Abstract

BackgroundIn Uganda, isoniazid plus ethambutol is used for 6 months (6HE) during the continuation treatment phase of new tuberculosis (TB) cases. However, the World Health Organization (WHO) recommends using isoniazid plus rifampicin for 4 months (4HR) instead of 6HE. We compared the impact of a continuation phase using 6HE or 4HR on total cost and expected mortality from the perspective of the Ugandan national health system.Methodology/Principal FindingsTreatment costs and outcomes were determined by decision analysis. Median daily drug price was US$0.115 for HR and US$0.069 for HE. TB treatment failure or relapse and mortality rates associated with 6HE vs. 4HR were obtained from randomized trials and systematic reviews for HIV-negative (46% of TB cases; failure/relapse –6HE: 10.4% vs. 4HR: 5.2%; mortality –6HE: 5.6% vs. 4HR: 3.5%) and HIV-positive patients (54% of TB cases; failure or relapse –6HE: 13.7% vs. 4HR: 12.4%; mortality –6HE: 16.6% vs. 4HR: 10.5%). When the initial treatment is not successful, retreatment involves an additional 8-month drug-regimen at a cost of $110.70. The model predicted a mortality rate of 13.3% for patients treated with 6HE and 8.8% for 4HR; average treatment cost per patient was predicted at $26.07 for 6HE and $23.64 for 4HR. These results were robust to the inclusion of MDR-TB as an additional outcome after treatment failure or relapse.Conclusions/SignificanceCombination therapy with 4HR in the continuation phase dominates 6HE as it is associated with both lower expected costs and lower expected mortality. These data support the WHO recommendation to transition to a continuation phase comprising 4HR.

Highlights

  • The public health burden of tuberculosis (TB) disproportionately affects developing countries

  • Due to severe skin reactions observed in HIV-positive individuals [4], the World Health Organization (WHO) recommended that national TB programs change the continuation phase to 6 months of isoniazid plus ethambutol (6HE) in 1991 [5]

  • In 2003, as evidence mounted in support of rifampicin throughout TB treatment, the WHO recommended one of two approaches for the continuation phase of TB treatment; 6 months of isoniazid plus ethambutol (6HE) or 4 months of isoniazid plus rifampicin (4HR)

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Summary

Introduction

The public health burden of tuberculosis (TB) disproportionately affects developing countries. Limited resources in these countries increase the risk of suboptimal treatment and necessitate financial analyses that inform health policy decisions. Six months of isoniazid plus thiacetazone (6HA) was recommended by the World Health Organization (WHO) for the continuation phase rather than a rifampicin-containing regimen. This was to preserve sensitivity to rifampicin for retreatment. Due to severe skin reactions observed in HIV-positive individuals [4], the WHO recommended that national TB programs change the continuation phase to 6 months of isoniazid plus ethambutol (6HE) in 1991 [5]. We compared the impact of a continuation phase using 6HE or 4HR on total cost and expected mortality from the perspective of the Ugandan national health system

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