by Katie McQue,
SCRIP World Pharmaceutical News
UK, 20 Apr 2009 - Multiple drug-resistant tuberculosis is rife in the former Soviet Union and parts of Southeast Asia, and efforts to fight resistance are inadequate, a study partly funded by Lilly of the worldwide prevalence of drug-resistant tuberculosis has revealed.
The report, published online in The Lancet on April 16th, found the highest resistant rate in Azerbaijan, with 22.3% of new treatment-naïve TB cases classified as multiple drug resistant (MDR).
Moldovia's MDR rates were the second highest, at 19.4%, followed by Ukraine, with a rate of 16%. Countries in the Americas, western and central Europe and Africa reported the lowest prevalence of MDR TB.
The epidemiology survey was conducted by the World Health Organisation's Global Project on Anti-tuberculosis Resistance, which gathered data from more than 90,000 patients in 83 countries between 2002 and 2007. Where possible, data for HIV status and resistance to second line drugs were also obtained.
"The countries of the former Soviet Union are facing a serious and widespread epidemic with the highest prevalence of MDR tuberculosis ever reported in 13 years of data collection. Almost half of all tuberculosis cases in countries of the former Soviet Union are resistant to at least one drug and one in five cases are MDR," said study author Dr Abigail Wright of the WHO. "In this region, MDR-tuberculosis cases have more extensive resistance patterns and the highest rate of XDR (extensively drug-resistant) tuberculosis."
The study called for anti-tuberculosis efforts to be accelerated and backed by strong political commitment in order to quash the growing epidemic.
"Outliers were identified in all regions, suggesting a prevalence of MDR tuberculosis is linked to the performance of national tuberculosis control programmes," added Dr Wright.
In 2000, the WHO implemented a directly observed therapy short course (DOTS); however, a WHO study published shortly after found that the strategy would not control multiple drug resistance in countries with widespread resistance.
DOTS consists of the administration of short-course chemotherapy regimens with first-line drugs under direct observation. New cases of TB receive an initial phase of treatment with four drugs (isoniazid, rifampicin, pyrazinamide and streptomycin or ethambutol) for two months under strict direct observation, followed by a continuation phase with rifampicin and isoniazid for four months.
"We know how to prevent the emergence of drug resistance: consistent use of good, basic tuberculosis control. The bad news is that this measure is not being done in affected countries," said Dr Martien Borgdorff, executive director of the KNVC Tuberculosis foundation, in The Lancet's commentary article.
"This drug-resistant epidemic is being tackled with antiquated and inadequate diagnostics, drugs, and vaccines. Fortunately, progress is being made: rapid diagnostic tests are in late stages of development, three drug candidates with new mechanisms of action have recently shown positive results in trials, and six vaccines will be in human trials by the end of the year," Dr Borgdoff continued.
Potential antibiotics in the clinic include Bayer's moxifloxacin, with Phase III results expected next year. The drug is already approved for various skin and respiratory infections.
Tibotec is developing novel adenosome triphosphate (ATP) synthase inhibitor, diarylquinoline (TMC-207), which promisingly displayed bactericidal activity of a similar magnitude to rifampicin and isoniazid in Phase II. The company says an NDA filing is expected by 2010.
The Japanese firm Otsuka also has a Phase II candidate, OPC-67683 – an oral mycolic acid synthesis inhibitor (scripnews.com, December 1st, 2006). The US FDA awarded it orphan status for pulmonary tuberculosis in 2007.