The incidence, distribution, and control of tuberculosis

Mar 1 2006

A reduction in tuberculosis (TB) incidence, prevalence and death rate can be achieved by 2015 in most parts of the world, with the greatest challenges occurring in Africa and Eastern Europe, according to a projection by the Stop TB Department of the World Health Organization.

This assessment appears in the first issue for March 2006 of the American Journal of Respiratory and Critical Care Medicine, published by the American Thoracic Society.

Tuberculosis is a contagious, potentially fatal infection primarily caused by the airborne bacterium Mycobacterium tuberculosis. Factors that contribute to the spread of TB, particularly in developing nations, include: overcrowding and unsanitary living conditions in urban areas, homeless shelters and prisons; the emergence of multi-drug resistant disease strains; and the spread of HIV and AIDS, which weaken the human immune system and make infection more likely.

Wing Wai Yew, M.B., of the Tuberculosis and Chest Unit at Grantham Hospital in Hong Kong, China, and a colleague examine the worldwide state of TB epidemiology, diagnosis and treatment as shown through research results published during 2005.

"In sub-Saharan Africa, tuberculosis remains the top cause of HIV-related mortality," said Dr. Yew. "The incidence of tuberculosis in adults receiving highly active anti-retroviral therapy is lower than in untreated HIV-infected adults, but still higher than among HIV-negative adults."

Another study cited by the authors highlights the importance of recent infection with M. tuberculosis in an area with high HIV prevalence, as shown by the situation in northern Malawi in Africa. "The proportion of (TB) strains found to be clustered [here] was among the highest in the world," noted the report.

In a study of South African gold miners, TB incidence doubled within the first year of HIV infection.

For detection of possible TB infection, the U.S. Food and Drug Administration has approved a new interferon-gamma blood test. It is currently evaluating the enzyme-linked immunospot (ELISPOT) assay, which has already been approved in Europe.

"The ELISPOT appears to be at least as sensitive as the tuberculin skin test (TST) for diagnosis of latent tuberculosis infection in contacts of patients with tuberculosis and is likely to be more specific than the TST in bacilli Calmette-Guirin (BCG) vaccine," said Dr. Yew.

(The BCG vaccine, which is not 100 percent effective, is used most often in developing countries.)

The most common antibiotics used to treat TB are isoniazid, rifampin, pyrazinamide, streptomycin and ethambutol. "Rifampin has a well-documented interaction with some highly active antiretroviral agents, especially HIV protease inhibitors," said Dr. Yew.

He noted that an alternate member of the rifamycin class called rifabutin has much less effect against the antiretroviral agents. "Thus, rifabutin-based therapy appears to be a better choice for HIV tuberculosis," he added.

However, another research study showed that rifabutin therapy for advanced HIV-related tuberculosis, while well-tolerated, could be associated with a high risk for either failure or relapse in the presence of significant immunosuppressive therapy.

In other research, a group of investigators concluded that lower plasma concentrations of rifabutin, and perhaps isoniazid, were associated with relapse in TB patients with HIV who received only twice-weekly antituberculosis therapy.

Finally, in animal studies, moxifloxacin, a drug with a long half-life that has potent bactericidal and sterilizing powers, has produced a stable cure, without relapse, in a mouse model of tuberculosis.