Disease Control Implications of India’s Changing Multi-Drug Resistant Tuberculosis Epidemic

Citation: Suen S-c, Bendavid E, Goldhaber-Fiebert JD (2014) Disease Control Implications of India's Changing Multi-Drug Resistant Tuberculosis Epidemic. PLoS ONE 9(3): e89822. doi:10.1371/journal.pone.0089822
Published: March 7, 2014

Abstract
Background: Multi-drug resistant tuberculosis (MDR TB) is a major health challenge in India that is gaining increasing public attention, but the implications of India's evolving MDR TB epidemic are poorly understood. As India's MDR TB epidemic is transitioning from a treatment-generated to transmission-generated epidemic, we sought to evaluate the potential effectiveness of the following two disease control strategies on reducing the prevalence of MDR TB: a) improving treatment of non-MDR TB; b) shortening the infectious period between the activation of MDR TB and initiation of effective MDR treatment.
Methods and Findings: We developed a dynamic transmission microsimulation model of TB in India. The model followed individuals by age, sex, TB status, drug resistance status, and treatment status and was calibrated to Indian demographic and epidemiologic TB time trends. The main effectiveness measure was reduction in the average prevalence reduction of MDR TB over the ten years after control strategy implementation. We find that improving non-MDR cure rates to avoid generating new MDR cases will provide substantial non-MDR TB benefits but will become less effective in reducing MDR TB prevalence over time because more cases will occur from direct transmission – by 2015, the model estimates 42% of new MDR cases are transmission-generated and this proportion continues to rise over time, assuming equal transmissibility of MDR and drug-susceptible TB. Strategies that disrupt MDR transmission by shortening the time between MDR activation and treatment are projected to provide greater reductions in MDR prevalence compared with improving non-MDR treatment quality: implementing MDR diagnostic improvements in 2017 is expected to reduce MDR prevalence by 39%, compared with 11% reduction from improving non-MDR treatment quality.
Conclusions: As transmission-generated MDR TB becomes a larger driver of the MDR TB epidemic in India, rapid and accurate MDR TB diagnosis and treatment will become increasingly effective in reducing MDR TB cases compared to non-MDR TB treatment improvements.


Introduction

Worldwide, tuberculosis (TB) prevalence has declined by over 30% since 1990 [1]. However, selective pressures from the increased use of TB medications have led to the emergence and growth of multi-drug resistant (MDR) TB, defined as strains of Mycobacterium tuberculosis resistant to at least isoniazid and rifampin, two first line anti-TB medications. Strains resistant to no more than one of these medications are referred to as non-MDR TB [1]–[4]. Drug resistance challenges TB control, as diagnostic technology to identify drug resistance is often unavailable, mortality rates are high, and MDR TB treatments are more lengthy, toxic, and costly [5]. Improving non-MDR TB treatment could provide an effective approach to MDR control as long as most incident MDR TB cases develop during treatment of non-MDR TB. However, if MDR TB prevalence increases sufficiently, transmission-generated disease could eventually account for the majority of incident MDR TB, as has been observed in South Africa and China [6], [7].

The challenge of addressing TB and MDR TB is critical for India, home to over 25% of the world's TB cases [1]. In 1997, India's Revised National Tuberculosis Control Programme (RNTCP) implemented the World Health Organization's (WHO) Directly Observed Treatment Short-Course (DOTS) strategy. Treatment success rates have improved since then, but effective TB control remains challenged by treatment provided outside of RNTCP and imperfect treatment completion rates, which can generate new MDR TB cases [8], [9]. Private clinics in India are often used by patients seeking TB treatment and may employ...

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