The Fever: How Malaria Has Ruled Humankind for 500,000 Years (4 page)

The parasite’s steady consumption of its victim’s blood drains him of vitality, making him easy pickings for other pathogens of various ilk. But while the parasite grows inside, aside from an enlarged abdomen—the spleen of the malaria-infected can swell to twenty times its normal weight while clearing the body of dead cells
²³
—its passage remains obscure. All the while, mosquitoes will bite, and imbibe the parasite roosting in the blood, and the cycle continues.

Just in case all this proves insufficient to secure malaria’s safe passage,
Plasmodium
manipulates its unwitting hosts to more pliantly succumb to its will. While gestating inside the mosquito, the malaria parasite somehow manipulates the mosquito to become more cautious, seeking less of the life-giving blood it needs for its young, thus reducing the insect’s risk of getting smashed or eaten and destroying the parasite developing within.
²⁴
Once fully developed inside an infected mosquito, though, the parasite shifts its calculus, manipulating the host insect to bite more often, and more persistently,
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by depressing the anti-clotting compound in her saliva, apyrase, so the mosquito can barely get enough. Unsated, she is more likely to seek out yet another victim, whom she can infect with yet more parasites.
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Genetically engineering mosquitoes to resist malaria infection weakens them. Could there be something about malaria infection that helps mosquitoes stay alive, despite the parasite’s selfish intentions?
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Not very much is known about how malaria infection manipulates human behavior to its own ends. Obviously, it leaves human victims passive, despondent, supine: in other words, more vulnerable to the bites of mosquitoes. Human attractiveness to mosquitoes depends on various factors—the smell of their feet, the chemicals on their breath, and the temperature around them—but according to studies of how mosquitoes behave around infected and uninfected people, being infected with malaria parasites alters human chemistry in some subtle way that mosquitoes find especially attractive.
²⁸

Certainly, malaria has left a deep fingerprint on our genomes. Today, one out of every fourteen human beings carries genetic mutations that first evolved to defend the body from malaria’s onslaught.
²⁹
This legacy has resulted in myriad conditions, reverbs of malarial destruction, some more debilitating than others.

Malaria is not just a human problem. During its long reign,
Plasmodium
has been able to spread its tentacles into a wide range of furry, fanged, and scaled bodies. More than one hundred different species of
Plasmodium
parasites specialize in infecting a veritable Noah’s ark of creatures. There are malarias in chimps, gorillas, and orangutans; in thicket rats, porcupines, and flying squirrels; in pheasant and jungle fowl. Malaria parasitizes lizards and occasionally snakes. As I write this, malaria parasites teem with purpose inside the veins of the house sparrows skittering outside my window.
³⁰

Malaria’s relentless pursuit of every available ecological niche from which it might suck sustenance includes a wide range of human habitats, from the deepest tropics of Asia to the deserts of Africa and the cool climes of northern Eurasia. In some, human-mosquito intimacy is intense; in others, distant. In some places it is sporadic; in others, continuous. At times, human defenses have been able to repel parasitic invasion; at others, we’ve fallen like sand castles in the tide. Throughout it all,
Plasmodium
has successfully maintained
its contagion of humankind, a long pillage that has left us with no fewer than four different species of malaria parasites stalking the human race.

The first human malarias probably made a fairly marginal living. The bite of a mosquito was a relatively rare thing millions of years ago when early humans roved the savannah in search of game. If the parasite managed to get deposited into them, it probably never got out: early humans might not be bitten again for years, even decades. Stuck in dead-end hosts, the malaria parasite inside them thus would have fed for a while, reproduced, and then perished, waiting for a ride that never came. That early proto-
Plasmodium
parasite could probably have infected only about 1 percent of the thirty trillion or so red blood cells that gushed through human veins.
³¹

Despite the difficult circumstances,
Plasmodium
found ways to hang on with the emergence of a species of malaria parasite called
Plasmodium malariae
, which preceded the familiar microbes that exploited the filth and population density of early farm life—measles, smallpox, cholera—by several hundred thousand years. Once it finds its way into a human body,
P. malariae
can persist in a kind of suspended animation for as long as seven decades, waiting for that fateful day when its victim might chance to be pierced by another mosquito.
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This was an advantage, but along with developing slowly inside the human,
malariae
also developed slowly inside the mosquito, which was a serious liability, especially given Africa’s much cooler climate in pre-agrarian times. Even though they never live free in the outside environment, malaria parasites are still highly vulnerable to it, subject to the fluctuating temperature inside the cold-blooded mosquito. If the mosquito’s body is warmed by summery weather, the malariae parasite can mate and produce the necessary slivery sporozoite forms in about two weeks. But in temperate weather—say, sixty-eight degrees Fahrenheit—
P. malariae
’s development inside the mosquito gets sluggish. It needs a month or more to mate and produce sporozoites. Its mosquito, by then, is long dead.
³³

P. malariae
’s prospects, therefore, were never that great. For thousands of years, it probably just barely hung on, perennially at risk of extinction given the uncertainty in its transmission cycle. Such is the fate of the pioneer.

Adjustments continued. Most likely there were dead ends, of which we know nothing. We do know that, in time, a new strain of malaria parasite emerged: intense, furious, awkward.
Plasmodium vivax
parasites use proteins studded along red blood cells to attach themselves to the cell before invasion.
P. vivax
could foil human defenses better than
P. malariae
, allowing it to multiply much faster within its human victims, a huge step forward from its slow-developing cousins.
P. vivax
could perform its cycle within the human host—reproducing an army of parasites, feasting on hemoglobin, and producing gametocytes, the form that is able to infect mosquitoes—in just three days.
³⁴
So long as the mosquitoes were biting, early human communities would have found themselves at its mercy.

But
P. vivax
could not sustain a constant contagion upon early peoples, either. Mosquito carriers in human communities were still too few and far between, and the parasite still dangerously vulnerable to the cool climate of Ice Age Africa.
P. vivax
’s transmission cycle remained uncertain. For the humans, this made it much more dangerous. For when
P. vivax
did emerge, it did so suddenly and with epidemic force, burning through entire tribes like an erupting volcano, only to vanish suddenly, leaving behind piles of bodies as carrion.
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We know that
P. vivax
must have exerted a powerful blow because of the way early peoples responded to it, with genetic mutations that stopped the parasite dead in its tracks. The stakes for anyone with an edge against
P. vivax
must have skyrocketed. With each assault, our ancestors’ immune system primed itself against the parasite, honing its ability to foil it. Its scrambling genes trotted out different permutations, holding out the possibility that one might outmaneuver the enemy.

One day a child was born who, despite seeming quite ordinary, held just such a secret weapon inside her genome. Her DNA, like
that of the rest of us, comprised millions of chemicals called nucleotides, arranged in elaborate and complex patterns. One of these had been switched out of order. Such switches, rare though they are, generally result in a swift death in utero or soon after. This child was lucky. She survived despite the hidden eccentricity. The nucleotide switch resulted in her blood cells lacking a certain variety of proteins protruding from their surfaces. Functionally speaking, this didn’t make a lick of difference.

As the child went about her business, mosquitoes flew into the soft wind of her exhalations, attracted by the carbon dioxide and lactic acid.
P. vivax
slid into the tiny painless wound the mosquitoes had made, and then hid in the girl’s liver, as always, gathering strength for their impending invasion of the red blood cells. But try as they might, the parasites could not hold on to her subtly transformed blood cells. Without those studded proteins—they’ve come to be called Duffy antigens—the mighty
P. vivax
that infected the girl was rendered toothless. The foiled parasite would have floated in her bloodstream unhitched, unfed, and exposed. Patrolling foot soldiers of the child’s immune system would have neutralized it with ease.

When
P. vivax
descended on the girl’s band of hunter-gatherer kin, their gnarled and arthritic bodies would have writhed with fever and chills, while the girl remained healthy. She’d have extricated herself from the carnage, found a mate, and pushed out babies similarly blessed with the gift of smooth red blood cells. In time, she’d have mothered an army of vivax-immune descendants.

Stepping over the bodies of
P. vivax
’s earliest human victims, these descendants swept across the continent of Africa like a tide, reaching as far as the Arabian peninsula and the fringes of Central Asia. By about five thousand years ago, the smooth-celled woman’s hegemony was complete, and there wasn’t a single African alive on the continent who wasn’t her descendant (or the descendant of someone similarly endowed with Duffy-less blood cells).
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With that, vivax malaria’s reign in Africa abruptly ended.

•    •    •

By then, however, both
P. malariae
and
P. vivax
had long escaped their cradle in Africa. Malaria-plagued pioneers had walked out of Africa and settled across Asia, the Middle East, and Europe, ferrying
P. vivax
and
P. malariae
with them.

The temperate regions presented yet another mortal challenge for
Plasmodium
. European
Anopheles
mosquitoes were larger, more fecund, and stronger fliers than their tropical cousins. This made them better carriers of malaria. But they also hibernated all winter, to survive the continent’s killing frosts. The long hiatuses between blood meals could disrupt the cycle of malaria transmission for good.
Plasmodium
can’t just linger inside the body of a mosquito for months on end; it can’t hibernate. After a few weeks trapped inside with no escape, it starts to disintegrate.
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And so vivax malaria evolved another stage in its convoluted life cycle. After entering the liver, the parasite developed the ability to transform into a dormant form called a hypnozoite, which can survive unnoticed inside the human body for months. In this state of arrested development, it waits out the winter. Later, activated by some as-yet-unknown trigger, the hypnozoite awakens, and the parasite restarts its development and its invasion of red blood cells. (The resulting attacks of malaria suffered by the victim are considered relapses, as opposed to new infections.) This adaptation allowed
P. vivax
to lie low until the bugs started biting again and its blood feasts could resume.
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We know that
P. vivax
’s burden must have been costly in Europe and Asia, because genetic mutations that lessened its toll emerged and spread among malaria’s prey, albeit weakening those who carried them. Normally, genes that deform people’s red blood cells impose enough of a disadvantage to their carriers that the gene slowly dies out, and yet in many regions of the world, such deformities persisted and spread. Hemoglobin E, a gene that deforms hemoglobin, slowed
P. vivax
’s progress in the body. A genetic condition called thalassemia reduced people’s risk of getting sick from
P. vivax
infection. Another called ovalocytosis makes red blood cells oval and so rigid that they resist invasion by malarial parasites. Thanks to
P. vivax
, hemoglobin E spread throughout Southeast Asia, thalassemia in the Middle East and Mediterranean, and ovalocytosis through the Pacific region.
³⁹

But vivax malaria, in its post-Africa incarnation, was not a killer. Rather, it enslaved its victims, imposing a constant and unrelenting tax in blood. The convulsions of fever and chills arrived every summer and fall, as soon as the first mosquitoes fed on the blood of an obliviously relapsing carrier of dormant parasites.
P. vivax
infected the placentas of growing fetuses. Infected babies withered, with stunted immune defenses that rendered them vulnerable to diarrhea and pneumonia. Under the spell of chronic vivax infection, grown men and women weakened to the point that their ambitions drained away and they became anemically prone and wan, just vital enough to make more blood cells available for a later parasitic feed.

Convulsed by much more dramatic pathogens such as cholera, measles, and smallpox, malaria’s victims may have barely noticed the parasite’s toll.
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The agrarian lifestyle they had come to lead—staying put on their fetid lands, weak from hunger, living together cheek by jowl—favored the spread of infectious diseases of every ilk.