Wall Street Journal - July 15, 2004
Marilyn Chase, marilyn.chase@wsj.com

BANGKOK, Thailand - More than one third of the planet's population carries tuberculosis, an often latent bacterial infection that haunts the developing world. While TB is an epidemic in its own right, its troubling relationship with AIDS is increasingly drawing the attention of public health researchers.

HIV wakes up latent TB germs, which erode the lungs. TB in turn agitates HIV, speeding its destruction of the immune system. The result: In many countries, it is TB that most often triggers death in AIDS patients.

Currently, about 14 million people are suffering from the lethal hit of HIV and TB together, a condition known as co-infection. AIDS kills about three million people and TB takes an additional two million lives each year. "We can't fight HIV/AIDS without also fighting TB," said Helene Gayle, director of HIV, TB and Reproductive Health for the Bill and Melinda Gates Foundation.

Today at the XV International AIDS Conference in Bangkok, the Gates Foundation, of Seattle, will take action against the dual threat by awarding $44.7 million to a big consortium of TB and AIDS researchers. The recipients, led by Johns Hopkins medical professor Richard Chaisson, are expected to announce a new TB prevention study among doubly vulnerable populations at risk of TB and AIDS in Zambia, South Africa and Brazil. Former South African President Nelson Mandela, a former TB patient and tireless campaigner against AIDS, is expected to stand with researchers and endorse the study.

The group, the Consortium to Respond Effectively to the AIDS-TB Epidemic (or Create), also includes the London School of Hygiene and Tropical Medicine, Aurum Health Research in South Africa, the University of Zambia, Stellenbosch University of South Africa, and the Municipal Health Secretariat of Rio de Janeiro. Other members are the World Health Organization and the U.S. Centers for Disease Control and Prevention.

Dr. Chaisson said the Create study's main goal is to reduce the incidence of active TB, thus denying a major source of fuel for the AIDS pandemic. Zambian adults and South African gold miners targeted by the study are at high risk of TB and have "extremely high rates of HIV" ranging from 10% to 15%, Dr. Chaisson said. In the Brazilian study site, TB risk runs high and all of the study volunteers will be HIV-positive.

Dr. Chaisson and his team hope to prevent TB from becoming active using an old antibiotic called isoniazid. The drug's main side effect is liver toxicity, and rarely, hepatitis. Though people suffering from liver damage or chronic alcoholism shouldn't use it, "the drug has been used safely around the world for decades," Dr. Gayle said.

Isoniazid has achieved high rates of success in holding latent TB infection in check and preventing active disease and lung erosion. It has never been tested and used in TB prevention in the era of AIDS with the intent of deploying it on a massive scale.

Dr. Chaisson said that two studies -- successful tests using isoniazid in South African gold miners and Alaskan Eskimo villagers in the 1960s -- "give good reason" to revive and expand the strategy in these tests. The South African gold miners were given the drug in an unusual fashion -- it was stirred into their beer rations. The antibiotic succeeded in keeping the infection at bay, and lowered active disease risk in five mines.

In the new research, three large-scale community studies will observe the drug's effectiveness in preventing active TB in Zambian adults, gold miners in South Africa, and people with HIV/AIDS in Rio de Janeiro. Rather than wait for a sick person with symptoms to seek out a clinic, the researchers intend to use community education and outreach, offering TB skin tests and sputum tests to find those infected. When cases of TB are found, researchers expect to treat the patient's entire household.

Dr. Gayle said public health officials have never attempted such a wide application of isoniazid, in large part because they lacked the resources. If the study succeeds, she hopes the results can be quickly disseminated to officials at the World Health Organization to enhance WHO's TB control strategies around the world. Public health officials are optimistic.

"There's good evidence that [isoniazid prevention] works in HIV-positive individuals," said Jim Yong Kim, a veteran TB expert at the WHO in Geneva, though he added, "We need more research."

The grant implicitly criticizes the World Health Organization's widespread program of simplified TB treatment known as DOTS (directly observed therapy). DOTS involves a group of inexpensive first-line drugs administered to patients who already have active tuberculosis, under close supervision. It has won major successes, but has been weakened in recent years by the rise of drug-resistant strains of the TB bacterium. While isoniazid often is used in DOTS, it is a treatment for TB in that regimen, not a preventative.

Dr. Gayle of the Gates Foundation said, "DOTS is great when HIV isn't a major problem. But once HIV moves in, control is undermined." The drugs used in DOTS aren't strong enough to hold back the tide of new TB cases when the germ is amplified by HIV. Recently, a resurgence of TB has occurred despite DOTS, and "DOTS just can't seem to catch up."

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