Diagnosing paediatric tuberculosis (TB) remains challenging. Currently available diagnostic tests have limited accuracy, and most sampling methods are invasive. In 2021, the World Health Organisation (WHO) endorsed the use of molecular WHO-recommended rapid diagnostic tests (mWRDs) with stool as an initial diagnostic tool for paediatric TB. In this study, we evaluated the diagnostic test accuracy (DTA) of stool samples processed with the Stool Processing Kit (SPK), one of three centrifugation-free methods available at the time. We conducted a multi-centre prospective diagnostic validation study in South Africa, Tanzania, Malawi, Mozambique, and India. Children (< 15 years) under investigation for TB provided at least two (induced) sputum samples at enrolment, one stool sample, and one nasopharyngeal aspirate (NPA) if aged < 5 years and a chest x-ray. TB testing included Xpert® MTB/RIF Ultra (Ultra) and culture. Diagnostic classification followed NIH consensus statements. Stool samples were processed using the SPK and tested with Ultra. We calculated DTA in the overall cohort and predefined subgroups of interest. Out of 5313 children screened, 975 were enrolled, and data from 817 children recruited between January 2019 and June 2021 were analysed. The overall microbiological confirmation rate was 203/817 (24.9

Background Centrifuge-free processing methods support stool Xpert Ultra testing for childhood tuberculosis, but data on their accuracy, acceptability, and usability are limited.Methods We conducted a prospective evaluation of stool Xpert Ultra in India, South Africa, and Uganda with 3 methods: the Stool Processing Kit (SPK), the Simple One-Step method (SOS), and the Optimized Sucrose Flotation method (OSF). Children <15 years old with presumptive tuberculosis underwent sputum testing with Xpert Ultra and culture. We compared the accuracy of each method against a microbiological reference standard (tuberculosis if Xpert Ultra or culture positive) and a composite reference standard (tuberculosis if confirmed or unconfirmed tuberculosis). We surveyed laboratory staff to assess the acceptability and usability of the methods.Results We included 607 children, with a median age of 3.5 years (interquartile range, 1.3-7 years); 15.5% were human immunodeficiency virus positive. Against the microbiological reference standard, the sensitivities of SPK, SOS, and OSF were 36.9% (95% confidence interval, 28.6%-45.8%), 38.6% (17.2%-51.0%), and 31.3% (20.2%-44.1%), respectively, and the specificities, 98.2% (96.4%-99.3%), 97.3% (93.7%-99.1%), and 97.1% (93.3%-99%). The methods were acceptable and usable, but SOS was reported as most feasible to implement in a peripheral facility. Across methods, sensitivities increased among children who were culture positive (range, 55.0%-77.3%) and were low (13%-16.7%) against the composite reference standard. Adding stool Xpert Ultra increased sensitivity from 0% (OSF) to 11.8% (SPK/SOS), compared with sputum alone.Conclusions Stool processing methods for Xpert Ultra were acceptable and usable and performed similarly, with highest sensitivity among children with culture-positive tuberculosis.

BACKGROUND:Stool-based molecular assays for childhood tuberculosis (TB) diagnosis have shown promise as an alternative to respiratory sample testing. While implementation is underway, evidence on cost-effectiveness is needed. Therefore, we aimed to evaluate the costs of stool testing with Xpert Ultra and model the cost-effectiveness of implementation scenarios at lower levels of care. METHODS:We measured costs for three new stool processing methods: Simple One-Step (SOS), Stool Processing Kit, and Optimized Sucrose Flotation. Each method mixed stool with Xpert Sample Reagent buffer, incubated to allow sedimentation, and then dispensed the supernatant into the Xpert Ultra cartridge. While the other methods required additional buffer and supplies, SOS used only the Sample Reagent. Using the least costly method, we modeled implementation for children under 5 years with presumptive TB at primary health clinics or district hospitals in Uganda. Clinical diagnosis with treatment-decision algorithms was compared to stool testing at primary clinics, stool testing at primary clinics with referral to district hospitals if negative, or evaluation only at district hospitals with Xpert Ultra testing on respiratory samples. Using decision-tree models, we calculated the cost in international dollars (I$) per life-years saved (LYS) and the incremental cost-effectiveness ratio (ICER) assessed against the country-specific willingness to pay threshold. One-way and probabilistic sensitivity analyses were conducted. RESULTS:SOS was the least costly stool processing method. Compared to diagnosis with only treatment-decision algorithms, the ICER of SOS/Ultra at primary clinics was I$1041.71/LYS, SOS/Ultra with referral was I$874.82/LYS, while the district hospital strategy was dominated. Sensitivity analyses showed stool testing was cost-effective compared to only clinical diagnosis if TB prevalence at primary clinics was above 5.7%, with higher diagnostic accuracy of stool-based testing, or lower testing costs. CONCLUSIONS:For young children, stool testing at primary clinics, with or without referral to district hospitals, lowered costs in relation to lives saved compared to implementing at district hospitals alone or only clinical diagnosis using the treatment-decision algorithms.

Introduction: Despite causing high mortality, tuberculosis (TB) in children is often undiagnosed. We investigated optimal microbiological sampling and testing strategies to confirm TB diagnosis in children across five low-and middle-income countries.Methods: RaPaed-TB was a diagnostic accuracy study enrolling children (<15 years) with presumptive TB. Respiratory and extrapulmonary specimens were analysed by culture and Xpert®MTB/RIF Ultra (Ultra). Children were categorised following NIH-consensus definitions.Findings: Among 965 children (median age 5·0 years [IQR: 1·8-9·0]; 16·1% [155/965] with HIV [CHIV]; 11·4% [110/965] had severe acute malnutrition [SAM]), 24·8% (239/965) had confirmed, 29·2% (282/965) unconfirmed, and 46·0% (444/965) unlikely TB. Most children were confirmed using Ultra (82·0% [196/239]: 46·0% [110/239] positive on Ultra and culture, 36·0% [86/239] on Ultra alone; 18·0% [43/239] on culture alone), with "trace" being the most common semi-quantitative result (39·3%, 77/196).Serial sampling and testing yielded high confirmation rates (1 specimen: 20·3% [97/478] versus ≥2 specimens: 20·3% [97/478]), especially in children <5 years (n=129): 19 were Ultra-positive on 1st nasopharyngeal aspirate (14·7% [19/129]), an additional 22 (+17·1%) were Ultra-positive on 1st sputum, and further two (+1·2%) on culture. An additional seven (+5·5%) were culture-positive on 2nd sputum.Interpretation: High rates of microbiological confirmation can be achieved in children using standardised serial sampling and multiple testing. Optimal strategies may differ for high-risk groups, such as CHIV or SAM.Funding: This project is part of the EDCTP2 programme supported by the European Union (grant number RIA2016MC -1623 – RaPaed TB); further funding is contributed by the German Center for Infection Research (DZIF); and Beckman Coulter, Inc. Cepheid, Inc. provided test kits and GeneXpert platforms at no cost to the Consortium.Declaration of Interest: LO, VPV, ZFS, IS, ENN, AM, DB, SV, CK, RS, MN, TDM, LSL, AR, RS, LLC, PN, AT, SMG, MH, CC, HJZ, JSM, NH declare receiving grant funding for this work from EDCTP, DZIF, and from Beckman Coulter to the study to their respective institutions. Cepheid provided testing kits at no cost. Additionally, ZFS and HJZ declare funding from SA-MRC Unit on Child and Adolescent Health to their institution. LO was supported by an ESPID Fellowship Award.Ethical Approval: The study was approved by the coordinators' and local investigators' ethics committees.

BACKGROUND:Despite causing high mortality worldwide, paediatric tuberculosis is often undiagnosed. We aimed to investigate optimal testing strategies for microbiological confirmation of tuberculosis in children younger than 15 years, including the yield in high-risk subgroups (eg, children younger than 5 years, with HIV, or with severe acute malnutrition [SAM]). METHODS:For this secondary analysis, we used data from RaPaed-TB, a multicentre diagnostic accuracy study evaluating novel diagnostic assays and testing approaches for tuberculosis in children recruited from five health-care centres in Malawi, Mozambique, South Africa, Tanzania, and India conducted between Jan 21, 2019, and June 30, 2021. Children were included if they were younger than 15 years and had signs or symptoms of pulmonary or extrapulmonary tuberculosis; they were excluded if they weighed less than 2 kg, had received three or more doses of anti-tuberculosis medication at time of enrolment, were in a condition deemed critical by the local investigator, or if they did not have at least one valid microbiological result. We collected tuberculosis-reference specimens via spontaneous sputum, induced sputum, gastric aspirate, and nasopharyngeal aspirates. Microbiological tests were Xpert MTB/RIF Ultra (hereafter referred to as Ultra), liquid culture, and Löwenstein-Jensen solid culture, which were followed by confirmatory testing for positive cultures. The main outcome of this secondary analysis was categorising children as having confirmed tuberculosis if culture or Ultra positive on any sample, unconfirmed tuberculosis if clinically diagnosed, and unlikely tuberculosis if neither of these applied. FINDINGS:Of 5313 children screened, 975 were enrolled, of whom 965 (99%) had at least one valid microbiological result. 444 (46%) of 965 had unlikely tuberculosis, 282 (29%) had unconfirmed tuberculosis, and 239 (25%) had confirmed tuberculosis. Median age was 5·0 years (IQR 1·8-9·0); 467 (48%) of 965 children were female and 498 (52%) were male. 155 (16%) of 965 children had HIV and 110 (11%) children had SAM. 196 (82%) of 239 children with microbiological detection tested positive on Ultra. 110 (46%) of 239 were confirmed by both Ultra and culture, 86 (36%) by Ultra alone, and 43 (18%) by culture alone. 'Trace' was the most common semiquantitative result (93 [40%] of 234). 481 (50%) of 965 children had only one specimen type collected, 99 (21%) of whom had M tuberculosis detected. 484 (50%) of 965 children had multiple specimens collected, 141 (29%) of whom were positive on at least one specimen type. Of the 102 children younger than 5 years with M tuberculosis detected, 80 (78%) tested positive on sputum. 64 (80%) of 80 children who tested positive on sputum were positive on sputum alone; 61 (95%) of 64 were positive on induced sputum, two (3%) of 64 were positive on spontaneous sputum, and one (2%) was positive on both. INTERPRETATION:High rates of microbiological confirmation of tuberculosis in children can be achieved via parallel sampling and concurrent testing procedures. Sample types and choice of test to be used sequentially should be considered when applying to groups such as children younger than 5 years, living with HIV, or with SAM. FUNDING:European and Developing Countries Clinical Trials Partnership programme, supported by the EU, the UK Medical Research Council, Swedish International Development Cooperation Agency, Bundesministerium für Bildung und Forschung, the German Center for Infection Research, and Beckman Coulter.

BACKGROUND:Childhood tuberculosis remains a major cause of morbidity and mortality in part due to missed diagnosis. Diagnostic methods with enhanced sensitivity using easy-to-obtain specimens are needed. We aimed to assess the diagnostic accuracy of the Cepheid Mycobacterium tuberculosis Host Response prototype cartridge (MTB-HR), a candidate test measuring a three-gene transcriptomic signature from fingerstick blood, in children with presumptive tuberculosis disease. METHODS:RaPaed-TB was a prospective diagnostic accuracy study conducted at four sites in African countries (Malawi, Mozambique, South Africa, and Tanzania) and one site in India. Children younger than 15 years with presumptive pulmonary or extrapulmonary tuberculosis were enrolled between Jan 21, 2019, and June 30, 2021. MTB-HR was performed at baseline and at 1 month in all children and was repeated at 3 months and 6 months in children on tuberculosis treatment. Accuracy was compared with tuberculosis status based on standardised microbiological, radiological, and clinical data. FINDINGS:5313 potentially eligible children were screened, of whom 975 were eligible. 784 children had MTB-HR test results, of whom 639 had a diagnostic classification and were included in the analysis. MTB-HR differentiated children with culture-confirmed tuberculosis from those with unlikely tuberculosis with a sensitivity of 59·8% (95% CI 50·8-68·4). Using any microbiological confirmation (culture, Xpert MTB/RIF Ultra, or both), sensitivity was 41·6% (34·7-48·7), and using a composite clinical reference standard, sensitivity was 29·6% (25·4-34·2). Specificity for all three reference standards was 90·3% (95% CI 85·5-94·0). Performance was similar in different age groups and by malnutrition status. Among children living with HIV, accuracy against the strict reference standard tended to be lower (sensitivity 50·0%, 15·7-84·3) compared with those without HIV (61·0%, 51·6-69·9), although the difference did not reach statistical significance. Combining baseline MTB-HR result with one Ultra result identified 71·2% of children with microbiologically confirmed tuberculosis. INTERPRETATION:MTB-HR showed promising diagnostic accuracy for culture-confirmed tuberculosis in this large, geographically diverse, paediatric cohort and hard-to-diagnose subgroups. FUNDING:European and Developing Countries Clinical Trials Partnership, UK Medical Research Council, Swedish International Development Cooperation Agency, Bundesministerium für Bildung und Forschung; German Center for Infection Research (DZIF).

Four moderate-complexity automated nucleic acid amplification tests for the diagnosis of tuberculosis are reported as having laboratory analytical and clinical performance similar to that of the Cepheid Xpert MTB/RIF assay. These assays are the Abbott RealTime MTB and RealTime MTB RIF/INH Resistance, Becton Dickinson MAX MDR-TB, the Hain Lifescience/Bruker FluoroType MTBDR, and the Roche cobas MTB and MTB RIF/INH assays. The study compared feasibility, ease of use, and operational charac-teristics of these assays/platforms. Manufacturer input was obtained for technical characteristics. Laboratory operators were requested to complete a questionnaire on the assays' ease of use. A time-in -motion analysis was also undertaken for each platform. For ease-of-use and operational requirements, the BD MAX MDR-TB assay achieved the highest scores (86% and 90%) based on information provided by the user and manufacturer, respectively, followed by the cobas MTB and MTB-RIF/INH assay (68% and 86%), the FluoroType MTBDR assay (67% and 80%), and the Abbott RT-MTB and RT MTB RIF/INH assays (64% and 76%). The time-in-motion analysis revealed that for 94 specimens, the RealTime MTB assay required the longest processing time, followed by the cobas MTB assay and the FluoroType MTBDR assay. The BD MAX MDR-TB assay required 4.6 hours for 22 specimens. These diagnostic assays exhibited different strengths and weaknesses that should be taken into account, in addition to affordability, when considering placement of a new platform. (J Mol Diagn 2023, 25: 46-56; https://doi.org/ 10.1016/j.jmoldx.2022.10.001)

Introduction: An estimated 1.2 million children develop tuberculosis (TB) every year with 240,000 dying because of missed diagnosis. Existing tools suffer from lack of accuracy and are often unavailable. Here, we describe the scientific and clinical methodology applied in RaPaed-TB, a diagnostic accuracy study. Methods: This prospective diagnostic accuracy study evaluating several candidate tests for TB was set out to recruit 1000 children <15 years with presumptive TB in 5 countries (Malawi, Mozambique, South Africa, Tanzania, India). Assessments at baseline included documentation of TB signs and symptoms, TB history, radiography, tuberculin skin test, HIV testing and spirometry. Respiratory samples for reference standard testing (culture, Xpert Ultra) included sputum (induced/spontaneous) or gastric aspirate, and nasopharyngeal aspirate (if <5 years). For novel tests, blood, urine and stool were collected. All participants were followed up at months 1 and 3, and month 6 if on TB treatment or unwell. The primary endpoint followed NIH-consensus statements on categorization of TB disease status for each participant. The study was approved by the sponsor’s and all relevant local ethics committees. Discussion: As a diagnostic accuracy study for a disease with an imperfect reference standard, Rapid and Accurate Diagnosis of Pediatric Tuberculosis Disease (RaPaed-TB) was designed following a rigorous and complex methodology. This allows for the determination of diagnostic accuracy of novel assays and combination of testing strategies for optimal care for children, including high-risk groups (ie, very young, malnourished, children living with HIV). Being one of the largest of its kind, RaPaed-TB will inform the development of improved diagnostic approaches to increase case detection in pediatric TB.

Background In low-resource settings, antimicrobial resistance (AMR) is detected by traditional culture-based methods and ensuring the quality of such services is a challenge. The AMR Scorecard provides laboratories with a technical assessment tool for strengthening the quality of bacterial culture, identification, and antimicrobial testing procedures. Objective To evaluate the performance of the AMR Scorecard in 11 pilot laboratory evaluations in three countries also assessed with the Stepwise Laboratory Quality Improvement Process Towards Accreditation (SLIPTA) checklist. Methods Pilot laboratory evaluations were conducted in Cameroon, Ethiopia and Kenya between February 2019 and March 2019. Assessors with previous SLIPTA and microbiology experience were trained. Assessors performed the laboratory assessments using the SLIPTA and AMR Scorecard tools. Results Weaknesses in technical procedures and the quality management systems were identified in all areas and all laboratories. Safety had the highest mean performance score (SLIPTA: 68%; AMR Scorecard: 73%) while management review had the lowest (SLIPTA: 32%; AMR Scorecard: 8%) across all laboratories. The AMR Scorecard scores were generally consistent with SLIPTA scores. The AMR Scorecard identified technical weaknesses in AMR testing, and SLIPTA identified weaknesses in the quality management systems in the laboratories. Conclusion Since the AMR Scorecard identified important gaps in AMR testing not detected by SLIPTA, it is recommended that microbiology laboratories use SLIPTA and the AMR Scorecard in parallel when preparing for accreditation. Expanding the use of the AMR Scorecard is a priority to address the need for quality clinical microbiology laboratory services in support of optimal patient care and AMR surveillance.

The diagnosis of latent tuberculosis (TB) infection (LTBI) is critical to improve TB treatment and control, and the T-SPOT. TB test is a commercial enzyme-linked immunosorbent spot assay used for this purpose. The objective of the study was to increase automation and extend the time between blood collection and processing for the T-SPOT. TB test from 0 to 8 h to 0 to 54 h.

Reducing diagnostic delay is key toward decreasing tuberculosis-associated deaths in people living with human immunodeficiency virus. In tuberculosis patients with retrospective urine testing, the point-of-care Fujifilm SILVAMP TB LAM (FujiLAM) could have rapidly diagnosed tuberculosis in up to 89% who died. In FujiLAM negative patients, the probability of 12-week survival was 86-97%.

Failure to rapidly identify drug-resistant tuberculosis (TB) increases the risk of patient mismanagement, the amplification of drug resistance, and ongoing transmission. We generated comparative analytical data for four automated assays for the detection of TB and multidrug-resistant TB (MDR-TB): Abbott RealTime MTB and MTB RIF/INH (Abbott), Hain Lifescience FluoroType MTBDR (Hain), BD Max MDR-TB (BD), and Roche cobas MTB and MTB-RIF/INH (Roche). We included Xpert MTB/RIF (Xpert) and GenoType MTBDRplus as comparators for TB and drug resistance detection, respectively. We assessed analytical sensitivity for the detection of the Mycobacterium tuberculosis complex using inactivated strains (M. tuberculosis H37Rv and M. bovis) spiked into TB-negative sputa and computed the 95% limits of detection (LOD95). We assessed the accuracy of rifampicin and isoniazid resistance detection using well-characterized M. tuberculosis strains with high-confidence mutations accounting for.85% of first-line resistance mechanisms globally. For H37Rv and M. bovis, we measured LOD95 values of 3,781 and 2,926 (Xpert), 322 and 2,182 (Abbott), 826 and 4,301 (BD), 10,398 and 23,139 (Hain), and 2,416 and 2,136 (Roche) genomes/ml, respectively. Assays targeting multicopy genes or targets (Abbott, BD, and Roche) showed increased analytical sensitivity compared to Xpert. Quantification of the panel by quantitative real-time PCR prevents the determination of absolute values, and results reported here can be interpreted for comparison purposes only. All assays showed accuracy comparable to that of Genotype MTBDRplus for the detection of rifampicin and isoniazid resistance. The data from this analytical study suggest that the assays may have clinical performances similar to those of WHO-recommended molecular TB and MDR-TB assays.

Implementing new diagnostics in public health programs can involve difficult trade-off decisions between individual patient benefits and public health considerations. Such decision-making processes are often not documented and may not include engagement of affected communities. This paper examines the perspectives of stakeholders on the trade-off between over-treatment and missed diagnosis captured during decision-making workshops on the transition from use of Xpert MTB/RIF to diagnose tuberculosis to Xpert MTB/RIF Ultra in Kenya and Swaziland. Xpert MTB/RIF Ultra has an overall increase in sensitivity but a decrease in specificity when compared to its predecessor. We conducted a qualitative study using four focus group discussions with a total of 47 participants and non-participant observation. The analysis reveals how participants deemed Xpert MTB/RIF Ultra's reduced specificity vis-à-vis its increased sensitivity to be an acceptable trade-off. The way participants assessed this trade-off was shaped by their experiences with the general uncertainty of all diagnostic tests, alternative testing options, historical evolution of diagnostic practices, epidemiological factors and resource constraints. In assessing the trade-off community and individual benefit and harm was frequently discussed together. Qualitative research on stakeholder engagement activities for diagnostic development and implementation can identify everyday experiences and situate assessments and perspectives of key stakeholders and as such aid in decision-making, improving implementation as well as patient outcomes. Further research is needed on the intended and unintended consequences of such engagement activities, how findings are being incorporated by decision-makers, and the impact on programmatic implementation.

FujiLAM point-of-care rapid urine test for TB detects a large proportion of pulmonary and traditionally difficult-to-diagnose extra-pulmonary forms of TB in hospitalised patients with advanced HIVhttp://bit.ly/36Dl0Eo

Background Most tuberculosis-related deaths in people with HIV could be prevented with earlier diagnosis and treatment. The only commercially available tuberculosis point-of-care test (Alere Determine TB LAM Ag [AlereLAM]) has suboptimal sensitivity, which restricts its use in clinical practice. The novel Fujifilm SILVAMP TB LAM (FujiLAM) assay has been developed to improve the sensitivity of AlereLAM. We assessed the diagnostic accuracy of the FujiLAM assay for the detection of tuberculosis in hospital inpatients with HIV compared with the AlereLAM assay. Methods For this diagnostic accuracy study, we assessed biobanked urine samples obtained from the FIND Specimen Bank and the University of Cape Town Biobank, which had been collected from hospital inpatients (aged >= 18 years) with HIV during three independent prospective cohort studies done at two South African hospitals. Urine samples were tested using FujiLAM and AlereLAM assays. The conduct and reporting of each test was done blind to other test results. The primary objective was to assess the diagnostic accuracy of FujiLAM compared with AlereLAM, against microbiological and composite reference standards (including clinical diagnoses). Findings Between April 18, 2018, and May 3, 2018, urine samples from 968 hospital inpatients with HIV were evaluated. The prevalence of microbiologically-confirmed tuberculosis was 62% and the median CD4 count was 86 cells per mu L. Using the microbiological reference standard, the estimated sensitivity of FujiLAM was 70.4% (95% CI 53.0 to 83.1) compared with 42.3% (31.7 to 51.8) for AlereLAM (difference 28.1%) and the estimated specificity of FujiLAM was 90.8% (86.0 to 94.4) and 95.0% (87.7-98.8) for AlereLAM (difference -4.2%). Against the composite reference standard, the specificity of both assays was higher (95.7% [92.0 to 98.0] for FujiLAM vs 98.2% [95.7 to 99.6] for AlereLAM; difference -2.5%), but the sensitivity of both assays was lower (64.9% [50.1 to 76.7] for FujiLAM vs 38.2% [28.1 to 47.3] for AlereLAM; difference 26.7%). Interpretation In comparison to AlereLAM, FujiLAM offers superior diagnostic sensitivity, while maintaining specificity, and could transform rapid point-of-care tuberculosis diagnosis for hospital inpatients with HIV. The applicability of FujiLAM for settings of intended use requires prospective assessment. Copyright (C) 2019 The Author(s). Published by Elsevier Ltd.

Growth-based drug susceptibility testing (DST) is the reference standard for diagnosing drug-resistant tuberculosis (TB), but standard time to result (TTR) is typically ≥ 3 weeks. Rapid tests can reduce that TTR to days or hours, but accuracy may be lowered.

The End Tuberculosis Strategy of the World Health Organization (WHO) calls for the early diagnosis of tuberculosis (TB) and use of universal drug susceptibility testing (DST) in order to start patients on the most effective treatment regimen as early as possible. DST using solid or liquid media and rapid molecular-based DST to detect drug-resistant TB are available and endorsed by WHO; however, in 2015, WHO reported that among new cases of bacteriologically confirmed TB, only 12% had undergone DST [1]. Most national tuberculosis programmes do not offer universal DST [2], and in 2015, 12 countries reported no capacity to perform phenotypic DST [1] while 28 countries had neither in-country capacity nor a linkage with a partner laboratory for second-line DST. A new multinational study of the noncommercial MODS assay shows excellent performance in detecting M/XDR-tuberculosis The authors would like to acknowledge the site investigators, Valeriu Crudu (Phthisiopneumology Institute), Tommie Victor (Stellenbosch University) and Camilla Rodriques (P.D. Hinduja National Hospital and Medical Research Centre), as well as their clinical and laboratory staff for their assistance in acquiring and testing patient specimens.

Background: Quality-assured tuberculosis laboratory services are critical to achieve global and national goals for tuberculosis prevention and care. Implementation of a quality management system (QMS) in laboratories leads to improved quality of diagnostic tests and better patient care. The Strengthening Laboratory Management Toward Accreditation (SLMTA) programme has led to measurable improvements in the QMS of clinical laboratories. However, progress in tuberculosis laboratories has been slower, which may be attributed to the need for a structured tuberculosis-specific approach to implementing QMS. We describe the development and early implementation of the Strengthening Tuberculosis Laboratory Management Toward Accreditation (TB SLMTA) programme.Development: The TB SLMTA curriculum was developed by customizing the SLMTA curriculum to include specific tools, job aids and supplementary materials specific to the tuberculosis laboratory. The TB SLMTA Harmonized Checklist was developed from the World Health Organisation Regional Office for Africa Stepwise Laboratory Quality Improvement Process Towards Accreditation checklist, and incorporated tuberculosis-specific requirements from the Global Laboratory Initiative Stepwise Process Towards Tuberculosis Laboratory Accreditation online tool.Implementation: Four regional training-of-trainers workshops have been conducted since 2013. The TB SLMTA programme has been rolled out in 37 tuberculosis laboratories in 10 countries using the Workshop approach in 32 laboratories in five countries and the Facility based approach in five tuberculosis laboratories in five countries.Conclusion: Lessons learnt from early implementation of TB SLMTA suggest that a structured training and mentoring programme can build a foundation towards further quality improvement in tuberculosis laboratories. Structured mentoring, and institutionalisation of QMS into country programmes, is needed to support tuberculosis laboratories to achieve accreditation.