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Buruli ulcer is one of the 20 neglected tropical diseases in the world. This necrotizing hypodermitis is a chronic debilitating disease caused by an environmental Mycobacterium ulcerans. At least 33 countries with tropical, subtropical and temperate climates have reported Buruli ulcer in African countries, South America and Western Pacific regions. Majority of cases are spread across West and Central Africa. The mode of transmission is unclear, hindering the implementation of adequate prevention for the population. Currently, early diagnosis and treatment are crucial to minimizing morbidity, costs and preventing long-term disability. Biological confirmation of clinical diagnosis of Buruli ulcer is essential before starting chemotherapy. Indeed, differential diagnosis are numerous and Buruli ulcer has varying clinical presentations. Up to now, the gold standard biological confirmation is the quantitative PCR, targeting the insertion sequence IS2404 of M. ulcerans performed on cutaneous samples. Due to the low PCR confirmation rate in endemic African countries (under 30% in 2018) for numerous identified reasons within this article, 11 laboratories decided to combine their efforts to create the network "BU-LABNET" in 2019. The first step of the network was to harmonize the procedures and ship specific reagents to each laboratory. With this system in place, implementation of these procedures for testing and follow-up was easy and the laboratories were able to carry out their first quality control with a very high success rate. It is now time to integrate other neglected tropical diseases to this platform, such as yaws or leprosy.

Drug-resistant tuberculosis (DR-TB) poses a significant public health challenge, particularly in resource-limited settings. The prevalence and management of DR-TB in African countries require comprehensive strategies to improve patient outcomes and control the spread of the disease. Aggregated routine data (from 2018 to 2022) on multidrug-resistant TB (MDR-TB) were collected from the National TB Programs (NTPs) from all six countries. The diagnostic capacity for MDR-TB was globally insufficient. The system for collecting and transporting samples was sometimes inoperative. A total of 2353 cases of MDR-TB were reported, with 86.4% receiving treatment. The gap between the expected number of MDR-TB cases and the number reported per country varied from 51.5% to 88.0%, depending on the year. Fifty-two extensively drug-resistant (XDR) TB cases received treatment regimens over five years, with variations across countries. All patients received free follow-up examinations, nutritional and financial support for travel expenses to the outpatient care and treatment centers. The MDR-TB treatment success rates for all regimens between 2018 and 2021 ranged from 44.4 to 90.9%, varying by country and year. The information system relied on primary tools, reporting tools, and digital solutions. Progress has been made in MDR-TB management; however, challenges persist, necessitating resources to enhance access to rapid molecular screening tests.

Introduction: An effective rifampicin-resistant tuberculosis (RR-TB) treatment regimen should include prevention of resistance amplification. While bedaquiline (BDQ) has been recommended in all-oral RR-TB treatment regimen since 2019, resistance is rising at alarming rates. This may be due to BDQ's delayed bactericidal effect, which increases the risk of selecting for resistance to fluoroquinolones and/or BDQ in the first week of treatment when the bacterial load is highest. We aim to strengthen the first week of treatment with the injectable drug amikacin (AMK). To limit the ototoxicity risk while maximising the bactericidal effect, we will evaluate the safety of adding a 30 mg/kg AMK injection on the first and fourth day of treatment., Methods and Analysis: We will conduct a single-arm clinical trial on 20 RR-TB patients nested within an operational study called ShoRRT (All oral Shorter Treatment Regimen for Drug resistant Tuberculosis). In addition to all-oral RR-TB treatment, patients will receive two doses of AMK. The primary safety endpoint is any grade 3-4 adverse event during the first 2 weeks of treatment related to the use of AMK. With a sample size of 20 patients, we will have at least 80% statistical power to support the alternative hypothesis, indicating that less than 14% of patients treated with AMK experience a grade 3-4 adverse event related to its use. Safety data obtained from this study will inform a larger multicountry study on using two high doses of AMK to prevent acquired resistance., Ethics and Dissemination: Approval was obtained from the ethics committee of Rwanda, Rwanda Food and Drug Authority, Universitair Ziekenhuis, the Institute of Tropical Medicine ethics review board. All participants will provide informed consent. Study results will be disseminated through peer-reviewed journals and conferences., Trial Registration Number: NCT05555303., Competing Interests: Competing interests: CSM is a staff member of the WHO. The other authors declare that they have no competing interests., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Antiseptics, disinfectants, and hand hygiene products can be contaminated with bacteria and cause healthcare-associated infections, which are underreported from low- and middle-income countries. To better understand the user-related risk factors, we conducted a knowledge, awareness, and practice survey among hospital staff in sub-Saharan Africa., Methods: Self-administered questionnaire distributed among healthcare workers in three tertiary care hospitals (Burkina Faso, Benin, Democratic Republic of the Congo)., Results: 617 healthcare workers (85.3% (para)medical and 14.7% auxiliary staff) participated. Less than half (45.5%) had been trained in Infection Prevention & Control (IPC), and only 15.7% were trained < 1 year ago. Near two-thirds (64.2%) preferred liquid soap for hand hygiene, versus 33.1% for alcohol-based hand rub (ABHR). Most (58.3%) expressed confidence in the locally available products. Knowledge of product categories, storage conditions and shelf-life was inadequate: eosin was considered as an antiseptic (47.5% of (para)medical staff), the shelf life and storage conditions (non-transparent container) of freshly prepared chlorine 0.5% were known by only 42.6% and 34.8% of participants, respectively. Approximately one-third of participants approved using tap water for preparation of chlorine 0.5% and liquid soap. Most participants (> 80%) disapproved recycling soft-drink bottles as liquid soap containers. Nearly two-thirds (65.0%) declared that bacteria may be resistant to and survive in ABHR, versus 51.0% and 37.4% for povidone iodine and chlorine 0.5%, respectively. Depicted risk practices (n = 4) were ignored by 30 to 40% of participants: they included touching the rim or content of stock containers with compresses or small containers, storing of cotton balls soaked in an antiseptic, and hand-touching the spout of pump dispenser. Filling containers by topping-up was considered good practice by 18.3% of participants. Half (52.1%) of participants acknowledged indefinite reuse of containers. Besides small differences, the findings were similar across the study sites and professional groups. Among IPC-trained staff, proportions recognizing all 4 risk practices were higher compared to non-trained staff (35.9% versus 23.8%, p < 0.0001)., Conclusions: The present findings can guide tailored training and IPC implementation at the healthcare facility and national levels, and sensitize stakeholders' and funders' interest., (© 2024. The Author(s).)

Background: Tuberculosis (TB) is a public health problem worldwide, particularly in resource-limited countries. It is considered a social disease with a medical component that persists over time due to several social determinants, most of which are closely linked to poverty and difficult socioeconomic conditions. The objective of this exploratory study is to describe the social protection interventions available for people with TB in Africa., Methods: Searches will be carried out systematically in MEDLINE (PubMed), Embase (Ovid), Web of Science, Scopus and The Cochrane Library, Africa-Wide Information (EBSCOhost), Google Scholar. Articles will be considered if they describe the social protection, successes and challenges associated with the implementation and delivery of social protection interventions offered to people with TB in African countries. Data from the grey literature will also be considered., Presentation of Results: We will present a narrative description highlighting the successes and challenges of the social protection interventions identified, and a synthesis accompanied by maps (Africa), figures or tables to summarize the data., Conclusion: This exploratory study will map the existing literature on social protection interventions for TB patients and guide future research to inform policy and practice decisions., Competing Interests: The Authors declare that no competing interest exists, (Copyright © 2024 by West African Journal of Medicine.)

Objective: To evaluate the performance of Xpert Mycobacterium Tuberculosis/rifampicin (MTB/RIF) Ultra (Ultra) for diagnosis of childhood tuberculosis (TB) within public health systems., Methods: In this cross-sectional study, children aged <15 years with presumptive pulmonary TB were consecutively recruited and evaluated for TB at tertiary-level hospitals in Benin, Mali, and Ghana. Bivariate random-effects models were used to determine the pooled sensitivity and specificity of Ultra against culture. We also estimated its diagnostic yield against a composite microbiological reference standard (cMRS) of positive culture or Ultra., Results: Overall, 193 children were included in the analyses with a median (interquartile range) age of 4.0 (1.1-9.2) years, 88 (45.6%) were female, and 36 (18.7%) were HIV-positive. Thirty-one (16.1%) children had confirmed TB, 39 (20.2%) had unconfirmed TB, and 123 (63.7%) had unlikely TB. The pooled sensitivity and specificity of Ultra verified by culture were 55.0% (95% confidence interval [CI]: 28.0-79.0%) and 95.0% (95% CI: 88.0-98.0%), respectively. Against the cMRS, the diagnostic yield of Ultra and culture were 67.7% (95% CI: 48.6-83.3%) and 70.9% (95% CI: 51.9-85.8%), respectively., Conclusion: Ultra has suboptimal sensitivity in children with TB that were investigated under routine conditions in tertiary-level hospitals in three West African countries., Competing Interests: Declaration of competing interest None declared., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Invasive non-typhoidal Salmonella (iNTS) disease manifesting as bloodstream infection with high mortality is responsible for a huge public health burden in sub-Saharan Africa. Salmonella enterica serovar Typhimurium (S. Typhimurium) is the main cause of iNTS disease in Africa. By analysing whole genome sequence data from 1303 S. Typhimurium isolates originating from 19 African countries and isolated between 1979 and 2017, here we show a thorough scaled appraisal of the population structure of iNTS disease caused by S. Typhimurium across many of Africa's most impacted countries. At least six invasive S. Typhimurium clades have already emerged, with ST313 lineage 2 or ST313-L2 driving the current pandemic. ST313-L2 likely emerged in the Democratic Republic of Congo around 1980 and further spread in the mid 1990s. We observed plasmid-borne as well as chromosomally encoded fluoroquinolone resistance underlying emergences of extensive-drug and pan-drug resistance. Our work provides an overview of the evolution of invasive S. Typhimurium disease, and can be exploited to target control measures., (© 2023. Springer Nature Limited.)

Methicillin-resistant Staphylococcus aureus (MRSA) constitutes a serious public health concern, with a considerable impact on patients' health, and substantial healthcare costs. In this study, patients and healthcare workers (HCWs) from six public hospitals in Benin were screened for MRSA. Strains were identified as MRSA using conventional microbiological methods in Benin, and confirmed using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry in Belgium. Whole-genome sequencing (WGS) was used on the confirmed MRSA isolates, to characterize their genomic content and study their relatedness. Amongst the 305 isolates (304 wound swabs and 61 nasal swabs) that were collected from patients and HCWs, we detected 32 and 15 cases of MRSA, respectively. From this collection, 27 high-quality WGS datasets were obtained, which carried numerous genes and mutations associated with antimicrobial resistance. The mecA gene was detected in all the sequenced isolates. These isolates were assigned to five sequence types (STs), with ST8 (55.56%, n = 15/27), ST152 (18.52%, n = 5/27), and ST121 (18.52%, n = 5/27) being the most common. These 27 isolates carried multiple virulence genes, including the genes encoding the Panton-Valentine leukocidin toxin (48.15%, n = 13/27), and the tst gene (29.63%, n = 8/27), associated with toxic shock syndrome. This study highlights the need to implement a multimodal strategy for reducing the risk of the cross-transmission of MRSA in hospitals.

Antiseptics, disinfectants, and hand hygiene products can act as reservoirs of Gram-negative bacteria causing healthcare-associated infections. This problem is rarely documented in low- and middle-income countries, particularly in sub-Saharan Africa. In a cross-sectional survey, we assessed the bacterial contamination of antiseptics, disinfectants, and hand hygiene products in two university hospitals in Burkina Faso and Benin. During ward visits and staff interviews, in-use products were cultured for the presence of Gram-negative bacteria. The growth of Gram-negative bacteria was absent or rare in alcohol-based products, povidone iodine, and Dakin solution. Contamination was highest (73.9% (51/69)) for liquid soap products (versus antiseptic/disinfectants (4.5%, 7/157) ( p < 0.0001)), mostly used in high-risk areas and associated with high total bacterial counts (>10,000 colony-forming units/mL). Contaminating flora (105 isolates) included Enterobacterales and the Vibrio non-cholerae/ Aeromonas group (17.1%) and non-fermentative Gram-negative rods (82.8%). Multidrug resistance was present among 9/16 Enterobacterales ( Klebsiella and Enterobacter spp.) and 3/12 Acinetobacter spp., including carbapenem resistance ( Acinetobacter baumannii : NDM, Pseudomonas stutzeri : VIM). The risk factors for contamination included the type of product (cleaning grade and in-house prepared liquid soap), use of recycled disposable containers and soft drink bottles, absence of labeling, topping-up of containers, dilution with tap water (pharmacy and ward), and poor-quality management (procurement, stock management, expiry dates, and period after opening).

Competing Interests: We declare no competing interests. This project is part of the EDCTP2 programme supported by the EU (grant number RIA2020I-3270 – SIMBLE). FM and AOG contributed equally.

Background: The World Health Organization recommends tuberculosis (TB) preventive treatment (TPT) for all people living with HIV (PLH) and household contacts (HHC) of index TB patients. Tests for TB infection (TBI) or to rule out TB disease (TBD) are preferred, but if not available, this should not be a barrier if access to these tests is limited for high-risk people, such as PLH and HHC under 5 years old. There is equipoise on the need for these tests in different risk populations, especially HHC aged over 5., Methods: This superiority cluster-randomized multicenter trial with three arms of equal size compares, in Benin and Brazil, three strategies for HHC investigation aged 0-50: (i) tuberculin skin testing (TST) or interferon gamma release assay (IGRA) for TBI and if positive, chest X-Ray (CXR) to rule out TBD in persons with positive TST or IGRA; (ii) same as (i) but GeneXpert (GX) replaces CXR; and (iii) no TBI testing. CXR for all; if CXR is normal, TPT is recommended. All strategies start with symptom screening. Clusters are defined as HHC members of the same index patients with newly diagnosed pulmonary TBD. The main outcome is the proportion of HHC that are TPT eligible who start TPT within 3 months of the index TB patient starting TBD treatment. Societal costs, incidence of severe adverse events, and prevalence of TBD are among secondary outcomes. Stratified analyses by age (under versus over 5) and by index patient microbiological status will be conducted. All participants provide signed informed consent. The study was approved by the Research Ethic Board of the Research Institute of the McGill University Health Centre, the Brazilian National Ethical Board CONEP, and the "Comité Local d'Éthique Pour la Recherche Biomédicale (CLERB) de l'Université de Parakou," Benin. Findings will be submitted for publication in major medical journals and presented in conferences, to WHO and National and municipal TB programs of the involved countries., Discussion: This randomized trial is meant to provide high-quality evidence to inform WHO recommendations on investigation of household contacts, as currently these are based on very low-quality evidence., Trial Registration: ClinicalTrials.gov NCT04528823., (© 2022. The Author(s).)

Background: The WHO-recommended tuberculosis screening and diagnostic algorithm in ambulatory people living with HIV is a four-symptom screen (known as the WHO-recommended four symptom screen [W4SS]) followed by a WHO-recommended molecular rapid diagnostic test (eg Xpert MTB/RIF [hereafter referred to as Xpert]) if W4SS is positive. To inform updated WHO guidelines, we aimed to assess the diagnostic accuracy of alternative screening tests and strategies for tuberculosis in this population., Methods: In this systematic review and individual participant data meta-analysis, we updated a search of PubMed (MEDLINE), Embase, the Cochrane Library, and conference abstracts for publications from Jan 1, 2011, to March 12, 2018, done in a previous systematic review to include the period up to Aug 2, 2019. We screened the reference lists of identified pieces and contacted experts in the field. We included prospective cross-sectional, observational studies and randomised trials among adult and adolescent (age ≥10 years) ambulatory people living with HIV, irrespective of signs and symptoms of tuberculosis. We extracted study-level data using a standardised data extraction form, and we requested individual participant data from study authors. We aimed to compare the W4SS with alternative screening tests and strategies and the WHO-recommended algorithm (ie, W4SS followed by Xpert) with Xpert for all in terms of diagnostic accuracy (sensitivity and specificity), overall and in key subgroups (eg, by antiretroviral therapy [ART] status). The reference standard was culture. This study is registered with PROSPERO, CRD42020155895., Findings: We identified 25 studies, and obtained data from 22 studies (including 15 666 participants; 4347 [27·7%] of 15 663 participants with data were on ART). W4SS sensitivity was 82% (95% CI 72-89) and specificity was 42% (29-57). C-reactive protein (≥10 mg/L) had similar sensitivity to (77% [61-88]), but higher specificity (74% [61-83]; n=3571) than, W4SS. Cough (lasting ≥2 weeks), haemoglobin (<10 g/dL), body-mass index (<18·5 kg/m 2 ), and lymphadenopathy had high specificities (80-90%) but low sensitivities (29-43%). The WHO-recommended algorithm had a sensitivity of 58% (50-66) and a specificity of 99% (98-100); Xpert for all had a sensitivity of 68% (57-76) and a specificity of 99% (98-99). In the one study that assessed both, the sensitivity of sputum Xpert Ultra was higher than sputum Xpert (73% [62-81] vs 57% [47-67]) and specificities were similar (98% [96-98] vs 99% [98-100]). Among outpatients on ART (4309 [99·1%] of 4347 people on ART), W4SS sensitivity was 53% (35-71) and specificity was 71% (51-85). In this population, a parallel strategy (two tests done at the same time) of W4SS with any chest x-ray abnormality had higher sensitivity (89% [70-97]) and lower specificity (33% [17-54]; n=2670) than W4SS alone; at a tuberculosis prevalence of 5%, this strategy would require 379 more rapid diagnostic tests per 1000 people living with HIV than W4SS but detect 18 more tuberculosis cases. Among outpatients not on ART (11 160 [71·8%] of 15 541 outpatients), W4SS sensitivity was 85% (76-91) and specificity was 37% (25-51). C-reactive protein (≥10 mg/L) alone had a similar sensitivity to (83% [79-86]), but higher specificity (67% [60-73]; n=3187) than, W4SS and a sequential strategy (both test positive) of W4SS then C-reactive protein (≥5 mg/L) had a similar sensitivity to (84% [75-90]), but higher specificity than (64% [57-71]; n=3187), W4SS alone; at 10% tuberculosis prevalence, these strategies would require 272 and 244 fewer rapid diagnostic tests per 1000 people living with HIV than W4SS but miss two and one more tuberculosis cases, respectively., Interpretation: C-reactive protein reduces the need for further rapid diagnostic tests without compromising sensitivity and has been included in the updated WHO tuberculosis screening guidelines. However, C-reactive protein data were scarce for outpatients on ART, necessitating future research regarding the utility of C-reactive protein in this group. Chest x-ray can be useful in outpatients on ART when combined with W4SS. The WHO-recommended algorithm has suboptimal sensitivity; Xpert for all offers slight sensitivity gains and would have major resource implications., Funding: World Health Organization., Competing Interests: Declaration of interests AC reports grants from National Institutes of Health (NIH), Global Health Labs, and Stop TB Partnership, and consulting fees from the US Centers for Disease Control and Prevention (CDC). AK reports grants from Sanofi. FAK reports grants from WHO, Canadian Institutes of Health Research, Fonds de Recherche Quebec, and McGill Interdisciplinary Initiative on Infection and Immunity. GT reports receipt of consumables and equipment from Boditech and Cepheid. NM reports grants from Pfizer and Roche. REC reports grants from NIH, CDC, and Unitaid, and consulting fees from Sanofi. SML reports grants from NIH and CDC. SSk reports grants from Swedish Heart-Lung Foundation. TKr reports consulting fees from WHO. All other authors declare no competing interests., (© 2022 World Health Organization; licensee Elsevier. This is an Open Access article published under the CC BY 3·0 IGO license which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. In any use of this article, there should be no suggestion that WHO endorses any specific organisation, products or services. The use of the WHO logo is not permitted. This notice should be preserved along with the article's original URL.)

Objectives: We sought to evaluate the yield, cost, feasibility, and acceptability of routine tuberculosis (TB) screening of pregnant women in Cotonou, Benin., Design: Mixed-methods, cross-sectional study with a cost assessment., Setting: Eight participating health facilities in Cotonou, Benin., Participants: Consecutive pregnant women presenting for antenatal care at any participating site who were not in labor or currently being treated for TB from April 2017 to April 2018., Interventions: Screening for the presence of TB symptoms by midwives and Xpert MTB/RIF for those with cough for at least two weeks. Semi-structured interviews with 14 midwives and 16 pregnant women about experiences with TB screening., Primary and Secondary Outcome Measures: Proportion of pregnant women with cough of at least two weeks and/or microbiologically confirmed TB. The cost per pregnant woman screened and per TB case diagnosed in 2019 USD from the health system perspective., Results: Out of 4,070 pregnant women enrolled in the study, 94 (2.3%) had a cough for at least two weeks at the time of screening. The average (standard deviation) age of symptomatic women was 26 ± 5 years and 5 (5.3%) had HIV. Among the 94 symptomatic women, 2 (2.3%) had microbiologically confirmed TB for a TB prevalence of 49 per 100,000 (95% CI: 6 to 177 per 100,000) among pregnant women enrolled in the study. The average cost to screen one pregnant woman for TB was $1.12 USD and the cost per TB case diagnosed was $2271 USD. Thematic analysis suggested knowledge of TB complications in pregnancy was low, but that routine TB screening was acceptable to both midwives and pregnant women., Conclusion: Enhanced screening for TB among pregnant women is feasible, acceptable, and inexpensive per woman screened, however in this setting has suboptimal yield even if it can contribute to enhance TB case finding., Competing Interests: CSM is currently a staff member of the World Health Organization; the author alone is responsible for the views expressed in this publication and they do not necessarily represent the decisions, policy or views of the WHO.

Background: Although global surveillance of antimicrobial resistance (AMR) is considered key in the containment of AMR, data from low- and middle-income countries, especially from sub-Saharan Africa, are scarce. This study describes epidemiology of bloodstream infections and antimicrobial resistance rates in a secondary care hospital in Benin., Methods: Blood cultures were sampled, according to predefined indications, in BacT/ALERT FA Plus and PF Plus (bioMérieux, Marcy-l'Etoile, France) blood culture bottles (BCB) in a district hospital (Boko hospital) and to a lesser extent in the University hospital of Parakou. These BCB were incubated for 7 days in a standard incubator and twice daily inspected for visual signs of growth. Isolates retrieved from the BCB were processed locally and later shipped to Belgium for reference identification [matrix-assisted laser desorption/ionization time-of-flight spectrometry (MALDI-TOF)] and antibiotic susceptibility testing (disk diffusion and E-tests)., Results: From October 2017 to February 2020, 3353 BCB were sampled, corresponding to 3140 blood cultures (212 cultures consisting of  > 1 BCB) and 3082 suspected bloodstream infection (BSI) episodes. Most of these cultures (n = 2471; 78.7%) were sampled in children < 15 years of age. Pathogens were recovered from 383 (12.4%) cultures, corresponding to 381 confirmed BSI. 340 of these pathogens were available and confirmed by reference identification. The most common pathogens were Klebsiella pneumoniae (n = 53; 15.6%), Salmonella Typhi (n = 52; 15.3%) and Staphylococcus aureus (n = 46; 13.5%). AMR rates were high among Enterobacterales, with resistance to third-generation cephalosporins in 77.6% of K. pneumoniae isolates (n = 58), 12.8% of Escherichia coli isolates (n = 49) and 70.5% of Enterobacter cloacae isolates (n = 44). Carbapenemase production was detected in 2 Escherichia coli and 2 Enterobacter cloacae isolates, all of which were of the New Delhi metallo-beta lactamase type. Methicillin resistance was present in 22.4% of S. aureus isolates (n = 49)., Conclusion: Blood cultures were successfully implemented in a district hospital in Benin, especially among the pediatric patient population. Unexpectedly high rates of AMR among Gram-negative bacteria against commonly used antibiotics were found, demonstrating the clinical and scientific importance of clinical bacteriology laboratories at this level of care., (© 2022. The Author(s).)

Over the past 15 years, and despite many difficulties, significant progress has been made to advance child and adolescent tuberculosis (TB) care. Despite increasing availability of safe and effective treatment and prevention options, TB remains a global health priority as a major cause of child and adolescent morbidity and mortality-over one and a half million children and adolescents develop TB each year. A history of the global public health perspective on child and adolescent TB is followed by 12 narratives detailing challenges and progress in 19 TB endemic low and middle-income countries. Overarching challenges include: under-detection and under-reporting of child and adolescent TB; poor implementation and reporting of contact investigation and TB preventive treatment services; the need for health systems strengthening to deliver effective, decentralized services; and lack of integration between TB programs and child health services. The COVID-19 pandemic has had a significant negative impact on case detection and treatment outcomes. Child and adolescent TB working groups can address country-specific challenges to close the policy-practice gaps by developing and supporting decentral ized models of care, strengthening clinical and laboratory diagnosis, including of multidrug-resistant TB, providing recommended options for treatment of disease and infection, and forging strong collaborations across relevant health sectors.

Summary Background: Multidrug-resistant (MDR) tuberculosis (TB) poses an important challenge in TB management and control. Rifampicin resistance (RR) is a solid surrogate marker of MDR-TB. We investigated the RR-TB clustering rates, bacterial population dynamics to infer transmission dynamics, and the impact of changes to patient management on these dynamics over 27 years in Rwanda., Methods: We analysed whole genome sequences of a longitudinal collection of nationwide RR-TB isolates. The collection covered three important periods: before programmatic management of MDR-TB (PMDT; 1991-2005), the early PMDT phase (2006-2013), in which rifampicin drug-susceptibility testing (DST) was offered to retreatment patients only, and the consolidated phase (2014-2018), in which all bacteriologically confirmed TB patients had rifampicin DST done mostly via Xpert MTB/RIF assay. We constructed clusters based on a 5 SNP cut-off and resistance conferring SNPs. We used Bayesian modelling for dating and population size estimations, TransPhylo to estimate the number of secondary cases infected by each patient, and multivariable logistic regression to assess predictors of being infected by the dominant clone., Results: Of 308 baseline RR-TB isolates considered for transmission analysis, the clustering analysis grouped 259 (84.1%) isolates into 13 clusters. Within these clusters, a single dominant clone was discovered containing 213 isolates (82.2% of clustered and 69.1% of all RR-TB), which we named the "Rwanda Rifampicin-Resistant clone" (R3clone). R3clone isolates belonged to Ugandan sub-lineage 4.6.1.2 and its rifampicin and isoniazid resistance were conferred by the Ser450Leu mutation in rpoB and Ser315Thr in katG genes, respectively. All R3clone isolates had Pro481Thr, a putative compensatory mutation in the rpoC gene that likely restored its fitness. The R3clone was estimated to first arise in 1987 and its population size increased exponentially through the 1990s', reaching maximum size (∼84%) in early 2000 s', with a declining trend since 2014. Indeed, the highest proportion of R3clone (129/157; 82·2%, 95%CI: 75·3-87·8%) occurred between 2000 and 13, declining to 64·4% (95%CI: 55·1-73·0%) from 2014 onward. We showed that patients with R3clone detected after an unsuccessful category 2 treatment were more likely to generate secondary cases than patients with R3clone detected after an unsuccessful category 1 treatment regimen., Conclusions: RR-TB in Rwanda is largely transmitted. Xpert MTB/RIF assay as first diagnostic test avoids unnecessary rounds of rifampicin-based TB treatment, thus preventing ongoing transmission of the dominant R3clone. As PMDT was intensified and all TB patients accessed rifampicin-resistance testing, the nationwide R3clone burden declined. To our knowledge, our findings provide the first evidence supporting the impact of universal DST on the transmission of RR-TB., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2022 The Authors.)

Background&#160;: International Health Regulations require countries to establish laboratory systems for rapid and safe confirmation of public health emergencies.Objective&#160;: This study assessed the capacity of the National Laboratory System for the detection of infectious threats to global health security in Benin.Method&#160;: The study was descriptive, cross-sectional, and evaluative. The targets were laboratories performing the confirmation of infectious threats. The sampling method was non-probabilistic with the reasoned choice of 74 laboratories. Four collection tools were used. The World Health Organization&#8217;s laboratory assessment tool for health facilities was used to assess the national public health laboratory. The assessment was based on the capacities of peripheric laboratories and of the national reference laboratory. The capacity was rated good if at least 80% of peripheric laboratories met at least 80% of the criteria and if the national public health laboratory had an average indicator of at least 80%. Otherwise, the capacity was rated insufficient.Results&#160;: The national laboratory system capacity was insufficient. Only 54% of peripheric laboratories had good capacity. The national reference laboratory had an average indicator of 71%. In this reference laboratory, specimen collection and transport, laboratory testing performance, consumables and reagents, and public health functions had the best scores, above 80%. Biorisk management, organization and management, and documents had the lowest scores. In peripheric laboratories, the testing performance was the only domain with good capacity.Conclusion&#160;: To ensure effective Global Health Security in Benin, a National Laboratory System capacity improvement strategic plan need to be developed and implemented.

The increasing worldwide prevalence of extended-spectrum beta-lactamase (ESBL) producing Escherichia coli constitutes a serious threat to global public health. Surgical site infections are associated with high morbidity and mortality rates in developing countries, fueled by the limited availability of effective antibiotics. We used whole-genome sequencing (WGS) to evaluate antimicrobial resistance and the phylogenomic relationships of 19 ESBL-positive E. coli isolates collected from surgical site infections in patients across public hospitals in Benin in 2019. Isolates were identified by MALDI-TOF mass spectrometry and phenotypically tested for susceptibility to 16 antibiotics. Core-genome multi-locus sequence typing and single-nucleotide polymorphism-based phylogenomic methods were used to investigate the relatedness between samples. The broader phylogenetic context was characterized through the inclusion of publicly available genome data. Among the 19 isolates, 13 different sequence types (STs) were observed, including ST131 ( n  = 2), ST38 ( n  = 2), ST410 ( n  = 2), ST405 ( n  = 2), ST617 ( n  = 2), and ST1193 ( n  = 2). The bla CTX-M-15 gene encoding ESBL resistance was found in 15 isolates (78.9%), as well as other genes associated with ESBL, such as bla OXA-1 ( n  = 14) and bla TEM-1 ( n  = 9). Additionally, we frequently observed genes encoding resistance against aminoglycosides [ aac-(6')-Ib-cr , n  = 14], quinolones ( qnrS 1 , n  = 4), tetracyclines [ tet ( B ), n  = 14], sulfonamides ( sul2 , n  = 14), and trimethoprim ( dfrA17 , n  = 13). Nonsynonymous chromosomal mutations in the housekeeping genes parC and gyrA associated with resistance to fluoroquinolones were also detected in multiple isolates. Although the phylogenomic investigation did not reveal evidence of hospital-acquired transmissions, we observed two very similar strains collected from patients in different hospitals. By characterizing a set of multidrug-resistant isolates collected from a largely unexplored environment, this study highlights the added value for WGS as an effective early warning system for emerging pathogens and antimicrobial resistance., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Yehouenou, Bogaerts, De Keersmaecker, Roosens, Marchal, Tchiakpe, Affolabi, Simon, Dossou, Vanneste and Dalleur.)