A neat century back, in the first months of 1900, Italian epidemiologists carried out a rarely direct experiment. They engaged reliable families who lived in malarial regions and protected each home with tight screening, on condition that the family would remain indoors from sunset to sunrise. Malaria struck only 10 among 207 well-screened experimenters, whereas 44 of 51 unscreened next-door neighbors fell ill as usual. No doubt remained: it was the excludable mosquitoes that brought the ancient periodic fever, important then even in Rome.
This logic of exclusion is witty. The screens kept mosquitoes out--and malaria. We need to recall the originator of the logic, Francesco Redi, court physician of Florence. Long ago, in 1668, he exposed fresh meat out of doors behind a gauze screen. Flies came, and maggots thrived on unscreened meat nearby but not on the screened morsel. Spontaneous origins, dust and air could not cause maggots, for the mesh had not stopped them.
By 1900 we knew that malaria, too, was the work of microscopic parasites, and now we know their intricate double life. First, they multiply sexually within the infected mosquito. Once the female injects them into the human bloodstream, the organisms seek the cells of the liver, sooner or later to emerge and enter the red blood cells. There they divide again and again asexually by fission until they burst out, to begin an epidemic among red cells in many billions. The periodic fever and chills are signs of repeated significant loss of those cells, their essential red hemoglobin eaten away within, an acute partial anemia. The famous recurrences after some days of respite follow from timed emergence of the teeming parasites as they ripen in concert one evening to match the schedule of their nocturnal couriers. Back in a mosquito, the tiny forms mate and multiply, to crowd into the salivary glands of the blood thief, who may then inject them into another human during t he blood meals that nourish the next egg-laying forays.
All this dovetailing is the elegant product of coevolution. Here is no recent affliction like the new human immunodeficiency virus (HIV). Many mammals, birds, even reptiles fall to a similar mosquito-borne disease, plausibly much older than our species, possibly a disease of our ancestral primates. Four distinct species of the human parasite are known; a few far-flung mosquito species within one large mosquito genus of anophelines ferry most of the organisms from person to person airborne. How engage this complex enemy? First of all, the human genome itself adapted to the selection pressure of the infection. Many people of West African origin bear a biochemical genetic trait not common elsewhere. Their hemoglobin is slightly modified: resistance to infestation appears, usually at minor cost in function. Experience everywhere had suggested the unhealthiness of wetland living; part of that concern was the mosquitoes it brings.
Of course, no one enjoys mosquito bites. Screens exclude the fliers, and defense by bed netting close around sleepers is even less expensive. (Recent improvement has followed new netting impregnated with pesticides.) Drained wetlands, sewers and paved streets, animals kept at a distance, tight housing, less outdoor work, drugs and clinical help are now easily available. Together such changes have banished mosquitoes and malaria in well-off countries. Warm, wet climates are the major concern, yet not so long ago malaria was a summertime risk even in Denmark.
Finally, we combat the parasites themselves. The bitter Peruvian cinchona bark, a wide-spectrum natural plant defense against many enemies, was soon purified into quinine and much modified became chloroquine, the chief malarial preventative of the recent decades. (The Sunday-to-Sunday pill is still routine--one every seventh day and don't forget, we told ourselves in the late 1990s in both South Africa and India.) Effective new drugs, such as artemisinin, derived by Chinese pharmacologists from a traditional herbal remedy, are also at handOne graph in the World Health Report of 1999 (WHO) estimates losses to malaria since 1900; we use their figures.
In 1930 the regional sub-Saharan risk of death by malaria was comparable to, if somewhat larger than, the risk in the rest of the world. By 1970, after an intensive worldwide campaign, the sub-Saharan risk had indeed fallen by more than half, although it lagged the much faster decline outside the region. By 1997 sub-Saharan malaria had counterattacked. While regional risk almost doubled, the world risk fell very steeply. Sub-Saharan personal risk of fatal malaria is now 160 times greater than it is outside. Nearly a million die every year in that region alone, six times the total of malarial deaths in the entire world.
Why? In the mosquito-harboring world, some 100 bites per year is an average human burden. But an unprotected West African is likely to receive 1,000 bites a year. Sub-Saharan Africa is malaria's homeland; there ecology, climate and land use all favor fast transmission of the disease, as does general disorder. The world antimalarial campaigns of mid-century rested on simple measures of control: both prophylactic drugs and the now suspect insecticide DDT, peculiarly effective against mosquitoes, were cheap. Success was sweet but uneven. The strategy eventually turned into a strong selection among mosquitoes favoring resistance to DDT and among parasite species for resistance to common drugs. The rarer malignant strain of malaria has in many places become abundant, probably a more recent adaptation to human infection than the common forms. Drug doses effective against it have been unaffordable to poor farmers; debilitated and fearful, they are unlikely to become bette r off. The decision that endemic African countries would not require a special campaign had led along a trail of linked feedbacks straight to regional disaster.
Molecular biology holds the wild card: immunization. But the enemy, the malarial parasite, is no virus, no bacterium, but a unicellular protozoan, its cells rather animallike, growing to some 10 microns. It is a eukaryote, like us, with a true cell nucleus and a chromosomal apparatus for maneuvers that make new combinations among 6,000 mapped genes. Armed as well with a battery of sensory organelles at its front end, it searches out and affixes to its prey, your red cells. Different progeny of a single infectious entry adhere differently. No one surface protein is vital to this hunt. The parasite can even change its protein spots. Unaided, the human immune system has never done much against malaria. We have little hope to win now by blocking one receptor with a single gene change; the experts work with dozens of new proteins to induce the complex mix of antibodies needed.
WHO has now targeted malaria again, right in its last stronghold, in Africa south of the Sahara. Operation Roll Back Malaria is under way. Health systems in place will be improved, multiple drugs will be made available and widely resupplied, and the world, with private and public sectors beginning to work together, can reasonably expect to halve the million annual deaths from African malaria at a bargain cost of about $1 billion a year, until some high-tech vaccine shall come to end the war.
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