Non-tuberculous mycobacteria isolated from patients with suspected tuberculosis in Abidjan, Ivory Coast

Background: Apart from tuberculosis caused by Mycobacterium tuberculosis complex (MTBc) species, there are many other  mycobacterial infections due to nontuberculous mycobacteria (NTM). These are rarely identified in many low resource settings in Africa because of the lack of accurate identification methods. The aim of the study is to identify NTM species involved in respiratory infections in Abidjan, Ivory Coast.Methodology: Isolates routinely identified as NTM by the detection of MPT64 antigen between 2015 and 2018 at the Centre for Diagnosis and Research on AIDS and other Infectious Diseases (CeDReS) of the University Hospital of Treichville, were included in the study. Bacterial strains were sub-cultured on three different Lowenstein-Jensen media in order to determine their cultural characteristics, and molecular identification of the strains was performed first by polymerase chain reaction (PCR) assay followed by reverse hybridization (GenoType Mycobacterium CM and AS kits, Hain Lifescience, Germany). The Cohen’s kappa statistical coefficientwas used to evaluate the degree of agreement of the phenotypic with the molecular method.Results: Of 62 NTM isolates tested with the molecular method, 54 (87.1%) tested positive and the main species identified were Mycobacterium fortuitum (52%), followed by Mycobacterium abscessus (13%) alone or in combination with other species. Thirty-six (58.1%) of the 62 NTM isolates were identified phenotypically, out of which 31 (86.1%) were correctly identified by molecular method. The comparison of molecular and phenotypic methods revealed a good concordance, allowing the use of cultural patterns as identification tests in resource limited settings. However, MTBc isolates were identified among the NTM isolates, indicating that even if the rapid test for detection of MPT64 antigen is quite accurate, it could lack sensitivity and specificity in some cases.Conclusion: Mycobacterium fortuitum and M. abscessus were identified as the main NTM species circulating in Abidjan but there is need for additional evaluation of MPT64 antigen detection assay for MTBc. Keywords: non-tuberculous mycobacteria, identification, PCR, GenoType CM/AS, culture   French Title: Mycobactéries non tuberculeuses isolées chez des patients suspects de tuberculose à Abidjan, Côte d'Ivoire Contexte: Outre la tuberculose causée par les espèces du complexe Mycobacterium tuberculosis (MTBc), il existe de nombreuses autres infections mycobactériennes dues à des mycobactéries non tuberculeuses (MNT). Ceux-ci sont rarement identifiés dans de nombreuses régions à ressources limitées, notamment en Afrique en raison du manque de méthodes d'identification précises. Le but de l'étude était d'identifier les espèces de MNT impliquées dans les infections respiratoires à Abidjan, en Côte d'Ivoire.Méthodologie: Des isolats identifiés en routine comme étant des MNT par la détection de l'antigène MPT64 entre  Non-tuberculous mycobacteria in Ivory Coast  2015 et 2018 au Centre de diagnostic et de recherche sur le sida et autres maladies infectieuses (CeDReS) sis au sein du CHU de Treichville, ont été inclus dans l'étude. Les souches bactériennes ont été réisolées sur trois milieux de Lowenstein-Jensen différents afin de déterminer leurs caractéristiques culturales, et l'identification moléculaire des souches a d'abord été réalisée par un test réaction de polymérisation en chaîne (PCR) suivi d'une hybridation inverse (kits GenoType Mycobacterium CM et AS, Hain Lifescience, Allemagne). Le test statistique kappa de Cohen a été utilisé pour évaluer le degré d’accord entre le phénotype et la méthode moléculaire.Résultats: Sur 62 isolats de NTM testés avec la méthode moléculaire, 54 (87,1%) ont été trouvés positifs les principales espèces identifiées étant Mycobacterium fortuitum (52%), suivi de Mycobacterium abscessus (13%) seul ou en association avec d'autres espèces. Trente-six (58,1%) des 62 isolats de MNT ont été identifiés phénotypiquement, parmi lesquels 31 (86,1%) ont été correctement identifiés par la méthode moléculaire. La comparaison des méthodes moléculaires et phénotypiques a révélé une bonne concordance, permettant l'utilisation de caractères culturaux comme tests d'orientation dans des zones à ressources limitées. Cependant, des isolats de MTBc ont été identifiés parmi les isolats de MNT, indiquant que même si le test rapide de détection de l'antigène MPT64 est assez précis, il pourrait manquer de sensibilité et de spécificité dans certains cas. Conclusion: Mycobacterium fortuitum et M. abscessus ont été identifiés comme les principales espèces de MNT circulant à Abidjan mais il est nécessaire de procéder à une évaluation supplémentaire du test de détection de l'antigène MPT64 pour l'identification des MTBc. Mots clés: mycobactéries non tuberculeuses, identification, PCR, GenoType CM/AS, cultur

Molecular Characterization of the Resistance of Mycobacterium tuberculosis to Second Line Drugs in Côte d’Ivoire

Purpose: To characterize the resistance of Mycobacterium tuberculosis to second line drugs using a line probe assay.Methods: Multi-drug resistant strains of Mycobacterium tuberculosis isolated between December 2008 and December 2009 were tested for resistance to fluoroquinolones and second-line injectable drugs using GenoType® MTBDRsl.Results: Thirty eight strains gave interpretable results. None of them had a mutation in the gyrA gene. Regarding second-line injectable drugs, 4 strains (11 %) were resistant to aminoglycosides/ capreomycin and all of them harbored A1401G mutation.Conclusion: No extensive drug resistant strains were observed. A relatively high proportion of strains were resistant to at least one second-line injectable drug. Resistance mechanism seemed similar for all of them.Keywords: Mycobacterium tuberculosis, Line probe assay, GenoType® MTBDRsl, Aminoglycosides Capreomycin, Mutatio

A Trial of Early Antiretrovirals and Isoniazid Preventive Therapy in Africa

BACKGROUND: In sub-Saharan Africa, the burden of human immunodeficiency virus (HIV)-associated tuberculosis is high. We conducted a trial with a 2-by-2 factorial design to assess the benefits of early antiretroviral therapy (ART), 6-month isoniazid preventive therapy (IPT), or both among HIV-infected adults with high CD4+ cell counts in Ivory Coast. METHODS: We included participants who had HIV type 1 infection and a CD4+ count of less than 800 cells per cubic millimeter and who met no criteria for starting ART according to World Health Organization (WHO) guidelines. Participants were randomly assigned to one of four treatment groups: deferred ART (ART initiation according to WHO criteria), deferred ART plus IPT, early ART (immediate ART initiation), or early ART plus IPT. The primary end point was a composite of diseases included in the case definition of the acquired immunodeficiency syndrome (AIDS), non-AIDS-defining cancer, non-AIDS-defining invasive bacterial disease, or death from any cause at 30 months. We used Cox proportional models to compare outcomes between the deferred-ART and early-ART strategies and between the IPT and no-IPT strategies. RESULTS: A total of 2056 patients (41% with a baseline CD4+ count of ≥500 cells per cubic millimeter) were followed for 4757 patient-years. A total of 204 primary end-point events were observed (3.8 events per 100 person-years; 95% confidence interval [CI], 3.3 to 4.4), including 68 in patients with a baseline CD4+ count of at least 500 cells per cubic millimeter (3.2 events per 100 person-years; 95% CI, 2.4 to 4.0). Tuberculosis and invasive bacterial diseases accounted for 42% and 27% of primary end-point events, respectively. The risk of death or severe HIV-related illness was lower with early ART than with deferred ART (adjusted hazard ratio, 0.56; 95% CI, 0.41 to 0.76; adjusted hazard ratio among patients with a baseline CD4+ count of ≥500 cells per cubic millimeter, 0.56; 95% CI, 0.33 to 0.94) and lower with IPT than with no IPT (adjusted hazard ratio, 0.65; 95% CI, 0.48 to 0.88; adjusted hazard ratio among patients with a baseline CD4+ count of ≥500 cells per cubic millimeter, 0.61; 95% CI, 0.36 to 1.01). The 30-month probability of grade 3 or 4 adverse events did not differ significantly among the strategies. CONCLUSIONS: In this African country, immediate ART and 6 months of IPT independently led to lower rates of severe illness than did deferred ART and no IPT, both overall and among patients with CD4+ counts of at least 500 cells per cubic millimeter. (Funded by the French National Agency for Research on AIDS and Viral Hepatitis; TEMPRANO ANRS 12136 ClinicalTrials.gov number, NCT00495651.)

Effect of isoniazid preventive therapy on risk of death in west African, HIV-infected adults with high CD4 cell counts: long-term follow-up of the Temprano ANRS 12136 trial.

BACKGROUND: Temprano ANRS 12136 was a factorial 2 × 2 trial that assessed the benefits of early antiretroviral therapy (ART; ie, in patients who had not reached the CD4 cell count threshold used to recommend starting ART, as per the WHO guidelines that were the standard during the study period) and 6-month isoniazid preventive therapy (IPT) in HIV-infected adults in Côte d'Ivoire. Early ART and IPT were shown to independently reduce the risk of severe morbidity at 30 months. Here, we present the efficacy of IPT in reducing mortality from the long-term follow-up of Temprano. METHODS: For Temprano, participants were randomly assigned to four groups (deferred ART, deferred ART plus IPT, early ART, or early ART plus IPT). Participants who completed the trial follow-up were invited to participate in a post-trial phase. The primary post-trial phase endpoint was death, as analysed by the intention-to-treat principle. We used Cox proportional models to compare all-cause mortality between the IPT and no IPT strategies from inclusion in Temprano to the end of the follow-up period. FINDINGS: Between March 18, 2008, and Jan 5, 2015, 2056 patients (mean baseline CD4 count 477 cells per μL) were followed up for 9404 patient-years (Temprano 4757; post-trial phase 4647). The median follow-up time was 4·9 years (IQR 3·3-5·8). 86 deaths were recorded (Temprano 47 deaths; post-trial phase 39 deaths), of which 34 were in patients randomly assigned IPT (6-year probability 4·1%, 95% CI 2·9-5·7) and 52 were in those randomly assigned no IPT (6·9%, 5·1-9·2). The hazard ratio of death in patients who had IPT compared with those who did not have IPT was 0·63 (95% CI, 0·41 to 0·97) after adjusting for the ART strategy (early vs deferred), and 0·61 (0·39-0·94) after adjustment for the ART strategy, baseline CD4 cell count, and other key characteristics. There was no evidence for statistical interaction between IPT and ART (pinteraction=0·77) or between IPT and time (pinteraction=0·94) on mortality. INTERPRETATION: In Côte d'Ivoire, where the incidence of tuberculosis was last reported as 159 per 100 000 people, 6 months of IPT has a durable protective effect in reducing mortality in HIV-infected people, even in people with high CD4 cell counts and who have started ART. FUNDING: National Research Agency on AIDS and Viral Hepatitis (ANRS)

Biodiversity, dynamics and antimicrobial activity of lactic acid bacteria involved in the fermentation of maize flour for doklu production in C��te d'Ivoire

International audienceDoklu is a maize-based spontaneously fermented dough produced and consumed in parts of West Africa, particularly in Côte d'Ivoire. The characterization of the microbial ecosystem of doklu was carried out using a polyphasic approach. First, culture-dependent methods were used for bacterial enumeration and the phenotypic and molecular identification of 250 lactic acid bacteria (LAB) isolates. Then, culture-independent methods, including PCR-TTGE (V3 region of the 16S rRNA gene), provided a fingerprinting of bacterial DNA directly extracted from doklu. Bio preservative abilities were also tested and strains producing antimicrobial compounds were genotyped using PFGE. During maize dough fermentation, LAB became dominant and their load increased from 4.2 ± 0.2 log CFU/g to 9.0 ± 0.7 log CFU/g only after 48 h. Culture-dependent methods highlighted the presence of five LAB groups with the species Lactobacillus plantarum (28%), Lactobacillus fermentum (41.6%), Pediococcus acidilactici (6.8%), Pediococcus pentosaceus (18%) et Weissella cibaria (5.6%), succeeding during the fermentation. Lb. fermentum being practically the only species present at the end of fermentation, is with Lb. plantarum, the predominant species of fermenting dough. Culture-independent analysis underlined the undoubted role of Lb. fermentum, actively involved in the dough fermentation. These Lb. fermentum species, with a diversity of strains also showed important antimicrobial activity, due to production of bacteriocins. Being able to produce antimicrobial compounds, Lb. fermentum species may act as both bio protective culture as well as fermenting agent in cereal products and could be exploited to create functional starter cultures

Chimioprophylaxie antituberculeuse primaire à l'isoniazide : une stratégie d'actualité à l’ère du tester et traiter ; revue de la littérature

Position du problème : La tuberculose demeure une menace de santé publique responsable de plus d'un million de décès en 2018. La chimioprophylaxie à l'isoniazide est une des stratégies permettant le contrôle de cette maladie. Encore peu prescrite, son intérêt suscite encore plus de questions à l’ère du « tester et traiter » concernant les antirétroviraux. L'objectif de cette étude est donc de réaliser une revue des essais randomisés de chimioprophylaxie antituberculeuse primaire à l'isoniazide (« thérapie préventive à l'isoniazide », TPI), en distinguant les « essais d'efficacité (EE) » comparant la TPI à un placebo ou à l'absence de chimioprophylaxie ; et les « essais de régime » (ER), comparant la TPI à un ou plusieurs autres régimes. Méthodes : Recherche bibliographique (mots-clés sur les bases de données des articles publiés Medline, Scopus : « tuberculosis », « prophylaxis », « HIV », « randomized controlled trial ») et lecture standardisée d'articles sélectionnés rapportant des résultats d'essais randomisés de TPI chez les personnes infectées par le VIH. Résultats : Au total, 18 essais retenus (11 EE et 7 ER), incluant 19 725 participants. Les régimes étudiés étaient 3H, 6H, 9H, 12H, 36H/2RZ, 3RH, 3RZ, 3RHZ, et 3HP [H : Isoniazide, R : Rifampicine, Z : Pyrazinamide, P : Rifapentine]. Localisation : dix en Afrique, trois à Haïti, un en Inde, un aux USA, un aux Amériques et deux multi continentaux. Dans les EE avec ou sans ARV, la TPI réduit significativement le risque de tuberculose de 32 % à 71 %. Dans les EE avant les ARV, on ne retrouve aucune tendance à une réduction de la mortalité par la TPI. Dans les EE sous ARV, la TPI réduit la mortalité. Dans les ER, on ne trouve aucun argument pour préférer un autre régime à la TPI. La tolérance est bonne. La TPI diminue possiblement le risque de sélection de bacilles multirésistants, au lieu de l'aggraver, par la baisse du nombre d'épisodes de tuberculose et donc de l'utilisation des traitements antituberculeux curatifs. Conclusion : Loin d'avoir été rendue obsolète par le traitement ARV, la TPI reste une intervention d'actualité.BACKGROUND: Tuberculosis remains a public health threat responsible as recently as 2018 for more than one million deaths. Chemoprophylaxis with isoniazid is one of the strategies implemented to control the disease. Although it is not yet widely prescribed, its utilization raises additional questions in the "test and treat" era of for anti-retroviral therapy. The objective of this study is to review the different randomized controlled trials of antitubercular Isoniazid Preventive Therapy (IPT). We have distinguished (a) "efficacy trials" (ET) comparing IPT to a placebo or the absence of chemoprophylaxis and (b) "IPT regimen trials" (RT) comparing IPT to one or several other regimens. METHODS: Literature search (keywords from published articles found in the Medline and Scopus data bases: "tuberculosis", "prophylaxis", "HIV", "randomized controlled trial") and standardized reading of selected articles reporting results from randomized trials of IPT in HIV-infected people. RESULTS: Eighteen selected trials (11 ET and 7 RT), including 19,725 participants. The regimens studied were 3H, 6H, 9H, 12H, 12H, 36H/2RZ, 3RH, 3RZ, 3RHZ, and 3HP [H: Isoniazid, R: Rifampicin, Z: Pyrazinamide, P: Rifapentine]. LOCATIONS: Ten in Africa, three in Haiti, one in India, one in the USA, one in the Americas and two multi-continental trials. In ET with or without antiretrovirals (ART), IPT significantly reduces the risk of tuberculosis, by 32 to 71%. In ET prior to ART, IPT does not appear to reduce mortality. In ET in patients receiving ART, on the other hand, IPT reduces mortality. As regards RT, there seems to be no reason to prefer other regimens to IPT. Tolerance is good. Importantly, IPT may reduce (rather than worsen) the risk of multidrug-resistant bacilli selection by decreasing the number of TB episodes and, consequently, the number of curative tuberculosis treatments. CONCLUSION: Far from becoming obsolete due to ARV treatment, IPT has remained a timely and relevant intervention

Prognostic value of cross-sectional anthropometric indices on short-term risk of mortality in human immunodeficiency virus-infected adults in Abidjan, Côte d'Ivoire

In sub-Saharan Africa where weight loss is very difficult to estimate, cross-sectional anthropometric indicators could be useful to predict human immunodeficiency virus (HIV)-associated mortality. The study objective was to look for threshold values of baseline body mass index, arm muscle circumference, and fat mass to predict the risk of death in HIV-infected adults included in a 1996-1998 trial of early cotrimoxazole chemoprophylaxis in Abidjan, Côte d'Ivoire (COTRIMO-CI-ANRS 059 trial). The authors graphically determined if consecutive anthropometric categories with the closest hazards ratios of the risk of death could be clustered to obtain a unique threshold that distinctly separated two categories. When the threshold values were determined, the authors estimated the hazards ratio of mortality of this two-category model. A significant increase of mortality was observed for a body mass index of < or =20.3 in men (hazards ratio = 2.6; 95% confidence interval (CI): 1.4, 5.0) and of < or =18.5 in women (hazards ratio = 2.2; 95% CI: 1.05, 4.5) and for a fat mass of < or =6% in men (hazards ratio = 4.6; 95% CI: 2.3, 9.4) and of < or =18% in women (hazards ratio = 2.4; 95% CI: 1.2, 4.9). No simple threshold could be identified for arm muscle circumference. In Côte d'Ivoire where chemoprophylaxis of opportunistic infections has recently been recommended to be widely initiated on clinical criteria, such thresholds may help to screen patients with higher risks of mortality.info:eu-repo/semantics/publishe

15 Month follow up of African children following vaginal cleansing with benzalkonium chloride of their HIV infected mothers during late pregnancy and delivery

Objectives: To study mother to child HIV-1 transmission (MTCT) and infant mortality following benzalkonium chloride (BC) disinfection. Methods: A randomised, double blind phase II placebo controlled trial. Women testing positive for HIV-1 infection in prenatal care units in Abidjan, Côte d'Ivoire, and Bobo-Dioulasso, Burkina Faso, from November 1996 to April 1997 were eligible, with their informed consent. Women self administered daily a vaginal suppository of 1% BC (53) or matched placebo (54) from 36 weeks of pregnancy, plus a single dose during labour. The neonate was bathed with 1% BC solution or placebo within 30 minutes after birth. MTCT rate was assessed based on repeated polymerase chain reaction (PCR) and serology results. For the present analysis, children were followed up to 15 months. Results: A total of 107 women were enrolled. Of 103 eligible liveborn children, 23 were HIV infected, 75 uninfected, and five of indeterminate status. MTCT transmission rate was 24.2% overall (95% confidence interval (CI): 14.3% to 30.4%). On an intent to treat basis, the transmission rate did not differ between the two groups (23.5%, CI 13.8 to 38.5, in the BC group and 24.8%, CI 15.0 to 39.6, in the placebo group at 15 months). Similarly, there was no difference in mortality at 15 months (22.9%, CI 13.7 to 36.9, in the BC group and 16.5%, CI 9.0 to 29.4, in the placebo group). Conclusion: This analysis failed to suggest any benefit of BC disinfection on mother to child HIV transmission or perinatal and infant mortality

Capacity building in Sub-Saharan Africa as part of the INTENSE-TBM Project during the COVID-19 pandemic

Tuberculous meningitis (TBM) is the most severe and disabling form of tuberculosis (TB), with at least 100,000 cases per year and a mortality rate of up to 50% in individuals co-infected with human immunodeficiency virus type 1 (HIV-1). To evaluate the efficacy and safety of an intensified anti-tubercular regimen and an anti-inflammatory treatment, the INTENSE-TBM project includes a phase III randomised clinical trial (TBM-RCT) in four countries in sub-Saharan Africa (SSA). Within this framework, we designed a comprehensive capacity-building work package ensuring all centres had, or would acquire, the ability to conduct the TBM-RCT and developing a network of skilled researchers, clinical centres and microbiology laboratories. Here, we describe these activities, identify strengths/challenges and share tools adaptable to other projects, particularly in low- and lower-middle income countries with heterogeneous settings and during the coronavirus disease 2019 (COVID-19) pandemic. Despite major challenges, TBM-RCT initiation was achieved in all sites, promoting enhanced local healthcare systems and encouraging further clinical research in SSA. In terms of certified trainings, the achievement levels were 95% (124/131) for good clinical practice, 91% (39/43) for good clinical laboratory practice and 91% (48/53) for infection prevention and control. Platform-based research, developed as part of capacity-building activities for specific projects, may be a valuable tool in fighting future infectious diseases and in developing high-level research in Africa