COVID-19 in 16 West African Countries: An Assessment of the Epidemiology and Genetic Diversity of SARS-CoV-2 after Four Epidemic Waves.

West Africa faced the COVID-19 pandemic in early March 2020 and, as of March 31, 2022, had more than 900,000 confirmed cases and more than 12,000 deaths. During this period, SARS-CoV-2 genomes evolved genetically, resulting in the emergence of distinct lineages. This review was conducted to provide the epidemiological profile of COVID-19, the mutational profile of SARS-CoV-2, and the dynamics of its lineages in the 16 west African countries by analyzing data from 33 studies and seven situation reports. For a more complete representation of the epidemiology and genetic diversity of SARS-CoV-2, we used reliable public data in addition to eligible studies. As of March 31, 2022, the 16 west African countries experienced four epidemic waves with variable intensities. Higher mortality was noted during the third wave with a case fatality rate (CFR) of 1.9%. After these four epidemic waves, Liberia recorded the highest CFR (4.0%), whereas Benin had the lowest CFR (0.6%). Through mutational analysis, a high genetic heterogeneity of the genomes was observed, with a predominance of mutations in the spike protein. From this high mutational rate, different lineages emerged. Our analysis of the evolutionary diversity allowed us to count 205 lineages circulating in west Africa. This study has provided a good representation of the mutational profile and the prevalence of SARS CoV-2 lineages beyond the knowledge of the global epidemiology of the 16 African countries.

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.

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.

Validation of the point-of-care (POC) technologies Xpert HIV-1 Qual and m-PIMA HIV 1/2 detect for early diagnosis of HIV-1 and HIV-2 in Senegal.

Introduction: early infant diagnosis (EID) is crucial in the prevention of mother to child transmission (PMTCT) of human immunodeficiency virus (HIV) and is an essential component for the elimination of HIV. EID can be strengthened in resource-limited countries by the introduction and the roll out of real-time polymerase chain reaction (PCR) technologies via point-of-care (POC) devices which improves treatment in remote areas and reduces turnaround time for clinicians and patients to receive results and linkage to care. The objective of this study was to evaluate the performance of Xpert® HIV-1 Qual Assay (Cepheid) and m-PIMA™ HIV 1/2 Detect (ABBOTT) for EID of HIV-1 and HIV-2. Methods: the performance of the Xpert® HIV-1 qual device was evaluated with 192 samples including 100 dried blood spot (DBS) samples from the National Reference Laboratory biobank (71 negative and 29 positive samples) and an additional 92 whole blood samples collected from infants from neonatal departments. These infants from seven treatment centers in the Dakar region were born to mothers infected with HIV-1 (n=91), HIV-2 (n= 8) or HIV-1/2 (n=1). The m-PIMA™ HIV 1/2 detect assay was evaluated on whole blood samples (n=100) with 92 HIV-1 samples and 8 HIV-2 samples from children born to HIV-infected mothers. The Cobas AmpliPreP/Cobas TaqMan (CAP/CTM) platform from Roche Diagnostic Laboratories was used as a reference for HIV-1 diagnosis and the Generic HIV-2 Viral Load Assay (Biocentric) was used as a reference for HIV-2 diagnosis. Performance was evaluated by calculating sensitivity (Se), specificity (Sp), positive predictive value (PPV), negative predictive value (NPV) and Cohen's kappa coefficient. Results: for HIV-1 detection on GeneXpert and m-PIMA, no discordance was found on the samples tested, i.e. a sensitivity of 100% (95% CI: 93.9-100%), a specificity of 100% (95% CI: 97.5-100%), a positive predictive value (PPV) of 100% (95% CI: 93.9-100%) and a negative predictive value (NPV) of 100% (95% CI: 97.5-100%). Agreement with Cobas AmpliPrep/Cobas TaqMan (CAP/CTM) was 100% with a Kappa coefficient of 1 (p<0.001, 95% CI) for both techniques. Similarly, the comparison between m-PIMA and generic biocentric for the detection of HIV-2 on the 8 samples tested showed perfect agreement. Conclusion: these results confirm the excellent performance of the Xpert® HIV-1 qual and m-PIMA™ HIV1/2 detect tests for the detection of HIV-1 and HIV-2 and encourage the extension of POC tests to improve access to EID in Senegal.

HBV continuum of care using community- and hospital-based screening interventions in Senegal: Results from the PROLIFICA programme.

Background & Aims: Strategies to implement HBV screening and treatment are critical to achieve HBV elimination but have been inadequately evaluated in sub-Saharan Africa (sSA). Methods: We assessed the feasibility of screen-and-treat interventions in 3 real-world settings (community, workplace, and hospital) in Senegal. Adult participants were screened using a rapid HBsAg point-of-care test. The proportion linked to care, the proportion who had complete clinical staging (alanine transaminase [ALT], viral load, and FibroScan®), and the proportion eligible for treatment were compared among the 3 intervention groups. Results: In 2013-2016, a total of 3,665 individuals were screened for HBsAg in the community (n = 2,153) and in workplaces (n = 1,512); 199/2,153 (9.2%) and 167/1,512 (11%) were HBsAg-positive in the community and workplaces, respectively. In the hospital setting (outpatient clinics), 638 HBsAg-positive participants were enrolled in the study. All infected participants were treatment naïve. Linkage to care was similar among community-based (69.9%), workplace-based (69.5%), and hospital-based interventions (72.6%, p = 0.617). Of HBV-infected participants successfully linked to care, full clinical staging was obtained in 47.5% (66/139), 59.5% (69/116), and 71.1% (329/463) from the community, workplaces, and hospitals, respectively (p <0.001). The proportion eligible for treatment (EASL criteria) differed among community- (9.1%), workplace- (30.4%), and hospital-based settings (17.6%, p = 0.007). Acceptability of antiviral therapy, adherence, and safety at 1 year were very good. Conclusions: HBV screen-and-treat interventions are feasible in non-hospital and hospital settings in Senegal. However, the continuum of care is suboptimal owing to limited access to full clinical staging. Improvement in access to diagnostic services is urgently needed in sSA. Lay summary: Hepatitis B infection is highly endemic in Senegal. Screening for infection can be done outside hospitals, in communities or workplaces. However, the hepatitis B continuum of care is suboptimal in Senegal and needs to be simplified to scale-up diagnosis and treatment coverage.

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.

Heterogeneity of the Omicron variant in Senegal.

•Omicron variant continues to progress in Senegal with the appearance of new contaminations.•IRESSEF detected the first positive case of the Omicron variant on Friday, December 3, 2021.•Since this date, the number of Omicron variant infections has increased over the weeks.•Molecular surveillance of the Omicron variant allowed us to identify a strong variation of this variant in our country.

Hepatitis B in Senegal: A Successful Infant Vaccination Program but Urgent Need to Scale Up Screening and Treatment (ANRS 12356 AmBASS survey).

Senegal introduced the infant hepatitis B virus (HBV) vaccination in 2004 and recently committed to eliminating hepatitis B by 2030. Updated epidemiological data are needed to provide information on the progress being made and to develop new interventions. We estimated the prevalence of hepatitis B surface antigen (HBsAg) in children and adults living in rural Senegal and assessed hepatitis B treatment eligibility. A cross-sectional population-based serosurvey of HBsAg was conducted in 2018-2019 in a large sample (n = 3,118) of residents living in the Niakhar area (Fatick region, Senegal). Individuals positive for HBsAg subsequently underwent clinical and biological assessments. Data were weighted for age and sex and calibrated to be representative of the area's population. Among the 3,118 participants, 206 were HBsAg positive (prevalence, 6.9%; 95% confidence interval [CI], 5.6-8.1). Prevalence varied markedly according to age group in individuals aged 0-4, 5-14, 15-34, and ≥35 years as follows: 0.0% (95% CI, 0.00-0.01); 1.5% (95% CI, 0.0-2.3); 12.4% (95% CI, 9.1-15.6); and 8.8% (95% CI, 6.1-11.5), respectively. Of those subsequently assessed, 50.9% (95% CI, 41.8-60.0) had active HBV infection; 4 (2.9%; 95% CI, 0.9-9.4) were eligible for hepatitis B treatment. Conclusion: In this first population-based serosurvey targeting children and adults in rural Senegal, HBsAg prevalence was very low in the former, meeting the World Health Organization's (WHO) < 1% HBsAg 2020 target; however, it was high in young adults (15-34 years old) born before the HBV vaccine was introduced in 2004. To reach national and WHO hepatitis elimination goals, general population testing (particularly for adolescents and young adults), care, and treatment scale-up need to be implemented.

[Survey of patients admitted to the Regional Hospital Center (RHC) of Maradi following self-medication]. / Enquete chez les patients admis au Centre Hospitalier Regional (CHR) de Maradi a la suite d'une automedication.

OBJECTIVE: The objective of this study was to evaluate the impact and complications related to self-medication among patients admitted to the Maradi RHC. METHODOLOGY: We conducted a cross-sectional, descriptive and analytical study at the Maradi RHC, in the referral department from June 30 to September 30, 2021, by means of an interview. RESULTS: A total of 254 patients were interviewed. The frequency of self-medication at the Maradi CHR was 3.63%. The majority of the patients surveyed were women (53.94%). The average age was 42 years. Among them, 63.39% were attending Koranic school and 38.19% were housewives. Street vendors and traditional practitioners were the main suppliers of self-medication drugs, respectively 45.28% and 30.31%. The most commonly used products were traditional medicines, analgesics, antibiotics and anti-malarial (47.63%, 26.37%, 22.44% and 16.92% respectively). The lack of financial means and accessibility of treatment were the main reasons for this practice. Digestive diseases were the most frequent pathology group. Jaundice was the first complication related to self-medication, followed by urticaria and Lyell's syndrome. Following management, 8% (n=20) patients were discharged cured and 6% (n=15) had died. CONCLUSION: Self-medication is a rapidly growing practice, favored by many factors despite the many risks that can arise from it. In order to prevent these risks, an awareness program is necessary to make the population adhere to a change of behavior.

OBJECTIF: Cette étude avait pour objectif d'évaluer l'impact et les complications liées à l'automédication chez les patients admis au CHR de Maradi. MÉTHODOLOGIE: Nous avons mené une étude transversale, descriptive et analytique au CHR de Maradi, dans le service d'aiguillage du 30 Juin au 30 septembre 2021, par le biais d'une interview. RÉSULTATS: Au total 254 patients ont été interviewés. La fréquence de l'automédication au CHR de Maradi était de 3,63%. La majorité des patients enquêtés étaient des femmes 53,94%. La moyenne d'âge était de 42 ans. Parmi eux, 63,39% fréquentaient l'école coranique et 38,19% étaient des ménagères. Les vendeurs de la rue et les tradipraticiensétaient les principaux acteurs qui fournissaient les médicaments d'automédication soit respectivement 45,28% et 30,31%. Les produitsles plus utilisées étaient les médicaments traditionnels, les antalgiques, les antibiotiques et les antipaludiques soit respectivement 47,63%, 26,37%, 22,44% et 16,92%. Le manque de moyen financier et l'accessibilité du traitement étaient les principales causes motivant cette pratique. Les affections digestives représentent le groupe de pathologie les plus fréquentes. L'ictère était la première complication liée à l'automédication suivi de l'urticaire et le syndrome de Lyell. A la suite de la prise en charge,8%(n=20) patients de étaient sortis sont sortis guéris et 6% (n=15) étaient décédés. CONCLUSION: L'automédication est une pratique en forte croissance, favorisée par bien de facteurs malgré les nombreux risques qui peuvent découler de celle-ci. En vue de prévenir ces risques un programme de sensibilisation s'avère nécessaire afin de faire adhérer la population à un changement de comportement.

Emergence of novel combinations of SARS-CoV-2 spike receptor binding domain variants in Senegal.

The emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) lineages that carry mutations in the spike gene are of concern for potential impact to treatment and prevention efforts. To monitor for new SARS-CoV-2 mutations, a panel of specimens were sequenced from both wave one (N = 96), and wave two (N = 117) of the pandemic in Senegal by whole genome next generation sequencing. Amongst these genomes, new combinations of SARS-CoV-2 spike mutations were identified, with E484K + N501T, L452R + N501Y, and L452M + S477N exclusively found in second wave specimens. These sequences are evidence of local diversification over the course of the pandemic and parallel evolution of escape mutations in different lineages.

Sibling status, home birth, tattoos and stitches are risk factors for chronic hepatitis B virus infection in Senegalese children: A cross-sectional survey.

Sub-Saharan Africa's hepatitis B virus (HBV) burden is primarily due to infection in infancy. However, data on chronic HBV infection prevalence and associated risk factors in children born post-HBV vaccination introduction are scarce. We estimated hepatitis B surface antigen (HBsAg) prevalence and risk factors in Senegalese children born during the HBV vaccination era. In 2018-2019, a community-based cross-sectional survey was conducted in Senegal among children born between 2004 and 2015 (ie after the three-dose HBV vaccine series was introduced (2004) but before the birth dose's introduction (2016)). HBsAg-positive children were identified using dried blood spots. A standardized questionnaire collected socioeconomic information. Data were age-sex weighted and calibrated to be representative of children living in the study area. Risk factors associated with HBsAg positivity were identified using negative binomial regression. Among 1,327 children, 17 were HBsAg-positive (prevalence = 1.23% (95% confidence interval [CI] 0.61-1.85)). Older age (adjusted incidence-rate ratio [aIRR] 1.31 per one-year increase, 95% CI 1.10-1.57), home vs healthcare facility delivery (aIRR 3.55, 95% CI 1.39-9.02), stitches (lifetime) (aIRR 4.79; 95% CI 1.84-12.39), tattoos (aIRR 8.97, 95% CI 1.01-79.11) and having an HBsAg-positive sibling with the same mother (aIRR 3.05, 95% CI 1.09-8.57) were all independently associated with HBsAg positivity. The low HBsAg prevalence highlights the success of the Senegalese HBV vaccination program. To further reduce HBV acquisition in children, high-risk groups, including pregnant women and siblings of HBsAg-positive individuals, must be screened. Vital HBV infection prevention measures include promoting delivery in healthcare facilities, and increasing awareness of prevention and control procedures.

Comparison of Amplix® hepatitis B virus and Roche COBAS AmpliPrep/COBAS Taqman hepatitis B virus assay in quantifying HBV DNA in plasma of chronic hepatitis B in Senegal.

INTRODUCTION: quantification of hepatitis B virus DNA, a key element in the management of chronic hepatitis B, allows a more direct and reliable measurement of viral replication and monitoring of the virological response to therapy. Polymerase chain reaction (PCR) platforms performing this quantification and adaptable to intermediate laboratories have been developed. Thus, this study was conducted to evaluate the on-site performance of the AMPLIX® hepatitis B virus (HBV) real-time PCR technique in comparison with the COBAS AmpliPrep™ technique. METHODS: performance of the AMPLIX® HBV real-time PCR technique was evaluated with repeatability and intermediate precision (reproducibility) determined. The comparison with COBAS Taqman was performed by testing, in parallel, 42 plasma samples. The statistical analysis using Meth Val® software was focused on correlation and concordance determination. RESULTS: AMPLIX® real-time PCR assay showed good reproducibility for the low (CV=6.65%) and high (CV=3.15%) control levels but also good repeatability for both the low (CV=2.12%) and high (CV=1.60%) concentration levels. Accuracy obtained in our study were less than acceptability limit fixed to 5%. Viral load measurements between Amplix and COBAS Taqman correlated strongly with a correlation coefficient of 0.97%. Concordance analysis gave an average of the differences of 0.54 log IU/L between the viral load measurements of the 2 techniques. CONCLUSION: based on these results, the Amplix real-time PCR platform for the quantification of HBV DNA can be considered as a reliable system for the monitoring of chronic hepatitis B and also a system adapted to intermediate laboratories.

Hepatitis B Vaccination in Senegalese Children: Coverage, Timeliness, and Sociodemographic Determinants of Non-Adherence to Immunisation Schedules (ANRS 12356 AmBASS Survey).

Detailed knowledge about hepatitis B virus (HBV) vaccination coverage and timeliness for sub-Saharan Africa is scarce. We used data from a community-based cross-sectional survey conducted in 2018-2019 in the area of Niakhar, Senegal, to estimate coverage, timeliness, and factors associated with non-adherence to the World Health Organisation-recommended vaccination schedules in children born in 2016 (year of the birth dose (BD) introduction in Senegal) and 2017-2018. Vaccination status was assessed from vaccination cards, surveillance data, and healthcare post vaccination records. Among 241 children with available data, for 2016 and 2017-2018, respectively, 31.0% and 66.8% received the BD within 24 h of birth (BD schedule), and 24.3% and 53.7% received the BD plus at least two pentavalent vaccine doses within the recommended timeframes (three-dose schedule). In logistic regression models, home birth, dry season birth, and birth in 2016 were all associated with non-adherence to the recommended BD and three-dose schedules. Living over three kilometres from the nearest healthcare post, being the firstborn, and living in an agriculturally poorer household were only associated with non-adherence to the three-dose schedule. The substantial proportion of children not vaccinated according to recommended schedules highlights the importance of considering vaccination timeliness when evaluating vaccination programme effectiveness. Outreach vaccination activities and incentives to bring children born at home to healthcare facilities within 24 h of birth, must be strengthened to improve timely HBV vaccination.

Hepatitis B Virus Genotype Study in West Africa Reveals an Expanding Clade of Subgenotype A4.

Hepatitis B virus (HBV) classification comprises up to 10 genotypes with specific geographical distribution worldwide, further subdivided into 40 subgenotypes, which have different impacts on liver disease outcome. Though extensively studied, the classification of subgenotype A sequences remains ambiguous. This study aimed to characterize HBV isolates from West African patients and propose a more advanced classification of subgenotype A. Fourteen HBV full-length genome sequences isolated from patients from The Gambia and Senegal were obtained and phylogenetically analyzed. Phylogenetic analysis of HBV genotype A sequences isolated from Senegalese and Gambian patients exhibited separate clusters from the other known and confirmed subgenotypes A (A1, A2, A6). Most of the sequences (10/14) clustered with an isolate from Cuba, reported as subgenotype A4 (supported by maximal bootstrap value). Four isolates from The Gambia and Senegal clustered separately from all other subgenotypes and samples sequenced in the study. Three of which from The Gambia, designated as an expanding clade of subgenotype A4, exhibited a mean inter-subgenotypic nucleotide divergence over the entire genome sequence higher than 4% in comparison with the other subgenotypes and the other isolates sequenced in the study, except with subgenotype A4 isolates (3.9%), and this was supported by a maximal bootstrap value. The last one from Senegal seemed to be an expanding subgenotype close to the new clade of A4. Amino acid analysis unveiled a novel motif specific to these isolates. This study revealed an expanding evolution of HBV subgenotype A and novel amino acid motifs. It also highlighted the need for a consensus regarding the analysis and classification of HBV sequences.

Clinical utility of quantifying hepatitis B surface antigen in African patients with chronic hepatitis B.

The clinical utility of quantifying hepatitis B surface antigen (qHBsAg) levels in African subjects with chronic hepatitis B virus (HBV) infection has been poorly documented. From a multicentre cohort of 944 HBV-infected African patients, we aimed to assess whether qHBsAg alone can accurately identify i) those in a HBeAg-negative chronic HBV infection phase at low risk of liver disease progression and ii) those in need of antiviral therapy according to the 2017 EASL guidelines. We analysed 770 HBV mono-infected treatment-naïve patients, mainly males (61%) from West Africa (92%), median age 35 years (IQR: 30-44), median HBV DNA: 95.6 IU/ml (10.0-1,300.0), median qHBsAg 5,498 IU/ml (1,171-13,000) and HBeAg-pos 38 (5%). A total of 464/770 (60.2%) patients were classified as HBeAg-negative chronic infection (median age 36 years (31-46), median ALT 23 IU/l (18-28), median HBV-DNA 33.5 IU/ml (3.8-154.1), median LSM 4.8 kPa (4.1-5.8)) and qHBsAg levels had poor accuracy to identify these subjects with an AUROC at 0.58 (95%CI: 0.54-0.62), sensitivity 55.0% and specificity 55.6%; 118/770 (15.3%) patients were eligible for treatment according to the 2017 EASL criteria. qHBsAg correlated poorly with HBV DNA and had poor accuracy to select patients for antiviral therapy with an AUROC at 0.54 (0.49-0.60), sensitivity 46.6% and specificity 46.9%. In African treatment-naïve HBV-infected subjects, the clinical utility of qHBsAg to identify subjects in HBeAg-negative infection phase or subjects eligible for antiviral therapy seems futile. Whether qHBsAg levels can be used as a predictor of long-term liver complications in Africa needs to be further investigated.

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.

Absence of association between polymorphisms in the pfcoronin and pfk13 genes and the presence of Plasmodium falciparum parasites after treatment with artemisinin derivatives in Senegal.

Due to resistance to chloroquine and sulfadoxine/pyrimethamine, treatment for uncomplicated Plasmodium falciparum malaria switched to artemisinin-based combination therapy (ACT) in 2006 in Senegal. Several mutations in the gene encoding the kelch13 helix (pfk13-propeller) have been identified as associated with in vitro and in vivo artemisinin resistance in Southeast Asia. Additionally, three mutations in the pfcoronin gene (G50E, R100K and E107V) have been identified in two culture-adapted Senegalese field isolates that became resistant in vitro to artemisinin after 4 years of intermittent selection with dihydroartemisinin. The aims of this study were to assess the prevalence of pfcoronin and pfk13 mutations in Senegalese field isolates from Dakar and to investigate their association with artemisinin derivative clinical failures. A total of 348 samples of P. falciparum from 327 patients, collected from 2015-2019 in Dakar, were successfully analysed. All sequences had wild-type pfk13 allele. The three mutations (G50E, R100K and E107V), previously identified in parasites with reduced susceptibility to artemisinin, were not found in this study, but a new mutation (P76S) was detected (mean prevalence 16.2%). The P76S mutation was identified in 5 (31.3%) of 16 isolates collected from patients still parasitaemic on Day 3 after ACT treatment and in 31 samples (15.3%) among 203 patients considered successfully cured. There was no significant association between in vivo reduced efficacy to artemisinin derivatives and the P76S mutation (P = 0.151, Fisher's exact test). These data suggest that polymorphisms in pfk13 and pfcoronin are not the best predictive markers for artemisinin resistance in Senegal.

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.

Modulation of in vitro antimalarial responses by polymorphisms in Plasmodium falciparum ABC transporters (pfmdr1 and pfmdr5).

The emergence of resistance to artemisinin-based combination therapies (ACT) was described in Southeast Asia. In this context, the identification of molecular markers of ACT resistance partner drugs is urgently needed for monitoring the emergence and spread of resistance. Polymorphisms in transporter genes, especially of the ATP-binding cassette (ABC) superfamily, have been involved in anti-malarial drug resistance. In this study, the association between the mutations in the P. falciparum multidrug resistance 1 gene (pfmdr1, N86Y, Y184 F, S1034C, N1042D and D1246Y) or repetitive amino acid motifs in pfmdr5 and the ex vivo susceptibility to anti-malarial drugs was evaluated. Susceptibility to chloroquine, quinine, monodesethylamodiaquine, lumefantrine, piperaquine, pyronaridine, mefloquine and dihydroartemisinin was assessed in 67 Senegalese isolates. The shorter DNNN motif ranged from to 2 to 11 copy repeats, and the longer DHHNDHNNDNNN motif ranged from 0 to 2 in pfmdr5. The present study showed the association between repetitive amino acid motifs (DNNN-DHHNDDHNNDNNN) in pfmdr5 and in vitro susceptibility to 4-aminoquinoline-based antimalarial drugs. The parasites with 8 and more copy repeats of DNNN in pfmdr5 were significantly more susceptible to piperaquine. There was a significant association between parasites whose DHHNDHNNDNNN motif was absent and replaced by DHHNDNNN, DHHNDHNNDHNNDNNN or DHHNDHNNDHNNDHNNDNNN and increased susceptibility to chloroquine, monodesethylamodiaquine and pyronaridine. A significant association between both the wild-type allele N86 in pfmdr1 and the N86-184 F haplotype and reduced susceptibility to lumefantrine was confirmed. Further studies with a large number of samples are required to validate the association between these pfmdr5 alleles and the modulation of 4-aminoquinoline-based antimalarial drug susceptibility.