Poor infection control, not poor adherence, responsible for vast majority of drug-resistant TB in Chinese study

A new Chinese study suggests that the majority of cases of drug-resistant tuberculosis (TB) among patients undergoing treatment for the disease may be due to new infections, not acquired resistance. If confirmed in future studies, the research, in the March 15 issue of the Journal of Infectious Diseases, may drive a major shift in strategy for controlling TB. In particular it suggests that poor infection control, not poor adherence, is the main driver of drug resistance

The authors of the new study, Qian Gao, PhD, and coworkers in Shanghai, China and elsewhere, used molecular genetics and drug susceptibility testing to investigate patients with TB who were treated in Shanghai hospitals during 1999-2004. They focused on 38 patients from whom samples were available before and during treatment. The researchers found that the strains of TB in the samples taken before treatment were genetically different from those taken during treatment in 87% (33 out of 38) of patients.

To determine the relative proportion of drug resistance caused by re-infection or mutation, the authors excluded six patients who were initially infected with resistant TB and then became drug-susceptible or resistant to fewer drugs. In the remaining 32 patients, the initial sample was drug-susceptible or resistant to at least one drug and the subsequent sample resistant to one or more drugs.

Of these patients, 84% (27 patients) had before-and-during samples with different genetic patterns and only 16% (five patients) had identical patterns. Thus, there were more than five times as many cases caused by re-infection compared to mutation.

"It was surprising to find a high rate of primary drug-resistant strains among treated patients," said Dr Gao. "This overturned the common belief that drug resistance among treated patients is always acquired."

The investigators also noted that one-quarter of the patients acquired a multi-drug resistant strain between their first and second samples, indicating the extent to which the spread of MDR TB may be a consequence of patient-to-patient transmission rather than poor adherence to the treatment regimen.

The median time between the first and second samples was four months.

Limitations of the study included the exclusion of many patients without sample results, reliance on previously collected data in which some patients might have been misclassified, use of computerised drug susceptibility data, and the unknown contribution of mixed infections. Nevertheless, the findings are a warning, say the authors.

Although better diagnostics, drugs, and effective vaccines for TB are clearly needed, the authors said, "Our findings highlight the urgency of accelerating efforts to interrupt the transmission of drug-resistant tuberculosis." The research shows improved methods of preventing TB transmission may be needed in the very facilities and communities where TB patients are treated.