To test or not? Xpert MTB/RIF as an alternative to smear microscopy to guide line probe assay testing for drug-resistant tuberculosis

Abstract

Background: Xpert MTB/RIF (Xpert) revolutionised tuberculosis (TB) diagnosis, however, laboratory decision making on whether widely-used reflex drug susceptibility assays (MTBDRplus, MTBDRsl) are done on specimens is often based on smear microscopy status. Method: We performed receiver operator characteristic (ROC) curve analyses using sputum bacterial load measures [smear microscopy grade, Xpert semi-quantitation category and minimum cycle threshold (CTmin) values] for the classification of likely non-actionable (not resistant or susceptible) line probe assays results. We evaluated the actionable-to-non-actionable result ratio and pay-offs with missed isoniazid and fluoroquinolone resistance compared to if LPAs were done universally. Findings: Smear-negatives were more likely than smear-positives to generate a non-actionable MTBDRplus [23% (133/559) vs. 4% (15/381)] or MTBDRsl [39% (220/559) vs. 12% (47/381)] result, however, excluding smear-negatives would result in missed rapid diagnoses [e.g., only 51% (273/537) of LPA-diagnosable isoniazid resistance detected if smear-negatives omitted]. Within smear-negatives, testing ; ≥medium specimens had a high ratio of actionable-to-non-actionable results (12.8 or a 4-fold improvement vs. test all for MTBDRplus, 4.5 or 3-fold improvement for MTBDRsl), which would capture 64% (168/264) and 77% (34/44) of LPA-detectable resistance. If CTmin were used, greater resolution and higher ratios offset against fewer missed resistant cases were obtained. Conclusion: Routinely-generated Xpert quantitative information permits identification of smear-negatives in whom the ratio of actionable-to-non-actionable LPA results may prove acceptably high to laboratories depending on their local contexts. Xpert CTmin or, if unavailable, semiquantitation category should be used to guide reflex DST; permitting the rational expansion of direct DST to certain paucibacillary specimens.

Competing Interest Statement

The authors have declared no competing interest.

Funding Statement

Hain Lifesciences donated MTBDRsl kits and GT and RW have receiving funding from Hain Lifesciences for other studies. Hain Lifesciences had no role in this study. GT acknowledges funding from the EDCTP2 programme supported by the European Union (RIA2018D-2509, PreFIT; RIA2018D-2493, SeroSelectTB; RIA2020I-3305, CAGE-TB) and the National Institutes of Health (D43TW010350; U01AI152087; U54EB027049; R01AI136894).

Author Declarations

I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained.

Yes

The details of the IRB/oversight body that provided approval or exemption for the research described are given below:

This study was approved by the Health Research Ethics Committee of Stellenbosch University (N16/04/045) and Western Province Department of Health (2016/RP18/637).

I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals.

Yes

I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance).

Yes

I have followed all appropriate research reporting guidelines and uploaded the relevant EQUATOR Network research reporting checklist(s) and other pertinent material as supplementary files, if applicable.

Yes

Data Availability

All data produced in the present work are contained in the manuscript.

留言 (0)

沒有登入
gif