HANOVER, NH -- 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, Medecins Sans Frontieres (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, professor of medicine at Dartmouth Medical School and chief 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 performed 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, Medecins Sans Frontieres 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.

(First published in News @ DMS )

The DARDAR Health Project at DMS has been fighting AIDS in Tanzania—one patient, one scientist, and one student at a time. The project began in 2000 as an ambitious but singlefocus study of tuberculosis (TB) in AIDS patients. Now it encompasses a health clinic in Dar es Salaam, an elective for DMS students, a fellowship underwritten by the National Institutes of Health's Fogarty International Center, and studies related to HIV, TB, and hepatitis C. Next on the horizon is the establishment of a pediatric program in Dar es Salaam, thanks to a $2-million grant from the Foundation for the Treatment of Children with AIDS (FTCA).

"The new grant actually provides money for a number of different projects," explains Dr. Fordham von Reyn, principal investigator for DARDAR. "The most important of these is a comprehensive HIV-care program for HIV-positive children of the mothers in our DARDAR study. We have done a survey of approximately 1,200 women in the study and have estimated that they have about 100 HIV-positive children, none of whom are in treatment."

Antiviral: "Many of the women in the study have already lost children to AIDS," continues von Reyn. "A major part of this grant will be to build a facility, hire . . . staff, provide the purchase of the expensive antiviral drugs for HIV, and then begin a treatment program."

The grant will also fund a study aimed at keeping pregnant women with HIV and TB from transmitting TB to their babies. (There are already programs to prevent mother-to-child HIV transmission.) Von Reyn and his colleagues in Dar es Salaam have found that about 15% of people with HIV in Tanzania also have previously unrecognized active TB; they suspect that a similar percentage of HIV-positive pregnant women have undiagnosed TB. "There is very little known about how to diagnose that," von Reyn explains, "the best way to treat it, and the best way to manage their newborns."

Endowment: A new DMS faculty endowment—named in honor of John L. Steffens, a 1963 Dartmouth College alumnus and a major supporter of FTCA—is also being funded by the grant. The position will be filled by an infectious-disease specialist who will serve as director of the new pediatric program.

Investing in the future is an important component of DARDAR, which provides learning opportunities for students from DMS and Muhimbili University College of Health Sciences. This past fall, Cara Mathews, DMS '05, became the first student to do DARDAR's six-week elective. The experience affected her deeply. "It is part of me, a part of every day, and a part of my future," says Mathews.

She divided her time in Tanzania between seeing patients at the DARDAR clinic and participating in rounds at the Muhimbili University-affiliated hospital in Dar es Salaam. "I got to see the patients when they were ill, and that was a great experience for me because the diseases are so different than what we would see here," recalls Mathews. While she was fascinated by the cases of malaria, which is uncommon in the U.S., the Tanzanian students were intrigued by the one patient who had had a heart attack—a condition Mathews had seen any number of times but the Tanzanians had not. "I had kind of thought, 'Okay, we'll treat him, and let's move on.' [But] we just stayed there and stayed there and talked about him."

Encounter: Students who go to Dar es Salaam will "encounter both infectious diseases and other diseases . . . that they would never encounter in their careers here," says Dr. Richard Waddell, a research assistant professor of medicine at DMS and one of the directors of DARDAR.

"You also get to see how these diseases are dealt with in a resource-poor setting," says Dr. Lisa Adams. Adams is a member of the DMS faculty and oversees the Fogarty Fellowship part of DARDAR. It allows graduate students and postdoctoral fellows from Muhimbili University to study at DMS and Boston University in one of several areas related to HIV and TB—vaccine research, mucosal immunology, behavioral change, and treatment research.

The name DARDAR is based on the first syllables of Dartmouth and Dar es Salaam; in addition, "dada" means "sister" in Kiswahili, one of the local languages. That way of describing the relationship between Dartmouth and Muhimbili University has become ever more apt in the years since the program's founding. Not only strong working relationships but friendships, too, have arisen from the collaboration, according to Dr. Kisali Pallangyo, the principal of Muhimbili University College of Health Sciences.

Infected: Although HIV statistics in Tanzania remain daunting—as many as 3.3 million of the country's 36 million residents are infected—DARDAR "holds great promise for growing and serving a community that has been severely affected by the AIDS epidemic," according to Dr. Gary Noel, a 1977 Dartmouth College graduate and one of the founders of FTCA.

Pallangyo agrees. "The future of this collaboration is very promising," he says.

Grant will fund children's clinic in Tanzania - A national foundation with a mission of supporting programs for children with AIDS made its final grant on Wednesday - World AIDS Day - with the distribution of $1.6 million to the section of Infectious Disease and International Health at Dartmouth Medical School and Dartmouth-Hitchcock Medical Center.

Full story at Medical News Today.