Rifampicin-resistant tuberculosis in Botswana: barriers and risk factors influencing patient outcomes, case detection, and linkage to effective care and treatment

Boyd, Rosanna M

Rifampicin-resistant tuberculosis in Botswana: barriers and risk factors influencing patient outcomes, case detection, and linkage to effective care and treatment

Doctoral Thesis

2019

Abstract

Background: Botswana reports high treatment success for rifampicin-resistant tuberculosis (RR-TB), but many challenges remain. Case detection is lower than expected and varies by year, and mortality rates are high. Research aims included identifying: factors associated with mortality, access to culture and drug susceptibility testing (DST) for patients at risk of RR-TB, access to first- and second-line DST among RR-TB patients, time to RRTB treatment, and patient and provider experiences with RR-TB management. Methods: Retrospective data (multiple cohorts across 2006-2014) were extracted from Botswana national registers and information systems, with additional data collected by standardized, qualitative interviews (2017). Data analyses (Cox proportional hazards regression, survival and hazards curves, logistic regression) were conducted to describe significant associations. A systematic review and meta-analysis was conducted. Thematic analysis was performed for qualitative research. Results: There was low access (42%) to culture testing among patients at risk of RR-TB (previously-treated TB patients); particularly associated with rural residence and having previous successful TB treatment, compared to previous treatment failure. While confirmation of first-line drug resistance was available for 85% of patients initiating RR-TB treatment, access to second-line DST was poor (24%), impacted by limited in-country laboratory capacity. Genotypic DST by Xpert MTB/RIF at peripheral laboratories was associated with faster time to treatment from diagnosis compared to phenotypic DST at the centralized national lab, 5 versus 22 days (median, p<0.001), consistent with systematic review findings of time to RR-TB treatment. Risk factors for mortality during treatment included unconfirmed RR-TB (aHR 2.9), Pre/XDR-TB (aHR 2.5), HIV positivity without ART (aHR 3.6) and receiving treatment at two (of five) specific facilities (aHR 2.6 and 2.3). Qualitative interviews confirmed inconsistent adherence to national policies and identified additional challenges including frequent medication and reagent stock-outs, misperceptions about disease transmission from both providers and patients, and inadequate national level support for the RR-TB program. Conclusion: Several clinical and demographic factors negatively influencing case detection and RR-TB mortality in Botswana were identified. General health system dysfunction and poor political commitment to the RR-TB program also contributed. Recommendations include increased focus on: early diagnosis through universal DST, consistent access to effective drugs, and overall adherence to policies.

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PhD / Doctoral

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