Tuberculosis

Re-emergence of Drug-resistant Tuberculosis in HIV Positive People Is Due to Re-infection, Not Treatment Failure

Over the past 2 years, researchers have reported a growing number of cases of multidrug-resistant (MDR) and extensively drug-resistant (XDR) tuberculosis (TB) in people with HIV/AIDS.

The first large outbreak of rapidly fatal XDR-TB, in rural KwaZulu-Natal province in South Africa, was reported at the XVI International AIDS Conference in Toronto in August 2006.

More recently, at the at the 15th Conference on Retroviruses and Opportunistic Infections this month in Boston, investigators with the Tugela Ferry Care and Research Collaboration provided further information from a case-control study of patients at Church of Scotland Hospital in KwaZulu-Natal. Overall, more than 530 cases of MDR or XDR TB were seen at the hospital between June 2005 and August 2007, more than 300 of them extensively drug-resistant.

The present analysis looked at patients who had recurrent TB with increasing drug resistance (susceptible to MDR or XDR, or MDR to XDR). Among 170 patients in the retrospective case-control study, 43 had baseline and follow-up sputum cultures obtained at least 1 month after the initial culture. A polymerase chain reaction method known as spoligotyping was used to determine TB genotypes.

Results

• Among these 17 patients (11 men, 6 women), 15 tested HIV positive and the median CD4 cell count was about 90 cells/mm3.
• All had differing spoligotypes between the initial and follow-up TB isolates, suggesting re-infection with a new strain.
• 15 of the 17 patients died within 2 weeks after collection of the second sputum sample and before MDR or XDR TB had been confirmed.

Conclusion

"Exogenous re-infection with drug-resistant strains was responsible for all new drug resistance among patients in the first year after TB diagnosis," the researchers concluded -- rather than emergence of drug resistance due to failed treatment related to insufficiently potent drugs or poor adherence.

The investigators expressed concern over these repeat infections, recommending that, "In addition to supporting medication adherence, TB control programs must urgently address infection control to reduce transmission of resistant TB and curtail the rise of MDR and XDR TB in HIV-infected patients."

Speaking at a press briefing at the conference, investigator Neel Gandhi said that the hospital had instituted several such measures, including better isolation of patients with coughs, more rapid diagnosis and treatment, and steps to reduce the time HIV positive people spend in the hospital, where drug-resistant TB is prone to spread.

Yale Univ Sch of Med, New Haven, CT; Albert Einstein Coll of Med, Bronx, NY; Nelson R Mandela Sch of Med, Durban, South Africa; Philanjalo and Church of Scotland Hosp, Tugela Ferry, South Africa.

Reference

J Andrews, Neel Gandhi, P Moodley, and others (Tugela Ferry Care and Research Collaboration). Exogenous Re-infection with Multidrug- and Extensively Drug-resistant TB among TB/HIV Co-infected Patients in Rural South Africa. 15th Conference on Retroviruses and Opportunistic Infections (CROI 2008). Boston, MA. February 3-6, 2008. Abstract 143.