Malaria: Amid the death, new hope

ILHA JOSINA, Mozambique - The babies yowled, the babies flailed, the babies scrunched their faces, and blew spit in protest. To no avail: Every infant was plunked onto a weighing scale. Then they were handed to doctors and nurses who palpated bellies, took temperatures with armpit probes, and peered intently into tiny mouths.

The test subjects were next bundled, one at a time, into a small, shedlike structure at the corner of the outdoor pavilion to become part of a major pharmaceutical trial and, perhaps, medical history. Within, there came the quick prick of a hypodermic needle. And more wails.

If the babies emerged tear-streaked, their mothers were beaming - for hope was here. Maybe, just maybe, the experimental jab would protect their precious ones from Africa's most relentless slayer of infants.

Of the 24,000 people worldwide who die needlessly every day of preventable diseases, more than 3,000 are victims of malaria, according to the World Health Organization and United Nations Children's Fund. The parasitical illness, spread by mosquitoes, was vanquished generations ago in the West but continues to cast a terrible shadow over the planet's most impoverished people.

In Africa, malaria is the number one killer of children under age 5, rivaled only by AIDS as a waster of lives and devastator of economies. Conservative estimates peg the number of malaria deaths at more than 1.2 million per year, 90 percent of them in Africa.

Meanwhile, some 500 million people in Africa, Asia, and Latin America are newly infected by malaria each year. About 300 million victims will survive but may suffer from chronic illness, weakness, and, in some cases, permanent brain damage.

For decades, malaria has remained on the back burner of international public health efforts. The past year, however, has seen a major new drive to prevent spread of the disease, burgeoning efforts to bring new medicines to patients, and a renewed push to develop the first effective malaria vaccine.

On a scorching day in October, Ilha Josina's ramshackle pavilion - a cracked concrete slab shaded by a metal roof - was a makeshift lab for Africa's largest test of a malaria vaccine.

The innoculation of 2,000 children in Ilha Josina and nearby Manhica, funded by an infusion of money from software magnate Bill Gates, marked a big if belated step toward testing a vaccine that could have been saving lives since the 1980s.

The drug, called RTSS, was developed some 15 years ago by the pharmaceutical company GlaxoSmithKline and the United States military, but dropped for lack of interest - an all-too-familiar tale in the on-again, off-again fight against the disease.

Even if the ongoing trials prove successful, it will be at least a decade before an approved malaria vaccine goes into full-scale production and distribution, according to epidemiologists. That represents the minimum amount of time needed for testing and government approvals.

Still, the field work underway by the Manhica Health Research Center offers a ray of hope in the struggle against a parasitical nemesis believed to be as old as humanity itself. Perhaps because malaria today stalks only the poorest places on earth, especially Africa, finding new ways to prevent it has not excited much international interest in recent times.

"Where malaria prospers most, human societies have prospered least," said Jeffrey D. Sachs, professor of health policy and director of the Earth Institute at Columbia University. "It is shocking that a disease that should have been brought under control so long ago is still rampaging so widely."

There are a few bright spots beyond the vaccine tests. The use of innovative insecticide-treated bed nets purchased by the United Nations Children's Fund has reduced spread of the disease dramatically in parts of East Africa. But the distribution of the low-cost nets remains haphazard and hindered by logistical snafus, poor training, and petty corruption.

In Mixixine, a Mozambique settlement sprawling among neglected coconut groves and rice fields, a distribution program has been underway for months, but only 60 nets have been allocated to the 2,113 villagers deemed priority cases - pregnant women and children under age 5. And a disproportionate number of recipients are local officials.

Some of the peasant women who have received nets seemed mystified about how to use them, claiming no one provided instructions. One woman kept hers wrapped in its packaging and tucked under the family's sleeping mat, believing it to be a sort of charm to ward off illness and bad luck. She did not associate malaria with mosquitoes, anyway.

"Malaria comes from the air," Rosa Cossa said. "It comes from the mist. No one can hide from malaria."

On yet another front, epidemiologists are heartened by potent new antimalarial medications derived from a plant called artemisia. But few cheers are sounding in Africa. Although these drugs have helped bring the disease under control in much of Asia, the cure is seen by many aid groups and Western governments as too costly for this stricken continent.

The artemisinin-based drugs typically cost 10 times as much as the less effective antimalarial medications presently used in Africa, a difference that would translate into hundreds of millions of dollars in spending for already overwhelmed international agencies and African health systems.

Some decry the priorities set by international public health officials.

"There is an international unwillingness to shift the status quo on this disease," said Nathan Ford, head of the medical department of the British arm of Medecins Sans Frontieres, an international medical relief agency also known as Doctors Without Borders. "Obsolete drugs are still distributed solely because they happen to be cheaper. Skewed strategies are employed - emphasizing preventions that don't really work over new medicines that certainly do.

Not a priority

George Washington shivered from it. US Cavalry troops on the southwestern frontier feared it more than Indian arrows. Construction of the Panama Canal was delayed for years by it.

But malaria was effectively eradicated from North America and Europe by the middle of the last century thanks to wonder drugs, powerful insecticides, drainage of wetlands, and the near-universal use of window screens.

In the decades since, the disease not been a priority for international health agencies and rich donor countries. One result: Malaria remains the world's most pernicious and widespread tropical parasitical illness, cutting a swath stretching from Southeast Asia to Central America - wherever there is warmth and water. In the tropics, a single leaf can trap enough water to spawn swarms of infection-carrying mosquitoes.

The disease's deadliest bite is felt in Africa, where rates of mortality and infection have exploded over the past 20 years but have raised little alarm outside the continent.

"To a large extent, malaria remains a hidden epidemic," said Dr. Filip Dubovsky, scientific director for the Malaria Vaccine Inititiative, a private US organization that coordinates efforts to find a vaccine. "The disease has been with humanity for so long, even people [in regions of high infection] shrug it off as a normal condition of life."

In Africa, malaria's ravaging effects on public health and national economies rival those of the the AIDS/HIV pandemic. And yet, perhaps because the disease - unlike AIDs - has been omnipresent in the subsahara since ancient times, it does not elicit similar dread.

"Malaria is cruel, yes, but its face is so familiar we hardly see it," said Clara Antonio Temele, 22, whose malaria-stricken son, Fernando, 2, quaked in her arms outside the family's mud-and-straw hut. "It has forever crept among us, like a ghost, making this man sick, making that woman convulse, making so many babies dead. Malaria is our fate."

Because record-keeping ranges from poor to nonexistent in much of Africa, no one knows the true annual death toll from malaria here. UNICEF pegs the figure at more than 1.2 million, but other estimates by health agencies exceed 2.5 million.

What no one disputes, however, is that the overwhelming majority of deaths occur among African infants and toddlers. UNICEF estimates that every 30 seconds some mother's baby is lost to a treatable and largely preventable disease.

"Malaria is the single greatest agent of death among African children under age 5, vastly overshadowing AIDS," said Dr. Carlos C. "Kent" Campbell, senior adviser on malaria for UNICEF.

"Until something is done about malaria, nothing is going to happen to the appalling rates of childhood death in Africa," Campbell said. "Malaria is the classic end-of-the-road disease. It most savagely affects rural, impoverished people with little access to health care and no political clout."

A false dawn

Half a century ago, malaria still topped the international health agenda, as scientists drew a steady bead on both the disease and the mosquitoes that carry it. The antimalarial drug chloroquine, introduced in the 1950s, was hailed as a miracle medicine. Paul Muller, the Swiss chemist who pioneered use of the insecticide DDT, was awarded the 1948 Nobel Prize for work that led to wiping out mosquitoes and other harmful insects, saving untold millions of lives.

But it was a false dawn. DDT was discovered to harm songbirds and raptors, making it anathema to environmentalists. The United States withdrew from Vietnam, after which the military's once-obsessive quest for a malaria vaccine was eased onto the back burner. And across malarial zones, the hardy parasite started mutating into forms resistant to chloroquine and another cheap antimalarial drug, sulphadoxine-pyrimethamine.

"There came a mindset, as much among Africans as Westerners, that malaria was something that `just happened,' a bit like the common cold but with a big body count," said Louis Da Gama, director of Malaria Foundation International.

But attention finally seems to be refocusing on the disease. One spur has been the outrage of the world's richest individual. Over the past few years, Microsoft founder Gates and his wife, Melinda, through their foundation, have committed $295 million to malaria programs - including $155 million solely for vaccine research - the largest single infusion of money ever to combat the disease. By comparison, public spending on malaria - by the United Nations and individual countries - is about $100 million a year, according to WHO.

"Before we got involved, we thought human life was valued at some reasonable rate around the world," Gates said recently. "We thought medical research was driven by how many lives it could save. But there is this vacuum. . . . A very big health gap exists between the rich and poor countries."

Indeed, malaria infection rates in Africa have jumped fourfold since the 1960s, according to a study this year by Medecins Sans Frontieres. Death rates from Plasmodium falciparum, most lethal of the four malarial parasites that infect humans, are also on the rise: Forty years ago, malaria killed 107 of every 100,000 Africans; today, the death rate is 165 per 100,000.

"After some improvement, malaria is roaring back in Africa," said Ford, the organization's malaria specialist.

The malaria parasite's resistance to chloroquine and sulphadoxine-pyrimethamine has become so high in many parts of Africa that "both drugs are virtually useless," according to the Medecins Sans Frontieres study.

Drawing criticism, the United States Agency for International Development, like many private relief agencies, continues to distribute chloroquine and sulphadoxine-pyrimethamine to African hospitals and clinics, arguing that the drugs still cure substantial numbers of people, and that - in any event - newer generations of drugs are too expensive for Africa.

Meanwhile, the powerful new artemisinin-based drug therapy widely used in Asia is barely known on the world's poorest continent; it is being tested in just one African country - Burundi. The treatment combines various Western medicines with a Chinese remedy derived from an herb known as "sweet wormwood," familar to traditional healers in Asia for centuries but only recently winning raves from Western epidemiologists.

Artemisinin-based drugs cost upwards of $1.30 per dose, however, compared to a few cents for chloroquine. That's a huge difference on a continent where most malaria victims are penniless. Public health experts also note that artemisinin treatment is more complicated to administer than current drugs, a major obstacle in Africa, where most people live miles from clinics run by workers with only rudimentary health training.

"It may be the future," said a senior American aid official of artemisinin therapy. "But it's not ready for African prime time."

Transmitted to humans by the anopheles mosquito, malaria is caused by a protozoan - a microscopic one-celled animal - that infects the blood and reproduces at an extraordinarily fast rate in the liver. Symptoms of the disease range from mild fevers and joint pain to convulsions, coma, and death. Children who do not die from malaria can suffer brain damage.

Malaria's impact goes beyond lost lives and ruined health. Economists say malaria wipes out savings of poor people desperate for medicine; lowers the output of workers; places a crushing burden on health care systems; and deters tourism and foreign investment, both crucial to economic progress.

"Malaria creates a vicious cycle of disease and poverty," said Sachs. "It undercuts economic development. Countries where malaria is endemic are poverty traps where infrastructure is in collapse. Productivity is in decline, and foreign businesses fear to tread."

The fight against malaria is occurring on many fronts, although too often amid confusion and poor coordination between Western aid agencies. The corruption and indifference of many African officials also subvert programs .

For example, insecticide-treated bed nets represent a low-tech but efficent approach to slowing malaria's transmission. The newest nets, created by Japanese scientists, are infused with bug repellant that lasts four years. But even nets requiring a fresh dousing in insecticide every few months provide a barrier against the anopheles female.

Nontheless, 26 of 44 African countries stll impose heavy taxes and tariffs on insectide-treated nets, despite public pledges made by African leaders to Western aid donors to remove the government fees, according to watchdog agencies. These push up prices by as much as 35 percent in some countries, forcing humanitarian agencies to provide still greater subsidies.

"It's lunacy, in countries where kids are dying in droves, where millions are suffering, where hospitals are in near-collapse because of malaria intakes, officials are still demanding their cut," Da Gama said. "They are squandering the lives of their own people."

UNICEF is a particulary strong proponent of the insecticide-treated shrouds. The organization last year became the world's No. 1 procurer of bed nets, spending $12.5 million to purchase 4.4 million meshes and insecticide treatment kits.

"The aim is to get affordable nets to the most vulnerable populations - pregnant women and children under age 5," said Tim Freeman, UNICEF's malaria officer in Mozambique. "It's fine to talk about better medicines. But the hard, ugly fact in Africa is that 60 percent of people are beyond the reach of any health system."

'Covered by bites'

In the Mozambique village of Mocuba, scores of women thronged around a nurse allocating subsidized nets provided by US aid agency World Vision. They wagged fistfuls of frayed meticais - the local currency - and clamored for the veillike cloth that might mean the difference between life and death in a region where 321 of every 1,000 children die before reaching age 5, most commonly of malaria.

"When I can afford it, I burn small bits of charcoal to keep mosquitoes from my hut," said Veronica Adriano, 36, heavy with her seventh child. Last year, malaria killed her youngest. "But still every morning my children are covered by bites."

The nets and insecticide treatment are sold for roughly $1.25 apiece. Relief agencies levy a small charge, less than the actual cost of the nets, hoping that if people get used to paying for nets, local sellers will be moved to stock more.

On this day in Mocuba, there were only 13 nets available for the crowd of anxious women gathered under a giant mango tree. Many of the women had walked miles for the chance. And World Vision's Ben Ngwenya, director of agency operations in Zambezia province, was frustrated that so few nets were on hand.

"We've had shiploads of nets blocked at port [by Mozambique Customs officials] for unknown reasons," he said. "Are they after bribes? Is it just incompetence? Who knows? But the result is that nets are getting out to only a tiny percentage of the people who need them most urgently."

That pattern is seen across Africa, where public health clinics in rural areas often run out of malaria medicines at mid-month because of bungled supply orders by far-off bureaucrats; where public health laboratories routinely "lose" or simply toss out blood smears, meaning that true numbers of malaria infections are often just a guess; where, in many countries, health workers extort bribes in exchange for proper medicines and treatment; and where, in every country, outdoor market stalls do brisk business in useless outdated pills or counterfeit drugs made of sugar or talc.

Against this backdrop of cynicism and mismanagement, however, there are also legions of committed doctors and nurses battling the scourge. "It's exhausting, but also exciting," said Dr. Caterina Guinovart, a young epidemiologist from Barcelona who puts in 14-hour days as project manager for vaccine research with the Manhica Health Research Center. "This is such an extraordinary time. In these little towns by a swamp, we could be on the edge of medical history."

She was speaking of Ilha Josina and Manhica, where women were bringing their babies to receive the third and final round of experimental vaccine RTSS, the drug abandoned 15 years ago but at last undergoing effectiveness trials.

Hopes are running high. But even true believers in the "holy grail" of immunization warn against expecting miracles.

"Malaria is a tough old adversary," said Dr. Regina Rabinovich, head of the infectious diseases program of the Bill and Melinda Gates Foundation. "There may never be a magic bullet. We must be pushing for vaccines, certainly, but also better medicines and better preventative techniques. Humanity probably needs a whole arsenal to fight this parasite, not just a single weapon."

© Copyright 2003 Globe Newspaper Company.