Half of Russian XDR-TB patients cured with aggressive treatment

Just under half of 29 patients diagnosed with extensively drug-resistant tuberculosis (XDR-TB) in a Russian TB treatment programme were cured through aggressive treatment between 2000 and 2004, US and Russian researchers report in the online edition of The Lancet on August 25^th.

Tuberculosis is classified as extensively drug-resistant when a patient’s TB is resistant to the most commonly used second-line TB drugs (any aminoglycoside TB drug or capreomycin, and any fluoroquinolone). It usually arises as a result of the failure of multiple courses of TB treatment, due either to non-adherence to treatment, failure to complete the course of medication, poor quality drugs or an incorrect choice of drugs for second-line treatment.

MDR- (multi-drug-resistant) and XDR-TB can also be transmitted from one person to another, particularly in settings where large numbers of vulnerable people are congregated with poor ventilation, such as hospitals and prisons.

XDR-TB is a growing problem in many parts of the world, particularly South Africa, and is commonly described in press reports as a `killer strain` or as being untreatable. However there is little information on the treatment responses of people diagnosed with XDR-TB.

Russia has a high frequency of MDR-TB: by 2002, just over 13% of new TB cases in the Tomsk district of western Siberia were multi-drug-resistant, and 43% of previously treated TB cases had MDR-TB. This was despite the introduction of directly observed short-course (DOTS) treatment for all TB cases, as well as individualised treatment of MDR-TB based on drug susceptibility testing, in the period leading up to 2002.

The study reported in The Lancet was led by Dr Salmaan Keshavjee of the Department of Global Health and Social Medicine at Harvard University in the United States.

It evaluated treatment responses in 608 consecutive patients diagnosed with MDR-TB between 2000 and 2004 in the Tomsk district. MDR-TB was defined as baseline resistance to isoniazid and rifampicin.

MDR-TB was diagnosed through drug susceptibility testing and subsequent treatment was individualised according to the drug resistance report and previous treatment history, containing at least five active drugs wherever possible and given as directly observed therapy. Patients received inpatient treatment for the entire duration of the treatment phase involving intravenous treatment (six to nine months), and were then treated in the community unless they were alcoholic, homeless or a prisoner. Treatment generally lasted 18 months after culture conversion.

Twenty-nine of 608 patients had XDR-TB (4.8%). Less than 1% of all MDR-TB patients were HIV-positive, and none of these had XDR-TB.

Treatment outcomes were significantly better in those with MDR-TB than in the XDR-TB group, but almost half of XDR-TB patients (48%) were cured by their course of treatment. In comparison 63% of those with MDR-TB were cured (p = 0.04).

Although there was a significantly higher rate of treatment failure in XDR TB patients (31% vs 8%, p=0.0008), there was no significant difference in the death rate (7% vs 5%), the treatment default rate (14% vs 20%), median time to culture conversion (two months), adherence or the rate of adverse events.

In an accompanying editorial Helen Cox and Cheryl McDermid, doctors working with Médecins Sans Frontières in South Africa note the high cure rate that was achieved for MDR-TB, and highlight the characteristics of the health service that delivered the results. The programme was the result of a partnership between the regional TB programme and prison services, a laboratory equipped to carry out drug susceptibility testing and an international NGO that improved local skills in treating MDR-TB. Local ownership of the programme was key, as was the commitment of local government to treat MDR-TB.

However they also note the key limitation of the study: the low HIV prevalence among TB patients treated. “We should be cautious in our hope to attain such success rates in settings with a high prevalence of HIV,” they say. Keshavjee’s findings need to be urgently replicated in other settings, particularly for HIV-positive individuals, they recommend.

Nevertheless, “aggressive treatment is the logical strategy to provide the best chance of cure while avoiding the creation of additional drug resistance,” they conclude.