Quest for a vaccine

A drug-defiant disease

In the life-or-death struggle of pharmacy against pathology, malaria is a cunning opponent.


ILIFI, Kenya -- It's a calamity occurring in slow-motion, something that many see happening but no one is sure how to stop. Here in Africa, where AIDS and tuberculosis rage, doctors are witnessing another health catastrophe in the making, a surge in fatal cases of malaria.

The reason? The rise of resistance to anti-malarial drugs. First came the collapse of chloroquine -- one of the wonder drugs of the 20th century -- as a reliable treatment. Now health officials are turning to their second line of defense, a drug called Fansidar. But resistance to Fansidar has already appeared, and if it spreads too fast, there may be no cheap, safe and effective drug to take its place.

"It's really a human disaster waiting to happen," says Dr. Kevin Marsh, an Oxford University scientist working at Kenya Medical Research Institute labs on Kenya's coast.

The failure of Fansidar would be a disaster piled on top of an existing disaster. Malaria already kills 1.1. million people a year, most of them children, in the tropics. Drug resistance threatens to add to the horrendous losses, especially in Africa, where 90 percent of the deaths occur.

"Malaria remains out of control in Africa, causing massive problems," says Dr. Charles Newton, a pediatric neurologist also working in Kilifi. "And the most urgent problem is the spread of resistance to cheap anti-malarial drugs."

Chloroquine's erosion has been keenly felt. One 1998 study found that the risk of death from malaria in two regions of Senegal more than doubled as chloroquine resistance rose over an 11-year period. In a third region, the risk of death for children under the age of 5 shot up eight times.

Kenya banned the use of chloroquine last year because, says Dr. John Odandi, head of the Nyanza Provincial Hospital in Kenya, the drug was "useless" and too often caused fatal delays in effective treatment.

The veteran physician knows a lot about the treatment of malaria. His sparsely equipped, 359-bed hospital, located in the dusty city of Kisumu, is flooded with a quarter of a million patients each year. In four cases out of 10, the primary diagnosis is malaria.

Chloroquine resistance has probably contributed to the death toll in a series of recent outbreaks in Kenya. After the Long Rains of late April and May last year, people were dying so fast in the hospital in a town called Kisii -- in the highlands of western Kenya -- that some corpses lay for hours before they were discovered. More than 18,000 people were stricken, and some 600 died. This year, more than 100 people died in Kisii, although the malaria season was considered moderate.

Doctors working at Kilifi were overwhelmed last year as twice the normal number of malaria patients arrived. During the height of the outbreak, three children died in the pediatric intensive care ward in a 24-hour period. Dr. Faith Osier, a 27-year-old Kenyan physician, says she had to teach herself to shut off her emotions. "You have to have some distance, or you would be crying every day," she says.

Health officials in many African countries have been reluctant to give up chloroquine because it is so cheap. The drug costs only a few cents for a course of treatment. Fansidar costs about 40 cents a pill, a significant amount of money in countries where per capita spending on health is around $3 to $5 a year. The next drugs in line cost $6 to $10 a pill. In Africa, expensive drugs are as bad as no drugs at all.

Resistant organisms appear through the overuse and misuse of drugs. Patients who don't finish their treatment kill all but the hardiest parasites, which survive and spread. The indiscriminate use of anti-malarial drugs to treat other illnesses makes it more likely that resistance will arise.

Drugs work by gumming up a microbe's working parts, blocking one or more vital biochemical reaction. Some malaria parasites have evolved new chemicals that work despite the presence of chloroquine. Others have developed the ability to pump the drug out of their cells.

Resistance to chloroquine first appeared in South America in the early 1960s, during a doomed World Health Organization campaign to eradicate malaria in most of the world. Chloroquine was a key to the eradication strategy. (In Brazil, the health minister ordered the drug put in table salt.) As American troops gobbled drugs during the Vietnam War, strains resistant to chloroquine and other drugs appeared. Chloroquine resistance spread to the coast of East Africa by the early 1980s.

One of the first documented victims of chloroquine-resistant malaria in Africa was an American -- a secretary to the U.S. ambassador in Dar es Salaam, Tanzania. A physician gave her chloroquine after she complained of severe fever and chills. Then she disappeared. Friends broke into her apartment a few days later and found her in a coma on the floor.

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