A suggested algorithm for detection of multi drug-resistant tuberculosis in Zimbabwe

Abstract

Introduction: Rapid genotypic and phenotypic methods for multi-drug-resistant-tuberculosis (MDR-TB) detection are now widely available. Zimbabwe adopted the use of GeneXpert-MTB/RIF, microscopic-observation-drug-susceptibility-assay (MODS) and Mycobacteria-GrowthIndicator-Tube (MGIT) drug-susceptibility-testing (DST). Data is limited on the ideal combination of use of these methods in resource limited settings. Methodology: Between August 2014 to July 2015, 211 sputa from MDR-TB suspects were tested with GeneXpert-MTB/RIF, MODS, manual-MGIT and Lowenstein-Jensen (LJ)-DST to determine diagnostic accuracy and turnaround-time (TAT), with LJ-DST as the gold standard. A performance score ranking table for diagnostic accuracy, TAT, costs, facilities and expertise requirements, was used to determine the most favourable tool. Results: GeneXpert-MTB/RIF sensitivity was 96% (95%CI:80-100) and specificity was 95% (95%CI:90-97). MODS sensitivity was 88% (95%CI:68-97) and specificity was 97% (95%CI:87-100). Manual MGIT-DST had slightly lower sensitivity of 80% (95%CI:59-93). Median time to detection of MDR-TB was <1 day (IQR:0-0) for Xpert, 14 days (IQR:11-31) for MODS, 21 days (IQR:7-22) for MGIT-DST and 28 days (IQR:25-28) for LJ-DST. Operational costs for MODS, MGIT-DST, and GeneXpert-MTB/RIF were $21.20, $27.52 and $39.76 respectively. From a summation of scores including facility and expertise requirements per diagnostic technique, GeneXpert-MTB/RIF was the most favourable tool, followed by MODS and MGIT-DST. Conclusions: For best scale-up of MDR-TB diagnosis in Zimbabwe, GeneXpert-MTB/RIF can be used for rapid detection of TB in smear negative cases, RIF-susceptibility for early treatment initiation and probable MDR-TB. MODS can rapidly confirm probable MDR-TB detected by GeneXpert-MTB/RIF, manual-MGIT can provide early results for susceptibility to other antibiotics, with affordable costs, with LJ-DST confirming discordant DSTs.

Xpert MTB/RIF and Xpert MTB/RIF Ultra for pulmonary tuberculosis and rifampicin resistance in adults

“…In the Patient Selection domain, we considered 36 studies (63%) to have low risk of bias because the study enrolled a consecutive or random sample of eligible participants and avoided inappropriate exclusions. We considered 10 studies (18% ) to have high risk of bias because the study did not avoid inappropriate exclusions and instead enrolled participants preselected on the basis of their sputum specimens being either smear‐positive or smear‐negative or the study exclusively enrolled retreatment participants ( Ali 2017 ; Friedrich 2011 ; Lee 2013 ; Le Palud 2014 ; Makamure 2017 ; N'Guessan 2016 ; Tadesse 2016 ; Theron 2013 ; Van Rie 2013 ; Williamson 2012 ). We considered 11 studies (19%) to have unclear risk of bias because the manner of participant selection was not reported ( Barmankulova 2015 ; Barnard 2015 ; Bates 2013a ; Huang 2015 ; Kim CH 2015 ; Luetkemeyer 2016 ; Meawed 2016 ; Moussa 2016 ; Nosova 2013a ; Pimkina 2015 ; Singh 2016 ).…”

“…Several studies designed to enrol participants suspected of MDR‐TB had high percentages of participants previously treated for tuberculosis ( Lorent 2015 ; Makamure 2017 ; Meawed 2016 ; Metcalfe 2016 ; N'Guessan 2016 ; Pimkina 2015 ; Zetola 2014 ). In these studies (7 studies, 1062 participants), Xpert MTB/RIF pooled sensitivity at 98% (95% CrI 94% to 99%) was higher than the pooled sensitivity of 95% (93% to 97%) in studies that did not preferentially enrol previously treated participants (41 studies, 6958 participants); and conversely, pooled specificity was lower at 97% (93% to 99%) than the pooled specificity of 99% (95% CrI 98% to 99%) in studies that did not preferentially enrol previously treated participants.…”