Around the Globe, Drug-Resistant TB Is Rampant

March 15, 2004

There may be as many as 300,000 new cases of drug-resistant tuberculosis a year in the world, and 79 percent of them are ''superstrains,'' resistant to any three of the four first-line drugs, a World Health Organization survey has found.

Patients in the former Soviet bloc countries are 10 times as likely to have drug-resistant strains as those elsewhere in the world, the survey said.

The researchers said the drug-resistance problem might be much bigger than they could measure, particularly in countries like India and China, where they had surveyed only a few areas, and in Bangladesh, Indonesia, Nigeria and others where they had done no surveys.

''The true burden is unknown,'' said Dr. Mohamed Abdel Aziz, the organization's tuberculosis expert and leader of the study. ''The more we survey, the more multi-drug-resistant TB we find.''

Despite 10 years of effort, the organization has examined only about one-fifth of the world's cases. Some countries have been reluctant to participate, and setting up regional laboratories, a worldwide effort led by the Prince Leopold Institute of Tropical Medicine in Belgium, is expensive and time-consuming.

In South Africa, only 1.6 percent of the cases are drug-resistant, said Abigail B. Wright, another author of the study, but the country's overall tuberculosis rate is so high that that translates into 6,000 cases. In India, which has a major TB problem, a survey limited to Tamil Nadu state found a 3 percent resistance rate.

The report highlights the need for new tuberculosis drugs, said a spokeswoman for the Global Alliance for TB Drug Development.

"The last new drug was introduced in 1963,'' said the spokeswoman, Gwynne Oosterbaan. Because tuberculosis is a bacterium, virtually all antibiotics attack it. But drug companies rarely test their new antibiotics against it because they might be pressured to limit the drugs' use to that disease, costing them billions.

Tuberculosis is common in very poor countries with many AIDS cases, because weakened immune systems allow the bacteria to grow. But drug-resistant cases are more common in moderately poor countries where patients receive inadequate treatment.

Many cases were found in Kazakhstan, Uzbekistan, Estonia, Latvia, Lithuania and parts of Russia, as well as in two Chinese provinces, South Africa and Ecuador. On a smaller scale, a high rate of cases per capita was also found in Israel, presumably through immigration from countries of the former Soviet bloc, the report said.

The situation in former Soviet Union countries is particularly bad because of the abrupt collapse of the bloc's economy in the 1990's, said Dr. Peter Cegielski, leader of the international multi-drug-resistant TB team at the Centers for Disease Control and Prevention in Atlanta who conducts studies in Russia.

Shortages forced many patients to cut back to one or two drugs ''and that's what leads to resistance,'' Dr. Cegielski said. Also, a number of prisoners with TB were released in amnesties, spreading the disease. In addition, said Dr. John Jereb, a C.D.C. epidemiologist, Soviet bloc countries used unusual treatments.

In the West and in poor countries following World Health Organization recommendations, all patients are supposed to get a cocktail of four ''first-line'' drugs: streptomycin, isoniazid, rifampicin and ethambutol. The standard therapy, ''directly observed treatment, short-course,'' or D.O.T.S., requires that a family member, a nurse, or even a traditional healer watch each pill swallowed every day for six months.

The first-line drugs are cheap and have few side effects. Resistance develops when patients skip pills. But researchers also suspect resistance is high anywhere that the same drugs are sold over the counter, as they are in Southeast Asia.

Second-line or third-line drugs can be hundreds of times as expensive. Some are as toxic as cancer chemotherapy and require hospitalization.

Before the Soviet collapse, patients there tended to get individually prescribed treatment, including streptomycin injections, and two drugs, kanamycin and ethionamide, that are considered second-line drugs elsewhere.

''As a consequence,'' Dr. Cegielski said, ''there's a substantial amount of resistance.''

Other countries have individual problems. In the Philippines, Ms. Oosterbaan of the drug alliance said, the antibiotic ciprofloxacin is heavily used, so resistance to that class of quinolone drugs may be high.

The survey found very few cases in Western Europe, and a decrease in Hong Kong, Thailand and the United States. In the late 1980's, there was an outbreak of drug-resistant tuberculosis in New York City prisons and shelters that cost millions of dollars to stop. The countries that appeared to be doing the best at treating difficult TB cases were Cuba, Switzerland, Britain and the United States. They recorded significant decreases in resistance among patients who were previously treated.

Botswana, which has the world's highest prevalence of AIDS, did relatively poorly at treating such cases.