Abstract
BackgroundDespite the existence of effective drug treatments, tuberculosis (TB) causes 2 million deaths annually worldwide. Effective treatment is complicated by multidrug-resistant TB (MDR TB) strains that respond only to second-line drugs. We projected the health benefits and cost-effectiveness of using drug susceptibility testing and second-line drugs in a lower-middle-income setting with high levels of MDR TB.Methods and FindingsWe developed a dynamic state-transition model of TB. In a base case analysis, the model was calibrated to approximate the TB epidemic in Peru, a setting with a smear-positive TB incidence of 120 per 100,000 and 4.5% MDR TB among prevalent cases. Secondary analyses considered other settings. The following strategies were evaluated: first-line drugs administered under directly observed therapy (DOTS), locally standardized second-line drugs for previously treated cases (STR1), locally standardized second-line drugs for previously treated cases with test-confirmed MDR TB (STR2), comprehensive drug susceptibility testing and individualized treatment for previously treated cases (ITR1), and comprehensive drug susceptibility testing and individualized treatment for all cases (ITR2). Outcomes were costs per TB death averted and costs per quality-adjusted life year (QALY) gained. We found that strategies incorporating the use of second-line drug regimens following first-line treatment failure were highly cost-effective compared to strategies using first-line drugs only. In our base case, standardized second-line treatment for confirmed MDR TB cases (STR2) had an incremental cost-effectiveness ratio of $720 per QALY ($8,700 per averted death) compared to DOTS. Individualized second-line drug treatment for MDR TB following first-line failure (ITR1) provided more benefit at an incremental cost of $990 per QALY ($12,000 per averted death) compared to STR2. A more aggressive version of the individualized treatment strategy (ITR2), in which both new and previously treated cases are tested for MDR TB, had an incremental cost-effectiveness ratio of $11,000 per QALY ($160,000 per averted death) compared to ITR1. The STR2 and ITR1 strategies remained cost-effective under a wide range of alternative assumptions about treatment costs, effectiveness, MDR TB prevalence, and transmission.ConclusionsTreatment of MDR TB using second-line drugs is highly cost-effective in Peru. In other settings, the attractiveness of strategies using second-line drugs will depend on TB incidence, MDR burden, and the available budget, but simulation results suggest that individualized regimens would be cost-effective in a wide range of situations.
Highlights
Mycobacterium tuberculosis infects nearly one-third of the world’s population, and 8 to 10 million infected persons progress to active tuberculosis (TB) each year [1]
We considered an incremental cost per quality-adjusted life year (QALY) that was less than the per capita gross domestic product (GDP) to be highly cost-effective, and we considered three times the per capita GDP to be a threshold beyond which an intervention would be considered too expensive
STR2, which utilized a test for multidrug-resistant TB (MDR TB) to screen out false positives, provided this incremental benefit at lower cost than STR1, and had an incremental cost-effectiveness of $720 per QALY ($8,700 per averted death) compared to the DOTS strategy
Summary
Mycobacterium tuberculosis infects nearly one-third of the world’s population, and 8 to 10 million infected persons progress to active tuberculosis (TB) each year [1]. Despite the existence of effective drug treatment, TB causes approximately 2 million deaths annually [1]. Efforts to treat patients with active disease and to control the spread of TB are complicated by resource constraints, co-infection with HIV, and the emergence of drug-resistant TB strains. Despite the existence of effective drug treatments, tuberculosis (TB) causes 2 million deaths annually worldwide. Effective treatment is complicated by multidrug-resistant TB (MDR TB) strains that respond only to second-line drugs. (See the link below for an explanation of what DOTS involves.) The antibiotics that are used in DOTS are described as ‘‘first-line’’ treatment drugs. They are highly effective against non-resistant TB but much less so against MDR TB. There are other, more expensive, ‘‘secondline’’ antibiotics that perform better against MDR TB
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