Background

Mycobacterium tuberculosis causes nearly 10 million new cases of tuberculosis and 1.7 million deaths annually, making it the leading worldwide cause of death from a single infectious agent. Over 50% of the world’s tuberculosis patients are in South or East Asia.

Multi-drug resistant tuberculosis (MDR-TB) is defined as resistance to both isoniazid and rifampicin and accounts for an increasing burden of overall tuberculosis disease in many countries.

In Vietnam, incidences of MDR-TB are rising by an estimated 4% per year. The country now ranks 14th amongst the world’s high-burden countries for MDR-TB. True incidence might still be higher.

MDR-TB takes longer to treat, with poorer compliance and worse patient outcomes than drug-susceptible diseases.

The question of how people get MDR-TB remains unanswered. Recent studies have demonstrated how drug-resistant strains transmit successfully, challenging the belief that the fitness cost of drug resistance prevents many transmissions. However, evidence of de novo acquisition of drug resistance within patients on treatment is also well documented. Understanding the relative contribution of transmission and de novo acquisition to overall incidence is vital to the design of effective intervention measures.

Objectives

To investigate the following questions:

• What is the proportion of transmitted versus newly evolved MDR-TB?
• What is the prevalence of isoniazid resistance among patients never previously exposed to the drug, and what proportion of patients with unsuccessful treatment outcomes evolve isoniazid resistance?
• What is the risk of evolving rifampicin resistance by treating isoniazid-resistant strains with first-line drugs? What proportion of patients who evolve rifampicin resistance after exposure to first-line drugs also evolved isoniazid resistance?
• Do host genotype and variable anti-tuberculosis drug pharmacokinetics contribute to evolving drug resistance?
• In addition, we will investigate why the MTB/RIF Xpert platform does not always report “M. tuberculosis detected” for patients with microscopy smear-positive samples: Is this because of infection or colonization with non-tuberculous mycobacteria (NTM), and if so, which ones?