Drug-resistant TB more widespread than thought

Multi-drug resistant tuberculosis is more widespread than thought, warn researchers, who are calling for improvements to the administration of treatments for the killer disease.

Misusing antimicrobial drugs can lead to multi-drug resistant tuberculosis (TB), which is defined as resistant to the two most powerful TB drugs, Isoniazid and Rifampicin.

But researchers warn that multi-drug resistant tuberculosis is only the precursor to extensively drug resistant TB, which is potentially incurable with available drugs as it resists all standard TB drugs and at least one of three second-class drugs.

Looking at four of the six most widely used TB drugs, the scientists — from the Global Project on Anti-tuberculosis Drug Resistance Surveillance — found that both multiple and extensive drug resistance were causing growing numbers of new infections, especially in parts of China and the former Soviet Union.

The results, published in the Lancet today (15 December), are from the third and last phase of the project, running from 1994 to 2002.

The global survey assessed the prevalence, patterns and trends of TB drug resistance in 109 countries.

In the 79 countries surveyed between 1999 and 2002, multi-drug resistance in new TB cases ranged from zero to 14.2 per cent, with a median of one per cent. In the Chinese provinces of Liaoning and Henan, the percentage was over 6.5 per cent.

Resistance to just one drug ranged from zero to 57 per cent, with a median of 10.2 per cent. In Botswana, however, there has been a worrying increase in resistance to any available TB drugs.

The researchers estimate that 424,000 cases of multi-drug resistant TB emerged worldwide in 2004, half of which in China, India and Russia alone.

About a third of the world’s population is latently infected with Mycobacterium tuberculosis, which killed almost two million people in 2004, many of whom were co-infected with HIV. 

While TB can usually be treated with a course of four standard, or first-line, drugs, expensive second-line drugs are needed to treat multi-drug resistant TB.

Because the multi-drug treatment is lengthy and difficult, patients often fail to follow it through. The misuse of second-line drugs that results can lead to extensively resistant TB, which is resilient to first- and second-line drugs.

The emergence of extensively resistant strains is ‘extremely worrisome’, says the report. This type of TB is particularly worrying for people with HIV/AIDS or otherwise compromised immune systems.

"The findings of the Global Project emphasise the importance of implementing sound tuberculosis control activities to prevent further creation of multi-drug resistance," said Mario Raviglione of the World Health Organization (WHO), which led the project with the International Union Against Tuberculosis and Lung Disease.

The results also reveal the need to include high-quality treatment for multi-drug resistance in routine TB control programmes, said Raviglione, head of the WHO’s Stop TB Department.

"Otherwise, extensively drug resistant TB is bound to keep emerging as a fatal variant of TB, especially in high HIV prevalence settings," he said.

The second Open Forum on TB Drug Development in London, United Kingdom, last week, stressed that ensuring the effective use of a new drug regimen is as crucial to TB control as developing the compounds themselves.

"What we need first and foremost is innovation," said Maria Freire, president and CEO of the Tuberculosis Alliance that convened the forum. 

The meeting, where scientists, national regulators, industry and civil society representatives discussed drug candidates, clinical trial design and regulation, represented a welcome resurgence of interest in TB drug development following reports denouncing a lack of awareness about the disease (see Better awareness needed to control TB epidemic).

Reference: The Lancet 2006; 368:2142-54