ILIFI, Kenya -- It's a calamity occurring in slow-motion, something thatmany see happening but no one is sure how to stop. Here in Africa, where AIDSand tuberculosis rage, doctors are witnessing another health catastrophe inthe making, a surge in fatal cases of malaria.
The reason? The rise of resistance to anti-malarial drugs. First came thecollapse of chloroquine -- one of the wonder drugs of the 20th century -- as areliable treatment. Now health officials are turning to their second line ofdefense, a drug called Fansidar. But resistance to Fansidar has alreadyappeared, and if it spreads too fast, there may be no cheap, safe andeffective drug to take its place.
"It's really a human disaster waiting to happen," says Dr. Kevin Marsh, anOxford University scientist working at Kenya Medical Research Institute labson Kenya's coast.
The failure of Fansidar would be a disaster piled on top of an existingdisaster. Malaria already kills 1.1. million people a year, most of themchildren, in the tropics. Drug resistance threatens to add to the horrendouslosses, especially in Africa, where 90 percent of the deaths occur.
"Malaria remains out of control in Africa, causing massive problems," saysDr. Charles Newton, a pediatric neurologist also working in Kilifi. "And themost urgent problem is the spread of resistance to cheap anti-malarial drugs."
Chloroquine's erosion has been keenly felt. One 1998 study found that therisk of death from malaria in two regions of Senegal more than doubled aschloroquine resistance rose over an 11-year period. In a third region, therisk of death for children under the age of 5 shot up eight times.
Kenya banned the use of chloroquine last year because, says Dr. JohnOdandi, 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. Hissparsely equipped, 359-bed hospital, located in the dusty city of Kisumu, isflooded with a quarter of a million patients each year. In four cases out of10, the primary diagnosis is malaria.
Chloroquine resistance has probably contributed to the death toll in aseries of recent outbreaks in Kenya. After the Long Rains of late April andMay last year, people were dying so fast in the hospital in a town calledKisii -- in the highlands of western Kenya -- that some corpses lay for hoursbefore they were discovered. More than 18,000 people were stricken, and some600 died. This year, more than 100 people died in Kisii, although the malariaseason was considered moderate.
Doctors working at Kilifi were overwhelmed last year as twice the normalnumber of malaria patients arrived. During the height of the outbreak, threechildren 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 toshut off her emotions. "You have to have some distance, or you would be cryingevery day," she says.
Health officials in many African countries have been reluctant to give upchloroquine because it is so cheap. The drug costs only a few cents for acourse of treatment. Fansidar costs about 40 cents a pill, a significantamount of money in countries where per capita spending on health is around $3to $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 totreat other illnesses makes it more likely that resistance will arise.
Drugs work by gumming up a microbe's working parts, blocking one or morevital biochemical reaction. Some malaria parasites have evolved new chemicalsthat work despite the presence of chloroquine. Others have developed theability to pump the drug out of their cells.
Resistance to chloroquine first appeared in South America in the early1960s, during a doomed World Health Organization campaign to eradicate malariain most of the world. Chloroquine was a key to the eradication strategy. (InBrazil, the health minister ordered the drug put in table salt.) As Americantroops gobbled drugs during the Vietnam War, strains resistant to chloroquineand other drugs appeared. Chloroquine resistance spread to the coast of EastAfrica by the early 1980s.
One of the first documented victims of chloroquine-resistant malaria inAfrica was an American -- a secretary to the U.S. ambassador in Dar es Salaam,Tanzania. A physician gave her chloroquine after she complained of severefever and chills. Then she disappeared. Friends broke into her apartment a fewdays later and found her in a coma on the floor.
She was flown to a Nairobi Hospital, where Dr. Jeffrey Chulay, then aWalter Reed Army Institute of Research scientist working in Kenya, put some ofher blood in a petri dish, added some chloroquine and watched the parasitesswim undisturbed in their chemical bath. Five days later the woman died. "Shebasically never woke up from her coma," Chulay recalls.
Today, for reasons no one understands, Central America is the only tropicalregion on earth without chloroquine resistance. But no one expectsdrug-resistant parasites to remain south of the Panama Canal forever.
Back in 1993, Malawi became the first African nation to restrict the use ofchloroquine and required doctors to use Fansidar. In a not-yet-publishedstudy, Dr. Christopher Plowe, chief of the malaria section of the Universityof Maryland's center for vaccine development, found that from 15 percent to 20percent of malaria cases in one Malawi township were Fansidar resistant.
The good news, Plowe says, was that after seven years of Fansidar use, 80percent of the patients still responded to it. The bad news was that Fansidarresistance was firmly established, and growing each year. "We still needurgently to identify the next drug and to have it on deck and affordable,"Plowe says. "Things haven't deteriorated as quickly as was predicted, butclearly Fansidar resistance is increasing."
Strains of malaria aren't just adapting to the cheapest drugs. The parasiteis increasingly able to evade the most powerful and expensive compounds.
Quinine, the first anti-malarial, was discovered by Jesuit missionaries inSouth America in the 1600s. Today, intravenous quinine is the therapy of lastresort for severe malaria in many tropical hospitals. Disturbingly, malariahas developed some resistance even to this difficult-to-administer, andpotentially toxic drug. "Quinine is becoming less and less effective," saysDr. Wil Milhous of the Walter Reed Army Institute of Research near SilverSpring, one of the world's leading centers for malaria research.
Resistance has also appeared in recent years to a drug called mefloquine --first developed to treat chloroquine-resistant malaria during the Vietnam War.Mefloquine is widely prescribed to Americans traveling to tropical areas, andis a drug of last resort for some victims. While still effective in mostareas, mefloquine is losing its power over parasites in southeast Asia. Inareas of Thailand, 60 to 70 percent of the parasites are mefloquine resistant.
If there were profits to be made in making new malaria drugs, drugcompanies would be scrambling to discover them. But most of the disease'svictims live in desperately poor countries. Only a handful of nonprofitgroups, the World Health Organization and the U.S. military are pushing thesearch for new drugs. Only a few drug companies are interested in taking newlydiscovered drugs from the lab to the marketplace.
"There aren't a lot of people working on malaria drugs," Milhous says.Scientists at the Walter Reed Army Institute of Research, he notes, "have beenbeen pretty much doing it solo for the last 20 years."
There are drugs in development that could replace Fansidar. Most areso-called "me-too" drugs -- compounds that are closely related to Fansidarchemically, but differ enough to evade the parasite's defenses. One is acompound nicknamed "Lap-Dap." It's being tested by the World HealthOrganization and SmithKline Beecham, the drug giant.
Another new malaria drug is malarone, being tested by Glaxo Wellcome. It ishighly effective, and the manufacturer has offered to donate the drug on alarge scale. But malaria experts fear that the donation program won't continueindefinitely. The demand for malaria drugs is huge: there are an estimated 300million to 500 million cases a year. Even if a new, affordable malaria drugappears, the decades-old arms race between man and malaria isn't about to end.(Resistance to Lap-Dap has already appeared in parts of South America, eventhough the drug is not yet approved for global use.)
"If you use it frequently enough and long enough, resistance will developto any drug," says Newton, the pediatric neurologist in Kilifi.
In the meantime, malaria experts say, perhaps the best way to keep malariain check is with multi-drug treatments, the same strategy used for AIDS andfor tuberculosis. The long-term hope for malaria control is a vaccine.
Progress has been made, notably by a team of U.S. Army scientists workingat Walter Reed. But a practical vaccine is probably at least eight years away."A malaria vaccine will not cure all the problems of the Third World, "saysMarsh. "But it could cure one of the biggest, and simplify some of theothers."
Odandi at Nyanza Provincial Hospital has seen malaria beaten back, only toresurge. The struggle, he predicts, will be a long one. "The war againstmalaria started a long, long time ago," he says. "Just when you think thatyou're winning, the enemy emerges from behind you and stabs you in the back."Copyright © 2014, The Baltimore Sun