Molecular characteristics of Hepatitis B and chronic liver disease in a cohort of HB carriers from Bamako, Mali.

BACKGROUND: Hepatitis B (HB) infection is common in Mali. However, there is little information on molecular and biochemical characteristics of HB carriers. METHODS: A group of 1466 adult volunteers was recruited in the district of Bamako. Confirmed HB carriers were tested for HB viral load by quantitative PCR and HBV was genotyped by sequencing of HBS. Fibrosis and hepatitis activity were measured using the Fibrotest-Actitest. A mutation of TP53 at codon 249 (R249S), specific for exposure to aflatoxin, was detected in cell-free DNA extracted from plasma. RESULTS: Overall, 276 subjects were HBsAg-positive (18.8%). Among 152 subjects tested for HBV load, 49 (32.2%) had over 10(4) copies/mL and 16 (10.5%) had levels below the limit of detection. The E genotype was found in 91.1% of carriers. Fibrotest scores ≥ F2 were observed in 52 subjects (35.4%). Actitest scores ≥ A2 were detected in 15 subjects (10.2%) and were correlated with Fibrotest scores (p = 0.0006). Among 105 subjects tested, 60% had detectable levels of R249S copies (>40 copies/mL plasma). CONCLUSION: Chronic HB carriage in adults in Bamako district is well over epidemic threshold. About 1/3 of carriers have moderate to severe liver fibrosis and 60% have detectable aflatoxin-related TP53 R249S mutation. These results support introduction of anti-HB therapies to reduce the progression towards severe liver disease.

Complex patterns of protease inhibitor resistance among antiretroviral treatment-experienced HIV-2 patients from Senegal: implications for second-line therapy.

Protease inhibitor (PI)-based antiretroviral therapy (ART) can effectively suppress HIV-2 plasma load and increase CD4 counts; however, not all PIs are equally active against HIV-2, and few data exist to support second-line therapy decisions. To identify therapeutic options for HIV-2 patients failing ART, we evaluated the frequency of PI resistance-associated amino acid changes in HIV-2 sequences from a cohort of 43 Senegalese individuals receiving unboosted indinavir (n = 18 subjects)-, lopinavir/ritonavir (n = 4)-, or indinavir and then lopinavir/ritonavir (n = 21)-containing ART. Common protease substitutions included V10I, V47A, I54M, V71I, I82F, I84V, L90M, and L99F, and most patients harbored viruses containing multiple changes. Based on genotypic data, we constructed a panel of 15 site-directed mutants of HIV-2ROD9 containing single- or multiple-treatment-associated amino acid changes in the protease-encoding region of pol. We then quantified the susceptibilities of the mutants to the HIV-2 "active" PIs saquinavir, lopinavir, and darunavir using a single-cycle assay. Relative to wild-type HIV-2, the V47A mutant was resistant to lopinavir (6.3-fold increase in the mean 50% effective concentration [EC50]), the I54M variant was resistant to darunavir and lopinavir (6.2- and 2.7-fold increases, respectively), and the L90M mutant was resistant to saquinavir (3.6-fold increase). In addition, the triple mutant that included I54M plus I84V plus L90M was resistant to all three PIs (31-, 10-, and 3.8-fold increases in the mean EC50 for darunavir, saquinavir, and lopinavir, respectively). Taken together, our data demonstrate that PI-treated HIV-2 patients frequently harbor viruses that exhibit complex patterns of PI cross-resistance. These findings suggest that sequential PI-based regimens for HIV-2 treatment may be ineffective.

Safety of Chloroquine or Hydroxychloroquine Plus Azithromycin for the Treatment of COVID-19 Patients in Burkina Faso: An Observational Prospective Cohort Study.

INTRODUCTION: Though chloroquine derivatives are used in the treatment of coronavirus disease 2019 (COVID-19) in many countries worldwide, doubts remain about the safety and efficacy of these drugs, especially in African communities where published data are scarce. METHODS: We conducted an observational prospective cohort study from April 24 to September 03, 2020, in Burkina Faso to assess (as primary outcome) the clinical, biological, and cardiac (electrocardiographic) safety of chloroquine or hydroxychloroquine plus azithromycin administered to COVID-19 patients. The main secondary outcomes were all-cause mortality and median time of viral clearance. RESULTS: A total of 153 patients were enrolled and followed for 21 days. Among patients who took at least one dose of chloroquine or hydroxychloroquine (90.1% [138/153]), few clinical adverse events were reported and were mainly rash/pruritus, diarrhea, chest pain, and palpitations. No statistically significant increase in hepatic, renal, and hematological parameters or electrolyte disorders were reported. However, there was a significant increase in the QTc value without exceeding 500ms, especially in those who received chloroquine phosphate. Three adverse events of special interest classified as serious (known from chloroquine derivatives) were recorded namely pruritus, paresthesia, and drowsiness. One case of death occurred. The average onset of SARS-CoV-2 PCR negativity was estimated at 7.0 (95% CI: 5.0-10.0) days. CONCLUSION: Hydroxychloroquine appeared to be well tolerated in treated COVID-19 patients in Burkina Faso. In the absence of a robust methodological approach that could generate a high level of scientific evidence, our results could at least contribute to guide health decisions that should be made based on different sources of scientific evidence including those from our study.

[Description of a new epidemic focus of cutaneous Leishmaniasis major in western Burkina Faso]. / Description d'un nouveau foyer épidémique de leishmaniose cutanée à Leishmania major à l'Ouest du Burkina Faso.

INTRODUCTION: in Burkina Faso, the only epidemic focus of cutaneous leishmaniasis confirmed in the literature by lab tests was in Ouagadougou. We report the epidemiological, clinical and biological results of the assessment of a new epidemic focus in Larama in western Burkina Faso. METHODS: camps were used to receive patients. Sociodemographic and clinical data were collected using a questionnaire. Confirmation was based on microscopy and polymerase chain reaction (PCR). RESULTS: a total of 108 suspected cases have been identified in Larama, reflecting an attack rate of 5.8%. Sex ratio was 1.08. The patients were most often farmers (35.2%) and traders (33.3%). The working population (15-49 years old) accounted for 51.9%. The number of lesions varied between 1 and 5 in 91.7% of the cases. The lesions manifested as raised and infiltrated ulcerative lesions on the limbs (87%) with evolution ranging from 1 to 5 months in 96.3% of the cases. Samples were collected from two patients; microscopy showed leishmanias and PCR confirmed Leishmania major. CONCLUSION: our results confirm the presence of a cutaneous leishmaniasis major outbreak in the western part of the country. Additional surveys are needed to clarify the burden of leishmaniasis in Burkina Faso.

Loa loa filariasis in a tropical savanna area: report of one case in Ouagadougou.

Loa loa filariasis is usually found in the forest areas of Central and West Africa. We report a case that was diagnosed in Ouagadougou (Burkina Faso), a savanna area. The patient lived in Gabon but was visiting his family in Ouagadougou. He complained of fatigue, fever, itchy legs with scratch marks, and intermittent edema of the legs. A blood smear was first examined for malaria parasites, but Loa loa microfilariae were observed. Laboratory tests showed hypereosinophilia (30%). Transient angioedema (Calabar edema) was observed. Loa loa filariasis was diagnosed based on these findings. There were no other laboratory test abnormalities, and ophthalmological examination was normal. The patient received a single dose of ivermectin at 200 µg/kg. After 1 month, the patient's course was favorable and a control blood smear was negative.

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.

Emergence of multiclass drug-resistance in HIV-2 in antiretroviral-treated individuals in Senegal: implications for HIV-2 treatment in resouce-limited West Africa.

BACKGROUND: The efficacy of various antiretroviral (ARV) therapy regimens for human immunodeficiency virus type 2 (HIV-2) infection remains unclear. HIV-2 is intrinsically resistant to the nonnucleoside reverse-transcriptase inhibitors and to enfuvirtide and may also be less susceptible than HIV-1 to some protease inhibitors (PIs). However, the mutations in HIV-2 that confer ARV resistance are not well characterized. METHODS: Twenty-three patients were studied as part of an ongoing prospective longitudinal cohort study of ARV therapy for HIV-2 infection in Senegal. Patients were treated with nucleoside reverse-transcriptase inhibitor (NRTI)- and PI (indinavir)-based regimens. HIV-2 pol genes from these patients were genotyped, and the mutations predictive of resistance in HIV-2 were assessed. Correlates of ARV resistance were analyzed. RESULTS: Multiclass drug-resistance mutations (NRTI and PI) were detected in strains in 30% of patients; 52% had evidence of resistance to at least 1 ARV class. The reverse-transcriptase mutations M184V and K65R, which confer high-level resistance to lamivudine and emtricitabine in HIV-2, were found in strains from 43% and 9% of patients, respectively. The Q151M mutation, which confers multinucleoside resistance in HIV-2, emerged in strains from 9% of patients. HIV-1-associated thymidine analogue mutations (M41L, D67N, K70R, L210W, and T215Y/F) were not observed, with the exception of K70R, which was present together with K65R and Q151M in a strain from 1 patient. Eight patients had HIV-2 with PI mutations associated with indinavir resistance, including K7R, I54M, V62A, I82F, L90M, L99F; 4 patients had strains with multiple PI resistance-associated mutations. The duration of ARV therapy was positively associated with the development of drug resistance (P = .02). Nine (82%) of 11 patients with HIV-2 with no [corrected] detectable ARV resistance had undetectable plasma HIV-2 RNA loads (<1.4 log(10) copies/mL), compared with 3 (25%) of 12 patients with HIV-2 with detectable ARV resistance (P = .009). Patients with ARV-resistant virus had higher plasma HIV-2 RNA loads, compared with those with non-ARV-resistant virus (median, 1.7 log(10) copies/mL [range, <1.4 to 2.6 log(10) copies/mL] vs. <1.4 log(10) copies/mL [range, <1.4 to 1.6 log(10) copies/mL]; P = .003). CONCLUSIONS: HIV-2-infected individuals treated with ARV therapy in Senegal commonly have HIV-2 mutations consistent with multiclass drug resistance. Additional clinical studies are required to improve the efficacy of primary and salvage treatment regimens for treating HIV-2 infection.

[HIV-2 infection in Senegal: virological failures and resistance to antiretroviral drugs (ARVs)]. / Infection à VIH-2 au Sénégal: échecs virologiques et résistances aux antirétroviraux (ARV).

INTRODUCTION: HIV-2, endemic in West Africa, has a natural resistance to non-nucleoside reverse transcriptase inhibitors (NNRTIs) which makes it difficult to treat it in developing countries. METHODS: We conducted a descriptive, longitudinal, prospective study over the period November 2005-June 2017. Virologic failure has been defined as any viral load greater than 50 copies/ml after 6 months of ARV treatment administered twice. Assays for detecting drug-resistance mutations was performed in the protease-coding region and in the reverse transcriptase-coding region. RESULTS: Data from a total of 110 patients were collected. The patients had a median age of 46 years (ranging from 18 to 67) with a sex-ratio F/M of 2.54. At inclusion, viral load could be assessed in 44% of cases with a median of 935cp/ml (ranging from 17 to 144038). Antiretroviral regimen consisted of a combination of 2 NRTIs and 1IP in 94% of cases. The median follow-up was 1200 days (ranging from 1 to 3840); 94 then 76 patients completed their 12-month and 24-month assessments respectively. At 24-month follow-up, 39 patients had virologic failure, reflecting a prevalence of 39% estimated at 33% at 12-month follow-up and at 11% at 24-month follow-up; NRTIs resistance was observed in 45% of patients, IP resistance in 41% of patients while multi-NRTIs resistance and multi-IP resistance in 30% of patients. CONCLUSION: Currently, there is an urgent need to make available the new therapeutic classes of ARV for second line ART for patients living with HIV-2 with therapeutic failure in resource-limited settings.

[Manicure and pedicure in the city of Ouagadougou (Burkina Faso): practices and risks]. / La manucure et la pédicure dans la ville de Ouagadougou (Burkina Faso): pratiques et risqué.

Pedicure-manicure represents the aesthetic care of hands, feet and nails. In Burkina Faso, the use of manicure-pedicure products, the techniques used and the level of risk remain unknown. The aim of our study was to evaluate the practice of manicure-pedicure in the city of Ouagadougou. We conducted a descriptive cross-sectional study of all practitioners with at least six months experience in aesthetic care and customers present at the time of the survey from December 2010 to November 2012. We interviewed a total of 313 practitioners and 313 clients. The average age of practitioners was 19 years and of customers was 32.2 years. Fixed location practitioners were mostly women (96.87%) while mobile practitioners were mostly men (68.37%); 64.53% of customers were women. The percentage of practitioners who did not receive professional training was 93.92%. 29.7% of practitioners soaked the instruments in javel water for at least ten minutes; 75.71% knew that the use of certain tools was dangerous and 26.51% had side effects. 40.25% of customers knew that the used equipment may pose some risks and 30.35% were victims of accidents. The manicure and pedicure is done in hair salons by untrained hairdressers to the professional practice. The origin and composition of the products is not known. Not recommended products are used (foot soak shampoo, razor blade and scissors for feet scraping). The use of manicure and/or pedicure is sometimes necessary but that should not obscure the risks to which it exposes customers. Customers education and practitioners training seem necessary to minimize risks.

[Epidemiological features of tumors of the skin and mucosal membranes in the department of dermatology at the Yalgado Ouedraogo National Hospital, Ouagadougou, Burkina Faso]. / Tumeur cutanéo-muqueuses: aspects épidémiologiques dans le service de dermatologie du centre hospitalier national Yalgado Ouedraogo de Ouagadougou, Burkina Faso.

We conducted a retrospective study of the files of all patients seen from 1 January 1992 through 31 December 1996 with tumors of the skin and mucosal membranes at the Yalgado Ouédraogo National Hospital in order to determine the epidemiologic features of this disease. The records revealed 988 patients presented 1024 tumors, which could be classified into 33 categories. Most of the patients (60.6%) were in the age bracket of 20 to 39 years. Nearly all cases (988 or 96.5%) were benign skin tumors, mainly of infectious origin, especially viral (51.7%). We observed a substantial number of sexually transmissible infections, such as condylomata. We also found 36 cases (3.5%) of malignant tumors, including 29 cases of Kaposi sarcoma, five skin carcinoma (13.8%), three spinocellular and two basocellular; we also noted two borderline malignant tumors: a dermatofibrosar-coma protuberans and a nodular hidradenoma. The elevated prevalence of condyloma (151 cases) may explain the predominance of the 20-39 year age group, which is the most sexually active. Our series also confirmed the relative rarity (3.5%) of cutaneous cancers among African blacks. The predominance of Kaposi sarcoma may be explained by the high prevalence of HIV infection in our country.

Stevens-Johnson syndrome and toxic epidermal necrolysis in sub-Saharan Africa: a multicentric study in four countries.

OBJECTIVE: The purpose of this study was to document the clinical profile, etiologies, and outcomes of Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) in hospitals in four sub-Saharan African countries. PATIENTS AND METHODS: A retrospective study on cases of SJS/TEN treated in dermatology departments and/or intensive care units in four sub-Saharan African countries (Benin, Burkina Faso, Central African Republic, and Togo) from 2000 to 2010. The study focuses on variables such as age, sex, type of SJS/TEN, epidermal detachment of the skin surface, HIV status, drug(s) involved, and outcomes (death and sequelae). RESULTS: This study identified 177 cases of SJS/TEN from 2000 to 2010: 129 with SJS; 37 TEN; and 11 overlapping SJS/TEN. The average age of patients was 32.3 ± 15.4 years, and the sex ratio (M/F) was 0.6. HIV serology was positive in 69 (54.8%) of the 126 patients tested. Antibacterial sulfonamides (38.4%) were the most commonly used drugs followed by nevirapine (19.8%) and tuberculosis drugs (5.6%). We recorded 22 deaths (i.e. six cases of SJS, 15 of TEN, and one of overlapping SJS/TEN). Of the 22 patients who died, 16 were infected with HIV; among them, seven had an opportunistic infection (four cases of cerebral toxoplasmosis and three of pulmonary tuberculosis). Twenty-seven cases of sequelae were noted with a large part of eye complications. CONCLUSION: This study has highlighted: (i) the high proportion of patients infected with HIV among patients who had SJS/TEN in sub-Saharan Africa; (ii) the high frequency of antiretroviral drugs as new SJS/TEN causes in sub-Saharan Africa; and (iii) the impact of HIV infection on morbidity and mortality of these affections.

HIV-2 integrase variation in integrase inhibitor-naïve adults in Senegal, West Africa.

BACKGROUND: Antiretroviral therapy for HIV-2 infection is hampered by intrinsic resistance to many of the drugs used to treat HIV-1. Limited studies suggest that the integrase inhibitors (INIs) raltegravir and elvitegravir have potent activity against HIV-2 in culture and in infected patients. There is a paucity of data on genotypic variation in HIV-2 integrase that might confer intrinsic or transmitted INI resistance. METHODS: We PCR amplified and analyzed 122 HIV-2 integrase consensus sequences from 39 HIV-2-infected, INI-naive adults in Senegal, West Africa. We assessed genetic variation and canonical mutations known to confer INI-resistance in HIV-1. RESULTS: No amino acid-altering mutations were detected at sites known to be pivotal for INI resistance in HIV-1 (integrase positions 143, 148 and 155). Polymorphisms at several other HIV-1 INI resistance-associated sites were detected at positions 72, 95, 125, 154, 165, 201, 203, and 263 of the HIV-2 integrase protein. CONCLUSION: Emerging genotypic and phenotypic data suggest that HIV-2 is susceptible to the new class of HIV integrase inhibitors. We hypothesize that intrinsic HIV-2 integrase variation at "secondary" HIV-1 INI-resistance sites may affect the genetic barrier to HIV-2 INI resistance. Further studies will be needed to assess INI efficacy as part of combination antiretroviral therapy in HIV-2-infected patients.