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
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.
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.
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.
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.
all (94%) had had a previous case of TB and 52% were hospitalised
when they were enrolled in the study.
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.
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
was seen in 7% of study participants. Prevalence ranged from 1% in the Philippines to 15%
in South Korea.
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).
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.
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.
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.”