Non-actionable results, accuracy and effect of the first- and second-line line probe assays for diagnosing drug resistant tuberculosis, including on smear-negative specimens, in a high-volume laboratory
Pillay, S
Non-actionable results, accuracy and effect of the first- and second-line line probe assays for diagnosing drug resistant tuberculosis, including on smear-negative specimens, in a high-volume laboratory - 2022-07-05.
/pmc/articles/PMC7614164/ /pubmed/35788278
BACKGROUND: Rapid drug susceptibility testing (DST) is crucial to confirm eligibility for new tuberculosis (TB) regimens. Genotype MTBDRsl is a widely-deployed World Health Organization (WHO)-endorsed assay yet programmatic performance data, including non-actionable results from smear-negative sputum, are scarce. METHODS: Sputa from Xpert MTB/RIF-rifampicin resistant individuals (n=951) were tested by Genotype MTBDRplus and MTBDRsl (both v2) in a routine laboratory. Phenotypic DST was the second-line drug reference standard. Discrepant results underwent Sanger sequencing. FINDINGS: 89% (849/951) individuals were culture-positive [56% (476/849) smear-negative]. MTBDRplus had at least one non-actionable result (control and/or TB-detection bands absent or invalid, precluding resistance reporting) in 19% (92/476) of smear-negatives and, for MTBDRsl, 40% (171/427) were non-actionable [28% (120/427) false-negative TB, 17% (51/427) indeterminate]. In smear-negatives, MTBDRsl sensitivity for fluoroquinolones was 84% (95% CI 67-93), 81% (54-95) for second-line injectables, and 57% (28-82) for both. Specificities were 93% (89-98), 88% (81-93), and 97% (91-99), respectively. 23% (172/746) of Xpert rifampicin-resistant specimens were MTBDRplus isoniazid-susceptible. Days-to-second-line-susceptibility reporting with the programmatic advent of MTBDRsl improved [6 (5-7) vs. 37 (35-46); p<0.001]. CONCLUSION: MTBDRsl did not generate a result in almost half of smear-negative individuals (4/10 failed), resulting in substantial missed resistance. However, if MTBDRsl generates an actionable result, that result is accurate in ruling-in second-line resistance. Isoniazid susceptibility testing remains crucial. This study provides, in the context of WHO guidance, real-world direct second-line susceptibility testing performance data on non-actionable results (which, if unaccounted for, result in an overestimation of test utility), accuracy, and care cascade impact.
en
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Non-actionable results, accuracy and effect of the first- and second-line line probe assays for diagnosing drug resistant tuberculosis, including on smear-negative specimens, in a high-volume laboratory - 2022-07-05.
/pmc/articles/PMC7614164/ /pubmed/35788278
BACKGROUND: Rapid drug susceptibility testing (DST) is crucial to confirm eligibility for new tuberculosis (TB) regimens. Genotype MTBDRsl is a widely-deployed World Health Organization (WHO)-endorsed assay yet programmatic performance data, including non-actionable results from smear-negative sputum, are scarce. METHODS: Sputa from Xpert MTB/RIF-rifampicin resistant individuals (n=951) were tested by Genotype MTBDRplus and MTBDRsl (both v2) in a routine laboratory. Phenotypic DST was the second-line drug reference standard. Discrepant results underwent Sanger sequencing. FINDINGS: 89% (849/951) individuals were culture-positive [56% (476/849) smear-negative]. MTBDRplus had at least one non-actionable result (control and/or TB-detection bands absent or invalid, precluding resistance reporting) in 19% (92/476) of smear-negatives and, for MTBDRsl, 40% (171/427) were non-actionable [28% (120/427) false-negative TB, 17% (51/427) indeterminate]. In smear-negatives, MTBDRsl sensitivity for fluoroquinolones was 84% (95% CI 67-93), 81% (54-95) for second-line injectables, and 57% (28-82) for both. Specificities were 93% (89-98), 88% (81-93), and 97% (91-99), respectively. 23% (172/746) of Xpert rifampicin-resistant specimens were MTBDRplus isoniazid-susceptible. Days-to-second-line-susceptibility reporting with the programmatic advent of MTBDRsl improved [6 (5-7) vs. 37 (35-46); p<0.001]. CONCLUSION: MTBDRsl did not generate a result in almost half of smear-negative individuals (4/10 failed), resulting in substantial missed resistance. However, if MTBDRsl generates an actionable result, that result is accurate in ruling-in second-line resistance. Isoniazid susceptibility testing remains crucial. This study provides, in the context of WHO guidance, real-world direct second-line susceptibility testing performance data on non-actionable results (which, if unaccounted for, result in an overestimation of test utility), accuracy, and care cascade impact.
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