Immunoprophylaxis failure and vaccine response in infants born to mothers with chronic hepatitis B infection in Djibouti.

BACKGROUND: In endemic areas, vertical transmission of hepatitis B virus (HBV) remains a major source of the global reservoir of infected people. Eliminating mother-to-child transmission (MTCT) of HBV is at the heart of World Health Organization's goal of reducing the incidence of HBV in children to less than 0.1% by 2030. Universal screening for hepatitis B during pregnancy and neonatal vaccination are the main preventive measures. AIM: To evaluate the efficacy of HBV vaccination combined with one dose of immunoglobulin in children born to hepatitis B surface antigen (HBsAg)-positive mothers in Djibouti city. METHODS: We conducted a study in a prospective cohort of HBsAg-positive pregnant women and their infants. The study ran from January 2021 to May 2022, and infants were followed up to 7 mo of age. HBV serological markers and viral load in pregnant women were measured using aVidas microparticle enzyme-linked immunosorbent assay (Biomérieux, Paris, France) and the automated Amplix platform (Biosynex, Strasbourg, France). All infants received hepatitis B immunoglobulin and were vaccinated against HBV at birth. These infants were closely monitored to assess their seroprotective response and for failure of immunoprophylaxis. Simple logistic regression was also used to identify risk factors associated with immunoprophylaxis failure and poor vaccine response. All statistical analyses were performed with version 4.0.1 of the R software. RESULTS: Of the 50 pregnant women recruited, the median age was 31 years, ranging from 18 years to 41 years. The MTCT rate in this cohort was 4% (2/50) in HBsAg-positive women and 67% (2/3) in hepatitis B e antigen-positive women with a viral load > 200000 IU/mL. Of the 48 infants who did not fail immunoprophylaxis, 8 (16%) became poor responders (anti-HB < 100 mIU/mL) after HBV vaccination and hepatitis B immunoglobulin, while 40 (84%) infants achieved a good level of seroprotection (anti-HB > 100 mIU/mL). Factors associated with this failure of immunoprophylaxis were maternal HBV DNA levels (> 200000 IU/mL) and hepatitis B e antigen-positive status (odds ratio = 158, 95% confidence interval: 5.05-4958, P < 0.01). Birth weight < 2500 g was associated with a poor immune response to vaccination (odds ratio = 34, 95% confidence interval: 3.01-383.86, P < 0.01). CONCLUSION: Despite a failure rate of immunoprophylaxis higher than the World Health Organization target, this study showed that the combination of immunoglobulin and HBV vaccine was effective in preventing MTCT of HBV. Therefore, further studies are needed to better understand the challenges associated with immunoprophylaxis failure in infants in Djibouti city.

Genomic epidemiology of SARS-CoV-2 in Senegal in 2020-2021.

INTRODUCTION: In Senegal, molecular diagnosis was widely used for the detection and management of COVID-19 patients. However, genomic surveillance was very limited in the public sector. This study aimed to share the experience of a Senegalese public sector laboratory in response to the COVID-19 pandemic, and to describe the distribution of variants circulating in 2020 and 2021. METHODOLOGY: From July 2020 to December 2021, SARS-CoV-2 qRT-PCR was performed on nasopharyngeal samples from travelers and symptomatic patients at the Bacteriology and Virology Laboratory (LBV) of the Aristide le Dantec University Teaching Hospital. Samples with a cycle threshold (Ct) ≤ 30 were selected for whole-genome sequencing (WGS) using the Nanopore technology. In-house scripts were developed to study the spatial and temporal distribution of SARS-CoV-2 variants in Senegal, using our sequences and those retrieved from the GISAID database. RESULTS: Of 8,207 patients or travelers screened for SARS-CoV-2, 970 (11.8%) were positive and 386 had a Ct ≤ 30. WGS was performed on 133 samples. Concomitantly with high-quality sequences deposited in the GISAID database covering nine cities in Senegal in 2020 and 2021 (n = 1,539), we observed a high circulation of the 20A (B.1, B.1.416 and B.1.620) and 20B (B.1.1.420) lineages in 2020, while most of the samples belonged to Delta variants (AY34 and AY.34.1, 22%) in 2021. CONCLUSIONS: Despite its late involvement, COVID-19 diagnosis was routinely performed in LBV, but genomic characterization remained challenging. The genomic diversity of SARS-CoV-2 strains in Senegal reflected that observed worldwide during the first waves of the pandemic.

Field experience with the 8-HPV-type oncoprotein test for cervical cancer screening among HPV-positive women living with and without HIV in LMICs.

Overexpression of HPV-oncoproteins E6 and E7 is necessary for HPV-driven cervical carcinogenesis. Hence, these oncoproteins are promising disease-specific biomarkers. We assessed the technical and operational characteristics of the 8-HPV-type OncoE6/E7 Cervical Test in different laboratories using cervical samples from HPV-positive women living with (WLWH) and without HIV. The 8-HPV-type OncoE6/E7 Test (for short: "OncoE6/E7 test") was performed in 2833 HIV-negative women and 241 WLWH attending multicentric studies in Latin America (ESTAMPA study), and in Africa (CESTA study). Oncoprotein positivity were evaluated at each testing site, according to HIV status as well as type-specific agreement with HPV-DNA results. A feedback questionnaire was given to the operators performing the oncoprotein test to evaluate their impression and acceptability regarding the test. The OncoE6/E7 test revealed a high positivity rate heterogeneity across all testing sites (I2: 95.8%, p < .01) with significant lower positivity in WLWH compared to HIV-negative women (12% vs 25%, p < .01). A similar HPV-type distribution was found between HPV DNA genotyping and oncoprotein testing except for HPV31 and 33 (moderate agreement, k = 0.57). Twenty-one laboratory technicians were trained on oncoprotein testing. Despite operators' concerns about the time-consuming procedure and perceived need for moderate laboratory experience, they reported the OncoE6/E7 test as easy to perform and user-friendly for deployment in resource-limited settings. The high positivity rate variability found across studies and subjectivity in test outcome interpretation could potentially results in oncoprotein false positive/negative, and thus the need for further refinements before implementation of the oncoprotein testing in screen-triage-and-treat approaches is warranted.

Detection of Hepatitis E Virus (HEV) in Pork Sold in Saint-Louis, the North of Senegal.

The hepatitis E virus (HEV) is a zoonotic pathogen with various hosts, including pigs, which act as reservoirs. In industrialized countries, sporadic cases caused by genotype 3, contracted by ingesting contaminated uncooked or undercooked meat, have been reported. However, in developing countries, HEV infection is mainly dominated by genotype 2 and often associated with poor hygiene conditions and drinking water supplies. HEV infection and its circulation in domestic fauna in West Africa are poorly documented. This study aimed to assess the presence of HEV in pork sold in Saint-Louis, Senegal. Meat products (250 g samples, n = 74) were purchased in August 2022 from three locations. Then, 2 g/sample was minced to extract total nucleic acids using the Purelink™ Viral DNA/RNA kit. RT-PCR reactions were performed using the One-Taq™ One-Step RT-PCR kit targeting the HEV ORF2 genomic region. The products obtained were visualized on a 1% agarose gel. Of a total of 74 samples, divided into pork meat (n = 65) and pork liver (n = 9), 5.4% (n = 4) tested positive for HEV. In both cases, two samples were positive, representing a rate of 3.1% and 22.2% for meat and pork liver, respectively. All new viral sequences were obtained from a monophyletic group within HEV genotype 3. This study is the first to report the presence of HEV in pork sold in Senegal and the results reveal a potential circulation of HEV in the pig population. The high proportion of contamination in the pork liver samples highlights a major risk associated with their consumption.

m-PIMA™ HIV1/2 VL: A suitable tool for HIV-1 and HIV-2 viral load quantification in West Africa.

Point-of-Care for HIV viral RNA quantification seems to be a complementary strategy to the existing conventional systems. This study evaluated the performance of the m-PIMA™ HIV1/2 Viral Load for the quantification of both HIV-1 and HIV-2 RNA viral load. A total of 555 HIV-1 and 90 HIV-2 samples previously tested by Abbott RealTime HIV-1 (Abbott, Chicago, USA) and Generic HIV-2® Charge virale (Biocentric, France) were tested using the m-PIMA™ HIV1/2 Viral Load at the HIV National Reference lab in Senegal. For HIV-1, Pearson correlation and Bland-Altman plots showed a coefficient r = 0.97 and a bias of -0.11 log10 copies/ml (95% confidence interval [CI]: -0.086 to -0.133 log10 copies/ml) for the m-PIMA™ HIV1/2 Viral Load, respectively. Sensitivity and specificity at 3 log10 copies/ml (threshold of virological failure) were 93.6% (95%[CI]: 91.5% to 95.6%) and 99.1% (95%[CI]: 98.3% to 99.9%), respectively. For HIV-2, a correlation of r = 0.95 was also noted with a bias of - 0.229 log10 copies/ml (95%[CI]: -0.161 to -0.297 log10 copies/ml). Sensitivity and specificity at 3 log10 copies/ml were 97.6% (95%[CI]: 94.3% to 100%) and 93.9% (95%[CI]: 88.9% to 98.8%), respectively. These results confirmed that m-PIMA™ HIV1/2 VL could be a good alternative for HIV-1 and HIV-2 viral load testing in decentralized settings in Senegal.

Genomic Epidemiology of SARS-CoV-2 in Urban Settings in Senegal.

We used whole genome sequencing to identify and analyze mutations in SARS-CoV-2 in urban settings during the deadliest wave of the COVID-19 epidemic-from March to April 2021-in Senegal. Nasopharyngeal samples testing positive for SARS-CoV-2 were sequenced on the Illumina NovaSeq 6000 sequencing system using the COVIDSeq protocol. A total of 291 genotypable consensus genome sequences were obtained. Phylogenetic analyses grouped the genomes into 16 distinct PANGOLIN lineages. The major lineage was B.1.1.420, despite circulation of the Alpha variant of concern (VOC). A total of 1125 different SNPs, identified relative to the Wuhan reference genome, were detected. These included 13 SNPs in non-coding regions. An average density of 37.2 SNPs per 1000 nucleotides was found, with the highest density occurring in ORF10. This analysis allowed, for the first time, the detection of a Senegalese SARS-CoV-2 strain belonging to the P.1.14 (GR/20J, Gamma V3) sublineage of the Brazilian P.1 lineage (or Gamma VOC). Overall, our results highlight substantial SARS-CoV-2 diversification in Senegal during the study period.

Vaginal Carriage of Group B Streptococcus (GBS) in Pregnant Women, Antibiotic Sensitivity and Associated Risk Factors in Dakar, Senegal.

The eradication of neonatal Group B Streptococcus (GBS) infections, considered as a major public health priority, necessarily requires a mastery of the data on vaginal carriage in pregnant women. The aims of this study were to determine the prevalence of vaginal carriage of GBS in pregnant women, antibiotic susceptibility, and associated risk factors. This was a cross-sectional, descriptive study conducted over a period of 9 months (July 2020 to March 2021) in pregnant women between 34 and 38 weeks of gestation (WG) followed at the Nabil Choucair health center in Dakar. Identification and antibiotic susceptibility of GBS isolates were performed on the Vitek 2 from vaginal swabs cultured on Granada medium. Demographic and obstetric interview data were collected and analyzed on SPSS (version 25). The level of significance for all statistical tests was set at P < .05. The search of GBS vaginal carriage had involved 279 women aged 16 to 46 years, with a median pregnancy age of 34 (34-37) weeks' gestation. GBS was found in 43 women, for a vaginal carriage rate of 15.4%. In 27.9% (12/43) of volunteers screened, this carriage was monomicrobial, while in 72.1% (31/43) of women, GBS was associated with other pathogens such as Candida spp. (60.5%), Trichomonas vaginalis (2.3%), Gardnerella vaginalis (34.9%) and/or Mobiluncus spp. (11.6%). The level of resistance was 27.9% (12/43) for penicillin G, 53.5% (23/43) for erythromycin, 25.6% (11/43) for clindamycin and 100% for tetracycline. However, the strains had retained fully susceptible to vancomycin and teicoplanin. The main risk factor associated with maternal GBS carriage were ectocervical inflammation associated with contact bleeding (OR = 3.55; P = .005). The high rate of maternal vaginal GBS carriage and the levels of resistance to the various antibiotics tested confirm the importance of continuous GBS surveillance in our resource-limited countries.

Performance of Xpert HIV-1 viral load test in Senegal: a country of high circulation of CRF02_AG.

Introduction: the introduction of the point-of-care in HIV-1 viral load quantification appears to be a complementary strategy to the existing conventional system of the acceleration plan for the achievement of the three 90s in Senegal. The objective of this study was to evaluate the performance of the Xpert® HIV-1 viral load in the context of circulation of non-B, non-C subtypes. Methods: two hundred samples, were tested on Xpert® HIV-1 Viral Load using 1 ml of plasma in comparison to 600 µl on Abbott Real-time HIV-1 assay. The difference between viral load values was considered significant for Dlog <0.5 log copies/ml. Results: a good correlation (r=0.985) was noted and confirmed using passing-bablok regression (slope 1.048; 95% CI: 1.036 to 1.069) for 188 samples with samples. A mean difference of 0.0075 log10 copies/ml for a 95% confidence interval (CI) of 0.002 log10 copies/ml to 0.013 log10 copies/ml was obtained. Sensitivity and specificity were respectively 93.6% and 93.5% at the threshold of 1.6 log10 copies/ml and 100% and 99% at the threshold of 3.0 log10 copies/ml. Conclusion: these results show that Xpert® HIV-1 Viral Load has excellent performance. In Senegal, and can be used for HIV viral load monitoring.

Hepatitis E Virus Seroprevalence and Associated Risk Factors in Pregnant Women Attending Antenatal Consultations in Senegal.

In West Africa, research on the hepatitis E virus (HEV) is barely covered, despite the recorded outbreaks. The low level of access to safe water and adequate sanitation is still one of the main factors of HEV spread in developing countries. HEV infection induces acute or sub-clinical liver diseases with a mortality rate ranging from 0.5 to 4%. The mortality rate is more alarming (15 to 25%) among pregnant women, especially in the last trimester of pregnancy. Herein, we conducted a multicentric socio-demographic and seroepidemiological survey of HEV in Senegal among pregnant women. A consecutive and non-redundant recruitment of participants was carried out over the period of 5 months, from March to July 2021. A total of 1227 consenting participants attending antenatal clinics responded to a standard questionnaire. Plasma samples were collected and tested for anti-HEV IgM and IgG by using the WANTAI HEV-IgM and IgG ELISA assay. The overall HEV seroprevalence was 7.8% (n = 96), with 0.5% (n = 6) and 7.4% (n = 91) for HEV IgM and HEV IgG, respectively. One of the participant samples was IgM/IgG-positive, while four were declared indeterminate to anti-HEV IgM as per the manufacturer's instructions. From one locality to another, the seroprevalence of HEV antibodies varied from 0 to 1% for HEV IgM and from 1.5 to 10.5% for HEV IgG. The data also showed that seroprevalence varied significantly by marital status (p < 0.0001), by the regularity of income (p = 0.0043), and by access to sanitation services (p = 0.0006). These data could serve as a basis to setup national prevention strategies focused on socio-cultural, environmental, and behavioral aspects for a better management of HEV infection in Senegal.

Detection and quantitation of hepatitis B surface antigen (HBsAg) on dried blood spots: a solution for easy access for hepatitis B diagnosis and elimination in remote areas.

Hepatitis B virus (HBV) is generally endemic in resource-limited countries, which are characterized by a deficit of technical facilities that could delay diagnosis and treatment. To facilitate the accessibility to diagnostic and connection to treatment, evaluation, and promotion of alternatives and/or simplified strategies and inexpensive tools such as dried blood specimens need to be investigated and implemented. This study aimed to evaluate dried blood spots (DBS) for the detection and quantification of HBsAg. This study included 100 DBS from subjects tested positive for HBsAg, and 50 DBSs from subjects tested negative for HBsAg by the automate Architect i1000sr (Abbott Diagnostics, Ireland). Hepatitis B surface antigen detection was performed with determine HBsAg Alere® tests (Alere International Limited, Ireland) and Architect® HBsAg Qualitative II Assays (Abbott, Diagnostics, Ireland) after 15 and 30 days (D15, D30). For HBsAg-positive subjects, the quantification of HBsAg was performed at day zero (D0) from plasma and at D15 and D30 from the DBSs. At D15, the sensitivity and specificity were 96% and 100% for the Determine® tests and 100% and 100% for the Architect® tests, respectively. At D30, the sensitivity and specificity were 96% and 100% for the Determine® tests and 100% and 100% for the Architect® tests, respectively. For HBsAg quantification, the agreement rates were 96%, 96% and 100% between D0-D15, D0-D30 and D15-D30, respectively. This work showed that DBSs can be very useful for HBsAg detection and quantification and therefore in the management of HBV infection in resource-limited settings.

A NGS-based Blood Test For the Diagnosis of Invasive HPV-associated Carcinomas with Extensive Viral Genomic Characterization.

PURPOSE: Use of circulating tumor DNA (ctDNA) for diagnosis is limited regarding the low number of target molecules in early-stage tumors. Human papillomavirus (HPV)-associated carcinomas represent a privileged model using circulating viral DNA (ctHPV DNA) as a tumor marker. However, the plurality of HPV genotypes represents a challenge. The next-generation sequencing (NGS)-based CaptHPV approach is able to characterize any HPV DNA sequence. To assess the ability of this method to establish the diagnosis of HPV-associated cancer via a blood sample, we analyzed ctHPV DNA in HPV-positive or HPV-negative carcinomas. EXPERIMENTAL DESIGN: Patients (135) from France and Senegal with carcinoma developed in the uterine cervix (74), oropharynx (25), oral cavity (19), anus (12), and vulva (5) were prospectively registered. Matched tumor tissue and blood samples (10 mL) were taken before treatment and independently analyzed using the CaptHPV method. RESULTS: HPV prevalence in tumors was 60.0% (81/135; 15 different genotypes). Viral analysis of plasmas compared with tumors was available for 134 patients. In the group of 80 patients with HPV-positive tumors, 77 were also positive in plasma (sensitivity 95.0%); in the group of 54 patients with HPV-negative tumors, one was positive in plasma (specificity 98.1%). In most cases, the complete HPV pattern observed in tumors could be established from the analysis of ctHPV DNA. CONCLUSIONS: In patients with carcinoma associated with any HPV genotype, a complete viral genome characterization can be obtained via the analysis of a standard blood sample. This should favor the development of noninvasive diagnostic tests providing the identification of personalized tumor markers. See related commentary by Rostami et al., p. 5158.

High HIV-1 Virological Failure and Drug Resistance among Adult Patients Receiving First-Line ART for At least 12 Months at a Decentralized Urban HIV Clinic Setting in Senegal before the Test-and-Treat.

BACKGROUND: The feasibility of antiretroviral therapy (ART) monitoring remains problematic in decentralized HIV clinic settings of sub-Saharan Africa. We assessed the rates and correlates of HIV-1 virological failure (VF) and drug resistance (DR) in 2 pre-test-and-treat urban clinic settings of Senegal. METHODS: Consenting HIV-1-infected adults (⩾18 years) receiving first-line ART for ⩾12 months were cross-sectionally enrolled between January and March 2015, at the referral outpatient treatment center of Dakar (n = 151) and decentralized regional hospital of Saint-Louis (n = 127). In the 12 months preceding plasma specimens' collection patients at Saint-Louis had no viral load (VL) testing. Significant predictors of VF (VL ⩾ 1000 copies/ml) and DR (clinically relevant mutations) were determined using binomial logistic regression in R software. RESULTS: Of the 278 adults on EFV-/NVP-based regimens, 32 (11.5% [95%CI: 8.0-15.9]) experienced VF. Failing and non-failing patients had comparable median time [interquartile] on ART (69.5 [23.0-89.5] vs 64.0 [34.0-99.0] months; P = .46, Mann-Whitney U-test). Of the 27 viraemic isolates successfully genotyped, 20 (74.1%) carried DR mutations; most frequent were M184VI (55.6%), K103N (37.1%), thymidine analog mutations (29.6%), Y181CY (22.2%). The pattern of mutations did not always correspond to the ongoing treatment. The adjusted odds of VF was significantly associated with the decentralized clinic site (P < .001) and CD4 < 350 cells/mm3 (P < .006). Strong correlates of DR also included Saint-Louis (P < .009), CD4 < 350 cells/mm3 (P <. 001), and nevirapine-based therapies (comparator: efavirenz-based therapies; P < .027). In stratification analyses by site, higher rate of VF at Saint-Louis (20.5% [95%CI: 13.8-28.5] vs 4.0% [95%CI: 1.5-8.5] in Dakar) was associated with nevirapine-based therapies (OR = 3.34 [1.07-11.75], P = .038), self-reported missing doses (OR = 3.30 [1.13-10.24], P = .029), and medical appointments (OR = 2.91 [1.05-8.47], P = .039) in the last 1 and 12 months(s), respectively. The higher rate of DR at Saint-Louis (12.9% [95%CI: 7.6-20.1] vs 2.7% [95%CI: 0.7-6.7] in Dakar) was associated with nevirapine-based therapies (OR = 5.13 [1.12-37.35], P = .035). CONCLUSION: At decentralized urban settings, there is need for enhanced virological monitoring and adherence support. HIV programs in Senegal should intensify early HIV diagnosis for effective test-and-treat. These interventions, in addition to the superiority of efavirenz-based therapies provide a favorable framework for transitioning to the recommended potent drug dolutegravir, thereby ensuring its long-term use.

Respective prevalence of high-risk HPVgenotypes in cervical neoplasia in Senegal.

OBJECTIVES: With the perspective of prophylactic vaccination against high-risk human papillomavirus (HPV), we analyzed the viral epidemiology of cervical neoplasia in Senegal. METHODS: All patients were treated at the Institut Joliot Curie du Cancer in Dakar. HPV genotypes were characterized using a real-time polymerase chain reaction-based approach and sequencing. RESULTS: Histologically, there were 224 invasive carcinomas, 17 high-grade intraepithelial neoplasia (CIN), and five undetermined histologies. Molecular analysis was conclusive in 241 cases. HPV DNA was found in 207/241 (85.9%) cases while 34/241 (14.1%) remained HPV negative. There was one single genotype in 127/207 (61.4%) cases and several in 80/207 (38.6%) corresponding to 308 genotypes identified. Viral genotyping found HPV16 in 175 (56.8%) cases, HPV18 in 45 (14.6%), HPV45 in 40 (13.0%), HPV58 in 35 (11.4%), HPV33 in 6 (2.0%), HPV35 in 3 (1.0%), HPV31 in 2 (0.6%), HPV39 and HPV56 in one (0.3% each). CONCLUSION: Our analysis showed that 98.4% of the HPV-positive cases were associated with viral genotypes covered by the 9-valent HPV vaccine. However, 14.1% of cases remained HPV negative. Therefore, prophylactic vaccination using a 9-valent vaccine should dramatically reduce the incidence of HPV-associated neoplasia but the detection and treatment of CIN remain necessary for the optimal prevention of cervical cancer.

Contribution of the classical polymerase chain reaction in the diagnosis of a HIV-1 infected patient in Benin: a case report.

BACKGROUND: First ambitious target by 2020 of UNAIDS is that 90% of people living with HIV know their HIV status. In people older than 18 months of age, serological confirmation test is recommended to confirm HIV infection. CASE PRESENTATION: Here we report the case of a patient tested positive with HIV-1, ELISA, Murex® Ag/Ab Combination assay (OD450 = 0.802 and cutoff-OD = 0.279) and negative by using FIRST RESPONSE HIV1-2.O CARD TEST (version 2.0) RAPID HIV CARD TEST. Viral load performed with Cobas® TaqMan® 96/Cobas® Ampliprep® was 6.49log10. The virus could be sequenced in partial gag and pol genes and belonged to CRF02_AG clade. CONCLUSION: Conventional PCR is a complementary method for the diagnosis of inconclusive HIV-1 serologies by antibodies.

Prevalence and molecular characterization of hepatitis B virus infection in HIV-infected children in Senegal.

BACKGROUND AND AIMS: Sub-Saharan Africa (SSA) is the region with the most patients co-infected with the human immunodeficiency virus (HIV) and the hepatitis B virus (HBV) worldwide. However, few studies have focused on SSA children who are at a higher risk of developing a chronic infection than adults. Furthermore, children on first-line antiretroviral therapy (ART) including low genetic barrier drugs may develop both HBV and HIV resistance mutations. The aim of this work was to document HIV-HBV co-infection and to characterize the HBV isolates in children in Senegal. METHODS: This is a retrospective study of 613 children infected with HIV on ART or not. Dried blood spot (DBS) specimens were used to detect hepatitis B surface antigen (HBsAg) with a rapid diagnostic test (RDT). Confirmation of HBsAg status and hepatitis B e antigen (HBeAg) detection was performed on an automated platform using the chemiluminescence assay technology. HBV viral DNA was quantified by real-time polymerase chain reaction (PCR) and the preS1/preS2/HBsAg region was genotyped by nested PCR followed by sequencing using the Sanger technique. RESULTS: The prevalence of HIV-HBV co-infection was 4.1% (25/613). The median age of co-infected children was 13 years (2 years-16 years) and 40% (10/25) were girls. Almost all 19/20 (95%) were infected with HIV-1 and 79% (19/24) were treated with 3TC-based triple combination ART. The median duration of time on ART was 15 months (3 months-80 months). More than half of the children 53% (9/17) were experiencing HIV virologic failure and 75% (6/8) had at least one HIV-related resistance-associated mutation (RAM). Of the six children with resistance, none of the three administered treatments were effective on HIV. Of the 25 co-infected children, 82% (18/22) were HBeAg-positive, while the median HBV viral load (VL) was 6.20 log10 IU/mL (24/25 patients), and 62,5% (10/16) of the children had a persistent HBV viremia. Combination of ART was the only factor associated with HBV viremia persistence. Amplification was successful in 15 out of 16 patients (rate of 94%), and the ensuing phylogenetic analysis revealed that eight strains (53%) belonged to genotype A and seven (47%) to genotype E. HBV-related 3TC RAMs were uncovered in 20% of these patients (3/15). HBsAg escape mutations were found in 20% of the children (3/15). CONCLUSIONS: Our results showed a high level of drug resistance mutations to both HIV and HBV, a significant level of HBsAg escape mutations, HBV DNA persistence and HIV virologic failure in co-infected children in Senegal. The HBV genotypes found were A and E.

Moderate rate of transmitted resistance mutations to antiretrovirals and genetic diversity in newly HIV-1 patients diagnosed in Benin.

OBJECTIVE: Seventeen years after the start of the IBAARV (Beninese initiative for access to antiretrovirals), transmitted drug resistance mutations in ARV-naïve patients and HIV-1 genetic diversity were investigated in Benin. RESULTS: Drug resistance mutations were detected in (27/248; 10.9%) according to the WHO SDRM 2009 list, with a predominance of mutations directed against NNRTIs drugs (24/248; 10%). Phylogenetic and recombination analyses showed a predominance of CRF02_AG strains (165/248; 66.5%) and a high genetic diversity with five other variants and 39 URFs (15.7%) which contained portions of strains that co-circulate in Benin. Eight recent transmission chains revealed active ongoing transmission of HIV-1 strains among ARV-naïve patients. Our study showed a moderate primary drug resistance mutations rate and also provided recent data on the HIV-1 variants that circulate in Benin. Regular monitoring of primary drug resistance is required to adapt HIV-1 treatment strategies and adoption of new WHO recommendations in Benin.

Tenofovir resistance in early and long-term treated patients on first-line antiretroviral therapy in eight low-income and middle-income countries.

OBJECTIVE: We aimed to assess the frequency of tenofovir (TDF) resistance in people failing tenofovir/lamivudine or emtricitabine (XTC)/nonnucleotide reverse-transcriptase inhibitor-based first-line antiretroviral treatment (ART) using data from 15 nationally representative surveys of HIV drug resistance conducted between 2014 and 2018 in Cameroon, Guatemala, Honduras, Nicaragua, Senegal, Uganda, Vietnam and Zambia. METHODS: Prevalence of nucleoside reverse-transcriptase inhibitor resistance among participants with virological nonsuppression (viral load ≥1000 copies/ml) who had received TDF-based ART for 12-24 months (early ART group) and at least 40 months (long-term ART group) was assessed using Sanger sequencing and resistance was interpreted using the Stanford HIVdb algorithm. For each group, we estimated a pooled prevalence using random effect meta-analysis. RESULTS: Of 4677 participants enrolled in the surveys, 640 (13.7%) had virological nonsuppression, 431 (67.3%) were successfully genotyped and were included in the analysis; of those, 60.3% (260) were participants in the early ART group. Overall, 39.1, 57.9, 38.5 and 3.6% patients in the early ART group and 42.9, 69.3, 42.9 and 10.0% patients on long-term ART had resistance to TDF, XTC, TDF + XTC and TDF + XTC + zidovudine, respectively. Overall, tenofovir resistance was mainly due to K65R or K70E/G/N/A/S/T/Y115F mutations (79%) but also due to thymidine analogue mutations (21%) which arise from exposure to thymidine analogues but causing cross-resistance to TDF. CONCLUSION: Dual resistance to TDF + XTC occurred in more than 40% of the people with viral nonsuppression receiving tenofovir-based first-line ART, supporting WHO recommendation to optimize the nucleoside backbone in second-line treatment and cautioning against single drug substitutions in people with unsuppressed viral load.

Associations Between Economic Factors and Condom Use Behavior Among Female Sex Workers in Dakar and Mbour, Senegal.

Condom use remains a mainstay of HIV prevention programs around the world. However, data characterizing economic determinants of condom use among female sex workers (FSW) are limited, including in Senegal. We recruited 718 FSWs via respondent-driven sampling. Bivariate and multivariable regressions were conducted to assess the associations between economic variables and condom use at last sex. Paying rent (aRR: 1.07, 95%CI 1.01-1.13) was positively associated with condom use at last sex with new clients. No statistically significant associations were found between condom use and financial responsibility for dependent children, having additional source of income, sharing sex work earnings, or the ability to borrow from other FSWs, regardless of sexual partner types. The relationship between economic marginalization and consistent condom use among sex workers is complex reinforcing the need for behavioral economic research and prevention to be integrated into HIV prevention and treatment research and programs.

Hepatitis B virus (HBV) infection amongst children in Senegal: current prevalence and seroprotection level.

INTRODUCTION: Hepatitis B virus (HBV) infection is highly endemic in Senegal. HBV vaccine of all children has been introduced in 1999 and included in the Expanded Programme on Immunization in 2004. The aim of this study was to assess the HBV prevalence and immunity status against HBV amongst children in Senegal. METHODS: Between March and August 2016, consecutive children aged from 6 months to 16 years old were recruited in outpatient department of three main children hospitals in Senegal. Serum samples were analyzed for HBV serology (HBsAg, HBcAb, HBsAb) using ARCHITECT analyzer. Children with HBsAb levels ≥ 10 IU/l) were considered as seroprotected against HBV. RESULTS: During the study period, 295 children fulfilled the criteria for the study and were further analyzed. Three children were HBsAg positive giving a seroprevalence at 1.1% (95% CI: 0.2-3.3), 12/267 (4.5%, 95% CI=2.3-7.7) had positive HBcAb and 226/295 (76.6%, 71.4-81.3) had positive HBsAb including 191 (77.3%, 71.6-82.4) with isolated HBsAb related to previous active immunization. However only 165 children (56%, CI 50-62) had seroprotective HBsAb levels (HBsAb ≥ 10 UI/L) and 63 (21.4, 16.8-26) had a strong seroprotectiondefined by HBsAb ≥ 100 IU/L. CONCLUSION: Our results suggest that although HBV prevalence has significantly decreased in children in Senegal following a better HBV vaccine coverage, the number of children correctly seroprotected is insufficient (56%). Assessing the levels of HBsAb and providing HBV vaccine boosters should be considered in children in Senegal.

Effectiveness of the prevention of HIV mother -to-child transmission (PMTCT) program via early infant diagnosis (EID) data in Senegal.

BACKGROUND: To improve the care and treatment of HIV-exposed children, early infant diagnosis (EID) using dried blood spot (DBS) sampling has been performed in Senegal since 2007, making molecular diagnosis accessible for patients living in decentralized settings. This study aimed to determine the evolution of the HIV transmission rate in children from 2008 to 2015 and to analyze associated factors, particularly the mother's treatment status and/or child's prophylaxis status and the feeding mode. METHODS: The data were analyzed using EID reports from the reference laboratory. Information related to sociodemographic characteristics, HIV profiles, the mother's treatment status, the child's prophylaxis status, and the feeding mode was included. Descriptive statistics were calculated, and bivariate and multivariate logistic regression analyses were performed. RESULTS: During the study period, a total of 5418 samples (5020 DBS and 398 buffy coat) from 168 primary prevention of HIV mother-to-child transmission (PMTCT) intervention sites in Senegal were tested. The samples were collected from 4443 children with a median age of 8 weeks (1-140 weeks) and a sex ratio (M/F) of 1.1 (2309/2095). One-third (35.2%; N = 1564) of the children were tested before 6 weeks of age. Twenty percent (N = 885) underwent molecular diagnostic testing more than once. An increased number of mothers receiving treatment (57.4%; N = 2550) and children receiving prophylaxis (52.1%; N = 2315) for protection against HIV infection during breastfeeding was found over the study period. The transmission rate decreased from 14.8% (95% confidence interval (CI): 11.4-18.3) in 2008 to 4.1% (95% CI: 2.5-7.5) in 2015 (p < 0.001). However, multivariate logistic regression analysis revealed that independent predictors of HIV mother-to-child transmission included lack of mother's treatment (adjusted odd ratio (aOR) = 3.8, 95% CI: 1.9-7.7; p˂0.001), lack of child's prophylaxis (aOR = 7.8, 95% CI: 1.7-35.7; p = 0.009), infant age at diagnosis (aOR = 2.2, 95% CI: 1.1-4.3 for ≤6 weeks versus 12-24 weeks; p = 0.025) and protective effect of breastfeeding on ART against formula feeding (aOR = 0.4, 95% CI: 0.2, 0.7; p = 0.005). CONCLUSION: This study demonstrates the effectiveness of PMTCT interventions in Senegal but indicates also that increased efforts should be continued to reduce the MTCT rate to less than 2%.