TB drug resistance on rise in Botswana as HIV epidemic grows

Resistance to tuberculosis (TB) drugs in newly diagnosed TB patients grew threefold in Botswana between 1995 and 2002, jeopardising the country’s achievements in TB control, according to a study published in the July 30^th edition of The Lancet.

Botswana introduced Directly Observed Therapy (Short Course) (DOTS) in 1986 throughout the health care system. DOTS is intended to reduce the risk of treatment failure and drug resistance through direct observation of pill taking by health care workers.

TB drug resistance levels in Botswana remained relatively stable during the 1990s despite a threefold growth in new TB cases between 1989 and 1999.

However, a survey of all patients newly diagnosed with smear-positive TB between March and November 2002 (including previously cured patients who presented with a new TB infection) showed that 10.4% of isolates harboured resistance to at least one TB drug. In 86 of 123 cases the resistance was restricted to a single drug, predominantly streptomycin (52 cases), but ten newly diagnosed patients had multidrug resistance and eleven of 24 retreated patients had multidrug resistance.

The increase in drug resistance in newly diagnosed TB patients from 1995 to 2002 was significant (from 3.7% in 1995-96 and 6.3% in 1999 to 10.4% in 2002, p<0.0001). However there was no observed increase in the frequency of multidrug resistance, nor in the frequency of resistance in retreated patients.

Smear-positive samples were drawn from a larger set of sputum samples (n=2425) from potential TB patients. In order to estimate HIV prevalence among patients with TB, it was necessary to test the sputum samples in an unlinked way, so all available sputum samples were tested using the Oraquick saliva test. Testing revealed a prevalence of 60%, leading researchers to estimate an HIV prevalence of 56%-66% in individuals with confirmed tuberculosis.

Because the research was unlinked and anonymised it was not possible to examine any potential link between HIV status and TB or drug resistance.

The authors warn that the increase in drug resistance is likely to represent an increase in transmission of drug resistant TB in the community, partly driven by poor treatment adherence and interruptions to TB treatment, but also potentially influenced by malabsorption of rifampicin in HIV-positive patients.

They suggest that subsequent expansion of antiretroviral therapy and isoniazid preventive therapy in Botswana could have an impact on the rate of TB drug resistance, but more surveillance will be needed, both in Botswana and other African countries, to evaluate the long-term effects of antiretroviral therapy (ART) and isoniazid therapy on TB drug resistance patterns in individuals newly infected with TB.