Isoniazid (INH), recommended by WHO (World Health Organization) in the treatment of tuberculosis (TB), is metabolized primarily by the genetically polymorphic N-acetyltransferase 2 (NAT2) enzyme. The human population is divided into three different phenotypic groups according to acetylation rate: slow, intermediate, and fast acetylators. The objective of this study was to explore the relationship between NAT2 genotypes and the serum concentrations of INH. Blood samples from 96 patients with TB were taken for the analysis. NAT2 polymorphisms on coding region were examined by polymerase chain reaction (PCR) direct sequencing; the acetylation status was obtained by measuring isoniazid (INH) and its metabolite, acetylisoniazid (AcINH) in plasma was obtained by using the liquid chromatography coupled to mass spectrometry. TB patients were distributed into two groups of fast and slow acetylators according to the acetylation index calculated based on the plasma concentration of INH in the 3rd hour (T3) after an oral dose. Our PCR analysis identified several alleles, where NAT2*4, NAT2*5A, NAT2*6A, and NAT2*13A were the most important. The concentrations of INH varied between 1.10 mg/L and 13.10 mg/L at the 3rd hour and between 0.1 and 9.5 mg/L at the 6th hour. The use of the acetylating index I3 allowed the classification of tested patients into two phenotypic groups: slow acetylators (44.3% of TB patients), and rapid acetylators (55.7%). Patient’s acetylation profile provides valuable information on their therapeutic, pharmacological, and toxicological responses.

SummaryUse of medicinal plants is common and widespread throughout Africa, including in Senegal. Because efficacy has been demonstrated, public policies have been instituted that have allowed plant-based therapies to have an important role in general primary care. However, little is known about the cutaneous safety of many plant-based therapies. In this 6-month prospective study all cases of dermatitis induced or aggravated by exclusive use of medicinal plants were evaluated via skin allergy testing. The results were classified and compared with the available literature. Forty-three cases of plant-therapy-associated cutaneous reactions were identified, including worsening of existing conditions (56%), recurrence of a previously resolved condition (16%) and new dermatitis arising spontaneously (28%). In the cases where the condition was new, generalized exfoliative dermatitis occurred in 42% of cases with an average time of onset of 9 days. Specific plants were identified in 65% of cases and included 18 varieties. The frequency and severity of plant-induced cutaneous reactions should be the basis for the creation of a phytovigilance programme and re-evaluation of how traditional medicine is used in the general population. When irritation occurs, identification of the responsible plant and allergy testing should be the first steps towards relieving symptoms.In Africa, many plants are used empirically in traditional medicine. According to the World Health Organization, plantbased therapies represent a first-line medical recourse for more than 80% of people across all social classes in many African countries. This is due to the accessibility and low cost of plant-based medicine, along with advertisements in the media by an increasing number of traditional practitioners. However, these practitioners are sometimes illiterate and incompetent. The current cultural environment promotes self-medication and/or polymedication.Often called traditional phytotherapy, plant-based therapies can be delivered via either topical or oral routes. Topical delivery consists of direct application of the plant onto the skin, while the oral route encompasses ingestion of a liquid maceration of one or several plants. The benefits of plantbased therapies have been demonstrated; various administrative policies currently ensure that phytotherapy is an important component of primary-care medicine in Africa. However, the potential for harmful effects remains largely unknown by the general population, prescribers, and health and political authorities.Many dermatological afflictions diseases arise from or are exacerbated by the inappropriate and abusive use of these plants. The condition may be life-threatening when it is an erythroderma (exfoliative dermatitis) or leads to synechiae of ocular and genital mucous membranes. Despite the current use of hundreds of plants in traditional medicine, very few toxicological studies have been conducted in research laboratories. The present study was performed to evaluate the cutaneous safety of several com...

Tel (221) 77 569 80 01RÉSUMÉ L'objectif de cette étude est d'évaluer l'activité antifalcémiante d'extraits de racines de Leptadenia hastata sur des hémoglobines falciformes et d'identifier les principes actifs à l'origine de cette activité. La méthode employée étudie la réversibilité des drépanocytes, en fonction du temps d'incubation des extraits par rapport aux témoins (eau physiologique, phénylalanine et arginine) sur des échantillons de sang de patients drépanocytaires homozygotes. Des concentrations de 0,05; 0,5; 5 et 10 mg/ml de quatre extraits (méthanol, hexane, acétate d'éthyle et méthanol résiduel) ont été mises en contact avec des drépanocytes de type SS après avoir provoqué leur falciformation avec une solution à 2% de métabisulfite de sodium. L'évaluation a été effectuée toutes les 30 minutes pendant 120 minutes. Les différents extraits ont montré une activité dosedépendante sur la réversibilité de la falciformation des globules rouges avec plus de 80% d'inversion en 120 minutes pour l'extrait méthanolique, le plus actif. Un screening phytochimique a permis de faire une corrélation entre les flavonoïdes et l'activité antifalcémiante des extraits de Leptadenia hastata.

We report the results of a pilot open-label trial of a tenofovir (TDF)/emtricitabine (FTC)/efavirenz (EFV) combination conducted in Dakar, Senegal. Forty HIV-1-infected patients, naive of antiretroviral treatment and without active opportunistic disease, were included and followed through 96 weeks. At weeks 48 and 96, respectively, 82.5% and 85% of patients had HIV-1 RNA <400 copies/mL (72.5% and 77.5% with HIV-1 RNA <50 copies/mL). Between baseline and week 96, the mean (SD) CD4 count increased from 126 (102) to 338 (155) cells/mm(3). The mean (SD) creatinine clearance decreased from 92 (36) to 73 (19) mL/min (P = .001). Treatment adherence was at least 94% at all scheduled visits. The efficacy and tolerability of a TDF/FTC/EFV combination were high and similar to those observed in Northern countries. This drug combination can be recommended in limited-resource countries, as did the World Health Organization (WHO) and should be made readily available as a fixed-dose combination.

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The NAT2 genetic polymorphism determines the individual acetylator status and, consequently, the capacity to metabolize, or not, drugs and xenobiotics which are substrates of NAT2. As the nature and frequency of the NAT2 polymorphisms vary remarkably between populations of different ethnic origins, genotyping strategies used to predict the acetylation phenotype need to be adapted for each particular population regarding their genetic backgrounds at this locus. As few data on the genetic polymorphism of NAT2 are available in the Senegalese population, we performed an extensive identification of NAT2 variants in 105 healthy non-smoker Senegalese subjects by direct PCR sequencing of the coding region. Eleven previously described SNPs were identified in this Senegalese population. Upon allele analysis, the four most frequent alleles were of the NAT2*5- (35.7 %), NAT2*6- (21.0 %), NAT2*12- (16.7 %) and NAT2*14- (10.0 %) type, the remaining alleles, including the wild-type NAT2*4, having each a frequency lower than 10 %. According to the observed genotypes, 51 and 50 subjects were predicted to be of the rapid (48.6 %) and slow (47.6 %) acetylator phenotype, respectively, while four individuals (3.8 %) were considered of unknown phenotype as they carry at least one allele with a yet unknown functional effect. These baseline data would be of particular interest to set up an efficient genotyping strategy to predict the acetylation status of Senegalese patients with tuberculosis and, thus, to optimize their isoniazid treatment.

ObjectivesDisruption in HIV care provision may enhance the development and spread of drug resistance due to inadequate antiretroviral therapy. This study thus determined the prevalence of HIV-1 transmitted drug resistance (TDR) in settings of decentralized therapy and care in Senegal and, the Ebola outbreak in Guinea. Antiretroviral-naïve patients were enrolled following a modified WHO TDR Threshold Survey method, implemented in Senegal (January–March 2015) and Guinea (August–September 2015). Plasma and dried blood spots specimens, respectively from Senegalese (n = 69) and Guinean (n = 50) patients, were collected for direct sequencing of HIV-1 pol genes. The Stanford Calibrated Population Resistance program v6.0 was used for Surveillance Drug Resistance Mutations (SDRMs).ResultsGenotyping was successful from 54/69 (78.2%) and 31/50 (62.0%) isolates. In Senegal, TDR prevalence was 0% (mean duration since HIV diagnosis 4.08 ± 3.53 years). In Guinea, two patients exhibited SDRMs M184V (NRTI), T215F (TAM) and, G190A (NNRTI), respectively. TDR prevalence at this second site, however, could not be ascertained because of low sample size. Phylogenetic inference confirmed CRF02_AG predominance in Senegal (62.96%) and Guinea (77.42%). TDR prevalence in Senegal remains extremely low suggesting improved control measures. Continuous surveillance in both settings is mandatory and, should be done closest to diagnosis/transmission time and with larger sample size.

Diarrheal diseases are the second leading cause of child mortality worldwide, occurring in about one in every nine child deaths, and were associated with water, sanitation, and hygiene (WASH) access. In this study, we provided an overview of WASH indicators' evolution from 2000 to 2017 and their impact on the occurrence of diarrhea in children under 5 years old in Senegal. It was a retrospective cross-sectional study, in which we did a secondary analysis of data from the Joint Monitoring Program (JMP) for water supply and sanitation and from the Senegal Demographic and Health Survey 2018. Our results showed that access to safely managed services increased by 18.1 and 19.1%, respectively, for water and sanitation. The prevalence of diarrhea estimated at 18.16% was associated with straining water through a cloth (adjusted odds ratio (AOR) [95% confidence interval (CI)]: 1.21 [1.00–1.45]) and getting water supplies from a source not located in a dwelling (AOR [95% CI]: 1.59 [1.21–2.09]). The prevalence of diarrhea among children under 5 years old was still relatively high in Senegal and was significantly associated with a lack of WASH access. Although the latter continues to increase, additional efforts to make water safer to drink will significantly reduce the occurrence of diarrheal diseases among children under five in Senegal.