Dartmouth Medical School collaboration in Tanzania may alter assumptions about the diagnosis of tuberculosis in HIV-infected people

New findings from a Dartmouth Medical School collaboration in Tanzania may alter assumptions about the diagnosis of tuberculosis in HIV-infected people, and prompt a major change in way TB testing is routinely done in the developing world.

Writing in the journal, “Clinical Infectious Diseases,” researchers found that while the co-existence of HIV and TB is well-known, traditional screening methods for TB are allowing significant number of cases of subclinical, active tuberculosis to go undetected. In apparent response to the these findings, the international physicians’ group, Médecins Sans Frontières (Doctors Without Borders), has recommended that all HIV/AIDS patients receive the more sensitive and accurate TB culture test used in the Tanzania research project.

This latest research was reported by investigators in the DARDAR Health Study, a collaboration between Dartmouth Medical School and the Muhimbili University College of Health Sciences in Dar Es Salaam, Tanzania. C. Fordham von Reyn, MD, Chief of the Section of Infectious Disease and International Health at Dartmouth-Hitchcock Medical Center, is the leader of the DARDAR project and author of the new study with Lillian Mtei MD, and other colleagues in Tanzania.

“Our study team found that when we used the same comprehensive diagnostic approach to tuberculosis available in industrialized countries 15% of HIV-infected patients in Tanzania had previously unrecognized active tuberculosis,” von Reyn said. “These findings emphasize the importance of improving the availability of TB diagnostic tests in the developing world.”

In the developing world, TB is the leading cause of death among people with HIV infection. Thus, diagnosis and proper treatment of TB is a critical component of HIV treatment in these regions. Unfortunately, HIV infection can actually make TB more difficult to diagnose, creating additional challenges for health workers.

The DARDAR team, working from their clinic in Tanzania, tested HIV-positive subjects with traditional skin testing for TB and physical exams, followed by chest x-rays and microscopic examination of sputum samples. They then preformed cultures of these samples, incubating them in a controlled lab environment a procedure used widely in the industrialized countries, but typically not available or recommended in resource poor countries . In 10 cases sputum culture was the only positive test. These patients with “subclinical” tuberculosis denied symptoms when they were first examined and had normal chest x-rays.

“…Previously undiagnosed tuberculosis was common, often asymptomatic, and difficult to detect on the basis of a single evaluation,” the authors reported. In addition the authors noted that the HIV-infected patients with subclinical tuberculosis had a much better prognosis than previously observed, perhaps due to earlier diagnosis and treatment. Failure to diagnose an subclinical case of active TB and treat with standard multiple drug treatment could result in improper single drug treatment for latent TB, which has the potential to induce TB drug resistance.

The findings are important because existing standards for detection of TB rely on using cough as the indication for screening, with chest x-ray as the screening method. “Our study demonstrates that neither cough nor chest radiography would have identified the 10 subjects (in the study) with subclinical tuberculosis,” write the authors.

In an accompanying editorial in the same issue, Dr. David L. Cohn said the findings serve “as a reminder of the complexity of tuberculosis in HIV-infected patients in high-burden countries. This study … presents a potential new challenge for the diagnosis of subtle tuberculosis in asymptomatic patients and it may have implications with regard to treatment decisions.”

In the wake of the study, Médecins Sans Frontières issued an advisory from its South Africa office, urging patients to insist on the sputum culture test if traditional TB skin and X-ray tests come back negative.

In addition to Dr. von Reyn and colleagues from the Muhimbili University College of Health Sciences in Dar Es Salaam, Tanzania, fellow authors of the paper included members of the Department of Epidemiology at Boston University School of Public Health, the Public Health Research Institute in Newark, NJ, and the National Public Health Institute in Helsinki, Finland.