MDR-TB numbers could keep growing despite improved treatment

Up to one-in-three tuberculosis cases in Russia could be multidrug resistant by 2040, and one-in-eight in India, unless more is done to stop the person-to-person spread of drug-resistant TB and sub-optimal treatment, a modelling study published this week in The Lancet Infectious Diseases predicts.

The model found that 70% of all multidrug-resistant tuberculosis (MDR-TB) cases in the period between 2000 and 2040 will occur as a result of person-to-person transmission.

MDR-TB spreads with ease in prisons, health care settings and other crowded places that lack infection control measures. A lack of suitable diagnostics, a lack of active case finding and sub-optimal treatment exacerbate person-to-person spread, by slowing down diagnosis and treatment of MDR-TB.

Research carried out in South Africa into the spread of extensively drug-resistant tuberculosis (XDR-TB) found that household transmission was less important than previously assumed. The study found that in 83% of cases where two people with XDR-TB had infections that were genetically linked, those patients lived in different provinces from one another and had often travelled long distances to health care facilities or reported visiting non-healthcare settings where groups of people gather, so-called congregate settings.

The model published in The Lancet Infectious Diseases is designed to project the incidence of MDR-TB and XDR-TB up to 2040 in four countries with a high burden of MDR-TB: India, the Philippines, Russia and South Africa. The model also estimates the proportions of cases which occur due to sub-optimal diagnosis and treatment (acquired drug resistance) and to person-to-person transmission.

The model uses data from a large international study of second-line TB treatment, the Preserving Effective TB Treatment Study (PETTS). PETTS compared second-line treatment outcomes in countries that obtained lower-cost drugs through the World Health Organization (WHO)/Stop TB Partnership Green Light Committee. The Green Light Committee, established in 2000, reviews MDR-TB treatment programmes to check if the proposed use of second-line TB drugs obtained through the scheme will be rationally based on local drug resistance data and treatment protocols. PETTS showed that treatment programmes approved by the Green Light Committee had a lower rate of drug resistance after second-line treatment and better treatment outcomes.

The investigators took into account the incidence of TB in each country, the estimated burden of latent TB infection and progression to active TB, the burden of HIV in each country, population growth, and the impact of treatment of HIV and TB. The model also included stages of development of drug resistance and assumed that the roll-out of treatment for both drug-sensitive TB and MDR-TB would rise sharply for five years before levelling off at a higher rate of coverage. Finally, the model made the optimistic assumption that each country would achieve the UNAIDS target of 90% of people with HIV receiving treatment by 2020.

Modelling showed that the proportion of new TB cases that are multidrug resistant will rise in each country, with the biggest increase expected in Russia. By 2040, 12.4% of new TB cases will be multidrug resistant in India, 8.9% in the Philippines, 5.7% in South Africa and 32.5% in Russia.

Similarly, the proportion of new cases of drug-resistant TB that are extensively drug-resistant will grow to around 9% in each country by 2040.

To put these figures in context, the WHO’s Global Tuberculosis Report 2016 estimated that 115,000 new cases of TB occurred in Russia in 2016, of which 22% were drug resistant (24,000 cases). In India, approximately 2.8 million cases of TB occurred in 2016, of which 2.5% were drug resistant (70,000 cases).

Of new cases of MDR-TB, the researchers estimate that less than 30% will be acquired as result of a course of treatment that was sub-optimal or not completed. Person-to-person transmission will account for the majority of new cases of MDR-TB. More disturbingly, the proportion of new cases of XDR-TB that will be acquired as a result of treatment will continue to fall, so that around 60% of new cases of XDR-TB will be due to person-to-person transmission by 2040.

The investigators say that national TB programmes need to intensify case finding and reduce loss to follow-up between diagnosis and treatment in people diagnosed with MDR-TB, as well as improving the use of drug susceptibility testing to guide treatment decisions.

“Current tools are insufficient to reverse the epidemics of MDR or XDR tuberculosis,” the authors conclude. “Enhanced interventions to reduce tuberculosis transmission and expansion of improved treatment…are necessary to stop the spread of MDR and XDR tuberculosis.”