Scanning electron micrograph of TB bacteria. Image credit: NIAID (CC BY 2.0)
Multidrug-resistant tuberculosis, often shortened to MDR-TB, is a public health crisis with close to half a million patients falling ill each year globally. Some strains of the bacterium Mycobacterium tuberculosis, which causes tuberculosis disease, are resistant to the two most effective drugs used to treat the infection. As a result, patients with MDR-TB require a longer treatment of up to two years, often with severe side effects and a low chance of cure. Resistant strains of the bacteria are usually weaker than drug-susceptible strains. So, for a long time, large MDR-TB epidemics were considered to be unlikely and outbreaks of MDR-TB were often regarded as locally contained phenomenona.
Recent research has shown that MDR-TB strains are often just as likely as drug-susceptible strains to be transmitted and therefore just as likely to cause large country-wide outbreaks. It has also become clear that the resistant bacteria acquire additional mutations over time to compensate for any weakness. However, a lack of detailed history of outbreaks has meant the role of the genetics of MDR-TB bacteria has not been fully understood. Without this knowledge, prevention of future outbreaks and containment of the most successful strains in areas with a high burden of disease is difficult.
To address this, Merker, Barbier et al. reconstructed the evolutionary history of MDR-TB strains obtained in 2001–2006 from an outbreak in Uzbekistan. Whole genome sequencing followed by statistical analysis highlighted one predomininant strain that likely emerged in the mid-1970s, when the country was part of the former Soviet Union. This strain has since acquired mutations that make it resistant to eight different drugs. The most successful bacterial strains found also had compensatory mutations that seem to aid their survival.
In 1998, the health authorities implemented a TB treatment program in the region without knowing the true extent of the MDR-TB outbreak at that time. Testing for drug resistance was not routinely available, and Merker, Barbier et al. saw that MDR-TB strains resistant to the drugs used spread in the study region and were later also found independently in Russia.
A lack of routine testing for drug resistance in TB remains common in many countries with high burdens of the disease. These findings emphasize the need for universal access to tests for TB drug resistance, therapies tailored for individual patients, and access to new and repurposed drugs to reduce the risk of future outbreaks of drug-resistant TB.
