High Mortality Due to Multidrug-resistant Tuberculosis among HIV Positive Patients in South Africa

By Liz Highleyman

Tuberculosis (TB) is a second epidemic that co-exists with the HIV/AIDS epidemic in much of the developing world, and is responsible for considerable morbidity and mortality, especially among people coinfected with both TB and HIV.

At the XVI International AIDS Conference in Toronto, several presentations focused on HIV/TB coinfection. Kevin De Cock, MD, director of the World Health Organization HIV/AIDS Department, called for TB management to be prioritized "at the head of AIDS management."

In recent years there has been a growing awareness of the problem of multidrug-resistant (MDR) TB, which is resistant to the commonly used first-line therapies, as well as the emergence of extensively drug-resistant (XDR) TB, which is resistant to all first-line and most second-line drugs. The Centers for Disease Control and Prevention have documented about 350 cases of XDR TB worldwide.

In a late-breaker presentation at the conference, researchers from South Africa and the U.S. reported on a cross-sectional study to determine the extent and consequences of MDR TB among patients in a rural district in KwaZulu-Natal, South Africa. In this district, antiretroviral therapy has significantly reduced the rate of death among people with HIV/AIDS. Of the remaining deaths, however, more than two-thirds are due to MRD TB.

The researchers performed sputum cultures and drug susceptibility tests on individuals with known or suspected TB at a rural district hospital between January 2005 and March 2006. Spoligotyping (a PCR method that simultaneously detects and determines the type of TB) was performed on isolates resistant to all tested TB drugs (isoniazid, rifampin, ethambutol, streptomycin, ciprofloxacin, and kanamycin).

Results

Between January 2005 and March 2006, sputum collected from 1540 individuals revealed that 544 patients (35%) were culture-positive for Mycobacterium tuberculosis.

Of these, 221 (41%) had MDR TB resistant to isoniazid and rifampicin.

53 patients (24% of MDR isolates, 10% of all positive cultures) had XDR TB, with resistance to all first-line and second-line drugs tested.

Spoligotyping revealed that nearly 90% of XDR TB patients were infected with a genetically similar TB strain (26 out of 30 isolates).

52 of 53 XDR TB patients (98%) died during follow-up; the median survival time after sputum collection was just 16 days (range 11-136).

All 47 XDR TB patients with known HIV status were HIV positive, and many had AIDS.

51% of patients had not been previously treated for TB, indicating that they did not develop resistance due to suboptimal prior therapy.

36% had no history of prior hospitalization, suggesting that XDR TB was transmitted in the community outside of a hospital setting.

Conclusion

"Increased surveillance in rural South Africa revealed a markedly greater MDR TB prevalence than previously recognized, with evidence of recent nosocomial and community transmission of XDR TB in HIV coinfected patients," the researchers concluded. "The convergence of the TB/HIV epidemic with MDR and XDR TB in resource-poor settings is a deadly threat to gains in survival achieved by TB [directly-observed therapy] and antiretroviral therapy."

Reference
N R Gandhi, A Mol, R Pawinski, and others. High Prevalence and Mortality from Extensively-Drug Resistant (XDR) TB in TB/HIV Coinfected Patients in Rural South Africa. August 13-18, 2006. XVI International AIDS Conference. Toronto, August 13-18, 2006. Abstract THLB0210.