Article Tools

The Tenacious Buzz of Malaria

Sonia Shah, The Wall Street Journal, July 10, 2010

A 3-year-old girl plays under an insecticide-treated mosquito net in Nairobi, Kenya.

The Romans called malaria the "rage of the Dog Star," since its fever and chills so often arrived during the caniculares dies, the dog days of summer, when Sirius disappeared in the glow of the sun. To avoid it, ancient Romans built their grand villas high in the hills, fled the mosquito-ridden wetlands that encircled Rome, and prayed for relief at temples dedicated to the fever goddess, Febris.

It was the emperor Caracalla's physician, Serenus Sammonicus, who in the second century came up with Rome's first antimalaria quick-fix, one that later became literally synonymous with magical solutions everywhere. An amulet should be worn, Sammonicus advised, inscribed with a powerful incantation: "Abracadabra."

History of Malaria

In Myanmar, 1942, a man sprays stagnant water with an insecticide to kill mosquitoes.

2700 BC - The characteristics of malaria are first documented in "Nei Ching," a seminal text of ancient Chinese medicine, edited by Chinese Emperor Huang Ti.

2nd Century BC - The Qinghao plant is described in the medical treatise "52 Remedies." Its active ingredient, artemisinin, has been found to be effective in antimalarial drugs. In 1971, Chinese scientists isolate Qinghao's active ingredient, artemisinin.

Early 17th Century - Spanish missionaries learn about the medicinal qualities of bark from the Peruvian Cinchona tree from the indigenous people in the New World. The bark contains quinine, an effective antimalarial.

Nov. 6, 1880 - Charles Louis Alphonse Laveran, a French army surgeon, detects parasites in the blood of malaria patients, which leads him to win the Nobel Prize for Physiology or Medicine in 1907.

1886 - Camillo Golgi, an Italian neurophysiologist, discovers there are at least two types of malaria, each producing different amounts of parasites.

Aug. 20, 1897 - Ronald Ross, a British officer in the Indian Medical Service, discovers that malaria parasites can be transmitted through mosquitoes. This earns him the Nobel Prize for Physiology or Medicine in 1902.

1934 - Hans Andersag discovers chloroquine, a compound that later is developed into an antimalarial drug, in Eberfield, Germany. Chloroquine goes on to be recognized and established as a safe drug in preventing and treating malaria.

1939 - Paul Müller discovers the insecticidal property of DDT, which leads him to win the Nobel Prize for Physiology or Medicine in 1948. DDT, first synthesized in 1847, was used widely at the end of WWII to control for malaria.

1942 - The Office of National Defense Malaria Control Activities, which eventually changed its name to the Centers for Disease Control and Prevention, is formed, concentrating on controlling and eliminating malaria in the United States.

1947 - The CDC and 13 southeastern states develop the National Malaria Eradication Program. Within four years, malaria is considered eliminated in the U.S.

1955 - The World Health Organization submits a plan to eradicate malaria worldwide. The Global Malaria Eradication Program includes spraying homes with insecticides and antimalarial drug treatment. With mixed success, it is eventually abandoned in 1969. The current National Malaria Prevention and Control Programs is refocused on controlling malaria instead of eradicating it.

1963 - Mario Pinotti, who heads Brazil's malaria service, launches a campaign to infuse cooking salt with antimalarial drugs to medicate the population at large. But after $1.4 billion and 10 years, the World Health Assembly calls to dissolve the program.

2006 - The United Nations Foundation starts Nothing But Nets, a program to raise awareness about malaria and help fund the distribution of mosquito nets.

March 2007 - The World Health Assembly establishes World Malaria Day to raise awareness of the disease. This replaces Africa Malaria Day and is celebrated annually April 25.

2010 - Despite efforts to control malaria, the disease is still prevalent today. There were 247 million cases worldwide in 2008, most of them among African children, and almost 1 million died from it, according to the World Health Organization.
-Alice Truong
Sources: WSJ Research, Centers for Disease Control and Prevention

It didn't work, needless to say. Thanks to deforestation and flooding that extended mosquito habitat, malaria worsened near the end of the Roman empire, contributing to its decline. It took a lot more than Abracadabras for the malaria parasite, Plasmodium, to unclench its tentacles: a state-run quinine distribution program in the early 1900s, the ruthless swampland reclamation programs of Mussolini a few decades later, a blitz of DDT around midcentury, and the general economic transformation of the lot of the Italian peasant all had to run their long and arduous course before malaria departed from Italy, centuries after Rome fell.

Yet the spirit of Sammonicus's cure for malaria still beckons. You'd think a pathogen as wily as Plasmodium would command a bit more respect. The malaria parasite has been responsible for half of all human deaths since the Stone Age, and one in 14 of us alive today still carry genes that first arose to help protect us from its ravages. Malaria has shaped our trade and settlement patterns, and our demographics. Today, it sickens 300 million every year, and kills nearly 1 million, despite the fact that we've known how to cure it (with parasite-killing drugs) and prevent it (by avoiding mosquito bites) for over a century. And even as the fight against malaria gains momentum, research reveals that malaria's tentacles continue to dig ever deeper.

Part of malaria's wicked genius is that since ancient times, it has fooled us into thinking it is a trivial problem, easily solved. Diseases such as yellow fever, or plague, or polio, have always filled us with dread. But not malaria. Almost all of our attempts to squelch it, from thousands of years ago to today, have treated the disease as a weak foe, allowing malaria to flourish, nearly unchecked, to this day.

Ronald Ross, the British Army surgeon who in 1897 helped discover that malaria was transmitted by mosquitoes, came up with his Abracadabra cure in the early 1900s. Spend a few weeks skimming mosquito-infested puddles with a thin layer of oil, to smother the larvae as they come up to breathe, and malaria would be destroyed in a matter of months, he said. Malaria is a "very easily preventable disease," he opined. "In two years," Dr. Ross proclaimed, "we shall stamp malaria out of every city and large town in the tropics."

Dr. Ross called his quick-fix "mosquitoism." He hired a band of workers and tried it out in Freetown, Sierra Leone. Another enthusiast, Dr. Malcolm Watson, attempted mosquitoism on the rubber plantations of Malaysia. In 1915, Dr. Watson wrote that he'd soon "be able to abolish malaria with great ease, perhaps at hardly any expense." The malarial death toll barely budged.

In the 1950s, the Abracadabra cure that dazzled scientists and politicians was DDT, a "nearly perfect insecticide," as the Rockefeller Foundation malariologist Fred Soper put it. DDT made it "economically feasible for nations, however underdeveloped and whatever the climate, to banish malaria completely from their borders," said Dr. Soper's colleague Paul Russell. Simply spray a thin coating of DDT on the interior walls of domiciles, where mosquitoes rest, and malaria would be kaput within a handful of years. Then-senators John F. Kennedy and Hubert Humphrey introduced legislation to allocate funds for a five-year, world-wide malaria eradication program using DDT in 1958, in the same act that extended the Marshall Plan. Ninety-two other nations devoted themselves to the malaria eradication cause, too, dispatching armies of sprayers across the globe, DDT canisters tied to their backs.

The U.S.'s funding commitment for the DDT campaign ran out in 1963, just as another Abracadabra cure emerged from the head of Brazil's malaria service. This one entailed medicating the masses by spiking cooking salt with antimalarial drugs, so that millions would dose themselves against malaria with their daily bread. National malaria programs in southeast Asia and the tropical Americas flocked to the idea. British Guyana banned the sale of salt that didn't have any antimalarial drug in it. "At the end of eight weeks, there was simply no malaria" in Guyana, boasted U.S. government malariologist G. Robert Coatney in 1966. "It's a fantastic story. It works. No mosquito eradication, no nothing. Just the stuff in the salt."

Together, DDT and antimalarial drugs sent the global malaria toll plummeting from 350 million a year to 100 million.

It didn't last. By the late 1960s, the malaria toll had surged back to over 300 million, only now many malarial mosquitoes were resistant to DDT and malaria parasites inured to the drug chloroquine. The World Health Organization's Tibor Lepes called the eradication attempt "one of the greatest mistakes ever made in public health." In 1969, after 10 years and $1.4 billion (or $9 billion in 2009 dollars), the World Health Assembly called for its dissolution.

Part of the trouble has to do with biology. The malarial mosquito and the malaria parasite within it are nothing if not innovative. Smother a few million larvae in one village, and a few scores of mosquitoes hatched from the next village may well sail over. Douse millions of houses with DDT, and mosquitoes will learn to extract their blood in the evenings instead, before people go indoors. Bombard billions of malaria parasites with drugs and the creatures will evolve progeny that can withstand them.

Once Bitten

The life cycle of the malaria parasite, Plasmodium.

• A female Anopheles mosquito bites a person infected with malaria, taking in a small amount of blood with microscopic Plasmodium parasites. The mosquito's
immune system attacks the parasites, causing it to massively reproduce in order to survive. After one or two weeks, tens of thousands of the resulting sporozoites swarm up to the mosquito's salivary gland.

• The mosquito bites again. Slivery sporozoites escape into its human host.

• The sporozoites invade the liver, growing, dividing and producing tens of thousands of so-called merozoites. (This can take a week or two, depending on the species of parasite.) The merozoites enter the bloodstream. They latch onto red blood cells, feast on hemoglobin and replicate.

• Once the blood cells are depleted, the parasites break out of the cells to find fresh cells, leaving behind a stream of waste. The waste triggers a high fever, followed by chills and shivering, as the victim attempts to detoxify.

• After the fever and chills pass, there may be several days with no symptoms-until the parasite finishes its next batch of hemoglobin and moves on again, triggering another attack. The cycle continues until the victim becomes fatally anemic or suffers other complications, like coma, or the infection is brought under control by medication or the body's immune system.

A bigger part of it has to do with psychology. Malaria's most loyal allies, as always, have been the humans who host the parasite. British colonial officials laughed at Dr. Ross's ideas. "Better to leave it alone," the celebrated German bacteriologist Robert Koch said of malaria-mosquito-hunting, "so long as there remains anything else to be done in this world." During the early 1900s, when the Italian government doled out free anti-malarial quinine to the masses, malarious Italian peasants, suspecting a diabolical plot, fed the drugs to their pigs. In India during the eradication campaign, WHO and USAID investigators found, people saw the DDT sprayers coming and locked their doors-and sprayers sold the excess DDT on the black market.

Malaria parasites have rapidly evolved resistance to every drug we've thrown at the disease, including, over the past few years, those based on artemisinin, the first-line drug currently recommended by the WHO. But the truth is that less than a quarter of people with malaria visit health centers for treatment anyway, studies show. In a study conducted in Burkina Faso, German epidemiologists found that 20% of malaria patients are prescribed the wrong drugs at the wrong doses, 10% don't bother buying the drugs they're prescribed and more than 30% don't take the drugs as prescribed.

Perhaps there's something about a disease that worms its way so deeply into daily life, with such a wide range of diffuse symptoms, that somehow disarms us, cloaking its fearsome toll and staggering dynamism like a sheepskin on a wolf. People in malarious countries should fear malaria the way they fear HIV and cancer, but according to medical anthropologists, they don't. They think of it more like the cold. And we've named it accordingly. We don't call malaria anything like the "Black Death," despite it having caused more mayhem and for longer than the plague, but rather have named it after "bad air," the mal aria.

Add to that the cruel fact that malaria doesn't repel attacks against it immediately. There's always a period of decline, sometimes precipitous, entrancing the hopeful again and again. Battling malaria is like sitting on a spring. It goes down, but then as soon as you get up, it bounces back up again.

The latest attack on malaria began in 1998, when the WHO launched its Roll Back Malaria campaign. Between then and now, the annual kitty to fight malaria has zoomed from $100 million to $2 billion, with funds pouring in not only from donor countries, but the Global Fund to Fight AIDS, Tuberculosis and Malaria, the World Bank, the Gates Foundation and a raft of oil, mining, and other companies active in West Africa and other malarious regions. The Gates Foundation, which as a top financier of global health research and the third biggest contributor to the WHO, now sets the global health agenda, announced its intention to wipe malaria off the face of the earth during a private meeting in 2007.

Since then, over 200 million bed nets, doused with pyrethroid insecticides, have been distributed across Africa, and many more are on the way. Research to find new cures for malaria is booming. Drug giants such as GlaxoSmithKline have opened their massive drug libraries to public health researchers, who this May announced they'd screened two million compounds for antimalarial activity and had found over 13,000 potential new drug candidates. Dozens of malaria vaccines percolate in labs across the globe, and this spring, researchers began lining up 16,000 infants and children in seven African countries for a clinical trial of a malaria vaccine that could reduce malaria infection by 65%, if early results hold.

Malaria has started to decline in a handful of African countries, which is no small feat. But at the same time, malaria continues to stalk even the most well equipped among us, including two South Koreans involved in the World Cup festivities who died of malaria infections they contracted in South Africa, and the British singer and TV celebrity Cheryl Cole, hospitalized with drug-resistant malaria last weekend after a trip to Tanzania. The very idea of eradicating the disease has come into question, with the finding this winter that the most virulent human malaria parasite, Plasmodium falciparum, presumed since the 1930s to be an exclusively human pathogen, also finds succor inside the bodies of gorillas.

Noting the alarming spread of artemisinin-resistant malaria parasites and pyrethroid-resistant mosquitoes, USAID malariologist Michael Macdonald announced, at a Johns Hopkins University gathering this June, that "we are on thin ice."

The blanketing of Africa with treated bed nets continues, regardless, with less than 5% of malaria control programs conducting any surveillance for resistant parasites and insects. "It is unbelievable," Dr. Macdonald said, "how much money we are spending blindly."

And then there are those studies show that just over half of those given the nets actually hang them up and sleep under them. But who can blame them? We've all been underestimating malaria for millennia.

As malarious countries prosper and develop, the day will surely come when those still vulnerable to the bites of malarial mosquitoes will live in screened domiciles, more than a stone's throw away from stagnant, mosquito-infested waters-or will suffer the brief sting of a highly effective malaria vaccine-and malaria will be no more. Until then, let the Abracadabra cures continue.