BACKGROUND:Inadequate access to clinical bacteriology testing in low-resource settings compromises individual patient care and contributes to antimicrobial resistance. Funders, policy makers, and health administrators working to expand bacteriology testing in sub-Saharan Africa require evidence-based guidance. The aim of this study was to assemble a costed consensus list of minimum equipment and consumables required to implement and operate a functional clinical bacteriology laboratory in secondary and tertiary care hospitals in sub-Saharan Africa, to guide funders and health administrators. METHODS:A consensus list of minimum materials for diagnosing bloodstream infections was assembled by experts from Africa, North America, and Europe, representing academia, funders, and implementers. A modelling study was performed to estimate costs across several testing scenarios developed using a formal framework for forecasting testing volumes and reagent usage. Outcomes assessed were consumable costs per hospital admission and per investigation of septic episode and costs of non-recurring items at the time of establishment of a laboratory. Data from two accredited bacteriology laboratories providing individual patient care in Benin and Ethiopia were used to inform expected positivity rates, reagent usage, and testing volumes. Supplier quotes from North America and Europe were used to provide average unit costs and 95% uncertainty ranges. FINDINGS:The estimated mean consumable cost per hospital admission was, in 2023 USD, $6·23 (95% uncertainty range 5·42-7·54) in the strict minimum scenario and $10·86 (9·82-12·31) in the standard scenario. The mean cost for the minimal equipment list at the time of establishment of a laboratory was estimated at $30 763 (28 403-33 043; plus an annual equipment maintenance cost of $3076 [2840-3304]), which includes purchase of commercial quality control strains and other non-recurring consumables. Available data suggest that costs from national distributors in sub-Saharan Africa could be three-fold higher than those described. Finally, we provide a transparent and adaptable basis for estimating minimal testing volumes and reagent usage, enabling tailored procurement planning in regions currently without clinical bacteriology laboratories. INTERPRETATION:These results inform national antimicrobial resistance action plans on supply procurement, costing, and the ability to benchmark and forecast minimal acceptable testing volumes for the diagnosis of bloodstream infections for individual patient care. FUNDING:Fonds de recherche du Québec - Santé.

Importance:Escherichia coli and Klebsiella pneumoniae are major causes of urinary tract infections. While antibiotic resistance in these critical pathogens is a global concern, data from Africa remain sparse, cover short time frames, and aggregate multiple specimen types. Objective:To model antimicrobial resistance trends in urinary E coli and K pneumoniae isolates from 6 African countries between 2010 and 2022 and to project future resistance patterns. Design, Setting, and Participants:Data for this retrospective cross-sectional study were obtained from Pasteur Network clinical laboratories located in the capital cities of 5 African countries (Cameroon, Central African Republic [CAR], Madagascar, Morocco, and Senegal) and from 1 university hospital in Benin. Urine samples yielding E coli or K pneumoniae collected during routine clinical care were included. Data collection spanned 2008 to 2023, with a shared observation period from October 2014 to December 2021. Data were analyzed from March through December 2025. Main Outcomes and Measures:The primary outcome was resistance in E coli and K pneumoniae urinary isolates, measured as nonsusceptibility to aminopenicillins (for E coli), fluoroquinolones, third- and fourth-generation cephalosporins, β-lactam and β-lactamase inhibitor combinations, aminoglycosides, and carbapenems. Resistance trends were analyzed using logistic regression with generalized estimating equations. Results:A total of 44 367 urinary isolates (mean [SD] age of patients, 35.8 [30.2] years; 26 935 isolates from women among 42 839 samples with sex data [62.9%]) were included. Mean (SD) age ranged from 29.1 (30.5) years among patients with K pneumoniae-positive samples in Cameroon to 54.3 (23.4) years among patients with E coli-positive samples in Morocco. E coli-positive samples were more common in women, with the highest proportions in Madagascar (11 948 women among 16 137 patients [74.0%]) and CAR (1329 women among 1893 patients [70.2%]), whereas K pneumoniae positive samples showed no clear sex pattern. At study end, amoxicillin resistance in E coli exceeded 85% across sites (eg, 96.0% [95% CI, 93.5%-97.6%] in Morocco), and amoxicillin-clavulanate resistance surpassed 50% for E coli (eg, 84.9% [95% CI, 77.7%-90.1%] in Morocco) and K pneumoniae (eg, 96.1% [95% CI, 89.4%-98.7%] in Morocco) in most countries. E coli resistance to third-generation cephalosporins (3GCs) and fluoroquinolones surpassed 35% at study end, with increasing trends in most countries (eg, 34.5% [95% CI, 27.3%-42.6%] to 59.8% [95% CI, 55.7%-63.8%] for cefotaxime in Benin and 32.4% [95% CI, 25.1%-40.7%] to 75.9% [95% CI, 72.4%-79.1%] for norfloxacin in Senegal). For K pneumoniae, resistance to 3GCs increased in Cameroon, Madagascar, CAR, and Senegal, exceeding 50% in most settings (eg, 50.7% [95% CI, 45.6%-55.9%] to 76.6% [95% CI, 71.7%-80.9%] for cefotaxime in Madagascar). Rates remained stable in Benin and Morocco. Fluoroquinolone resistance increased in Cameroon, Senegal, and CAR (eg, 38.5% [95% CI, 25.7%-53.0%] to 65.8% [95% CI, 58.8%-72.2%] for ciprofloxacin in Senegal); remained high in Benin and Morocco; and decreased in Madagascar but remained elevated (eg, 63.7% [95% CI, 58.7%-68.3%] to 59.9% [95% CI, 54.1%-65.4%] for norfloxacin). For both bacteria, carbapenem resistance remained less than 18% (eg, 17.2% [95% CI, 11.8%-24.3%] for K pneumoniae resistance to ertapenem in Senegal), but resistance to ertapenem reached 28.0% (95% CI, 25.7%-30.5%) for E coli and 27.8% (95% CI, 22.0%-34.5%] for K pneumoniae in Madagascar. Projections suggest that 3GC and carbapenem resistance could exceed 90% by 2050 in most countries (eg, 2037 [95% CI, 2032-2053] for E coli resistance to imipenem in Benin). Conclusions and Relevance:In this study, elevated and increasing resistance levels were observed, underlining the urgent need for improved measures against antimicrobial resistance in Africa.

SUMMARY BACKGROUND Undernutrition is the leading risk factor for tuberculosis (TB), yet evidence on programmatic nutritional support during treatment is limited. Benin and Togo are neighboring West African counties. Benin provides in-kind food support to all people with drug-susceptible TB; neighbouring Togo does not. This created the opportunity for a natural experiment. METHODS We conducted a prospective cohort study at 13 sites in Benin and Togo (September 2023-June 2024). We compared recipients of nutritional support with non-recipients, using Beninese non-recipients as an internal comparison. Primary outcomes were ≥5% weight gain at month 2, change in 6-minute walk test (6MWT) distance, and pill-count adherence. We used multivariable regression adjusted for pre-specified covariates. RESULTS Of 769 participants, 450 received nutritional support and 319 did not. Recipients had higher odds of ≥5% weight gain at month 2 (adjusted odds ratio [aOR] 1.57, 95% CI 1.13–2.19) and ≥10% at month 6 (aOR 1.92, 1.35–2.74), greater 6MWT improvement (adjusted β 40.6 m, 26.5–54.6), and higher adherence (aOR 3.43, 1.81– 6.51). Mortality was lower among recipients (aOR 0.32, 0.11–0.93). Sputum conversion and treatment success did not differ. Beninese non-recipients resembled Togolese participants across outcomes. CONCLUSION Programmatic nutritional support was associated with improved weight gain, functional recovery, adherence, and lower mortality during TB treatment, supporting its integration into national TB programmes.

ABSTRACT The interpretation of genetic variants’ association (or not) with phenotypic resistance to newly introduced and repurposed antituberculosis drugs remains challenging, as many mutations detected by whole-genome sequencing (WGS) are classified as of uncertain significance (group 3) or not associated with resistance-interim (group 4) by the World Health Organization (WHO) mutation catalog v2. We evaluated the phenotypic impact of such variants on minimum inhibitory concentrations (MICs) for bedaquiline (BDQ), clofazimine (CFZ), delamanid (DLM), and pretomanid (PA) in Mycobacterium tuberculosis complex isolates from the multi-country DIAMA cohort in sub-Saharan Africa (SSA), which recruited RR/RS-TB patients naïve to these drugs. Among 1,475 isolates with available WGS data, 163 variants met eligibility criteria; due to viable strain unavailability, 89 isolates carrying 29 unique BDQ/CFZ-related and 60 unique DLM/PA-related variants were tested for MIC determination using broth microdilution. Additional structural modeling was performed to explore potential effects of amino-acid substitutions on protein stability. Among BDQ/CFZ-related variants, MICs above the critical concentrations (CCs) were consistently associated with mmpR5 variants, whereas variants in atpE , pepQ , and Rv1979c were not. DLM/PA variants ( ddn, fbiA–D, and fgd1 ) were frequently detected as non-fixed populations, yet rarely yielding MIC values above the CC. Predicted structural destabilization showed no consistent association with MIC values or variant fixation status. Under the conditions tested, phenotypic resistance was not detected for most group 3 and 4 variants detected by WGS. Our data provide evidence from SSA to support improved interpretation of resistance-associated mutations for new and repurposed antituberculosis drugs. IMPORTANCE Whole-genome sequencing increasingly detects Mycobacterium tuberculosis complex mutations classified by the World Health Organization (WHO) mutation catalog v2 as group 3 variants of uncertain significance or group 4 variants not associated with resistance-interim, limiting reliable prediction of resistance to new and repurposed antituberculosis drugs. By generating minimum inhibitory concentration (MIC) data for such variants identified in a multi-country sub-Saharan African cohort, this study provides phenotypic evidence to support future refinement and expansion of the WHO mutation catalog v2. Notably, mmpR5 variants associated with elevated bedaquiline/clofazimine MICs were identified in eight isolates, suggesting that some patients in this cohort may have harbored pre-existing resistance-associated variants yet remained potentially eligible for bedaquiline-containing regimens. These findings contribute to improving the interpretation of genomic resistance data and strengthening surveillance of resistance to bedaquiline, clofazimine, delamanid, and pretomanid.

National Tuberculosis Reference Laboratories (NTRLs) are central to tuberculosis (TB) control programs. Between 2018 and 2024, the Republic of Congo, a country of 6 million inhabitants, achieved a transformative strengthening of its TB diagnostic system, coordinated by the NTRL. Strategic investments, supported mainly by international partners, enabled a substantial decentralization of services, expanding the diagnostic network from 38 to 113 diagnostic and testing centers and increasing GeneXpert sites from 3 to 31. The expansion of the diagnostic network and specimen referral system was associated with a reduced structural gap in diagnostic coverage by extending access to GeneXpert testing to a larger number of peripheral and previously underserved centers. Critically, the establishment of a BSL-3 laboratory and the deployment of advanced assays like Xpert MTB/XDR ended the reliance on overseas testing by introducing in-country capacity for multidrug-resistant and pre-extensively drug-resistant TB detection. These systemic improvements were associated with significant positive outcomes, including an annual molecular testing surging from 11,609 in 2022 to over 27,000 in 2024 and bacteriological confirmation rates rising from 34 to 73%. This comprehensive laboratory systems strengthening, which also facilitated cross-programmatic initiatives like HIV and Mpox testing integration, underscores how sustained investment in infrastructure, logistics, and quality management is fundamental to improving case detection, surveillance, and progress toward the WHO End TB Strategy milestones.

Background:The World Health Organization-endorsed Xpert MTB/XDR assay provides a rapid method to detect resistance to isoniazid, fluoroquinolones, injectables aminoglycosides and ethionamide, yet evaluation of its performance, particularly in endemic settings, remains limited. Methods:We conducted a prospective multicentre study (June 2017 to March 2021) in nine sub-Saharan African countries, enrolling adults with pulmonary tuberculosis confirmed by Xpert MTB/RIF or Ultra. Xpert MTB/XDR results were compared to a World Health Organization-endorsed targeted next-generation sequencing reference used on the same sputum, with discordance resolved using whole genome sequencing and phenotypic drug-susceptibility testing when available. Diagnostic accuracy for each drug was calculated, also accounting for genotypic heteroresistance detection. Results:Among 1238 included patients, Xpert MTB/XDR demonstrated high specificity (≥98%) across all drugs yet showed variable sensitivity, detecting 606 out of 637 isoniazid-resistant (95%, 95% CI 94-97%), 22 out of 33 fluoroquinolones-resistant (67%, 95% CI 48-81%) and 159 out of 279 ethionamide-resistant (57%, 95% CI 51-63%) samples. The assay reliably detected most common resistance-conferring mutations, such as katG_S315T, fabG1_C-15T, and gyrA_A90V and D94G, yet failed to detect low-frequency heteroresistance (≤10-35%) and off-target mutations, mostly for ethionamide. Amikacin resistance was rare (0.2%). Sensitivity for fluoroquinolones was higher (78%) among rifampicin-resistant samples, highlighting its utility as a reflex test in rifampicin-resistant patients. Conclusions:Xpert MTB/XDR offers rapid diagnosis of resistance with high specificity. While limitations in detecting low-frequency and off-target variants affect its sensitivity, most frequent, fixed in-target mutations are readily detected. Future studies should evaluate strategies to integrate Xpert MTB/XDR with other diagnostic approaches in national tuberculosis programmes.

BACKGROUND:The World Health Organization recommends evaluation of all household contacts (HHC) of index tuberculosis (TB) patients for TB disease (TBD) and TB infection (TBI). Tests to identify TBI and TBD are preferred but can be skipped in persons living with HIV and children <5 years. There is equipoise on the need for these tests in other HHC. METHODS:We conducted a superiority, open label cluster-randomized trial in Benin and Brazil to compare three strategies to evaluate HHC aged 5-50 of persons newly diagnosed with drug susceptible pulmonary TBD: Standard: tuberculin skin testing (TST) for TBI and if positive, chest X-ray (CXR) to rule out TBD; rapid molecular test (RMT): same as Standard, except CXR replaced by an RMT; and No-TST: CXR for all but no TST. Randomization was computer-generated and stratified by country, in blocks of variable length. The primary outcome was TB preventive therapy (TPT) initiation among HHC considered eligible (positive TST, if done, and no evidence of TBD on CXR or RMT). Secondary outcomes were: completion of investigations to detect TBI and TBD, detection of TBD, TPT completion, severe adverse events, and societal costs. RESULTS:Among 1,589 participating HHC enrolled from 29 January 2020, to 30 November 2022, 474 were randomized to the standard, 583 to the RMT, and 532 to the no-TST strategies; all were included in the analyses. Of 848 HHC considered eligible for TPT, 802 (94.6%) initiated TPT, with no difference between strategies (95%, 94%, and 95% for the standard, RMT, and no-TST strategies, respectively). Of the secondary outcomes, protocol-mandated investigations to detect TBI and exclude possible TBD were completed for 93.4% overall, with slight differences between arms (93%, 95%, and 93% for the standard, RMT, and no-TST strategies, respectively). Adverse events resulting in discontinuation of TPT occurred in 3 (0.4%) participants in total (with 1, 0, and 2 events among participants in the Standard, RMT, and no-TST arms, respectively). The proportion completing TPT was similar with Standard and RMT strategies but was 13% lower (95% confidence interval: 3% to 23% lower) with the No-TST strategy. Societal costs per HHC completing investigations were $61 ($56-$65) with the standard strategy, compared to $52 ($49-$55) with the RMT strategy and $74 ($72-$77) with the no-TST strategy. CONCLUSION:This randomized trial provides high-quality evidence that TST followed by selected use of CXR or an RMT to exclude disease can achieve high rates of TPT initiation at reasonable costs. A limitation of the trial is the potential study effect, which may have affected adherence by providers and HHCs. RMT could replace CXR in the management of HHC in resource limited settings. REGISTRATION:clinicaltrials.gov NCT04528823.

BACKGROUND:Tuberculosis (TB) is a leading cause of morbidity and mortality in people living with human immunodeficiency virus (HIV). Data are very scarce on the burden of TB in HIV patients in Sub-saharan African populations. This study aimed to determine the prevalence of pulmonary tuberculosis (PTB) and associated factors among people living with human immunodeficiency virus (HIV) in three West African countries: Benin, Guinea, and Senegal. METHODS:A cross-sectional study was conducted among people living with HIV in three outpatient care centres (one in each country). All HIV-positive patients included in this study were routinely screened for PTB using microscopy, GeneXpert and culture. Participants free of TB were reassessed clinically and biologically six months later. Data were analyzed using R-3.4.3 software. Logistic regression was used to identify factors associated with PTB. RESULTS:A total of 2859 participants were enrolled in the study, of whom 2820 were screened for TB, 1000 were ARV-naive (35.46%), and 1820 were on ARV prior to screening (64.54%). A total of 127 cases of bacteriologically confirmed PTB (BCPTB) were diagnosed: 117 at baseline and 10 at the 6-month visit. The overall prevalence of BCPTB was 7.90% [95% CI: 6.38-9.75] for ARV-naive participants and 2.64% [95% CI: 1.99-3.48] for participants on ARV at the time of screening. Participants from Guinea were more likely to be diagnosed with TB (OR: 2.95 [95% CI: 1.60-5.45], p=0.001). Underweight HIV-positive patients had higher odds of TB diagnosis (OR: 2.09 [95% CI: 1.40-3.12], p<0.001), while overweight/obesity was associated with lower odds of TB (OR: 0.35 [95% CI: 0.15-0.81], p=0.015). Other factors associated with BCPTB in HIV patients were male sex (OR: 1.81 [95% CI: 1.18-2.77], p=0.007), CD4 count <200/ml (OR: 2.24 [95% CI: 1.15-4.37], p=0.018), and irregular disease follow-up (OR: 2.57 [95% CI: 1.29-5.15], p=0.018). CONCLUSION:The prevalence of TB among people living with HIV is high in Benin, Guinea and Senegal. These results highlight the need to improve TB screening and diagnosis in PLHIV, especially in ARV-naive patients.

National Tuberculosis Reference Laboratories (NTRLs) are central to tuberculosis (TB) control programs. Between 2018 and 2025, the Republic of Congo, a country of 6 million inhabitants, achieved a transformative strengthening of its TB diagnostic system, coordinated by the NTRL. Strategic investments, supported mainly by international partners, enabled a substantial decentralization of services, expanding the diagnostic network from 40 to 113 facilities and increasing GeneXpert sites from 3 to 31. This was bolstered by a national sample transport system that slashed diagnostic inequities and a robust External Quality Assessment framework to ensure reliability. Critically, the establishment of a BSL-3 facility and the deployment of advanced assays like Xpert MTB/XDR ended the reliance on overseas testing by introducing in-country capacity for multidrug-resistant and extensively drug-resistant TB detection. These systemic improvements directly translated into significant outcomes including an annual molecular testing surging from 11,609 to over 27,000, bacteriological confirmation rates rose from 34 to 73%. This comprehensive laboratory systems strengthening, which also facilitated cross-programmatic initiatives like HIV, Mpox testing integration, underscores how sustained investment in infrastructure, logistics, and quality management is fundamental to improving case detection, surveillance, and progress toward the WHO End TB Strategy milestones.

Tuberculosis remains a leading infectious disease killer in the World Health Organization African Region, with 2.5 million cases and 404,000 deaths in 2023, including 112,000 people with HIV. There is slow progress with only 42% of the 75% targeted reduction in death by 2025. Out of 60,266 estimated multidrug-resistant TB cases in 2023, only 22,515 were notified. Laboratory diagnostic services in the African region still need urgent attention. By 2005, the new smear-positive case detection rate was nearly 51%, falling short of the 70% target. By 2015, the benchmark for one microscopy center per 100,000 population was reached in some Member States, but gaps remained in culture and drug susceptibility testing coverage. Molecular tests were adopted, however there is slow uptake among countries to use them as initial diagnostic tests. The Global Laboratory Initiatives were established in 2007 and 2013 globally and in the WHO African Region respectively to enhance access to quality-assured TB laboratory services. The WHO TB Supranational Reference Laboratory (SRL) Network was established in 1994 and expanded to the African region, including South Africa, Uganda, and Benin. The nomination of Mozambique and Rwanda in 2021 as candidate SRLs aims to strengthen this network. Future perspectives involve leveraging the established TB laboratory networks to integrate systems for diagnosing multiple diseases while enhancing efficiency. Advocacy for increased funding is vital for sustaining gains in the laboratory capacities, advancing universal health coverage and enhancing health outcomes in the African region. Here we discuss the TB laboratory capacity building in the WHO African region, focusing on the past, present and the future perspectives. We suggest recommendation towards sustaining and strengthening the existing achievements, while accelerating the laboratory interventions towards the End TB Strategy.

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.

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.

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.

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.

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.

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.

Background Childhood tuberculosis (TB) accounts for 12% of the 10.6 million incident cases of TB globally, and 16% of all TB-related mortality. The majority of childhood TB cases and deaths occur in TB-endemic countries where difficulties with confirming TB diagnosis with conventional sputum-based approaches contribute to poor outcomes. We present the methodological approaches and progress report from a study investigating the added value of non-sputum-based approaches for the diagnosis of TB in children in West Africa. Methods This is a multi-country study recruiting children (age <15 years) with presumptive pulmonary TB at study sites in The Gambia, Ghana, and Benin. Participants undergo standardised conventional clinical, radiologic and microbiological investigations for TB diagnosis. In addition, early morning stool samples are simultaneously collected for testing with Xpert Ultra (‘stool Xpert’), while Computer-aided Detection for TB-version 7 (’CAD4TBv7’; Delft Imaging, Netherlands) abnormality score are derived for their digital chest radiographs (CXR). Bayesian latent class analysis will be used to determine the added value of the non-sputum-based tests in term of relative increases in sensitivity and specificity by combining CAD4TBv7 and stool Xpert results with conventional methods. Results Recruitment and investigation of eligible study participant have commenced at the three study sites, with more than 100 children enrolled from January 2023 till date. The CAD4TBv7 system has been set up at the Gambia study site. Digital CXR from the two other study sites are de-identified and transferred electronically to The Gambia, using an encrypted internet-based file transfer software, for CAD4TBv7 scoring. A blinded senior radiologist also provides independent assessment of the likelihood of TB on each CXR. Conclusion This study presents an opportunity to objectively determine how many additional childhood TB cases can be detected if CAD4TBv7 abnormality score and stool Xpert are combined with conventional diagnostic tests. Funding: EDCTP-TALENT PhD Fellowship (Ref: PSIA2020AGDG-3317-TALENT)

Introduction Treatment as prevention (TasP) and pre-exposure prophylaxis (PrEP) could impact the HIV epidemic among Female Sex Workers (FSW) but their cost-effectiveness is uncertain in this group. This study aims to model the cost-effectiveness of TasP and PrEP among FSW in Cotonou, Benin. Methods A demonstration study assessed TasP and PrEP use among FSW in Cotonou. A dynamic HIV transmission model was developed to estimate the impact of this intervention and published elsewhere. Incremental economic costs of the study were collected prospectively capturing both provider and FSW costs. The incremental cost-effectiveness ratio per HIV infection and disability-adjusted life years (DALY) averted were estimated over a 20 year time horizon with costs converted to USD 2020 and both costs and DALYs discounted at 4.5% per year. Different cost scenarios were modelled to investigate the cost-effectiveness of the intervention as delivered by the government reflecting current day implementation and resource costs. Results The mean provider annual economic cost per FSW on TasP was $646, with an initiation cost of $347 and mean annual user costs were $16. The mean initiation costs for PrEP were $268, mean annual provider costs were $359-$499 and annual user cost $15-$21 depending on adherence level. TasP was found to be cost saving for all cost scenarios examined compared to routine HIV care for FSW. PrEP was not cost-effective for any cost scenario, population coverage or adherence level examined. Conclusion Our results support TasP but not PrEP for FSW in our setting. A streamlined, outreach delivery model with reduced costs should be investigated to assess its cost-effectiveness in this setting. ### Competing Interest Statement The authors have declared no competing interest. ### Funding Statement Funded by the Bill and Melinda Gates Foundation (Grant no. OPP1098973). Complementary funding was provided by the Canadian Institutes of Health Research (Grant numbers ROH-115205 and FDN-143218). Truvada for pre-exposure prophylaxis was provided free of charge by Gilead Sciences. ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: The ethics committee of the CHU de Quebec University Laval, Quebec, Canada, and the Benin National Ethics Committee for Health Research gave ethical approval for this work. I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes All data produced in the present study are available upon reasonable request to the authors