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Objectives: Tuberculosis (TB) diagnosis in children remains challenging due to the paucibacillary nature of specimens and the difficulty in obtaining suitable samples. The use of alternative samples like nasopharyngeal aspirate (NPA) and stools, alongside Xpert MTB/RIF testing, offers promising improvements. This study aimed to assess the diagnostic performance of the Xpert MTB/RIF test on NPA and stool samples for detecting intrathoracic TB in children from Madagascar, Cameroon, and Ivory Coast. Methods: Children under 15 years with suspected intrathoracic TB were enrolled in hospitals in these countries’ capitals. Samples for analysis included standard specimens (gastric aspirate or sputum), NPA, stools, with additional HIV serology, tuberculin skin test tests, and chest X-rays. We used a composite reference standard to estimate the accuracy of the Xpert MTB/RIF test with alternative samples. Results: Of 1146 children analyzed, the sensitivity of Xpert MTB/RIF was 58.3% for NPA and 45.5% for stool samples, with a high specificity of more than 95%. The diagnostic performance of Xpert MTB/RIF with alternative samples did not differ according to age group or HIV status. Conclusions: The findings support the World Health Organization's recommendation for using Xpert MTB/RIF with alternative samples in childhood TB diagnosis, underscoring its utility across different settings and HIV statuses.

Abstract Background In Madagascar, the multidrug-resistant tuberculosis (MDR-TB) surveillance programme was launched in late 2012 wherein previously treated TB cases and symptomatic MDR-TB contacts (hereafter called presumptive MDR-TB cases) undergo drug susceptibility testing. This retrospective review had per aim to provide an update on the national MDR-TB epidemiology, assess and enhance programmatic performance and assess Madagascar’s MDR-TB cascade of care. Methods For 2012–2017, national TB control programme notification, clinical management data and reference laboratory data were gathered. The development and coverage of the surveillance programme, the MDR-TB epidemiology and programmatic performance indicators were assessed using descriptive, logistic and spatial statistical analyses. Data for 2017 was further used to map Madagascar’s TB and MDR-TB cascade of care. Results The geographical coverage and diagnostic and referral capacities of the MDR-TB surveillance programme were gradually expanded whereas regional variations persist with regard to coverage, referral rates and sample referral delays. Overall, the rate of MDR-TB among presumptive MDR-TB cases remained relatively stable, ranging between 3.9% in 2013 and 4.4% in 2017. Most MDR-TB patients were lost in the second gap of the cascade pertaining to MDR-TB cases reaching diagnostic centres but failing to be accurately diagnosed (59.0%). This poor success in diagnosis of MDR-TB is due to both the current use of low-sensitivity smear microscopy as a first-line diagnostic assay for TB and the limited access to any form of drug susceptibility testing. Presumptive MDR-TB patients’ sample referral took a mean delay of 28 days before testing. Seventy-five percent of diagnosed MDR-TB patients were appropriately initiated on treatment, and 33% reached long-term recurrence-free survival. Conclusions An expansion of the coverage and strengthening of MDR-TB diagnostic and management capacities are indicated across all regions of Madagascar. With current limitations, the surveillance programme data is likely to underestimate the true MDR-TB burden in the country and an updated national MDR-TB prevalence survey is warranted. In absence of multiple drivers of an MDR-TB epidemic, including high MDR-TB rates, high HIV infection rates and inter-country migration, Madagascar is in a favourable starting position for MDR-TB control and elimination.

Abstract Background Tuberculosis rapid molecular assays, including GeneXpert MTB/RIF® and Loopamp MTBC Detection Kit®, are highly sensitive and specific. Such performance does not automatically translate in improved disease control and highly depends on their use, local epidemiology and the diagnostic algorithms they’re implemented within. We evaluate the performance of both assays and assess their impact on additional cases notification when implemented within WHO recommended tuberculosis diagnostic algorithms in Madagascar. Methods Five hundred forty eight presumptive pulmonary tuberculosis patients were prospectively recruited between November 2013 and December 2014 in Antananarivo, Madagascar, a high TB incidence sub-Saharan African urban setting. Both molecular assays were evaluated as first line or add-on testing following negative smear microscopy. Based on locally defined assay performance characteristics we measure the impact of both assays and WHO-recommended diagnostic algorithms on additional tuberculosis case notifications. Results High sensitivity and specificity was confirmed for both GeneXpert MTB/RIF® (86.6% (95% CI 81.1–90.7%) and 97.4% (95% CI 94.9–98.8%)) and Loopamp MTBC Detection Kit® (84.6% (95% CI 78.9–89.0%) and 98.4% (95% CI 96.2–99.4%)). Implementation of GeneXpert MTB/RIF® and Loopamp MTBC Detection Kit® increased tuberculosis diagnostic algorithms sensitivity from 73.6% (95% CI 67.1–79.3%) up to 88.1% (95% CI 82.8–91.9%). This increase was highest when molecular assays were used as add-on testing following negative smear microscopy. As add-on testing, GeneXpert MTB/RIF® and Loopamp MTBC Detection Kit® respectively improved case detection by 23.8 and 21.2% (p

In 2020, the World Health Organization estimated that in Madagascar there were 238 cases of Mycobacterium tuberculosis complex infection per 100,000 persons, but fewer than half of infected persons were [...]