Tuberculosis outbreak

Science News, Jan 31, 1998 by Kathleen Fackelmann

The discovery of gold in Brazil in the 1980s sent an estimated 40,000 miners rushing into the heart of the Amazon rain forest. There, they encountered the Yanomami Indians, an indigenous population that had very rarely encountered outsiders.

The miners brought with them such 20th-century accoutrements as guns and plastic. They also brought an age-old plague--tuberculosis. Mycobacterium tuberculosis, the organism that causes tuberculosis, swept through the Yanomami like wildfire.

Epidemics are not unusual when indigenous populations first encounter Europeans. This time, however, there was a new twist.

The tuberculosis produced such atypical symptoms that doctors initially had no idea what was killing the Yanomami. They thought a lethal pneumonia might be responsible.

Now, researchers have documented for the first time the toll tuberculosis is taking on these people. The report is also one of the few to describe an initial outbreak in a population.

The findings suggest that an unusual immune reaction to M. tuberculosis increased the Indians' vulnerability. In fact, the researchers say, the Yanomami demonstrate how the human immune system first responded to M. tuberculosis eons ago.

"This is probably the last time we will see a worldwide disease like tuberculosis arriving for the first time," says Alexandra O. de Sousa of the Howard Hughes Medical Institute (HHMI) at Albert Einstein College of Medicine in New York. She and her colleagues report their findings in the Nov. 25, 1997 Proceedings of the National Academy of Sciences.

"This is the first really good study of the situation," comments James V. Neel, a geneticist at the University of Michigan Medical School in Ann Arbor who has studied the Yanomami population.

In 1992, de Sousa and her colleagues began their arduous journey into the rain forest.

They boarded a boat in Manaus for a 5-day trip up the Black River. From there, they embarked on a 2-day canoe trek to the remote region where the Yanomami have lived for centuries.

The goal of their research project, funded in part by the Brazilian Health Department, was to determine the extent of the tuberculosis outbreak among the Yanomami. During the 3-month study, de Sousa and her colleagues examined 625 Yanomami in five villages scattered throughout some 900 acres of forest. They did skin and blood tests, a physical exam, and checked sputum for M. tuberculosis.

Forty of the Indians had active tuberculosis, a prevalence of 6.4 percent, which is "astronomically high," says coauthor Barry R. Bloom, also of HHMI at Albert Einstein. "That rate is as high as any epidemic of tuberculosis that I know about," he adds.

The researchers knew that the first recorded case of tuberculosis in the Yanomami occurred in 1965 and was probably contracted from a researcher or one of the few other outsiders who reached the remote territory. But it wasn't until the 1980s gold rush that the illness really caught hold, creating an epidemic.

Tuberculosis in the Yanomami seems to run an unusual course, de Sousa says. The Indians quickly develop high fevers and become very ill, in contrast to North American or European patients, who usually suffer a low-grade fever, weight loss, and a cough--symptoms that can persist for years.

The researchers note that the Yanomami suffer from a form of tuberculosis that was common in medieval Europe but is rare in the United States and Europe today. The condition is called scrofula, an infection of the lymph nodes in the neck, which produces sores on the neck and face. Shakespeare mentions this unsightly condition in Macbeth, de Sousa says.

What could explain the way the Yanomami respond to M. tuberculosis? De Sousa, an immunologist by trade, decided to look more closely at the immune system of the Yanomami. Her team had performed tuberculin skin tests on 556 Yanomami. A positive skin test indicates that an individual has been exposed to M. tuberculosis.

The test also measures the response of T lymphocytes, a type of white cell, to M. tuberculosis. A successful attack on M. tuberculosis requires the mobilization of T cells and the cytokines they manufacture. This mobilization is called cell-mediated immunity.

People with an active cell-mediated response to M. tuberculosis develop a characteristic welt when given the tuberculin skin test. Surprisingly, only 50 percent of the Yanomami actively infected with M. tuberculosis had a positive skin test. If a similar test were performed on North Americans or Europeans, about 90 percent of those actively infected would test positive, Bloom says.

These findings suggest that in many cases, the Indians' T cells don't effectively rout M. tuberculosis, which multiplies in immune cells called macrophages. The T cells seem to react sluggishly or not at all to this microbial threat.

Even more curious, when de Sousa and her colleagues drew blood, they found that compared to Brazilians of European ancestry, the Yanomami have higher concentrations of antibodies, immune proteins directed against M. tuberculosis.