (Biosynex, Strasbourg, France) in the Central African Republic (CAR). A cross-sectional study was conducted on a representative national panel of 200 sera positive for HIV and 200 negative for HIV, randomly selected thorough the CAR for HIV seroprevalence surveillance survey, according to reference test. The Exacto® HIV self-test showed 99.5% (95% CI: 98.2-99.9) sensitivity and 100.0% (95% CI: 99.0-100.0) specificity. The Youden´s J index and Cohen´s Kappa coefficient were 0.995. At HIV-1 seroprevalence of 3.5% in the general adult population of the CAR, the positive and negative predictive values were 100% (95% CI: 99.0-100) and 99.9% (95% CI: 98.9-100), respectively. The results are within the limits required by the WHO (i.e. sensitivity ≥ 99.0% and specificity ≥ 98.0%), making Exacto® HIV self-test suitable for routine use in the CAR.

Purifying Selection in Human Immunodeficiency Virus-1 pol Gene in Perinatally Human Immunodeficiency Virus-1-Infected Children Harboring Discordant Immunological Response and Virological Nonresponse to Long-Term Antiretroviral Therapy.

BACKGROUND: Biological monitoring of antiretroviral treatment (ART) in human immunodeficiency virus (HIV)-infected pediatric population remains challenging. The aim of the present study was to assess the long-term HIV-1 genetic diversity in pol gene in HIV-1-infected children in virological failure under antiretroviral regimen adapted according to the successive World Health Organization (WHO) guidelines for resource-constrained settings. METHODS: HIV-1 diversity in pol gene was assessed in HIV-1-infected children and adolescents born from HIV-infected mothers (median age at follow-up: 13.8 years) in virological failure (VF+) despite long-term regimen recommended by the WHO. The numbers of nonsynonymous substitutions per potential nonsynonymous site (dN) and of synonymous substitutions at potential synonymous sites (dS) in HIV-1 pol gene and the dN/dS ratios were used to estimate the selective pressure on circulating HIV-1. RESULTS: The immunological responses to ART basically corresponded to: 1) Full therapeutic failure with immunological (I-) and virological nonresponses in one-quarter (24.6%) of study children ((I-, VF+) subgroup); 2) Discordant immunovirological responses with paradoxical high CD4 T cell counts (I+) and high HIV-1 RNA load in the remaining cohort patients (75.4%) ((I+, VF+) subgroup). The mean dS was 1.8-fold higher in (I+, VF+) than (I-, VF+) subgroup (25.9 ± 18.4 vs. 14.3 ± 10.8). In the (I+, VF+) subgroup, the mean dS was 1.6-fold higher than the mean dN. Finally, the mean dN/dS ratio was 2.1-fold lower in (I+, VF+) than (I-, VF+) subgroup (0.6 ± 0.3 vs. 1.3 ± 0.7), indicating purifying selection in the immunovirological discordant (I+, VF+) subgroup and positive selection in the immunovirological failure (I-, VF+) subgroup. CONCLUSIONS: Children and adolescents in immunovirological therapeutic failure harbor positive selection of HIV-1 strains favoring diversifying in pol-encoded amino acids. In contrast, children with persistent discordant immunovirological responses show accumulation of mutations and purifying selection in pol gene sequences, indicating limited genetic evolution and likely suggesting genetic adaptation of viruses to host functional constraints.

Escalating and sustained immunovirological dissociation among antiretroviral drug-experienced perinatally human immunodeficiency virus-1-infected children and adolescents living in the Central African Republic: A STROBE-compliant study.

Sub-Saharan Africa has the vast majority (∼90%) of new pediatric acquired immunodeficiency syndrome cases worldwide. Biologically monitoring HIV-infected pediatric populations remains challenging. The differential interest of human immunodeficiency virus (HIV)-1 RNA loads and CD4 T-cell counts is debated for the treatment of pediatric acquired immunodeficiency syndrome patients.Long-term antiretroviral treatment (ART) outcomes regarding immunological and virological surrogate markers were longitudinally evaluated between 2009 and 2014 (over 57 months) in 245 perinatally HIV-1-infected children and adolescents born from HIV-infected mothers, treated at inclusion for at least 6 months by the World Health Organization-recommended ART in Bangui, Central African Republic.Patients were monitored over time biologically for CD4 T-cell counts, HIV-1 RNA loads, and drug resistance mutation genotyping.Children lost to follow-up totaled 6%. Four categories of immunovirological responses to ART were observed. At baseline, therapeutic success with sustained immunological and virological responses was observed in 80 (32.6%) children; immunological and virologic nonresponses occurred in 32 (13.0%) children; finally, the majority (133; 54.2%) of the remaining children showed discordant immunovirological responses. Among them, 33 (13.4%) children showed rapid virological responses to ART with an undetectable viral load, whereas immunological responses remained absent after 6 months of treatment and increased progressively over time in most of the cases, suggesting slow immunorestoration. Notably, nearly half of the children (40.8% at baseline and 48.2% at follow-up) harbored discordant immunovirological responses with a paradoxically high CD4 T-cell count and HIV-1 RNA load, which are always associated with high levels of drug resistance mutations. The latter category showed a significant increase over time, with a growth rate of 1.23% per year of follow-up.Our STROBE-compliant study demonstrates the high heterogeneity of biological responses under ART in children with frequent passage from 1 category to another over time. Close biological evaluation with access to routine plasma HIV-1 RNA load monitoring is crucial for adapting the complex outcomes of ART in HIV-infected children born from infected mothers.

HSV-2 Infection as a Potential Cofactor for HIV Disease Progression and Selection of Drug Resistance Mutations in Adults under WHO-Recommended First-Line Antiretroviral Therapy: A Multicentric, Cross-Sectional Study in Cameroon, Central African Republic, Chad, and Gabon.

Although herpes simplex virus-2 (HSV-2) infection is a known cofactor for HIV transmission in Central Africa, its role in HIV disease progression is unclear. The aim of this study was to examine the potential link between HSV-2 infection and HIV disease progression, in addition to identifying the presence of genes conferring HIV antiretroviral resistance mutations. This was a cross-sectional study involving 302 HIV-infected adults in Central Africa with virological failure (viral load >1000 copies/mL) on first-line antiretroviral therapy from four different countries. The seroprevalence of HSV-2 was 32% (96/302). Amongst the HIV-infected individuals who were HSV-2 seropositive, the mean HIV viral load and CD4 count were 4.82 ± 0.83 log copies/mL and 243 ± 144 cells/microliter, respectively. Among the HIV-infected individuals who were HSV-2-seronegative, the mean HIV viral load and CD4 count were 3.48 ± 0.44 log copies/mL and 646 ± 212 cells/microliter, respectively (p < 0.001). There was a statistically significant relationship (p < 0.001) between HSV-2 seropositivity and the presence of resistance mutations to antiretrovirals (ARV), non-nucleoside reverse transcriptase inhibitors (NNRTI), and nucleoside reverse transcriptase inhibitors (NRTI) with odds ratios of 9.7, 10, and 11.9, respectively. There was no link between HSV-2 serostatus and protease inhibitor (PI) resistance mutations. There was a substantial accumulation of resistance mutations in HSV-2-seropositive compared to -seronegative patients. These findings support the link between HIV disease progression and HSV-2 infection. An association was observed between the presence of NNRTI and NRTI resistance mutations and HSV-2 seropositivity.

Infrequent detection of human papillomavirus infection in head and neck cancers in the Central African Republic: a retrospective study.

We carried out a retrospective study on the prevalence of HPV and genotype distribution by nested PCR and nucleotide sequencing analysis, in formalin-fixed, paraffin-embedded biopsies of 135 head and neck cancers (HNC) and 29 cervical cancers received between 2009 and 2017 for diagnosis at the Laboratoire National de Biologie Clinique et de Santé Publique of Bangui, the capital city of the Central African Republic. One oropharyngeal squamous cell carcinoma sample was positive for HPV type 16. The overall HPV prevalence in HNC biopsies was 0.74% (95% CI: 0.0-2.2). Among the 29 cervical cancer samples, 19 (65.5%; 95% CI: 48.2-82.8) were positive for HPV. These results indicate that HNC are infrequently associated with HPV infection in the Central African Republic.

Inhibition of HIV-1 transmission in trans from dendritic cells to CD4+ T lymphocytes by natural antibodies to the CRD domain of DC-SIGN purified from breast milk and intravenous immunoglobulins.

The present study demonstrates that human breast milk and normal human polyclonal immunoglobulins purified from plasma [intravenous immunoglobulins (IVIg)] contain functional natural immunoglobulin A (IgA) and IgG antibodies directed against the carbohydrate recognition domain (CRD) domain of the dendritic cell-specific intercellular adhesion molecule-3-grabbing non-integrin (DC-SIGN) molecule, which is involved in the binding of human immunodeficiency virus (HIV)-1 to dendritic cells (DCs). Antibodies to DC-SIGN CRD were affinity-purified on a matrix to which a synthetic peptide corresponding to the N-terminal CRD domain (amino-acid 342-amino-acid 371) had been coupled. The affinity-purified antibodies bound to the DC-SIGN peptide and to the native DC-SIGN molecule expressed by HeLa DC-SIGN+ cells and immature monocyte-derived dendritic cells (iMDDCs), in a specific and dose-dependent manner. At an optimal dose of 200 microg/ml, natural antibodies to DC-SIGN CRD peptide purified from breast milk and IVIg stained 25 and 20% of HeLa DC-SIGN+ cells and 32 and 12% of iMDDCs, respectively. Anti-DC-SIGN CRD peptide antibodies inhibited the attachment of virus to HeLa DC-SIGN by up to 78% and the attachment to iMDDCs by only 20%. Both breast milk- and IVIg-derived natural antibodies to the CRD peptide inhibited 60% of the transmission in trans of HIV-1(JRCSF), an R5-tropic strain, from iMDDCs to CD4+ T lymphocytes. Taken together, these observations suggest that the attachment of HIV to DCs and transmission in trans to autologous CD4+ T lymphocytes occur through two independent mechanisms. Our data support a role of natural antibodies to DC-SIGN in the modulation of postnatal HIV transmission through breast-feeding and in the natural host defence against HIV-1 in infected individuals.

Performance of HerpeSelect and Kalon assays in detection of antibodies to herpes simplex virus type 2.

The performances of commercial enzyme-linked immunosorbent assays (ELISAs) in detecting herpes simplex virus type 2 (HSV-2) antibodies have been inconsistent for African and human immunodeficiency virus (HIV)-positive populations. We compared the performances of the HerpeSelect and Kalon glycoprotein G2 ELISAs for patients with genital ulcer disease in Ghana and the Central African Republic. Sera from 434 women were tested with the HerpeSelect assay, and a subsample (n = 199) was tested by the Kalon assay. Ulcer swabs and cervicovaginal lavage samples were tested for HSV-2 DNA by PCR. HSV-2-seronegative women with detectable genital HSV-2 DNA were retested for HSV-2 antibodies 14 and 28 days later by the two ELISAs. A total of 346 (80%) women were positive by HerpeSelect at baseline, and 225 (54%) had detectable genital (lesional or cervicovaginal) HSV-2 DNA. Sixty-six (19%) HerpeSelect-positive samples had low-positive index values (1.1 to 3.5), and 58% of these samples had detectable genital HSV-2 DNA. Global agreement between the two serological assays was 86%. Concordance was high (99%) for sera that were negative by HerpeSelect or had high index values (>3.5). Defining infection detected by HSV-2 DNA PCR and/or Kalon assay as true infection, 71% of sera with low-positive index values were associated with true HSV-2 infection. Twenty-five women were identified as having nonprimary first-episode genital HSV-2 infection. Rates of HSV-2 seroconversion at day 14 were 77% (10/13 patients) by HerpeSelect assay and 23% (3/13 patients) by Kalon assay, with four additional seroconversions detected by Kalon assay at day 28. HIV serostatus did not influence assay performance. Low index values obtained with the HerpeSelect assay may correspond to true HSV-2 infection, in particular to nonprimary first episodes of genital HSV-2 infection, and need to be interpreted in the context of clinical history.