Scientists from the US and Russia studying the treatment of patients with extensively drug-resistant tuberculosis (XDR TB) in Tomsk, Russia, concluded that it was possible to contain the global threat from this highly resistant strain with aggressive treatment that reduces deaths and prevents further transmission. Success is maximized by individually assessing drug susceptibility in each patient, and making sure they follow their individually designed treatment programme which ideally includes at least five drugs to which their particular strain of TB is susceptible.
The research was the work of Dr Salmaan Keshavjee, from the Department of Global Health and Social Medicine at Harvard Medical School in Boston, Massachusetts, and colleagues, and is published in an early online issue of The Lancet.
According to the World Health Organization (WHO), one in three people in the world is infected with dormant TB bacteria. People only get ill when the bacteria become active, which can be as a result of a weakened immune system, such as old age, HIV, and certain medical conditions.
The normal treatment for TB is a course of four standard, or first-line, anti TB drugs. If these are misused or not managed correctly (for instance interruption or failure to complete the course), the result can be that non-resistant TB mutates into multidrug-resistant TB (MDR-TB). This form takes longer to treat with second-line drugs, which cost more and have more side effects.
If the second-line drugs are also misused or mismanaged, then the MDR TB can turn into XDR TB, the most drug-resistant form of the disease. It is therefore important that TB control is managed properly to prevent the rise of resistant forms.
For this retrospective cohort study, Keshavjee and colleagues looked at 608 patients with MDR TB in Tomsk, Russia, who were treated in civilian or prison health centres between 2000 and 2004. Their treatment followed the protocol recommended by WHO.
Drug susceptibility testing (DST) on all patients showed that 4.8 per cent (29 patients) had XDR TB, while the rest has non-XDR TB. Each patient was given an individually designed treatment programme based on the result of their DST and any treatments they had been given before. The aim was to give each patient at least five drugs to which their particular strain of TB was susceptible.
If the doctors could not get hold of five effective drugs for a patient, they considered using drugs to which resistance was known, especially if that patient had no history of exposure to them.
The results showed that treatment failure was more common in XDR TB patients than non-XDR TB patients, (31 versus 9 per cent failure respectively). 48 per cent of XDR TB patients and 67 per cent of non-XDR TB patients were either cured or completed their programme.
Frequency and management of adverse events were the same in both XDR and non-XDR TB patients.
Keshavjee and colleagues concluded that:
“The chronic features of tuberculosis in these patients suggest that extensively drug-resistant tuberculosis may be acquired through previous treatments that include second-line drugs. Aggressive management of this infectious disease is feasible and can prevent high mortality rates and further transmission of drug-resistant strains.”
“48 per cent of patients with XDR tuberculosis — often termed untreatable in press reports — responded favourably to treatment,” they added.
In an accompanying Comment, Dr Helen Cox, of the Macfarlane Burnet Institute for Medical Research and Public Health in Melbourne, Australia, and Médecins Sans Frontières (MSF), Cape Town, South Africa, and Dr Cheryl McDermid, also from MSF, Cape Town, South Africa, said:
“Keshavjee and colleagues have shown that both MDR and XDR tuberculosis can be cured with aggressive treatment, with use of the most effective antituberculosis drugs available.”
“Although we should be cautious in our hope to attain such success rates in settings with a high prevalence of HIV, aggressive treatment is the logical strategy to provide the best chance of cure while avoiding the creation of additional drug resistance,” added Cox and McDermid.
“Treatment of extensively drug-resistant tuberculosis in Tomsk, Russia: a retrospective cohort study.”
Salmaan Keshavjee, Irina Y Gelmanova, Paul E Farmer, Sergey P Mishustin, Aivar K Strelis, Yevgeny G Andreev, Alexander D Pasechnikov, Sidney Atwood, Joia S Mukherjee, Michael L Rich, Jennifer J Furin, Edward A Nardell, Jim Y Kim, Sonya S Shin.
The Lancet, Early Online Publication, 25 August 2008.
DOI:10.1016/S0140-6736(08)61204-0.
“XDR tuberculosis can be cured with aggressive treatment.”
Helen Cox, Cheryl McDermid.
The Lancet, Early Online Publication, 25 August 2008.
DOI:10.1016/S0140-6736(08)61205-2.
Sources: The Lancet, WHO.
Written by: Catharine Paddock, PhD