The Fever: How Malaria Has Ruled Humankind for 500,000 Years (3 page)

Terrie Taylor is one of the world’s leading experts on pediatric malaria. Since the 1980s, she’s spent six months of every year inside malaria’s epicenter in central Africa, unraveling the mysteries of a disease that takes the lives of three thousand African children every day. Taylor meets me at the airport in Blantyre, a 500,000-strong city in southern Malawi, at the beginning of the 2007 rainy season. Suffering an average of 170 bites from malaria-infected mosquitoes every year,
¹
between 40 and 70 percent of the entire populace of malaria-plagued nations such as Malawi harbor malaria parasites in their blood.
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In her fifties, Taylor wears long loose skirts and keeps her frizzy brown hair parted in the middle. She starts talking straightaway, as if we’ve known each other for years, grabbing my shoulder and making gently irreverent cracks. She marches through the airport waving and calling out greetings to nearly everyone we pass.

The air in Blantyre, as we exit the airport, is scorching and heavy with humidity. Soon the rains will start, and the public hospital where Taylor works will be full of frightened parents proffering their limp, fevered children. During a typical malaria season, the research ward where Taylor works admits 250 malaria-infected children, of
whom between 25 and 40 will die. And yet despite the passage of decades, being separated from her new husband (who is back home in Michigan), the oppressive heat, and the inevitable malaria deaths she will most certainly witness, Taylor exudes excitement. She’s more like an avid camp counselor at the beginning of summer than a doctor about to minister to an epidemic.
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She extols the friendliness of the staff at Blantyre’s ramshackle airport, the beautiful views along our drive, the easy-to-clean halls of the hospital.
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Perhaps this is her coping method, I think to myself. Or perhaps not. For Taylor is a scientist, too. In a matter of days she will venture into the beating heart of the malarial beast she’s stalked for decades. As with Captain Ahab and the whale, there’s a certain giddy anticipation to it.

Most pathogens mellow as they age. It’s enlightened self-interest, as the theory goes. Diminishing virulence is a superior strategy for survival. It doesn’t make much sense for a pathogen to rapidly destroy its victim—a dead body just means it’s time to move on. Take measles and smallpox, for example. In Europe, when those pathogens first emerged, they were probably reckless killers, taking millions of lives. The survivors learned how to withstand the diseases’ ravages, though, and in time both measles and smallpox settled into being unremarkable childhood illnesses, felling scores only when encountering virgin populations, such as those in the New World of the fifteenth century.
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Which begs the question as to malaria’s tenacity and continuing malevolence. Malaria has been plaguing humans in Africa for some five hundred thousand years, with the first encounters between human, mosquito, and malaria parasite probably occurring around the time our ancestors discovered fire. Malaria existed in Africa before then, too, feeding on the birds, chimps, and monkeys that lived in the canopy.
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We’ve had plenty of time—our entire evolutionary history, in fact—to adapt to malaria, and it to us. Or, at least, to devise tools and strategies to blunt its appetite. And yet, despite the
millennia-long battles between us, malaria still manages to infect at least three hundred million of us—that is one out of twenty-one human beings on the planet—and kills nearly one million, year after year. As an extinguisher of human lives, write the malariologists Richard Carter and Kamini Mendis, malaria historically and to this day “has few rivals.”
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It remains essentially wild and untamed, despite its great antiquity.

And experts such as Terrie Taylor have spent lifetimes trying to figure out why.

One simple reason for malaria’s ferocity is that the protozoan creature that causes the disease is, by definition, a cheater at the game of life. It is a parasite, a creature that can eke out its livelihood only by depleting others of theirs. The rest of us all do our obscure little part in the drama of life, weaving ourselves deeper into local ecology and strengthening its fabric, the bees pollinating the flowers, predators culling the herds of their weakest members. Parasites don’t help anyone. They’re degenerates.

Take the parasitic barnacle,
Sacculina carcini
. It is born with a head, mouth, segmented body, and legs, just like any respectable barnacle. But then, because it is a parasite, it stops developing into an independent creature. It burrows into the shells of the crabs off of which it will spend its life feeding. There it loses its segments, its legs, its tail, and even its mouth, devolving into a pulsing plantlike form, little more than a blob with tendrils sucking food from the forlorn crab’s body.
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It’s the very definition of repellent. In 1883, Scottish lecturer Henry Drummond called parasitism “one of the gravest crimes of nature” and a “breach of the law of Evolution.” Who can blame him?
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And yet parasites such as
Plasmodium
are not anomalous on this earth. According to the science writer Carl Zimmer, one third of all described species practice the parasitic lifestyle.
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To be fair, for
Plasmodium
, parasitism arose as an accommodation to newfound
opportunities, not because of any intrinsic quality or irreversible mechanism within it.
Plasmodium
did not start out life hardwired to steal. This killer first emerged on the planet as a plantlike creature, most likely some kind of aquatic algae. We know this because 10 percent of the proteins in modern-day
Plasmodium
parasites contain vestiges of the machinery of photosynthesis.
¹¹

Plasmodium
’s ancestors probably rubbed shoulders with the eggs and larvae of mosquitoes, similarly floating on sun-dappled waters.
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When the mosquitoes took wing, malaria’s ancestors likely went quietly along with them.
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It must have happened, then and again, that when a mosquito pierced a bird or chimp or some other blood-filled creature, malaria’s algae ancestors fell into the wound. Most probably died. But through the blind ticking clock of evolution, one day some subset of the interlopers found themselves thriving in those crimson seas, and a vampiric parasite was born.

Such are the ironies of surviving on this protean planet. A creature at the very bottom of the zoological scale, a humble being beneficently converting sunlight into living tissue (and thereby providing the basis for the planet’s entire food chain), turns into one of the most ruthlessly successful parasites ever known, commanding two separate spheres of the living world, human and entomological.
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Henry Drummond would have been appalled.

Delve into even the most rudimentary scientific literature on malaria and you will soon be confronted with a dizzying range of unpronounceable words. There is
exflagellation
,
erythrocytic schizogony
, and
exo-erythrocytic schizogony
. There are
gametocytes
and
trophozoites
and
sporozoites
. These are not obscure terms for little-discussed facets of the parasite whispered over cluttered lab benches by a few old-school malaria nerds, but rather basic stages in the parasite’s life cycle bandied about by nearly everyone in the malaria world, from ponytailed Harvard undergrads to queenly Cameroonian researchers and grizzled
Italian vaccine makers. It is as if scientists had to come up with a whole new language just to talk about malaria.

That’s because during the course of its life,
Plasmodium
transmogrifies into no fewer than seven different forms, which vary in both morphology and physiology. Its parasitic modus operandi demands such shape-shifting wiliness. After all, in order to survive, the malaria parasite must extort from two different species: the animal whose blood it feeds upon, and the insect who deposits it into that animal’s blood. It’s sort of like robbing a bank while stealing a car. Things get complicated.

The mosquito’s immune system instinctively attacks the parasite, encapsulating the intruder in scabs and bombarding it with toxic chemicals.
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To survive, the parasite must unleash armies of progeny in such massive numbers that fighting it off becomes more trouble than it’s worth.
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Male and female forms of the parasite, called gametocytes, then fuse, and the resulting parasites create cysts that cling to the walls of the bug’s gut. (The spasmodic waving of the male gametocyte’s long tail, which precedes the act of fusing with the female—yes, this microbe reproduces sexually as well as asexually—is called exflagellation.) Tens of thousands of slithering threads explode from the cysts and swarm up to the mosquito’s salivary gland. This is the form the parasite must take to infect human beings. Malariologists call it the sporozoite. When the mosquito starts a blood feed, some two dozen slivery sporozoites will escape into their next host.

The parasite’s shtick fails in most of the world’s 3,200 species of mosquito. It works only in a single genus, called
Anopheles
(rhymes with “enough of peas”), most likely because of that mosquito’s strangely tepid defenses. This restriction doesn’t hinder the parasite terribly, though: there are some 430 known species of
Anopheles
, distributed in every corner of the planet except for Polynesia, east of Vanuatu. At least 70 species are known to carry malaria.
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Outwitting the human body’s defenses, though, requires orders of magnitude more cunning. The parasite must conceal its appetite
and indeed its very presence inside the body. The object of its desire—the hemoglobin inside red blood cells, which it feasts upon—is particularly precious. Produced from iron in bone marrow, hemoglobin makes it possible for blood cells to attach to oxygen molecules, and thus ferry life-giving oxygen to the body’s tissues. Without hemoglobin, lone oxygen molecules maraud unattached, degrading cells, proteins, and DNA as surely as they brown sliced apples and rust metal, and the body weakens, becomes anemic, and ultimately perishes.

The parasite must hide. First, the sporozoites retreat to the liver, where they spend a few surreptitious days shifting, regenerating, dividing, and generating again, secretly transforming into an army of fifty thousand parasites in a new form capable of infecting red blood cells: the merozoite. In the next stage of the invasion, the merozoites pour into the bloodstream. They are cleverly disguised inside the liver cells they’ve gagged and murdered,
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but an epic battle ensues nevertheless, and the body’s immune fighters slaughter thousands. It isn’t a perfect victory. If a few stragglers in this marauding horde manage to escape, they latch onto red blood cells, and within moments penetrate the cells’ interior. There, they quietly feast on hemoglobin, and a new round of shifting, regenerating, dividing, and generating ensues. Some transform from tiny ring-shaped beings into fat, rounded creatures and unleash a wave of progeny. When nothing is left of the former oxygen-carrying cell besides a stream of waste and a bulge of fattened parasites, the parasites burst out of the cell and rush out to invade and consume a fresh crop of cells. Others quietly shape-shift into the male and female forms called gametocytes and lie in wait inside their hijacked blood cells. With any luck, they will be picked up by another bloodthirsty
Anopheles
mosquito.
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A creature this protean and multifarious defies easy challenge.

Nor is there any simple way for humans or mosquitoes to foil the parasite by avoiding the behaviors it so ably exploits.

The blood-feeding of mosquitoes, for example, is probably the most important thing a mosquito ever does—so crucial, in fact, that it risks its very life to do it. Piercing the skin of some creature many times larger than yourself is not for the fainthearted, particularly when your body can be pulverized with a simple wave of the hand or swish of the tail. Plus, blood is thick and therefore crushingly heavy for the average mosquito, which weighs significantly less than, say, a drop of water. Swollen with bloody bounty, a mosquito can barely fly, which is a mortal debility.
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But because velvety blood, rich with life-giving protein, is pure cream compared to the nectar they generally dine on, mosquitoes have devised clever strategies to circumvent each of these challenges. For one, they reserve blood-feeding to just a few precious moments in life, when it really counts. Emboldened by the promise of impregnation, only the female dares do it, using the rich meal to nurture her eggs. She finds her victim by following a trail of lactic acid and carbon dioxide in its exhalations. Then she numbs her chosen spot with a drop of saliva, which is spiked with compounds that deaden pain and retard clotting. Once sated with a volume of blood several times heavier than her own body, she departs immediately for the nearest vertical surface, where she spends forty-five death-defying minutes excreting all the water from her feast until, unburdened, she’s once again light enough to flap her tiny wings and sail away.
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Malarial sporozoites that spilled into the wound with her drop of saliva, meanwhile, have by then already infected her victim’s liver. But what else can the mosquito doff? The survival of her progeny depends on her blood-feed.

Plasmodium
’s wiles similarly thwart overt human challenge, mostly because in the vast majority of cases, victims are completely oblivious to the fact of infection until it is far too late to do anything to impede the parasite’s progress—even if they knew how. Almost all of
Plasmodium
’s manuevers inside the body occur in utter secrecy. When it slips into the body, while it hides in the liver, and even after it emerges into the bloodstream and attacks blood cells, there is
no itch, no rash, no sweaty forehead that belies the infestation roiling within. It is only after malaria parasites rupture out of their hijacked cells, well into the parasitic invasion, that the infected person feels sick. The waste from the parasite’s hemoglobin feast leaks out of the destroyed cells, and that tiny spike of poison triggers a round of detoxification, throwing the victim into a high fever, followed by chills and shivering. When the waste disperses, the fever passes, and for several days there might be no symptoms at all—until the parasite finishes gobbling up its next batch of hemoglobin and explodes again in search of more, triggering another attack of fever and chills.
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