It is an epidemic of unprecedented proportions. It kills more adults worldwide than all other infectious diseases combined, and nearly half of the world's refugees may be infected with it. It is the leading killer of people with human immunodeficiency virus (HIV) and orphans more children than any other infectious disease. It's not AIDS, nor hepatitis, nor malaria, but an ancient disease that was nearly eradicated a generation ago: tuberculosis.

According to the World Health Organization (WHO), almost two billion people-one third of the world's population-are infected with tuberculosis (TB) bacteria.

Each year eight million new cases of TB appear, along with three million TB-related deaths. At current rates the WHO estimates that as many as 500 million people will become ill from TB during the next 50 years.

TB is not a disease limited to the developing world. In the United States alone it is estimated that 10 million to 15 million people are infected with the TB bacterium, and 22,000 new cases of TB occur each year.

Yet, only 15 to 20 years ago, health authorities were about ready to declare that TB, like smallpox and polio, had been wiped off the face of the earth. In the United States during the early 1900s, TB was the No. 1 killer. Then, in the 1940s, the introduction of antibiotic drugs that could kill TB bacteria meant that the disease could be cured. For three decades, from the 1950s to the mid-1980s, TB cases steadily declined.

But in the 1980s the battle against tuberculosis took a turn for the worse. The disease reemerged and spread in industrialized countries and underdeveloped nations. Between 1985 and 1992 the number of TB cases increased by nearly 20 percent in the United States. Worldwide, the modern TB epidemic led the WHO in 1993 to declare its first "global emergency." At the time, TB was killing more adults each year than AIDS, malaria and tropical diseases combined.

TB is caused by a bacillus, Mycobacterium tuberculosis. A person can become infected with the tuberculosis bacterium when microscopic airborne particles of infected sputum are inhaled. The bacteria get into the air when someone who has tuberculosis infection of the lung coughs, sneezes, shouts or even laughs. People who are nearby can breathe the bacteria into their lungs.

For most people who inhale TB bacteria and become infected, the body is able to fight the bacteria to stop them from spreading. The bacteria become inactive, but they remain alive in the body and can become active later. This is called TB infection. People with TB infection do not feel ill, have no symptoms and do not spread TB to others. The infection can remain dormant in a person's body for decades, then flare into active disease when the body's immune system is weakened for any reason. About 10 percent of infected people develop TB at some point.

TB can attack any part of the body but usually targets the lungs. When a person breathes in TB bacteria, they can settle in the lungs and begin to grow, then move through the blood to other parts of the body, such as the kidney, spine and brain. Although TB in the lungs or throat can be contagious, TB in other parts of the body is usually not contagious. Usual symptoms of the disease are a general fatigue or weakness, extreme weight loss, fever and night sweats. If the infection in the lung worsens, then further symptoms can develop, including persistent coughing, chest pain, coughing up of blood and shortness of breath.

Because TB is spread through airborne bacteria, anyone can become infected. Groups with the highest risk are the poor and homeless, as well as those with undeveloped or suppressed immune systems: young children, the elderly, HIV-positive people and patients with certain types of cancer.

New and deadly strains

Health-care officials are increasingly concerned about emerging new forms of drug-resistant TB. According to the WHO, outbreaks of drug-resistant tuberculosis are showing up all over the world and threaten to touch off a worldwide epidemic of virtually incurable tuberculosis.

Drug-resistant strains have appeared in New York City prisons, a hospital in Milan, Italy, and many places in between. "Everyone who breathes air, from Wall Street to the Great Wall of China, needs to worry about this risk," says Dr. Arata Kochi, director of the WHO Global TB program.

An October 1997 survey by the WHO, the U.S. Centers for Disease Control and Prevention and the International Union Against Tuberculosis and Lung Disease estimates that 50 million people are infected with a strain of TB that is drug-resistant. Many of those are said to carry multi-drug-resistant tuberculosis-incurable by two or more of the standard drugs. In underdeveloped countries, where the vast majority of multi-drug-resistant TB cases have occurred, it is usually fatal.

"The world is becoming smaller and the TB bugs are becoming stronger," Dr. Kochi says. "While international travel has increased dramatically, the world has been slow to realize the implications for public health. Only recently have wealthy governments begun to recognize that the poor TB treatment practices of other countries are a threat to their own citizens."

The WHO study identifies hot zones of untreatable tuberculosis that threaten a worldwide crisis. These zones are home to nearly 75 percent of the world's TB cases and include Russia, Bangladesh, Brazil, China, Ethiopia, India, Indonesia, Mexico, Pakistan, the Philippines, South Africa, Thailand and Zaire.

Many of the hot zones are regional centers for travel, immigration and international economic activity. WHO officials admit that little can be done to prevent people infected with drug-resistant TB from traveling and spreading the bacilli to other countries.

According to the WHO, one third of the world's nations have a strain of TB resistant to multiple drugs. Untreatable cases account for 2 to 14 percent of the world's total. That number is low, but the WHO said lethal tuberculosis could spread rapidly because only one in 10 patients gets medical care that could overcome drug resistance.

Drug-resistant strains of TB develop when patients do not complete the course of treatment, fail to take their medicine or don't use medication properly. Tuberculosis often can be cured with a combination of four drugs taken for six to nine months. But some patients may begin to feel better after just two to four weeks of treatment, so they stop their medication. But not enough of the medication has been taken to kill all the TB bacteria in the patient. The remaining bacteria survive and mutate, becoming a tenacious, more deadly form of the disease.

TB can be diagnosed in several ways. Chest X rays can reveal evidence of active tuberculosis pneumonia, or they may show scarring, suggesting contained inactive TB. Examination of sputum under the microscope can show the presence of tuberculosis bacteria. A sample of the sputum can also be grown in special incubators, and tuberculosis bacteria can subsequently be identified.

Several types of skin tests are used to screen for TB. Tuberculin skin tests include the Mantoux test, the Tine test and the PPD. In each of these tests, a small amount of dead tuberculosis bacteria is injected under the skin. If a person is not infected with TB, no reaction at the site of the injection will become apparent. However, if a person has become infected with tuberculosis, an area around the site of the test injection will redden and swell. This reaction occurs 48 to 72 hours after the injection.

Treatments can work

Health-care authorities believe one of the best ways to treat TB is something known as "DOTS" (directly observed treatment, short course). Health workers make sure that TB patients take their medicine by watching them swallow every dose they take. Patients take all their medicine, their TB is cured, and the development of drug-resistant tuberculosis is prevented.

According to the WHO, only 10 percent of the world's TB patients are being treated using DOTS. If DOTS were used, WHO officials maintain that nearly three fourths of TB cases could be cured.

"DOTS cures sick patients and prevents drug resistance," says Dr. Kochi. "Alarmingly, only about one in 10 TB patients today has access to DOTS. We have to quickly put more DOTS programs in place to stop multi-drug-resistant TB from increasing."

"The TB epidemic must be fought globally to protect people locally," Dr. Kochi warns. "It is in the interest of the wealthy countries to help less-developed countries fight tuberculosis, before their own countries become the battleground."