Performance and Impact of GeneXpert MTB/RIF® and Loopamp MTBC Detection Kit® Assays on Tuberculosis Case Detection in Madagascar

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 < 0.05).Conclusion: Including GeneXpert MTB/RIF® or Loopamp MTBC Detection Kit® molecular assays for TB detection on sputum samples from presumptive TB cases can significantly increase case notification in TB diagnostic centers. The TB case detection rate is further increased when those tests are use as second-line follow-on testing following negative smear microscopy results. A country wide scale-up and digital integration of molecular-based TB diagnosis assays shows promises for TB control in Madagascar.

Multidrug-resistant tuberculosis surveillance and cascade of care in Madagascar: a five-year (2012–2017) retrospective study

“…Supranational WHO data, NTP notification and clinical management data, NRLM data on TB diagnosis and DST, previously published and locally assessed laboratory assays' performance characteristics and systematic review data on the natural history of TB disease were used to map Madagascar's TB and MDR-TB cascade of care for 2017 only [19,20]. As recently proposed, the number of patients with prevalent active disease, reaching and being evaluated at TB diagnostic facilities, being diagnosed with disease, accessing treatment, completing treatment and achieving recurrence-free survival were used as the specific 'steps' of the cascade for TB and MDR-TB care [21].…”

Comparison of the Three Molecular Diagnostic Assays for Molecular Identification ofMycobacterium tuberculosisand Nontuberculous Mycobacteria Species in Sputum Samples

“…Mycobacterial culture is considered the gold standard method in the identification of mycobacteria isolates; however, culture tests usually require about four to eight weeks because of the slow growth of the mycobacteria (Chae and Shin, 2018;Rakotosamimanana et al, 2019). Although automated liquid culture systems have complemented the limitations, classical diagnostic methods still have low sensitivity and are time-consuming (Wang et al, 2014;Zhu et al, 2010;Şamlı and İlki, 2016;Wang et al, 2015).…”