Profil épidémiologique de la Tuberculose, Sénégal, 2009-2018: Epidemiological profile of Tuberculosis, Senegal, 2009-2018

Introduction: Le fardeau de la tuberculose (TB) pose un grave problème de santé publique au Sénégal. Nous avons analysé les données de surveillance de la tuberculose pour décrire le poids et la tendance de la tuberculose au Sénégal. Méthodes: Nous avons effectué une analyse secondaire des données de surveillance de la tuberculose du 1er janvier 2009 au 31 décembre 2018 du programme national de lutte contre la tuberculose (PNT). Résultats: Au total, 128 836 cas de tuberculose toutes formes ont été analysées dont 67,42% de nouveaux cas de TB pulmonaire confirmée par microscopie. Les personnes âgées de 25-34 ans représentaient 29,66%. Le sex-ratio H/F était de 2,33. Dakar avait rapporté la plupart des cas 44,17%. L'incidence pour 100 000 habitants était de 91, 87 et 86 en 2009, 2008 et 2011, de 93, 95 et 95 en 2012, 2013 et 2014 et de 92, 86, 87 et 84 en 2015, 2016, 2017 et 2018. La majorité des cas (77%) avaient été testés pour le VIH, dont 6,84% co-infectés. Le taux de TB multirésistante (TB-MR) était de 11%. Conclusion: Au Sénégal, l'incidence de la tuberculose a légèrement diminué en raison du faible taux de détection qui était de 62% en 2018. Le nombre de cas détecté a augmenté entre 2013 et 2014, mais elle restait inférieure à celle estimée par l'organisation mondiale de la santé. Une surveillance accrue de la tuberculose et un suivi des tuberculeux pour éviter la pharmaco-résistance sont nécessaires. Introduction: The burden of tuberculosis (TB) is a serious public health problem in Senegal. We analysed TB surveillance data to describe the burden and trend of TB in Senegal. Method: We conducted a secondary analysis of TB surveillance data from 1 January 2009 to 31 December 2018 from the national TB control programme (NTP). Results: A total of 128,836 cases of all forms of tuberculosis were analysed, of which 67.42% were new cases of microscopically confirmed pulmonary TB. Persons aged 25-34 years accounted for 29.66%. The sex ratio M/F was 2.33. Dakar reported most cases 44.17%. The incidence per 100 000 populations was 91, 87 and 86 in 2009, 2008 and 2011, 93, 95 and 95 in 2012, 2013 and 2014 and 92, 86, 87 and 84 in 2015, 2016, 2017 and 2018. The majority of cases (77%) had tested positive for HIV, with 6.84% co-infected. The rate of multidrug-resistant TB (MDR-TB) was 11%. Conclusion: In Senegal, the incidence of TB has slightly decreased due to the low detection rate which was 62% in 2018. The number of detected cases increased between 2013 and 2014, but it remained below that estimated by the World Health Organization. Increased surveillance of TB and monitoring of TB patients to avoid drug resistance is needed. &nbsp

Anesthesie au cours des ventriculocisternostomies au Mali : Une serie de 31 cas

Introduction La ventriculocisternostomie est une technique moderne du traitement des hydrocéphalies. Elle est peu fréquente en Afrique. Objectif:  Décrire la prise en charge anesthésique et l’évolution des patients opérés par ventriculocisternostomie. Patients et Méthode: Etude de cohorte prospective de 15 mois de janvier 2014 au 31 mars 2015. La saisie et l’analyse des données ont été effectuées par Microsoft word 2010 Epi info 3.5.3.fr. Résultats:  Les nourrissons prédominaient avec un sexe ratio de 1,81 en faveur du sexe masculin. Un antécédent de méningite ou d’infection respiratoire à répétition a été retrouvé chez 10 patients (32,2%). L’indication de la ventriculocisternostomie était une hydrocéphalie chez 30 patients (96, 8%). La classe ASA était II chez 19 patients (61,3%). L’intubation était prévue difficile chez 28 patients (90,3%).Tous les patients ont été opérés sous anesthésie générale. Une antibioprophylaxie a été faite chez tous les patients. La tachycardie isolée a été le seul évènement indésirable per opératoire observé chez 13 patients (41,9%). La durée de la chirurgie était de 62, 25 ± 20,9 minutes celle de l’anesthésie était de 93,5 ± 25,4 minutes. En postopératoire, une complication a été observée chez 7 patients (22,6%). Il s’agissait d’une méningite chez 3 patients (42,9%), d’une souffrance cérébrale, d’une obstruction de la stomie, d’un abcès cérébral et une paralysie du nerf III dans 14,3% chacune (1 patient). L’évolution était favorable chez 29 patients (93,5%). La durée médiane d’hospitalisation était de 3 jours. Conclusion:  Au Mali, la prise en charge anesthésique au cours de la ventriculocisternostomie s’adresse à une population pédiatrique avec un terrain précaire.   English title: Anesthesia during endoscopic third ventriculostomy in Mali: A series of 31 cases Introduction: Endoscopic Third Ventriculostomy (ETV) is a modern technique for the treatment of hydrocephalus. It is uncommon in Africa. Objective To describe ananesthesic management and the outcome of patients operated on by ETV. Patients and Methods Prospective cohort study over 15 months to January 2014 at 31 march 2015. The data entry and analysis were done by word office, Epi info 3.5.3.fr. Results: Infants predominated with a sex ratio of 1.81 in favor of men. A history of meningitis or recurrent respiratory infection was found in 10 patients (32.2%). The indication of ETV was hydrocephalus in 30 patients (96.8%). The ASA class was II in 19 patients (61.3%).  Intubation was expected to be difficult in 28 patients (90.3%). All patients were operated on under general anesthesia. Antibiotic  prophylaxis was done in all patients. Isolated tachycardia was the only peroperative adverse event observed in 13 patients (41.9%). The duration of the surgery was 62.25 ± 20.9 minutes that of the anesthesia was 93.5 ± 25.4 minutes. Postoperatively, a complication was observed in 7 patients (22.6%). It was meningitis in 3 patients (42.9%), brain pain, obstruction of the stoma, brain abscess and nerve III paralysis in 14.3% each (1 patient). The outcome was favorable in 29 patients (93.5%). The median hospital stay was 3 days. Conclusion:  In Mali, anesthetic management during ETV is aimed at a pediatric population with precarious terrain

A Phase 3, Double-Blind, Randomized, Active Controlled Study to Evaluate the Safety of MenAfriVac in Healthy Malians

Background. A safe, affordable, and highly immunogenic meningococcal A conjugate vaccine (PsA-TT, MenAfriVac) was developed to control epidemic group A meningitis in Africa. Documentation of the safety specifications of the PsA-TT vaccine was warranted, with sufficient exposure to detect potential rare vaccine-related adverse reactions. Methods. This phase 3, double-blind, randomized, active controlled clinical study was designed to evaluate the safety—primarily vaccine-related serious adverse events (SAEs)—up to 3 months after administration of a single dose of the PsA-TT vaccine to subjects aged 1-29 years in Mali. Safety outcomes were also compared to those following a single dose of a licensed meningococcal ACWY polysaccharide vaccine (PsACWY). Results. No vaccine-related SAEs occurred during the 3 months of follow-up of 4004 subjects vaccinated with a single dose of PsA-TT. When compared to PsACWY (1996 subjects), tenderness at the injection site appeared to be more frequent in the PsA-TT group. However, rates of local induration, systemic reactions, adverse events (AEs), and SAEs were similar in both groups, and unsolicited AEs and SAEs were all unrelated to the study vaccines. Conclusions. The study confirmed on a large scale the excellent safety profile of a single dose of PsA-TT when administered to its entire target population of 1-29 years of age. Clinical Trials Registration. PACTR ATMR20100300019131

SARS-CoV-2 infection and antibody seroprevalence in routine surveillance patients, healthcare workers and general population in Kita region, Mali: an observational study 2020–2021

Objective: To estimate the degree of SARS-CoV-2 transmission among healthcare workers (HCWs) and general population in Kita region of Mali. Design: Routine surveillance in 12 health facilities, HCWs serosurvey in five health facilities and community serosurvey in 16 villages in or near Kita town, Mali. Setting: Kita region, western Mali; local health centres around the central (regional) referral health centre. Participants: Patients in routine surveillance, HCWs in local health centres and community members of all ages in populations associated with study health centres. Main outcome measures: Seropositivity of ELISA test detecting SARS-CoV-2-specific total antibodies and real-time RT-PCR confirmed SARS-CoV-2 infection. Results: From 2392 routine surveillance samples, 68 (2.8%, 95% CI: 2.2% to 3.6%) tested positive for SARS-CoV-2 by RT-PCR. The monthly positivity rate was 0% in June–August 2020 and gradually increased to 6% by December 2020 and 6.2% by January 2021, then declined to 5.5%, 3.3%, 3.6% and 0.8% in February, March, April and May 2021, respectively. From 397 serum samples collected from 113 HCWs, 175 (44.1%, 95% CI: 39.1% to 49.1%) were positive for SARS-CoV-2 antibodies. The monthly seroprevalence was around 10% from September to November 2020 and increased to over 40% from December 2020 to May 2021. For community serosurvey in December 2020, overall seroprevalence of SARS-CoV-2 antibodies was 27.7%. The highest age-stratified seroprevalence was observed in participants aged 60–69 years (45.5%, 95% CI: 32.3% to 58.6%). The lowest was in children aged 0–9 years (14.0%, 95% CI: 7.4% to 20.6%). Conclusions: SARS-CoV-2 in rural Mali is much more widespread than assumed by national testing data and particularly in the older population and frontline HCWs. The observation is contrary to the widely expressed view, based on limited data, that COVID-19 infection rates were lower in 2020–2021 in West Africa than in other settings

Community Perspectives Associated With the African PsA-TT (MenAfriVac) Vaccine Trials.

BACKGROUND: The Meningitis Vaccine Project (MVP) was established to address epidemic meningitis as a public health problem in sub-Saharan Africa and, to that end, worked to develop a group A meningococcal conjugate vaccine, PsA-TT. METHODS: Experiences in 4 clinical trial sites are described. Culturally sensitive collaborative strategies were adopted to manage acceptable communication methods, peculiarities with the consent process, participant medical issues, community care, and death. RESULTS: The clinical trials were completed successfully through community acceptance and active community collaboration. The trials also strengthened the capacities in the participating communities, and actively worked to resolve community problems. CONCLUSIONS: The understanding and integration of sociocultural realities of communities were major assets in the conduct and acceptance of these trials. MVP succeeded in these sites and provided a sound example for future clinical studies in Africa. CLINICAL TRIALS REGISTRATION: ISRTCN78147026 (PsA-TT 002); ISRCTN87739946 (PsA-TT 003); ISRCTN82484612 (PsA-TT 004); PACTR ATMR2010030001913177 (PsA-TT 006); and PACTR201110000328305 (PsA-TT 007)

Augmentation de la résistance aux antibiotiques des Entérobactéries isolées à l’Institut National d’Hygiène de Lomé de 2010 à 2017: Increase in antibiotic resistance of Enterobacteriaceae isolated at the National Institute of Hygiene of Lomé from 2010 to 2017

Introduction: La résistance des Entérobactéries aux antibiotiques est un problème d’importance croissante en pratique médicale. L’objectif de cette étude était de déterminer le profil de résistance aux antibiotiques des Entérobactéries isolées à l’institut national d’hygiène (INH) de Lomé et d’analyser son évolution dans le temps. Méthodes: Il s’agissait d’une analyse rétrospective, sur une période de huit ans (2010-2017), portant sur l’ensemble des souches d’Entérobactéries isolées des prélèvements pathologiques analysés au laboratoire de bactériologie de l’INH. Résultats: Au total, 5910 Entérobactéries ont été isolées majoritairement des urines (59,59%), avec une prédominance d’Escherichia coli (63,93%) suivie de Klebsiella spp (22,86%). Entre 2010 et 2017, le taux de résistance des souches d’Escherichia coli a augmenté significativement de 18,69% à 39,26% (p< 0,0001) à la Ceftazidime ; de 1,68% à 40,22% à la Ceftriaxone (p< 0,0001) et de 42,37% à 63,23% (p< 0,0001) à la Ciprofloxacine. La résistance des souches de Klebsiella spp à la Ceftazidime a augmenté significativement de 25,26% à 42,54% (p< 0,0001) et celle à la Ceftriaxone de 2,17% à 41,79% (p< 0,0001) respectivement de 2010 à 2017. Conclusion: L’augmentation de la résistance des Entérobactéries aux antibiotiques et surtout l’évolution des résistances aux Céphalosporines de 3e Génération et aux Fluoroquinolones est un phénomène réel. Ceci exposera à des difficultés de prise en charge thérapeutique et nécessite la mise en place des dispositions idoines. Background: Antibiotic resistance in Enterobacteriaceae is a growing problem in medical practice. The objective of this study was to determine the antibiotic resistance profile of Enterobacteriaceae isolated at the National Institute of Hygiene (INH) of Lomé and to analyse its evolution over time. Method: This was a retrospective analysis, over a period of eight years (2010-2017), of all strains of Enterobacteriaceae isolated from pathological samples analysed in the bacteriology laboratory of the INH. Results: A total of 5910 Enterobacteriaceae were isolated mainly from urine (59.59%), with a predominance of Escherichia coli (63.93%) followed by Klebsiella spp (22.86%). Between 2010 and 2017, the resistance rate of Escherichia coli strains increased significantly from 18.69% to 39.26% (p<0.0001) to Ceftazidime; from 1.68% to 40.22% to Ceftriaxone (p<0.0001) and from 42.37% to 63.23% (p<0.0001) to Ciprofloxacin. Resistance of Klebsiella spp strains to Ceftazidime increased significantly from 25.26% to 42.54% (p< 0.0001) and to Ceftriaxone from 2.17% to 41.79% (p< 0.0001) respectively from 2010 to 2017. Conclusion: The increase in antibiotic resistance in Enterobacteriaceae and especially the evolution of resistance to 3rd generation cephalosporins and fluoroquinolones is a real phenomenon. This will lead to difficulties in therapeutic management and requires the implementation of appropriate measures

Profil épidémiologique de la rougeole au Mali de 2009 à 2018: Epidemiological profile of measles in Mali from 2009 to 2018

Introduction: La rougeole, maladie virale hautement contagieuse causée par un Morbillivirus, reste un important problèeme de santé publique dans de nombreux pays malgré l'existence d'un vaccin efficace. La surveillance de la rougeole est l'un des aspects clés de la lutte contre cette maladie. La présente étude avait pour objectif de décrire la mortalité et la morbidité de la rougeole au Mali entre 2009 et 2018. Méthodes: Il s'agissait d'étude transversale descriptive. Les données de surveillance de la rougeole au Mali de 2009 à 2018 ont été analysées en personne, lieu et temps. Résultats: De 2009 à 2018, le nombre de cas confirmés de rougeole était de 6461 dont 29 décès soit une létalité de 0,45%. La confirmation des cas avait été faite par le laboratoire pour 2551 cas (39,48%), par lien épidémiologique pour 3738 cas (57,85%) et cliniquement pour 172 cas (2,66%). Les enfants de moins de 5 ans représentaient 50,97% des cas et 75,86% des décès. La majorité des cas (95,71 %) n'avaient jamais été vaccinés contre la rougeole. Les incidences les plus élevées avaient été observées en 2009 (22,65 pour 100 000 hbts) et 2010 (11,81 pour 100 000 hbts). Tombouctou, Gao et Mopti avaient enregistrés les plus grands nombres de cas en 2009 et Bamako, Koulikoro et Mopti en 2010. Conclusion: La majorité des cas et des décès étaient les enfants non vaccinés de moins de cinq ans. Un renforcement du programme élargi de vaccination de routine, une riposte aux épidéemies et des stratéegies de vaccination couvrant tout le pays sont nécessaires. Introduction: Measles, a highly contagious viral disease caused by a Morbillivirus, remains an important public health problem in many countries despite the availability of an effective vaccine. Measles surveillance is one of the key aspects of measles control. The objective of this study was to describe measles mortality and morbidity in Mali between 2009 and 2018. Methods: This was a descriptive cross-sectional study. Measles surveillance data in Mali from 2009 to 2018 were analysed by person, place and time. Results: From 2009 to 2018, the number of confirmed measles cases was 6461 including 29 deaths, i.e. a case-fatality rate of 0.45%. Cases were confirmed by the laboratory for 2551 cases (39.48%), by epidemiological link for 3738 cases (57.85%) and clinically for 172 cases (2.66%). Children under 5 years of age represented 50.97% of cases and 75.86% of deaths. The majority of cases (95.71%) had never been vaccinated against measles. The highest incidences were observed in 2009 (22.65 per 100,000 inhabitants) and 2010 (11.81 per 100,000 inhabitants). Timbuktu, Gao and Mopti had the highest number of cases in 2009 and Bamako, Koulikoro and Mopti in 2010. Conclusion: The majority of cases and deaths were among unvaccinated children under five years of age. Strengthening of the routine expanded programme of immunisation, response to epidemics and nationwide immunisation strategies are needed

Testing the effects of mass drug administration of azithromycin on mortality and other outcomes among 1–11-month-old infants in Mali (LAKANA) : study protocol for a cluster-randomized, placebo-controlled, double-blinded, parallel-group, three-arm clinical trial

Background: Mass drug administration (MDA) of azithromycin (AZI) has been shown to reduce under-5 mortality in some but not all sub-Saharan African settings. A large-scale cluster-randomized trial conducted in Malawi, Niger, and Tanzania suggested that the effect differs by country, may be stronger in infants, and may be concentrated within the first 3 months after treatment. Another study found no effect when azithromycin was given concomitantly with seasonal malaria chemoprevention (SMC). Given the observed heterogeneity and possible effect modification by other co-interventions, further trials are needed to determine the efficacy in additional settings and to determine the most effective treatment regimen. Methods: LAKANA stands for Large-scale Assessment of the Key health-promoting Activities of two New mass drug administration regimens with Azithromycin. The LAKANA trial is designed to address the mortality and health impacts of 4 or 2 annual rounds of azithromycin MDA delivered to 1–11-month-old (29–364 days) infants, in a high-mortality and malaria holoendemic Malian setting where there is a national SMC program. Participating villages (clusters) are randomly allocated in a ratio of 3:2:4 to three groups: placebo (control):4-dose AZI:2-dose AZI. The primary outcome measured is mortality. Antimicrobial resistance (AMR) will be monitored closely before, during, and after the intervention and both among those receiving and those not receiving MDA with the study drugs. Other outcomes, from a subset of villages, comprise efficacy outcomes related to morbidity, growth and nutritional status, outcomes related to the mechanism of azithromycin activity through measures of malaria parasitemia and inflammation, safety outcomes (AMR, adverse and serious adverse events), and outcomes related to the implementation of the intervention documenting feasibility, acceptability, and economic aspects. The enrolment commenced in October 2020 and is planned to be completed by the end of 2022. The expected date of study completion is December 2024. Discussion: If LAKANA provides evidence in support of a positive mortality benefit resulting from azithromycin MDA, it will significantly contribute to the options for successfully promoting child survival in Mali, and elsewhere in sub-Saharan Africa. Trial registration: ClinicalTrials.gov NCT04424511. Registered on 11 June 2020.publishedVersionPeer reviewe

Use of ChAd3-EBO-Z Ebola virus vaccine in Malian and US adults, and boosting of Malian adults with MVA-BN-Filo: a phase 1, single-blind, randomised trial, a phase 1b, open-label and double-blind, dose-escalation trial, and a nested, randomised, double-blind, placebo-controlled trial

SummaryBackgroundThe 2014 west African Zaire Ebola virus epidemic prompted worldwide partners to accelerate clinical development of replication-defective chimpanzee adenovirus 3 vector vaccine expressing Zaire Ebola virus glycoprotein (ChAd3-EBO-Z). We aimed to investigate the safety, tolerability, and immunogenicity of ChAd3-EBO-Z in Malian and US adults, and assess the effect of boosting of Malians with modified vaccinia Ankara expressing Zaire Ebola virus glycoprotein and other filovirus antigens (MVA-BN-Filo).MethodsIn the phase 1, single-blind, randomised trial of ChAd3-EBO-Z in the USA, we recruited adults aged 18–65 years from the University of Maryland medical community and the Baltimore community. In the phase 1b, open-label and double-blind, dose-escalation trial of ChAd3-EBO-Z in Mali, we recruited adults 18–50 years of age from six hospitals and health centres in Bamako (Mali), some of whom were also eligible for a nested, randomised, double-blind, placebo-controlled trial of MVA-BN-Filo. For randomised segments of the Malian trial and for the US trial, we randomly allocated participants (1:1; block size of six [Malian] or four [US]; ARB produced computer-generated randomisation lists; clinical staff did randomisation) to different single doses of intramuscular immunisation with ChAd3-EBO-Z: Malians received 1 × 1010 viral particle units (pu), 2·5 × 1010 pu, 5 × 1010 pu, or 1 × 1011 pu; US participants received 1 × 1010 pu or 1 × 1011 pu. We randomly allocated Malians in the nested trial (1:1) to receive a single dose of 2 × 108 plaque-forming units of MVA-BN-Filo or saline placebo. In the double-blind segments of the Malian trial, investigators, clinical staff, participants, and immunology laboratory staff were masked, but the study pharmacist (MK), vaccine administrator, and study statistician (ARB) were unmasked. In the US trial, investigators were not masked, but participants were. Analyses were per protocol. The primary outcome was safety, measured with occurrence of adverse events for 7 days after vaccination. Both trials are registered with ClinicalTrials.gov, numbers NCT02231866 (US) and NCT02267109 (Malian).FindingsBetween Oct 8, 2014, and Feb 16, 2015, we randomly allocated 91 participants in Mali (ten [11%] to 1 × 1010 pu, 35 [38%] to 2·5 × 1010 pu, 35 [38%] to 5 × 1010 pu, and 11 [12%] to 1 × 1011 pu) and 20 in the USA (ten [50%] to 1 × 1010 pu and ten [50%] to 1 × 1011 pu), and boosted 52 Malians with MVA-BN-Filo (27 [52%]) or saline (25 [48%]). We identified no safety concerns with either vaccine: seven (8%) of 91 participants in Mali (five [5%] received 5 × 1010 and two [2%] received 1 × 1011 pu) and four (20%) of 20 in the USA (all received 1 × 1011 pu) given ChAd3-EBO-Z had fever lasting for less than 24 h, and 15 (56%) of 27 Malians boosted with MVA-BN-Filo had injection-site pain or tenderness.Interpretation1 × 1011 pu single-dose ChAd3-EBO-Z could suffice for phase 3 efficacy trials of ring-vaccination containment needing short-term, high-level protection to interrupt transmission. MVA-BN-Filo boosting, although a complex regimen, could confer long-lived protection if needed (eg, for health-care workers).FundingWellcome Trust, Medical Research Council UK, Department for International Development UK, National Cancer Institute, Frederick National Laboratory for Cancer Research, Federal Funds from National Institute of Allergy and Infectious Diseases

Antibody Persistence 1-5 Years Following Vaccination With MenAfriVac in African Children Vaccinated at 12-23 Months of Age.

BACKGROUND: Following mass vaccination campaigns in the African meningitis belt with group A meningococcal conjugate vaccine, MenAfriVac (PsA-TT), disease due to group A meningococci has nearly disappeared. Antibody persistence in healthy African toddlers was investigated. METHODS: African children vaccinated at 12-23 months of age with PsA-TT were followed for evaluation of antibody persistence up to 5 years after primary vaccination. Antibody persistence was evaluated by measuring group A serum bactericidal antibody (SBA) with rabbit complement and by a group A-specific IgG enzyme-linked immunosorbent assay (ELISA). RESULTS: Group A antibodies measured by SBA and ELISA were shown to decline in the year following vaccination and plateaued at levels significantly above baseline for up to 5 years following primary vaccination. CONCLUSIONS: A single dose of PsA-TT induces long-term sustained levels of group A meningococcal antibodies for up to 5 years after vaccination. CLINICAL TRIALS REGISTRATION: ISRTCN78147026