International study finds "worrying" levels of XDR-TB

Results of an international study published in The Lancet show that 7% of people receiving second-line treatment for tuberculosis (TB) have extensively drug-resistant TB (XDR-TB). The investigators describe this finding as “worrying”.

A total of 1278 people from eight countries were included in the study. All were receiving treatment for multidrug-resistant TB (MDR-TB; resistance to the key first-line drugs isoniazid and rifampicin) between 2005 and 2008. Testing of sputum samples showed that 44% of people in the study had resistance to at least one second-line drug. Prevalence of XDR-TB (defined as resistance to at least one drug in each of the two most important groups of anti-TB therapies – fluoroquinolones and injectable drugs) was as high as 15% in one setting.

Drug-resistant TB is a growing problem. MDR-TB accounted for between 4 and 5% of all new TB cases in 2008. The emergence of XDR-TB has raised the prospect of virtually untreatable cases of TB.

XDR-TB has been reported in 77 countries, but the exact prevalence is unclear. Worryingly, only 27 of the countries hardest hit by MDR-TB routinely test for resistance to second-line therapies.

The Preserving Effective TB Treatment Study (PETTS) was established to examine the risks for and frequency and consequences of acquired resistance to second-line drugs in people with MDR-TB.

Investigators from the study group examined sputum samples from people with confirmed MDR-TB in eight countries (Estonia, Latvia, Peru, Philippines, Russia, South Africa, South Korea and Thailand) before they started second-line therapy. They wished to gain a clear understanding of the prevalence and risk factors of resistance to second-line anti-TB drugs and of the prevalence of XDR-TB.

Almost two-thirds (64%) of the study participants were men and the majority (54%) were aged between 25 and 44. Less than half (46%) were employed, 3% had a history of homelessness, a quarter smoked and 13% were HIV-positive.

Nearly all (94%) had had a previous case of TB and 52% were hospitalised when they were enrolled in the study.

Overall, 44% of people in the study had resistance to a second-line TB drug. But prevalence differed between countries, ranging from 33% in Thailand to 62% in Latvia.

A fifth of participants had resistance to an injectable second-line drug and 13% were resistant to fluoroquinolones. Resistance to other second-line drugs was seen in all countries, with an overall prevalence of 27%.

XDR-TB was seen in 7% of study participants. Prevalence ranged from 1% in the Philippines to 15% in South Korea.

Risk factors for XDR-TB included being male (p = 0.0002); previous therapy for MDR-TB (p < 0.001); previous therapy with injectable second line drugs (p < 0.0001); previous treatment with fluoroquinolones (p < 0.0001); previous third-line treatment (p < 0.0001); and hospitalisation at the time of enrolment (p < 0.0001).

However, the investigators found that prevalence was significantly lower in countries with Green Light Committee approved programmes. The Green Light Committee is a joint Stop TB Partnership and WHO initiative to increase access to high-quality, second-line anti-TB drugs at low prices.

Resistance to second-line injectable therapies was associated with a number of social factors, including imprisonment, unemployment, alcohol abuse and smoking. “Social factors should be taken into account in the management of tuberculosis,” write the investigators.

Commenting on the study, Sven Hoffner of the Swedish Institute for Communicable Diseases said: “These results show that XDR tuberculosis is increasingly a cause for concern.” However, he cautioned that epidemiological surveillance of the condition was still inadequate: “Information remains insufficient to give a clear view of the worldwide distribution and true magnitude of XDR tuberculosis...Updated information on MDR tuberculosis and investigation of the trends are urgently needed, especially since the true scale of the burden of MDR and XDR tuberculosis might be underestimated and seem to be rapidly increasing.”

Dalton T et al. Prevalence of and risk factors for resistance to second-line drugs in people with multidrug-resistant tuberculosis in eight countries: a prospective cohort study. The Lancet, online edition: dx.doi.org/10.1016/S0140-6736(12)60734x, 2012.

Hoffner S Unexpected high levels of multidrug-resistant tuberculosis present new challenges for tuberculosis control. The Lancet, online edition: doi:10.1016/S0140-6736(12)61069-1, 2012.