Isoniazid preventive therapy in child household contacts of adults with active TB in Bamako, Mali.

BACKGROUND AND OBJECTIVE: Isoniazid preventive therapy (IPT) is known to reduce the risk of developing active TB in about 59% in children aged ⩽15 years. We assessed adherence, completion and adverse events among children who were household contacts of a newly diagnosed adult with smear-positive TB in Bamako, Mali. METHODS: Children aged <15 years living in the same house with an adult smear-positive index case were enrolled in the study in the Bamako Region after consent was obtained from the parent or legal guardian. Adherence was assessed based on the number of tablets consumed during 6 months. RESULTS: A total of 260 children aged <15 years were identified as household contacts of 207 adult patients with smear-positive TB during the study period. Among all child contacts, 130/260 (50.0%) were aged 0-4 years and were eligible for IPT; 128/130 (98.5%) were started on IPT and 83/128 (64.8%) completed with good adherence at the end of the 6 months, and without any significant adverse events. CONCLUSION: We successfully implemented IPT with good acceptance, but low completion rate. The Mali National TB Program and partners should expand this strategy to reach more children in Bamako and the whole country and create greater awareness in the population.

CADRE ET OBJECTIF: Le traitement préventif par isoniazide (IPT) réduit le risque de développer une TB active chez environ 59% des enfants ⩽15 ans. Nous avons évalué l'observance, l'achèvement du traitement et les évènements indésirables chez des enfants qui étaient contacts domestiques d'un adulte ayant récemment reçu un diagnostic de TB à microscopie positive à Bamako, Mali. MÉTHODES: Les enfants âgés <15 ans vivant sous le même toit qu'un cas index adulte de TB à microscopie positive ont été inclus dans l'étude dans la région de Bamako, après obtention du consentement des parents ou du tuteur légal. L'observance a été évaluée en fonction du nombre de comprimés consommés au cours d'une période de 6 mois. RÉSULTATS: Au total, 260 enfants âgés <15 ans ont été identifiés comme contacts domestiques de 207 patients adultes atteints de TB à microscopie positive pendant la période d'étude. Parmi tous les contacts pédiatriques, 130/260 (50,0%) étaient âgés de 0­4 ans et étaient éligibles à l'IPT ; 128/130 (98,5%) ont été mis sous IPT et 83/128 (64,8%) ont achevé leur traitement avec une bonne observance à la fin de la période de 6 mois, sans évènement indésirable significatif. CONCLUSION: Nous avons mis en place l'ITP avec succès. L'acceptation était bonne mais le taux d'achèvement du traitement était faible. Le programme national de lutte contre la TB du Mali et ses partenaires devraient élargir cette stratégie afin d'inclure davantage d'enfants de Bamako et du pays, et d'accroître la sensibilisation de la population.

Fluorescein diacetate and rapid molecular testing for the early identification of rifampicin resistance in Mali.

BACKGROUND: Non-conversion on auramine smear microscopy indicates a lack of treatment response, possibly associated with initial rifampicin-resistant tuberculosis (RR-TB). However, dead bacteria still stain positive and may be detected. Fluorescein diacetate smear microscopy (FDA) shows live mycobacteria only. Therefore, we studied the potential of 2-month (2M) FDA for the identification of initial RR-TB.METHODS: Between 2015 and 2018, we enrolled new smear-positive pulmonary TB patients from five local centres in Bamako, Mali. After baseline screening, sputum samples were collected at 1M, 2M, 5M and 18M. We used rpoB sequencing to identify initial RR-TB.RESULTS: Of 1359 patients enrolled, 1019 (75%) had rpoB sequencing results. Twenty-six (2.6%, 95%CI: 1.7-3.7) had mutations conferring rifampicin resistance. Most frequent rpoB mutations were located at the codons Asp435Val (42.4%) and Ser450Leu (34.7%). Among patients with initial RR-TB, 72.2% were FDA-negative at 2M (P = 0.2). The positive and negative predictive value of 5M FDA for culture-based failure was respectively 20.0% and 94.7%.CONCLUSION: FDA did not identify the majority of patients with initial RR-TB or culture-based failure. As the full spectrum of mutations identified on sequencing was identified using Xpert, our data support its rapid universal implementation in Mali.

Performance of Mali's biosafety level 3 laboratory in the external quality assessment in preparedness of laboratory accreditation and support to clinical trials.

Background: The external quality assessment (EQA) or external quality control is an evaluation conducted by a certified external organization to inquire about the quality of the results provided by a laboratory. The primary role of EQA is to verify the accuracy of laboratory results. This is essential in research because research data should be published in international peer-reviewed journals, and laboratory results must be repeatable. In 2007, the University Clinical Research Center (UCRC's) biosafety level 3 (BSL-3) laboratory joined the EQA program with the College of American Pathologists in acid-fast staining and culture and identification of mycobacteria as per laboratory accreditation preparedness. Thus, after 11 years of participation, the goal of our study was to evaluate the performance of our laboratory during the different interlaboratory surveys. Methods: We conducted a descriptive retrospective study to evaluate the results of UCRC mycobacteriology laboratory from surveys conducted during 2007 and 2017. Results: Of the 22 evaluations, the laboratory had satisfactory (100% of concordance results) in 18 (81.8%) and good (80% of concordance results) in 4 (18.2%). Overall, the laboratory was above the commended/accepted limits of 75%. Conclusion: So far, UCRC's BSL-3 performed well during the first 11 years of survey participation, and efforts should be deployed to maintain this high quality in the preparedness for laboratory accreditation and support to clinical trials.

Diabetes Mellitus among new tuberculosis patients in Bamako, Mali.

INTRODUCTION: Diabetes Mellitus (DM) increases worldwide, mostly in low- and middle-income countries. In Mali, the prevalence in the adult population is estimated at 1.8%, but tuberculosis (TB) patients are not systematically screened. The goal of our study was to determine the prevalence of DM among newly diagnosed TB patients. METHODS: We conducted a cross sectional study and a pilot prospective cohort study in four health centers in Bamako. All patients underwent fasting capillary-blood glucose (FCBG) test at Day 0, and repeated after one-week of TB treatment. Venous FBG test was performed for discrepancies between the two FCBG results. Thereafter, FCBG was performed for pilot study at month-2 (M2) and M5 of TB treatment. RESULTS: Two hundred and one patients were enrolled in this study. Impaired fasting blood glucose was identified in 17 (8.5%), of whom 11 (5.5%) had DM (VFBG >7 mmol/L). Among patients with DM, seven (63.6%) had successful TB treatment outcome, versus 142 (74.7%) of those without DM (p = 0.64), and (OR: 1.69, 95%CI 0.47-6.02). CONCLUSION: The prevalence of DM among TB patients in Bamako exceeds that of the general population and screening at TB diagnosis suffices to identify those with DM. Systematic screening of both diseases will allow better treatment.

[Targeted newborn screening for sickle-cell anemia: Sickling test (Emmel test) boundaries in the prenatal assessment in West African area]. / Dépistage néonatal ciblé de la drépanocytose : limites du test de falciformation (test d'Emmel) dans le bilan prénatal en zone ouest africaine.

BACKGROUND: Newborn screening for sickle cell anemia is necessary in Africa where the disease is more frequent. Hemoglobin electrophoresis is used for screening, but is limited by a high cost and difficult access. Sickling test (Emmel test), which is more affordable and technically more accessible, is often requested for prenatal assessment of pregnant women in West African areas to reserve screening for newborns from mothers in whom the positive sickling test attests the presence of hemoglobin S. This study aims to evaluate the number of undetected sickle cell anemia newborns by a screening policy targeting only newborns from mothers in whom a sickling test would have been positive. METHODS: From 2010 to 2012, in Bamako, Mali, West Africa, 2489 newborns were routinely screened for sickle cell anemia at the umbilical cord or heel by isoelectrofocusing and, if necessary, by high-performance liquid chromatography. These newborns were born from 2420 mothers whose hemoglobin was studied by isoelectrofocusing. The data was recorded and processed using Excel software version 14.0.0. We calculated the frequency of the sickle cell gene in mothers and newborns as well as the number of SCA newborns from heterozygous or C homozygous mothers. RESULTS: Of the 2489 newborns, 16 had sickle cell anemia (6 SS and 10 SC); 198 had the sickle cell trait; 139 were AC and 1 was CC. Of the 10 newborns with SC profile, 3 were born from mothers not carrying the S gene but the C gene of hemoglobin and in which an Emmel test would have been negative. CONCLUSION: Targeted newborn screening, based on the results of sickling test in pregnant women, would misdiagnose more than one of six sickle cell anemia newborns who would not benefit from early care. Cost-effectiveness studies of routine newborn screening for sickle cell anemia should lead to a better screening strategy in contexts where hemoglobin S and other hemoglobin defect genes coexist.

Clinical characteristics of non-tuberculous mycobacterial pulmonary infections in Bamako, Mali.

The global spread of non-tuberculous mycobacteria (NTM) may be due to HIV/AIDS and other environmental factors. The symptoms of NTM and tuberculosis (TB) disease are indistinguishable, but their treatments are different. Lack of research on the epidemiology of NTM infections has led to underestimation of its prevalence within TB endemic countries. This study was designed to determine the prevalence and clinical characteristics of pulmonary NTM in Bamako. A cross-sectional study which include 439 suspected cases of pulmonary TB. From 2006 to 2013 a total of 332 (76%) were confirmed to have sputum culture positive for mycobacteria. The prevalence of NTM infection was 9.3% of our study population and 12.3% of culture positive patients. The seroprevalence of HIV in NTM group was 17.1%. Patients who weighed <55 kg and had TB symptoms other than cough were also significantly more likely to have disease due to NTM as compared to those with TB disease who were significantly more likely to have cough and weigh more than 55 kg (OR 0.05 (CI 0.02-0.13) and OR 0.32 (CI 0.11-0.93) respectively). NTM disease burden in Bamako was substantial and diagnostic algorithms for pulmonary disease in TB endemic countries should consider the impact of NTM.

[Prevalence and risk factors for sickle retinopathy in a sub-Saharan comprehensive Sickle Cell Center]. / Prévalence et facteurs de risque de la rétinopathie drépanocytaire dans un centre de suivi drépanocytaire d'Afrique subsaharienne.

INTRODUCTION: Retinopathy is a chronic complication with severe functional consequences in patients with sickle cell disease. Its prevalence is not well known in sub-Saharan Africa because of the absence of screening. We report here the results of a routine screening for sickle retinopathy in a Comprehensive Sickle Cell Center in Sub-Saharan Africa. METHODS: Screening of sickle retinopathy was carried out in all sickle cell patients aged 10 and over, followed between 2010 and 2012. Retinopathy was screened by dilated indirect fundoscopic examination and retinal angiography, if necessary. The gender, age and hematological parameters of patients with sickle retinopathy were compared with those of controls randomly selected from the cohort of sickle cell patients without retinopathy followed during the same period. RESULTS: The overall prevalence of sickle cell retinopathy was 8.8% (142/1604): 12.4% (91/731) in SC, 5.2% (38/734) in SS, 9.4% (5/53) in Sß°-thalassemia patients and 9.3% (8/86) in Sß+-thalassemia patients. Proliferative retinopathy was more common in SC patients (P<0.01). High levels of hemoglobin or of hematocrit were associated with retinopathy in all patients and with proliferative retinopathy in SC patients. In SS or Sß0thalassemia patients, high leukocyte count was associated with proliferative retinopathy. Low fetal hemoglobin level was associated with retinopathy in all groups. CONCLUSION: The prevalence of sickle cell retinopathy is high and negatively associated to the level of fetal hemoglobin. The efficiency of a routine screening for sickle cell retinopathy must be assessed in Africa as well as the benefit of phlebotomy and hydroxyurea therapy as a preventive treatments.

Performance of microscopic observation drug susceptibility for the rapid diagnosis of tuberculosis and detection of drug resistance in Bamako, Mali.

OBJECTIVES: In Mali early detection and treatment of multidrug-resistant tuberculosis (MDR-TB) are still challenging due to the cost, time and/or complexity associated with regular tests. Microscopic Observation Drug Susceptibility (MODS) is a low-cost assay validated by WHO in 2010. It is a liquid-culture-based assay to detect the 'cording' characteristic of Mycobacterium tuberculosis complex and to assess susceptibility to both isoniazid and rifampicin defining multidrug-resistant tuberculosis (MDR-TB). In this study we aimed to evaluate the performance of MODS as diagnostic tool compared with a validated method-Mycobacteria Growth Indicator Tube/Antimicrobial Susceptibility Testing/Streptomycin, Isoniazid, Rifampicin and Ethambutol (MGIT/AST/SIRE). METHODS AND RESULTS: Between January 2010 and October 2015 we included 98 patients with suspected TB in an observational cohort study. The sensitivity and specificity of MODS assay for detecting TB were respectively 94.12% and 85.71% compared with the reference MGIT/7H11 culture, with a Cohen κ coefficient of 0.78 (95% CI 0.517-1.043). The median time to culture positivity for MODS assay and MGIT (plus interquartile range, IQR) was respectively 8 days (IQR 5-11) and 6 days (IQR 5-6). In detecting patients with MDR-TB, the sensitivity and specificity of MODS assay were respectively 100% and 95.92%. The positive predictive value and negative predictive value were, respectively, 66.7% and 100%. The median turnaround times for obtaining MDR-TB results using MODS assay and MGIT/AST/SIRE was respectively 9 days and 35 days. Hence, the MODS assay rapidly identifies MDR-TB in Mali compared with the MGIT/AST/SIRE. CONCLUSION: As an easy, simple, fast and affordable method, the MODS assay could significantly improve the management of TB.

Tuberculosis drug resistance in Bamako, Mali, from 2006 to 2014.

BACKGROUND: Although Drug resistance tuberculosis is not a new phenomenon, Mali remains one of the "blank" countries without systematic data. METHODS: Between 2006 and 2014, we enrolled pulmonary TB patients from local TB diagnostics centers and a university referral hospital in several observational cohort studies. These consecutive patients had first line drug susceptibility testing (DST) performed on their isolates. A subset of MDR was subsequently tested for second line drug resistance. RESULTS: A total of 1186 mycobacterial cultures were performed on samples from 522 patients, including 1105 sputa and 81 blood samples, yielding one or more Mycobacterium tuberculosis complex (Mtbc) positive cultures for 343 patients. Phenotypic DST was performed on 337 (98.3%) unique Mtbc isolates, of which 127 (37.7%) were resistant to at least one drug, including 75 (22.3%) with multidrug resistance (MDR). The overall prevalence of MDR-TB was 3.4% among new patients and 66.3% among retreatment patients. Second line DST was available for 38 (50.7%) of MDR patients and seven (18.4%) had resistance to either fluoroquinolones or second-line injectable drugs. CONCLUSION: The drug resistance levels, including MDR, found in this study are relatively high, likely related to the selected referral population. While worrisome, the numbers remained stable over the study period. These findings prompt a nationwide drug resistance survey, as well as continuous surveillance of all retreatment patients, which will provide more accurate results on countrywide drug resistance rates and ensure that MDR patients access appropriate second line treatment.

Tuberculosis specific responses following therapy for TB: Impact of HIV co-infection.

Characterizing perturbations in the immune response to tuberculosis in HIV can develop insights into the pathogenesis of coinfection. HIV+ TB+ and TB monoinfected (TB+) subjects recruited from clinics in Bamako prior to initiation of TB treatment were evaluated at time-points following initiation of therapy. Flow cytometry assessed CD4+/CD8+ T cell subsets and activation markers CD38/HLA-DR. Antigen specific responses to TB proteins were assessed by intracellular cytokine detection and proliferation. HIV+ TB+ subjects had significantly higher markers of immune activation in the CD4+ and CD8+ T cells compared to TB+ subjects. HIV+ TB+ had lower numbers of TB-specific CD4+ T cells at baseline. Plasma IFNγ levels were similar between HIV+ TB+ and TB+ subjects. No differences were observed in in-vitro proliferative capacity to TB antigens between HIV+ TB+ and TB+ subjects. Subjects with HIV+ TB+ coinfection demonstrate in vivo expansion of TB-specific CD4+ T cells. Immunodeficiency associated with CD4+ T cell depletion may be less significant compared to immunosuppression associated with HIV viremia or untreated TB infection.

Virology. Mutation rate and genotype variation of Ebola virus from Mali case sequences.

The occurrence of Ebola virus (EBOV) in West Africa during 2013-2015 is unprecedented. Early reports suggested that in this outbreak EBOV is mutating twice as fast as previously observed, which indicates the potential for changes in transmissibility and virulence and could render current molecular diagnostics and countermeasures ineffective. We have determined additional full-length sequences from two clusters of imported EBOV infections into Mali, and we show that the nucleotide substitution rate (9.6 × 10(-4) substitutions per site per year) is consistent with rates observed in Central African outbreaks. In addition, overall variation among all genotypes observed remains low. Thus, our data indicate that EBOV is not undergoing rapid evolution in humans during the current outbreak. This finding has important implications for outbreak response and public health decisions and should alleviate several previously raised concerns.

The association between female genital mutilation and intimate partner violence.

OBJECTIVE: To determine whether female genital mutilation (FGM) is a risk factor for intimate partner violence (IPV) and its subtypes (physical, sexual and emotional). DESIGN: Population-based cross-sectional study. SETTING: The study used the 2006 Demographic and Health Survey (DHS) conducted in Mali. POPULATION: A total of 7875 women aged 15-49 years who responded to the domestic violence and female circumcision modules in the 2006 administration of the DHS in Mali. METHODS: Multivariable logistic regression was used to compute adjusted odds ratios (aOR) and 95% confidence intervals (CI) to measure risk for IPV. MAIN OUTCOME MEASURES: The outcomes of interest were IPV and its subtypes. RESULTS: Women with FGM were at heightened odds of IPV (aOR 2.71, 95% CI 2.17-3.38) and IPV subtypes: physical (aOR 2.85, 95% CI 2.22-3.66), sexual (aOR 3.24, 95% CI 1.80-5.82), and emotional (aOR 2.28, 95% CI 1.68-3.11). The odds of IPV increased with ascending FGM severity (P for trend <0.0001). The most elevated odds were observed among women with severe FGM, who were nearly nine times as likely to experience more than one IPV subtype (aOR 8.81, 95% CI 5.87-13.24). CONCLUSIONS: Study findings underscore the need for multi-tiered strategies, incorporating policy and education, to reduce FGM and IPV, potentially improving the holistic health and wellbeing of Malian women.

Molecular strain typing of Mycobacterium tuberculosis complex in Bamako, Mali.

OBJECTIVE: To identify strains of Mycobacterium tuberculosis complex (MTC) circulating in Bamako and to examine the relationship between the strains and their drug susceptibility profiles. METHODS: Between 2006 and 2010, we conducted a cross-sectional study using spoligotyping to identify strains of MTC recovered from 126 tuberculosis (TB) patients under treatment in Bamako, Mali. RESULT: Three members of the MTC were isolated: M. tuberculosis (71.4%), M. africanum (27.8%) and M. bovis (0.8%). Of these, three strains were found to be the most prevalent: M. tuberculosis T1 (MTB T1; 38.9%), M. africanum F2 (MAF2; 26.2%) and M. tuberculosis Latin American and Mediterranean 10 (MTB LAM 10; 10.3%). MAF2 and MTB LAM 10 strains have a lower risk of multidrug resistance (MDR) than MTB T1 (respectively OR 0.1, 95%CI 0.03-0.4 and OR 0.1, 95%CI 0.01-0.8). Age ≥ 32 years (OR 1.4, 95%CI 0.4-3.9), negative human immunodeficiency virus status (OR 0.4, 95%CI 0.1-2.5) and male sex (OR 4, 95%CI 0.9-16.5) were not associated with MDR. The prevalence of MDR among treatment and retreatment failure patients was respectively 25% and 81.8% compared to new patients (2.9%). CONCLUSION: This study indicates a low level of primary drug resistance in Bamako, affirms the importance of using correct drug regimens, and suggests that the MTB T1 strain may be associated with the development of resistance.

Serum protein electrophoresis: any role in monitoring for antiretroviral therapy?

BACKGROUND: Developing world are always looking for monitoring tools during reagent shortage and equipments troubles which are very frequent. The aim of this study was to evaluate Serum Protein Electrophoresis (SPE) as a marker for assessing HIV treatment response. METHODS: A cross-sectional study was conducted with 220 participants in four distinct groups: Symptomatic HIV positive patients [specifically those on antiretroviral treatment (ART) versus those not on ART] asymptomatic HIV positive patients, and healthy blood donors. Five serum protein fractions (Albumin, Alpha-1, Alpha-2, Beta, and Gamma) were compared between these groups after measuring the density of the fractions. RESULTS: Concentration of gamma globulin was lowest among healthy blood donors, intermediate and comparable among asymptomatic HIV positive and symptomatic HIV positive on ART and highest among untreated symptomatic HIV positive. Concentration of gamma globulin was inversely correlated with the disease stage (p < 0.001). CONCLUSION: In this study, conducted in a setting where the burden of infectious diseases is high, the density of gamma globulin and albumin fractions were significantly associated with HIV status, and among HIV positive patients, with stage of HIV disease and ART. These results suggest that the feasibility of using SPE for monitoring the response of ART in low resource settings should be further explored.

Prevalence and predictors of HIV infection amongst Malian students.

The objectives of this cross-sectional study were to assess the prevalence and identify predictors of HIV-1 and HIV-2 infection among students in three cities of Mali. Between January and June 2005, we assessed HIV knowledge, attitudes, associated sexual behaviors and tested HIV serostatus among 950 high school and university students in Sikasso, Bamako, and Koulikoro cities, using a combination of enzyme-linked immunosorbent assay (ELISA) and Western blot testing. Univariate and logistic regression analyses were used to determine predictors of infection among students. Mean HIV prevalence was 3.1%, ranging from 1.8% in Sikasso to 3.6% in Bamako. The results showed the presence of all three HIV subtypes in Bamako, though HIV-1 predominated in all cities. Infection rates were slightly higher among males (3.6%) than among females (2.8%), but the difference was not significant. The single significant predictor of HIV infection was knowledge of HIV routes of transmission (p=0.01). HIV prevalence rates observed in this population were higher than general adult prevalence rates previously reported for Mali. HIV/AIDS education and prevention campaigns should be targeted to students at both the secondary and university levels. Students may represent an informative HIV sentinel population for Mali.

Retrospective surveillance of HIV prevalence in blood donors can help in the selection of the best social group for blood donation in Mali.

The National Centre for Blood Transfusion, Bamako, Mali has collected data that characterizes trend in HIV prevalence over 10 years by gender, age, occupation, marital status and donor category. These data help to describe national HIV prevalence and assist in formulating blood donation policies. Donations from 1993 to 2002 were categorized by donor age (decade), occupation (student, military and other), marital status (single, married and other), gender and donor status (volunteer, occasional and family). Comparisons were made using conservative estimates of donation frequency/donor category. Donations increased by more than 400%. By 1999, increased HIV prevalence in donations from women was consistently present. Donations from the age group of 30-39 years showed an increased prevalence beginning in 2000, which by 2002 was almost 10 times greater than in the low-prevalence (<20 years) group (5.9 vs. 0.6%). By 2000, both categories - students and military were less likely to be HIV positive than those from other occupational categories, and donations from married persons were less likely to be HIV positive by 1997. The highest prevalence was observed in the 'occasional' donor category, which increased to >14% by 2001; volunteer donation HIV positive peaked at 2.3% in 1999. HIV prevalence in blood donations in Bamako, Mali, demonstrates important trends from 1993 to 2002. The prevalence of > 14% in donations from occasional donors and significant trends by decade, gender, marital status and occupation argue for increased analysis of the blood donor population to improve blood safety and to understand the demographics of HIV infection in Mali.

Seroprevalence of HIV/HBV coinfection in Malian blood donors.

OBJECTIVES: A cross-sectional study was conducted to assess the prevalence of human immunodeficiency virus (HIV), hepatitis B virus (HBV), and their coinfection among blood donors at the National Blood Transfusion Center in Bamako, Mali, from November 2001 to July 2002. METHODS: Enzyme-linked immunosorbent assay techniques with reagents from Bio-Rad (France) were used to test the blood samples. RESULTS: 11,592 blood donors were tested for HIV and HBV surface antigens. The prevalence of HIV was 4.5% and the prevalence of HBV was 14.9%. The HIV/HBV coinfection rate was only 1.13% in this population. CONCLUSION: The coinfection rate was unexpectedly low in this blood donor population where monoinfection with HIV or HBV prevalence was high.