Strains of tuberculosis (TB) that are resistant to both first-line and second-line drugs could threaten the success of not only tuberculosis programs, but also HIV treatment programs worldwide, according to an article published online this week in The Lancet. The report details a study by a team of investigators from the United States and South Africa, who found that highly resistant strains of TB were more common than previously thought in a rural area of KwaZulu Natal, South Africa, and were associated with high death rates in patients with HIV infection. TB accounts for approximately 1.7 million deaths worldwide, each year, and is the leading cause of death in HIV-infected patients in low-income countries.

In the study, presented by Dr. Neel Gandhi, assistant professor of medicine at the Albert Einstein College of Medicine of Yeshiva University, the researchers tested patients with suspected tuberculosis for MDR and XDR strains. They found that of 1,539 patients, 221 had MDR tuberculosis, and 53 of these had XDR tuberculosis. The prevalence rates in a group of 475 patients with confirmed tuberculosis were 39% for MDR and 6% for XDR tuberculosis�higher rates than previously reported in the area. All patients with XDR disease who were tested for HIV were co-infected with the virus, and all but one died.

(Dr. Gandhi conducted this research while he completing fellowships at Yale University School of Medicine and Emory University. He joined the Einstein faculty in August 2006.)

Further complicating the problem posed by multidrug-resistance is the fact that the epidemics of tuberculosis and HIV in South Africa are closely linked. Risk of tuberculosis disease is greatly increased in people with HIV infection, and multidrug-resistant (MDR) tuberculosis is emerging as a major cause of death in these patients. The term extensively drug-resistant (XDR) tuberculosis has recently been used to describe strains that are resistant to second-line drugs�i.e., drugs that are used if the recommended first drug treatment regimen fails.

Investigation of the patients� histories and the genetic makeup of the infecting bacteria suggested that transmission of XDR strains had occurred recently, that transmission between individuals had occurred, and that some patients had been infected while in hospital. The researchers say that these findings are worrying, since hospitals in low-income countries have limited infection-control facilities and a high proportion of susceptible HIV-infected patients. They recommend action to tackle the problem of resistant strains that could jeopardise attempts to control tuberculosis and prevent mortality in HIV patients. 

In addition to Dr. Gandhi, other researchers involved in the collaborative project were Dr. Gerald Friedland, director of the AIDS Program at Yale University; Dr. Tony Moll, of the Church of Scotland Hospital in Tugela Ferry, South Africa; and Drs. Willem Sturm, Robert Pawinksi and Umesh Lalloo, of the Nelson R. Mandela School of Medicine, in Durban, South Africa.