Abstract
BackgroundMultidrug-resistant tuberculosis (MDR-TB) is a major threat to global TB control. MDR-TB treatment regimens typically have a high pill burden, last 20 months or more and often lead to unsatisfactory outcomes. A 9–11 month regimen with seven antibiotics has shown high success rates among selected MDR-TB patients in different settings and is conditionally recommended by the World Health Organization.MethodsWe construct a transmission-dynamic model of TB to estimate the likely impact of a shorter MDR-TB regimen when applied in a low HIV prevalence region of Uzbekistan (Karakalpakstan) with high rates of drug resistance, good access to diagnostics and a well-established community-based MDR-TB treatment programme providing treatment to around 400 patients. The model incorporates acquisition of additional drug resistance and incorrect regimen assignment. It is calibrated to local epidemiology and used to compare the impact of shorter treatment against four alternative programmatic interventions.ResultsBased on empirical outcomes among MDR-TB patients and assuming no improvement in treatment success rates, the shorter regimen reduced MDR-TB incidence from 15.2 to 9.7 cases per 100,000 population per year and MDR-TB mortality from 3.0 to 1.7 deaths per 100,000 per year, achieving comparable or greater gains than the alternative interventions. No significant increase in the burden of higher levels of resistance was predicted. Effects are probably conservative given that the regimen is likely to improve success rates.ConclusionsIn addition to benefits to individual patients, we find that shorter MDR-TB treatment regimens also have the potential to reduce transmission of resistant strains. These findings are in the epidemiological setting of treatment availability being an important bottleneck due to high numbers of patients being eligible for treatment, and may differ in other contexts. The high proportion of MDR-TB with additional antibiotic resistance simulated was not exacerbated by programmatic responses and greater gains may be possible in contexts where the regimen is more widely applicable.Electronic supplementary materialThe online version of this article (doi:10.1186/s12916-016-0723-2) contains supplementary material, which is available to authorized users.
Highlights
Multidrug-resistant tuberculosis (MDR-TB) is a major threat to global TB control
We present a mathematical model to estimate the likely impact of a 9–11 month MDR-TB regimen in Karakalpakstan on rates of disease and death, and compare this estimate with scenarios where alternative approaches are used to scale-up TB treatment programmes
The model is based on our previous work [14] and incorporates a number of aspects that we consider important to modelling TB epidemiology in regions highly endemic for both TB and MDR-TB, including partial vaccine efficacy [15, 16], declining risk of active disease with time from infection, reinfection during latency, and acquisition of drug resistance through de novo amplification
Summary
Multidrug-resistant tuberculosis (MDR-TB) is a major threat to global TB control. MDR-TB treatment regimens typically have a high pill burden, last 20 months or more and often lead to unsatisfactory outcomes. About 10% of all incident MDR-TB cases globally are known to successfully navigate the complex pathway from presentation to detection and identification as multidrug-resistant, and subsequently through the difficult, toxic and costly treatment regimen. The countries of Eastern Europe and the former Soviet Union report among the highest proportions of TB patients presenting with MDR-TB, both among new and retreatment cases [3]. A national drug resistance survey conducted in 2011 found that 23% of new cases and 62% of previously treated cases had MDR-TB [5] These levels varied within the country, and one region, Karakalpakstan in western Uzbekistan, with a population of 1.7 million, had the highest ratios (41% in new and 78% in retreatment cases). The model of care considers either inpatient or outpatient treatment, with a focus on providing early, supported ambulatory treatment, where possible
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