Stopping Malaria: The Wrong Road

The US eradicated malaria in 1951. Until then, this parasitic disease, transmitted largely by infected mosquitoes, had been endemic across much of the country. In the Tennessee River Valley, for example, malaria affected almost a third of the population in 1933. By the time the US National Malaria Eradication Program was launched on July 1, 1947, malaria had become concentrated in thirteen southeastern states. The program was led by the newly created federal Communicable Disease Center (now the Centers for Disease Control and Prevention, or CDC) based in Atlanta.

Justin M. Andrews, the CDC’s director at the time, was also Georgia’s chief malariologist. The CDC had itself evolved from the Office of Malaria Control in War Areas, which had been created to defeat malaria in the United States during World War II. Perhaps surprisingly to a modern audience that thinks of it as a disease of poor countries, the histories of American health and malaria are tightly bound. As the historian Margaret Humphreys has revealed, malaria “shaped southern and western [American] history in particular through its impact on labor patterns, mortality rates, and settlement choices.”¹

It is easy to forget today how dangerous malaria continues to be. Ninety-nine countries (40 percent of the world’s population, or about three billion people) live under the threat of malaria. The World Health Organization (WHO) reported 225 million cases worldwide in 2008, with 781,000 deaths. These figures are almost certainly underestimates. Most deaths—85 percent—are in children under five years of age.

For a disease that exacts such an enormous toll of human death and misery, it remains shocking that so little has been done by affected countries and large international donors to control malaria. This long epoch of neglect is gradually coming to an end. As Bill Shore explains in his survey of “baffling and surprising” strategies to eradicate the world’s most devastating parasite, “a small number of heroic idealists” are beginning to reverse decades of failure. They have recognized that traditional approaches to malaria control “always fall short.” Instead, defeating malaria requires “moral vision and imagination,” “a deeply intrinsic drive to achieve what others have dismissed as unachievable,” “a willingness to take risks,” and “irrational self-confidence.”

But Shore also shows an aspect of the organizations concerned with malaria that is less heroic, less moral, and certainly not at all idealistic. He exposes how a spirited culture of creativity, confidence, and competition in malaria research too often expresses itself as hyperbole, hubris, and personal enmity. There are frequent examples of scientists who confidently ridicule the work of fellow scientists: “Rival researchers are polite but mostly dismissive of one another,” Shore notes. As he concludes, “In each branch of the malaria war, there are many who believe their own approach embodies the best mix of compassion, realism, and effectiveness, and therefore occupies the moral high ground.” This extreme rivalry fosters islands of scientific inquiry separated by seas of bitter disagreement. Such a fetid environment is weakening the international effort to defeat malaria. This is the hidden story behind the “unreasonable men” Shore so admires.

1.

When Melinda Gates stood up at the Gates Foundation’s Malaria Forum on October 17, 2007, no one expected her to use a word—“eradicate”—that more experienced malaria experts had feared for almost forty years. She said of malaria that there was

an historic opportunity not just to treat malaria or to control it—but to chart a long-term course to eradicate it…. To aspire to anything less is just far too timid a goal for the age we’re in. It’s a waste of the world’s talent and intelligence, and it’s wrong and unfair to the people who are suffering from this disease.

The WHO’s director-general, Margaret Chan, immediately backed this call to action.² But others saw Melinda Gates’s words as inflammatory. Ann Veneman, UNICEF’s executive director, demurred, furious that Gates had failed to consult UN agencies before claiming moral leadership in eradicating one of the world’s most politically sensitive diseases.³

Shore is sympathetic to those who see Gates’s intervention as valuable additional pressure to mobilize more resources for malaria. “Not believing that malaria could actually be eradicated was a failure of imagination that distorted and undermined the way the malaria community went about its work,” he writes. Shore seems to view the Gates approach as little short of transformational. It is, he writes, spearheading a new attitude toward disease at “the intersection where science, philanthropy, and entrepreneurship are converging.” The Gates Foundation is “the catalyst for investing in global health…the modern day NASA of the global health field.” Many scientists who work in global health today—from those investigating new drugs for tuberculosis to those searching for an AIDS vaccine—would agree. Bill Gates has made the diseases of poverty fashionable.

But there is another view about the influence that modern philanthrocapitalists, such as Bill and Melinda Gates, have had on the fields they choose for their attention. The medical researcher David McCoy and his colleagues have argued that much of the Gates money is not invested where the foundation claims to show its greatest concern—in low-income settings, such as sub-Saharan Africa.⁴ Instead, over 80 percent of the cash that does not go to supranational organizations (the WHO, the Global Alliance on Vaccines and Immunisation, the Global Fund to fight AIDS, Tuberculosis, and Malaria, and the World Bank) goes mostly to organizations in the US. Worse, the patterns of Gates funding do not match the burden of diseases endured by those in deepest poverty. As a result, worthwhile programs—in child health, for example—suffer.⁵ The Gates billions, these critics argue, divert political priorities away from the needs of the poor.

Shore would say that these criticisms miss the point: “It is the character of the people doing the work that is the key.” The status quo of traditional programs led by well-intentioned but ultimately failing institutions should be swept aside. Instead, we need people who can fill “the imagination gap…[a] vitally important space between the impractical and the impossible.”

What Shore emphasizes is that the central problem in attacking malaria is the lack of a market mechanism to deliver technical solutions—a vaccine, for example, or efficient ways to produce and distribute effective medicines. The economic and political incentives to defeat it are simply absent. For Shore, what is right about the Gates approach is their use of “market mechanisms to accomplish social objectives.” If innovators in treating malaria can expect higher rewards for doing so, the results, in his view, will inevitably be better. And to be fair, Shore is just as critical of modern business as he is of governments and international agencies. “Imagination,” he observes, “cannot be bought and installed like the latest software, or taught in an MBA program.” That is why people like Bill Gates matter. Their “leaps of imagination are not so much about new ideas as about a new conviction of what is possible.”

The exemplar of the Gates approach, so strongly endorsed by Shore, is the medical researcher Stephen Hoffman. He is trying to create a vaccine against malaria and has been supported with almost $30 million of Gates investment to do so. Shore’s chief unreasonable man is Hoffman: he is “the classic entrepreneur,” someone who is “impatient with conventional wisdom,” a “counterculture rebel.” Shore tells Hoffman’s story as “our best modern example of how imagination…can lead to breakthroughs.”

Hoffman’s approach to creating a malaria vaccine is highly original. He is trying to devise one based on a weakened version of the entire malaria parasite. It is a live vaccine, similar to those that have been so successful against measles, smallpox, and polio. Announcing the first human trial of Hoffman’s whole-parasite malaria vaccine in 2009, the Gates-funded Malaria Vaccine Initiative described Hoffman’s study as a “watershed event,” one that “highlights the strength of public-private collaboration in tackling international health challenges.”

Shore portrays the quest for a malaria vaccine as a war between two competing philosophies—the market-based, entrepreneurial approach versus more traditional methods of vaccine discovery. Shore’s preference is “to find or create markets to enable nonprofit goods and services to get to scale and sustain themselves…. This means creating commercial markets.” He also sees it as a competition between individuals. Hoffman is the outsider, forced to create his own laboratory—Sanaria, Inc.—to overcome the wall of skepticism he faced from less audacious colleagues.

By contrast, the American vaccine scientist Pedro Alonso “does not talk much about market mechanisms.” Yet he is the more acceptable “public face of malaria vaccine development,” based in one of those old-fashioned institutions—the University of Barcelona—that represent the “incremental progress [that] has led to a frustrating plateau” in malaria research. On Shore’s visit to Alonso’s offices, he reports a place that “looked like that of many mission-driven non-profits, with walls sporting maps of Africa and photos of children at medical clinics in small villages.” Although the Gates Foundation, together with GlaxoSmithKline, has supported Alonso’s work, Alonso rejects Shore’s (and Gates’s) emphasis on a competitive social-marketing approach. Instead, he says, finding a vaccine “is something we simply must do,” irrespective of commercial gain. For him the answer to the question of which philosophy is right will not be found in abstract arguments about the efficiency of the private sector or the altruism of universities. What counts are the results.

In 2008, Alonso and his colleagues reported that their vaccine, which targets a protein on the malaria parasite, halved the number of malaria episodes among children of five to seventeen months of age.⁶ A larger trial to confirm this result is currently underway. Most malaria experts believe that the efficacy of Alonso’s vaccine will be confirmed, in which case it should be available within the next three to four years. By contrast, when the results of Hoffman’s much-applauded vaccine trial were reported in September, the vaccine failed. Only five out of eighty volunteers were protected. As one report noted, “the numbers were so bad that Dr. Stephen Hoffman did not even want to say them out loud.”⁷

2.

Is Melinda Gates’s call for eradication the only way to defeat malaria? There are other approaches that deserve consideration. The first is elimination. Eradication is the permanent reduction to zero of the worldwide incidence of malaria—the parasite will disappear from the planet. Elimination is the interruption of malaria transmission so that in a given geographic area there will be no locally contracted cases. The disease can be eliminated but only by a determined application of such measures as draining mosquito swamps, distributing bed nets and insecticides, and providing antimalarial drugs, all within a working system of public health and medical care. Elimination does not erase the threat of malaria completely. It can be reintroduced either by humans infected with the parasite or by infected mosquitoes.

In new work recently reported by the Malaria Elimination Group (and partly funded by the Gates Foundation), Richard Feachem and his colleagues showed how optimistic one might be if the goal is more modest than the one set by Melinda Gates in 2007.⁸ Of the ninety-nine nations that suffer from endemic malaria, thirty-two have adopted the goal of elimination. Most are not in zones where malaria causes the majority of deaths. Instead, they are countries where malaria is already under reasonable control. The question for any government when faced with this situation—good, but not complete, control—is what to do next. Should a government keep investing in intensive control efforts or should it switch to a different strategy—elimination? The benefits of turning to elimination instead of control are clear. If elimination is the objective, unprecedented political commitment will likely be mobilized against malaria. This political support is essential if investments are to be focused on malaria rather than on other diseases. The spur to such a commitment should be the awareness that defeating malaria will deliver economic benefits—a more physically fit working population.

The opportunity to eliminate malaria from a country, while it might be real and feasible technically, has its own unique difficulties, even with high-level political support. If a country is at war or internally unstable, marshaling long-term resources to tackle malaria will be impossible to guarantee. To deliver the necessary drugs, bed nets, and insecticides also requires a strong health system—a network of primary care centers and clinics, doctors and nurses, and reliable information about where the greatest risks of malaria are found across a country. Many nations have weak health systems (especially in Africa), and these make elimination impossible. And even if the country is stable and the health system is good, the size of the population at risk and access to that population both affect the likelihood of successful elimination.

Based on these kinds of criteria, eliminating malaria is least feasible (most observers would say impossible) in sub-Saharan Africa, where public health facilities are deeply inadequate. Elimination is most feasible in South America (Mexico, Argentina, Paraguay, El Salvador, Costa Rica, the Dominican Republic, and Panama), Southeast Asia (China, Malaysia, the Philippines, North and South Korea, Sri Lanka, and Bhutan), parts of Central Asia (Kyrgyzstan, Tajikistan, Uzbekistan, Azerbaijan, and Georgia) and the Middle East (Iran, Iraq, and Saudi Arabia), together with a few countries in southern Africa (South Africa, Namibia, Botswana, and Swaziland).⁹ Around two billion people would be free of malaria if these countries successfully eliminated the parasite.

Elimination does not mean more of the same old policies—more anti-malaria medicines, more bed nets to prevent infection, more spraying of insecticide to kill mosquitoes. Elimination is a much more thorough and targeted approach to defeating the parasite. Elimination means focusing on stubborn pockets of malarial disease that are resistant to traditional control measures. It means having high-quality laboratory facilities to diagnose all infections. It means a strong central command program to coordinate efforts across the entire country. It means an excellent ability to detect stray cases from abroad. And it means secure borders to prevent—or at least limit—such importation.

There are risks. The Global Malaria Eradication Programme from 1955 to 1969 overpromised and underdelivered, failing ignominiously to do for malaria what had been possible against smallpox. This defeat turned a generation of malaria experts away from elimination and eradication. Elimination enthusiasts today are fully aware that they must be realistic about what they can achieve. The dangers are many. If limited financial resources for malaria are switched away from control in Africa to elimination elsewhere, the regions where most deaths occur—principally in Africa—will be cruelly harmed. And even if countries do eliminate the parasite that causes malaria, there is always the risk of the disease returning with a vengeance to those same countries, and with greater severity since the population will no longer have sufficient levels of immunity to tolerate endemic disease.

There is also the question of money. Is elimination cost-effective? Or would resources be better spent doing something else—devoting greater investment to reducing malaria in Africa, for example? To eliminate the disease will be more expensive than controlling it. The spending required for prevention, diagnosis, treatment, and surveillance (to detect imported cases) in order to achieve elimination, plus the continued spending that will be needed to prevent malaria from returning, will together exceed the current costs of malaria control programs. If looked at coldly, the economic case for elimination simply does not add up. At a time of global fiscal restraint, malaria elimination seems like a luxury the world can ill afford.

Malaria elimination is not a policy for the short term. But if elimination is viewed more like immunization than like the treatment of a disease—that is, a cost that is delivering long-term benefits—then the resulting health and economic advantages over time, as for vaccination, are likely to be huge.

A fair conclusion seems to be that the goal of global malaria eradication, while it lends itself to a stirring message, is naive and simply not feasible. Elimination, by contrast, is just possible for a substantial part of the world’s population. There are still obstacles, the most difficult being that malaria is not a single disease. There are four types of malaria parasites—Plasmodium falciparum (the cause of most disease and deaths in Africa), P. vivax, P. malariae, and P. ovale. The latter two are relatively less serious forms of the disease. But P. vivax remains something of a dangerous mystery. The tools to eliminate P. vivax are largely absent. And P. vivax is an especially neglected problem in the countries that are trying to eliminate the disease. What is needed now are assessments of what is possible in the thirty-two countries where malaria transmission might be reasonably interrupted. Elimination remains an unfulfilled opportunity.

3.

But as we have seen, elimination is not the answer where malaria exerts its most lethal effects—in sub-Saharan Africa. The average malaria mortality in the Western Pacific (including China) is 0.3 deaths per 100,000 population. In the Americas it is 0.5 deaths per 100,000. In southeast Asia, it is 2.1 deaths per 100,000. These are the regions where elimination is most feasible. In Africa, the average number of deaths is 104 per 100,000—a huge figure. The highest death rates from malaria are in Niger (229), Equatorial Guinea (220), and Mali (201). In Africa, one in six child deaths is from malaria. Whatever one’s views about markets, vaccines, or the Gates Foundation, it is Africa that deserves our special attention.

There is evidence that recent increased investment in malaria control—notably by the Global Fund to Fight AIDS, Tuberculosis, and Malaria, which is funded by the UN and the G-8 nations, and by the US President’s Malaria Initiative—is making a difference in Africa. In Kenya and Gambia, for example, the burden of malaria is beginning to decline.¹⁰ But despite these encouraging signals, the promise that African heads of state made a decade ago—in the Abuja Declaration—to halve malaria mortality in Africa by 2010 will not be met.

The unpalatable truth is that despite strengthened advocacy and considerably more money, the interventions that Africa needs are simply in too short supply. Millions of children should be protected by insecticide-treated bed nets, and are not. Access to the most effective treatments—what is called artemisinin-based combination therapy—is still inadequate for most of those who become infected. And the funding for malaria control is still well below what is required. According to one estimate, investment in malaria control is 60 percent below the $4.9 billion needed in 2010.¹¹

Bill Shore emphasizes the urgent need for expanded access to medicines as a crucial part of the fight against malaria, especially in the absence of a highly effective vaccine. Paul Roepe, a malaria scientist focusing on drugs at Georgetown University, put it this way:

With all due respect to Steve Hoffman, a vaccine would be great, but that’s at least ten years away. And with 2 million kids dying every year from malaria, that’s 20 million freakin’ kids that will die. In my humble opinion the Gates Foundation ought to balance a bit more of its funding to get drugs to these kids now.

To get medicines to those who need them most requires a health system—facilities for basic treatment and prevention services. Too often, enthusiasts for a vaccine or a drug ignore the fact that without a health system, their magic bullet will fail to reach those for whom it is intended. Shore is sensitive to this important and neglected dimension in the global efforts to defeat disease. He identifies one surprising example of blinkered thinking in his brief mention of the programs to eradicate polio.

Polio eradication is what is called a vertical initiative: a top-down effort to parachute in a technology—in this case, a vaccine—and deliver it precisely to where it is most needed. Vertical programs can be amazingly successful. Smallpox eradication is one example. But vertical programs may not do much to build health services for those who do not need the particular technology in question. Horizontal programs, by contrast, build capacity to improve health care—including clinics, trained medical workers, and education about disease and infection—from the ground up. Strengthening the health system will, in theory at least, improve health for everyone, not just the few at risk of one disease. The debate between verticalists and horizontalists is passionate, and often angry. Bill Gates is a verticalist. Shore recognizes the inherent weaknesses of that approach. “Even Gates,” Shore writes, “suffered a failure of imagination when it came to fighting polio.” He forgot that “horizontal strategies [to defeat polio] can be just as important as the vertical ones to long-term success.”

If malaria’s effects are to be reversed, the solutions will be complex. Combined horizontal and vertical strategies are needed. Those at risk of malaria need both a vaccine and access to cheap, safe, and effective drugs. But they also need good basic medical care. Neither approach on its own will be sufficient.

The global strategy needed to deliver these solutions requires strong leadership. But here a further gap opens up in the effort to control malaria. There are many institutions involved in malaria programs today—from the WHO to the Global Fund, from Roll Back Malaria to the President’s Malaria Initiative. But amid this plurality and diversity, there is no one organization that coordinates international efforts to defeat malaria. This confusion is disabling. When one individual—Melinda Gates—raises the goal of eradication, the malaria community is plunged into chaos and recrimination.

The WHO should be the agency to lead global malaria programs. It is the only intergovernmental agency with a political mandate to work at country level with governments to tackle disease. And yet at a moment when the WHO should be leading, it is timidly waiting for others, especially the Gates Foundation, to make the first move. In today’s world, even in health, money talks. The Gates Foundation has billions of dollars at its disposal. The WHO ran a deficit in 2009 for the first time in its history.

New entrants into the world of malaria are now introducing innovations where the WHO is unable or unwilling to act. One such innovation is based on the fact that the public sector, often so weak in countries afflicted by malaria, is a poor instrument to improve access to medicines to treat the disease. Most antimalarial drugs in these countries are obtained through the private sector. Left to itself, the market for effective antimalarial medicines will set prices well out of the range for those most at risk of disease. The market might be the best way to distribute medicines, as Shore emphasizes, but the market needs to be manipulated if it is to deliver these medicines effectively.

An organization largely financed by the Gates Foundation and the Global Fund—the Affordable Medicines Facility–malaria—is working in Africa to reduce the prices of antimalarial drugs and subsidize their distribution to those who need them most.¹² It is an example of how the market can be tampered with for good ends. That said, such a program remains an unsustainable solution to the ills of most countries, especially in Africa. A nation such as Niger or the Democratic Republic of Congo will only benefit in the long run if organizations such as the Gates Foundation and the Global Fund invest in national health systems.

Too often, the WHO makes a grand commitment—for example, to join the Gates Foundation in its pledge to eradicate malaria—only to shrink from the implications of that commitment. It has failed to harness the expertise that is available to it to direct malaria control in Africa and elimination elsewhere. It has failed to lead, guide, and coordinate.

Conquering malaria in this century is a distant but still realizable goal.¹³ In the meantime, the effects of the parasite can be reduced so that it will have much less significance. But this will not happen through the market-driven organizations so beloved of Shore’s unreasonable men. Nor will it depend on the incremental progress of traditional research. What will matter is excellent science by excellent scientists, no matter where it, or they, comes from. And during this quest for discovering new ways of defeating malaria, the human tragedy of the disease must not be forgotten. The parasite is not only a burden on human health, it is a brake on human progress. Across Africa, malaria stops children from living. It also stops children from developing.¹⁴ This fact is the truly unreasonable challenge that malaria presents.