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Title: Addressing the challenges of recurrent tuberculosis in Malawi
Author: Cohen, D. B.
ISNI:       0000 0004 6059 6635
Awarding Body: University of Liverpool
Current Institution: University of Liverpool
Date of Award: 2016
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Background Each year, approximately 10% of people diagnosed with tuberculosis (TB) globally have previously received TB treatment, and are prescribed a standardised WHO ‘Category II regimen’ which includes daily intramuscular injections of streptomycin. Treatment success rates on this re-treatment regimen are low, yet reasons for poor outcomes are not well understood. Currently data are lacking about appropriate ways to deliver long term injectable agents used as part of TB treatment. Methods The study was conducted in Malawi, a small country in South-Eastern Africa with a high TB burden and a generalised HIV epidemic. A cohort study prospectively recruited adult patients receiving retreatment regimen. Patients were assessed at baseline, 2 and 8 months. Multivariate logistic regression analysis was used to determine associations between clinical outcome and microbiologically confirmed TB, drug resistance, clinical features at presentation and medical co-morbidities. A pragmatic, individually randomised trial assessed hospital versus community-based care during the intensive phase of TB retreatment. In the community arm guardians were trained to deliver intramuscular injections of streptomycin at home. An economic evaluation was conducted from a societal perspective; and a qualitative evaluation involved in depth interviews with trial participants, key informant interviews, and observations. Results In the cohort study, the prevalence of drug resistance was 9.6%. The prevalence of co-morbidity was high (HIV 82.9%; antiretroviral therapy failure 37.5%; severe anaemia 22.2%; chronic lung disease 88.2%; renal impairment 33.8%). Ototoxicity developed in 35.9% and nephrotoxicity in 14.6%. In multivariate analysis, successful outcome was associated only with hypotension at presentation, but not microbiologically confirmed TB, drug resistance or other co-morbidities. In the trial, 93.2% of patients who received community-based care successfully completed 2 months treatment, compared to 96.0% managed in hospital (RD -0.03; 95%CI -0.09 - 0.03). The mean cost of hospital-based care was US$ 1546 per person, compared to US$ 729.2 in the community. Community-based management reduced risk of catastrophic household costs by 84%. Qualitative data demonstrated social and financial benefits of community-based care. Conclusions This cohort study demonstrated a low prevalence of drug resistant TB but a high burden of medical co-morbidity in patients with recurrent TB in Malawi. Co-morbidity is likely to be contributing to poor outcomes on TB retreatment regimen. A novel community-based model of delivering injectable anti-TB drugs by training guardians to do injections at home is shown to be feasible, acceptable and highly cost effective.
Supervisor: Squire, S. B. ; Davies, G. Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral