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Scourge of Humankind

November 20, 2010 by ab

High-profile efforts to fight malaria confront an ever-changing enemy that has evolved alongside man

Bad Air. Even the word “malaria” tells us that the disease caused by the plasmodium pathogen is out of the ordinary. The name “Mal-Aria” didn’t come into common medical usage until about 300 years ago, but for many more centuries “swamp fever” expressed the same thing: a serious disorder that assaulted the human body and especially the brain. Associated with bad drainage, water-logged soil and damp climate, it was the quintessential disease of location.

Location still matters a great deal in the incidence of malaria, but it is no coincidence that the most intensely malarious locations in the world today—sub-Saharan Africa, Southeast Asia, parts of South America—are also some of the poorest. This connection between poverty and malaria is undeniable, but their causal chain is problematic. Does malaria cause poverty through premature death, chronic disability and low productivity? Or does poverty itself cause the social chaos and unhealthy conditions that permit malaria to take a stranglehold on a town, region, country and even a continent? This seemingly straightforward question has been fiercely debated for a century and more.

Siblings in Cambodia take protection beneath insecticide-laced anti-mosquito netting.

Ronald Ross, who won the 1902 Nobel Prize for medicine for his demonstration that malaria is transmitted by Anopheles mosquitoes, firmly believed that malaria causes poverty. Get rid of malaria and malarious areas of the world will begin to prosper. Jeffrey Sachs, the outspoken economist who heads Columbia University’s Earth Institute, has inherited Ross’s modern mantle. Other economists (and malariologists) have not been so certain. In many parts of the world, including Britain and the U.S., malaria lost its hold only as prosperity was gradually achieved. Malaria’s disappearance was a welcome byproduct of better nutrition, schools, roads, health care and methods of agriculture.

These two interpretations translate into two differing medical approaches to the disease—vertical and horizontal. A classic vertical response was the initial campaign by the World Health Organization, in the 1950s and 1960s, to eradicate malaria through the use of the insecticide DDT. Following its abandonment, there were strong calls among international health workers to go down a “horizontal” route: If prosperity brings health along with it, Western aid for developing countries ought to be devoted to helping provide modern infrastructure.

The results of the horizontal approach have been patchy at best. Childhood mortality in sub-Saharan Africa has been staggeringly intransigent. A million deaths is the figure typically reported for mortality world-wide, but that may not have much substance in reality, as investigative journalist Sonia Shah notes in “The Fever: How Malaria Has Ruled Humankind for 500,000 years.” We don’t know how many people die from malaria, or even die with the disease. What we do know is that current inroads against malaria are piecemeal and may not be sustainable.

Now the arrival of Bill and Melinda Gates on the international health scene has changed everything, placing a renewed emphasis on the vertical approach. The founder of Microsoft admirably wanted to put some of his vast fortune back into society, and “neglected diseases” (including malaria, AIDS, and drug-resistant tuberculosis) seemed to be a good place to start. Melinda Gates, in particular, has placed malaria eradication back on the agenda, and the Gates Foundation funds research toward improved drug treatments, safer insecticides and eventually an effective vaccine. But the lessons of history should give us pause.

Back in the 1930s, thoughtful malariologists such as S.P. James, who had worked in India shortly after Ross, believed that it was ill-advised even to attempt eradication in regions with high incidence of the disease. Despite the high infant mortality that malaria causes, individuals who survive the disease acquire sufficient immunity to cope as adults. Destroying that herd immunity, even for a generation, means risking that the disease will return with a vengeance.

Doctors like James and others who advised the League of Nations Malaria Commission also appreciated how complex malaria actually is. Four different species of parasites can cause it, and each evokes a different response in its human host. More than two-dozen species of Anopheles mosquitoes can transmit the parasite, and each species has its own breeding patterns and favored habitat. The consequence, as malariologist Lewis Hackett (1884-1962) wistfully wrote in the 1930s, is that malaria is “so moulded and altered by local conditions that it becomes a thousand different diseases and epidemiological puzzles.” The treatment that works best in one location may not work elsewhere—and “elsewhere” may be only a few miles away.

DDT briefly seemed to make these insights irrelevant. It formed the bedrock of the World Health Organization’s postwar campaign and achieved a good deal more than it is often given credit for. By 1963, when the funding for the DDT drive dried up amid concerns about the insecticide’s ecological effects, malaria had been eliminated from Europe, the U.S. and many other parts of the world. It had been almost eradicated from India and Sri Lanka.

In the rich countries it has stayed away—barring imported cases. In Asia, the gains quickly evaporated. India was down to about 50,000 cases when the spraying ended. By 1969 it had zoomed back to one million. Yet the WHO initiative may have failed even if it had been continued, due to the cunning adaptations of the enemy. The mosquitoes gradually grew resistant to DDT, while the parasites themselves became resistant to anti-malarial drugs such as chloroquine and atebrin.

All these issues, and many others, are brilliantly exposed in Ms. Shah’s book. She has read widely and appreciates the enormous efforts that even the modest goal of better malaria control will entail. Because she understands malaria’s history, she is also skeptical that the present eradication campaign will succeed, at least in the short term. Already some problems that bedeviled previous “vertical” efforts have raised their heads again.

Mosquitoes seem to be getting used to pyrethrum, the insecticide used to impregnate bed nets. (The nets are also not always used for the job they are designed for—having been discovered to be helpful in fishing and worth a bit of money on the black market.) Likewise, resistance to artemisinin-based treatments is beginning to be reported. Drugs are distributed but patients do not finish the course, stopping when they feel better or sharing the drugs with their friends and family. Self-medication is also a serious issue, since many drugs bought privately are fakes or contain a fraction of the medicine required. Inadequate dosing increases the probability that drug resistance will emerge in the parasites.

Supporters of a “horizontal” approach can point to even more basic problems. In many countries, the infrastructure for effective treatment is missing: Hospitals are often little more than makeshift facilities where patients come in hope or despair. The medications themselves are more expensive than most governments can afford, which is why international aid agencies and private philanthropy such as the Gates Foundation are attempting to bridge the gaps.

These groups are also, as we learn in Bill Shore’s “The Imaginations of Unreasonable Men,” backing a more ambitious approach: the development of a malaria vaccine. Mr. Shore, the well-known founder of Share Our Strength, a charity aimed at eliminating childhood hunger in the U.S., here provides an upbeat account of several American scientists researching malaria prevention. He and Sonia Shah sit at opposite ends of the inter national malaria problem—the vertical visionary and the horizontal historian. I prefer to the sober analysis of Ms. Shah to the well-meaning hype of Mr. Shore, but Mr. Shore tells his story well, making a virtue of his own studied naïveté in order to explain current efforts for a general reader.

What comes through very clearly is that the Gates money has transformed American malaria research. “The Gates Foundation very much acts like the general contractor responsible for eradicating malaria,” Mr. Shore writes, “using a wide variety of subcontractors who specialize in vaccines, drugs, diagnostic techniques, and public health systems.” Mr. Shore’s profiles thus include several recipients of Gates’s generosity, including Amyris Biotechnologies and the Institute for OneWorld Health. Sanaria, a start-up developing a malaria vaccine (one of 35 candidates currently tracked by WHO), might not have been able to continue its work without a timely Gates grant.

All the new ideas and energy coming from America have inevitably raised hopes, around the world, that perhaps Yankee ingenuity really can crack the malaria problem in the laboratory. The scientists themselves certainly seem confident. But should they be? Most malariologists agree that malaria cannot be eliminated without a vaccine. But that does not mean that a vaccine will necessarily eliminate malaria.

The depressing fact is that both mosquito and parasite are highly adaptable, and malaria has been central to human life for (to borrow from Ms. Shah’s subtitle) 500,000 years. Our battles with it have been written into the human genome: Sickle cell anaemia and other similar disorders, for instance, are genetic evidence of how humans and malaria have evolved together. Given this history, it is optimistic to think that the disease can be easily stamped out, especially considering that whatever magic solution might be discovered will still need to be delivered via a social infrastructure that doesn’t exist in much of the world.

The danger of the latest eradication attempt is that, with even the best will in the world, private philanthropy may not have staying power. The slog will be long and hard and the results slow in developing. We must not be paralyzed by the past. Nevertheless, the international health industry needs to set attainable goals—or risk repeating the failures of the initial malaria eradication program, which stopped when the money ran dry.

In most of the world today, malaria is a disease of poverty, and any doctor knows that the best way to get rid of a disease is to attack its cause.

Dr. Bynum is professor emeritus of the history of medicine at University College London.

__________

Full article and photo: http://online.wsj.com/article/SB10001424052748703326204575616452789851046.html

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