A hardy strain of tuberculosis (TB) bacteria spreading in many parts of the world, called W-Beijing, is known for causing disease that is difficult to treat. Although some studies point to drug resistance as the reason behind this, data from Indonesia published this week by Ida Parwati and colleagues suggest that traits inherent to the strain could be to blame.

 

The authors, from medical research institutions in Indonesia and the Netherlands, followed hundreds of patients admitted to three clinics in Jakarta and Bandung. They found that being infected with the W-Beijing genotype strain was an independent risk factor for having a positive TB test at the end of a six-month treatment regime.

 

“Tuberculosis treatment was less effective against Beijing genotype strains, and this was not explained by drug resistance,” they write in The Journal of Infectious Diseases.

 

Experts say the study is the largest and most complete investigation of whether particular strain families are associated with less successful treatment for TB. The findings help to explain why the Mycobacterium tuberculosis W-Beijing genotype, which emerged in Asia in the mid-1990s, is gaining ground in many parts of the world — a troubling prospect for global TB control efforts.

 

Under the Millennium Development Goals, the World health Organization aims to halve the prevalence of TB deaths by 2015, relative to 1990. The Organization estimates that more than two million people worldwide are infected with TB bacteria, and cases of the disease that show resistance to antibacterial drugs have appeared in every affected country. The death toll runs in the thousands per day, and countries in the developing world, particularly in Asia, are hardest hit.

 

The W-Beijing genotype family of M. tuberculosis bacteria is one of the more widespread, according to the authors. Although research in Vietnam and Russia has linked W-Beijing TB with cases of treatment failure, little is known about whether this is solely due to the strain’s capacity to withstand antibiotics.

 

Parwati and colleagues recruited a high number of patients for their study, which allowed the team to separate out drug resistance as a variable in their analysis. Between 2000 and 2005 they collected data on TB diagnosis, treatment, symptoms and disease history for 818 patients whose adherence to the six-month treatment regime was monitored closely. After two months and at the end of treatment, sputum samples that turned out positive for M. tuberculosis were examined further with a method used to detect and identify the type of bacteria involved.

 

“Almost twice as many patients who were initially infected with a W-Beijing genotype strain as those infected with another strain had a positive sputum culture result after 6 months,” write the authors. Because they tested the bacteria for susceptibility to the drugs isoniazid and rifampicin, they were able to show that the higher risk of treatment failure was also true for patients infected with TB bacteria sensitive to treatment.

 

The finding is “extremely interesting and concerning”, says Helen Cox, epidemiologist with Médecins Sans Frontières and the Burnet Institute in Melbourne, Australia. “[It] has significant implications for TB control internationally, particularly the use of current TB treatment regimens which may be inadequate for a small but important proportion of patients.”

 

Mark Nicol, from the University of Cape Town and National Health Laboratory Service in South Africa, notes the mounting evidence suggesting that W-Beijing strains of M. tuberculosis have a selective advantage over other strains. “This [study] adds one more piece to the puzzle explaining why this strain lineage may be particularly successful.”

 

Parwati et al. say that apart from a capacity to resist treatment with antimicrobial drugs, shown with previous research, “Beijing strains may have additional properties that give them a selective advantage”. Virulence could be one of these properties, they suggest. However, the illness caused by these bacteria was no more severe than that caused by other strains.

 

Most patients included in the study were able to stick to the long treatment regime, so adherence is unlikely to explain the result.

 

Nicol offers one possible explanation by suggesting that in the course of treatment, W-Beijing bacteria may have acquired drug resistance faster than other strains. “The authors do not comment on the proportion of drug resistant strains amongst the isolates cultured after 2 and 6 months of therapy — this would have been important to know.”

 

It is also possible that W-Beijing TB is resistant to drugs other than the two tested in the study, notes Nicol. These drugs, rifampicin and isoniazid, were given to patients for the entire six-month treatment period. But the first two months also included daily doses of pyrazinamid and ethambutol.

 

Otherwise, something about the make-up of this strain could be responsible for treatment failure, says Nicol — a possibility also noted by Parwati and colleagues. The authors call for further research to clarify the factors that could be responsible, and how they might affect TB treatment success.

 

Cox and Nicol point out that the W-Beijing strain is responsible for a rising proportion of the global number of TB cases. “It seems likely that this strain is going to pose a particular problem to TB control efforts worldwide,” says Nicol.

 

The independent link with treatment failure is one worry — but together with signs of drug resistance for the strain, it makes for an “alarming” outlook for efforts to treat the disease, according to Cox. “If Beijing is contributing further to our failure to control TB, then we have even more obstacles to overcome.”