Researchers Seek Elusive Vaccine to Stop Malaria’s Comeback
The fever once drove them to the sea here, to build huts atop stilts, free of the insects. It drove others into wicker cocoons at night, families huddled together in suffocating sleep.
On this day in Maprik, it brings Tom Eikuri to the hospital with his 3-year-old girl. She lies comatose on a thin mattress, her doll’s legs dancing with convulsions, her young brain starved of oxygen.
“Something must be done to stop this,” the grieving father says.
It’s a plea heard in village after village on this western Pacific island.
“The kids, literally their whole faces are covered with bites,” says Mary Chambers, a British mosquito researcher. “The parents come to me. ‘Mary, can you help us? Our children are all dying of malaria.’ ”
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Manuel Patarroyo wants to help.
On a chill night in Switzerland, the scientist from the Amazon strode coatless down Geneva’s streets, unmindful of anything, it seemed, but his self-appointed mission.
“I am not interested in making a million dollars, or in winning the Nobel Prize,” he told an interviewer. “I am interested in solving the problem. And that’s what bothers them.”
The “problem” is finding a vaccine for malaria. And “they” are those who question his way of doing it.
The outspoken Colombian, director of Bogota’s Institute of Immunology, has developed an experimental malaria vaccine and is promoting it in a crusade that has focused new attention on one of humanity’s ancient plagues.
But at the same time, his feud with those he calls “enemies” shows that conquering disease today means more than simply doing battle with contagions under the microscope. It also means contending with rivalries and politics in a big wide world.
“The competition is fierce. The jealousy is fierce,” a veteran malaria fighter said privately at the World Health Organization’s Geneva headquarters, where Patarroyo confers regularly with other specialists.
Researchers are competing for sponsorship and funds. They’re jealous of space in scientific journals and ink in newspaper headlines. They’re envious of resources--even of Patarroyo’s easy access to rare monkeys for his experiments.
This should not be happening in 1996. Malaria was supposed to have been eliminated by now.
In the mid-1950s, WHO predicted that anti-malaria drugs and anti-mosquito insecticides would wipe out the disease within 40 years. But a global “eradication” campaign petered out by 1970, and malaria roared back.
Today, 300 million to 500 million people in 90 countries suffer from malaria each year, WHO says. Ninety percent of the cases are in Africa. Around the globe, between 1.5 million and 2.7 million people die annually, mostly children under 5.
The reasons for malaria’s comeback are complex.
Population growth has pushed people into malarial areas. Economic development--irrigation, road building, logging--leaves more stagnant water for breeding mosquitoes. Health services have deteriorated in many places. Mosquitoes have grown resistant to some pesticides.
Perhaps most ominously, the mosquito-borne parasite, the plasmodium protozoa, is developing resistance to anti-malaria drugs.
Since the 1960s, strains resistant to chloroquine, the primary treatment, have spread around the world. Resistance to the second-line drug, sulfadoxine-pyrimethin, is widespread in Asia and South America. And strains that fend off the latest fallback drug, mefloquine, have gained a foothold in Thailand.
The parasite has proven to be a formidable foe.
“It’s probably older than mankind itself,” said WHO malaria specialist Anatoly V. Kondrachine. “What does this mean? That it has an enormous capability of adaptation.”
It adapts by rapidly changing its “coat of colors,” the biochemical makeup whose elements are targeted by drugs and by humans’ own antibodies. And those mutations are just part of malaria’s kaleidoscopic nature.
A bewildering 60 species of the anopheles family of mosquito carry the parasite, which itself comes in four varieties, the deadliest being plasmodium falciparum.
The protozoa’s life cycle compounds the complexity.
A female anopheles’ bite injects immature microbes into a victim’s bloodstream. They develop in the liver, reemerging to invade red blood cells, bursting them as they multiply, causing anemia, fever, chills and joint pain. In cerebral malaria, infected cells obstruct blood vessels to the brain, causing coma, convulsions, often death.
The cycle resumes when an infected person is bitten by an uninfected mosquito, and the parasites enter the insect’s gut.
For all that is known about malaria, the unknowns remain key, especially one big question: Why do some people develop limited immunity when repeatedly infected? If immunologists could understand this protective mechanism, they could try to mimic it.
Worldwide, on many fronts, hundreds of researchers are attacking malaria’s frustrating complexity. Some are investigating new drug therapies. Some hope to genetically alter mosquitoes so they can’t play host to the parasites. Here in Maprik, American immunologist Anuraj Shankar is looking at whether zinc and Vitamin A supplements help immunity.
But the ultimate goal, made urgent by malaria’s growing drug resistance, is a vaccine to provide long-term protection.
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“It’s perhaps the most important public health problem in the world,” Patarroyo said of his chosen disease.
The 49-year-old vaccinologist, lean, balding, intense, first made headlines in 1992, when he reported testing a vaccine that seemed to protect half those inoculated in South America.
He met with immediate skepticism.
For a decade, he had operated outside the U.S.-European mainstream of malaria research, at an Amazon jungle station where the Colombian government supplied him with owl monkeys, prized as the only good test animals for malaria vaccines.
Patarroyo’s approach was laborious: He synthetically produced proteins that appeared in plasmodium falciparum’s chemical makeup, and vaccinated monkeys with each, to see whether it triggered an immune response that protected them against malaria.
Over 14 years, he has gone through 106 proteins and protein components--and 2,000 monkeys. And he settled on one chemical mix, dubbed SPf66.
But when U.S. researchers tried to duplicate Patarroyo’s positive SPf66 results in monkeys, they came up negative. And when he announced his 1992 results, involving 45,000 people in four countries, outside scientists suggested that Patarroyo’s study was sloppily conducted.
Patarroyo accused his northern critics of “intellectual racism,” of prejudice against a Third World scientist. He found defenders among Third World health ministers and sympathy in important places. “If you’re coming from a situation that’s not Harvard, not Yale, you have to fight for recognition,” said Howard D. Engers, who oversees malaria vaccine research for WHO.
More trials were needed.
Under WHO supervision, SPf66 was tried out in malaria’s African epicenter, and in 1994 intriguing results were reported: It appeared to protect almost one-third of the 1- to 5-year-olds inoculated in a Tanzanian village.
But the sample was small and the margin of error large. And then, last year, British scientists reported SPf66 did no good at all when injected in children under 1 in West Africa.
Researchers now await the report from the latest trial, on children in Thailand, expected by mid-1996. Patarroyo, meanwhile, has donated the vaccine to WHO, forgoing any royalties for himself.
What if SPf66 proves to be 30% effective with a few years’ duration? Would that justify a worldwide vaccination campaign?
Engers says it would, that a WHO analysis found such a vaccine would cost just $10 to $20 per life saved.
Others disagree. “30% is not adequate,” Indian malaria specialist G.P. Singh Dhillon said in New Delhi. “It’ll last only a few years and it’s against falciparum, which is only 40% of India’s problem.”
Many malariologists say looking for a “silver bullet” is futile. The disease is too complex, the parasites too variable.
Patarroyo agrees--to a point.
“From the beginning, it was clear SPf66 was a partial solution, but it was the way to get to the final solution,” he said.
“It is amazing how they criticize me. . . . Where is their work? I want to see another vaccine candidate with 30% results.”
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Here in Papua New Guinea, researchers do have another vaccine, developed with Australian help, one of half a dozen on WHO’s “candidate” list.
Trials are beginning in the thatch-and-bamboo villages near Maprik, where half the children have at least low levels of the parasite in their blood. An unprotected person can get 400 mosquito bites in a night here.
The tests will take two years, but Michael Alpers, director of Papua New Guinea’s Institute of Medical Research, takes a long view.
After all, the vaccine is the product of 17 years of institute research, during which he once had to wait 18 months for clearance from the Americans to use their owl monkeys to test just one vaccine component.
And Alpers is realistic. “This is not going to be a be-all and end-all,” he said.
But he and colleague Blaise Genton, a vaccine specialist, know time may be short too.
“It’s one of the most unknown diseases. And the more I work in this area, the more I understand I don’t know,” Genton said.
