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Malaria vs. Mankind: Chemicals, Conservation And An Ancient Arms Race

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Part of a series investigating the complex linkages between human, animal and environmental health: The Infection Loop.

One steamy evening in July 1976, George Poinar Jr. climbed into a hammock strung up between two trees in West Africa's Ivory Coast. He swiftly zipped himself inside the tent of canvas and mosquito netting to ensure that the buzzing swarms didn't follow. Nevertheless, he awoke the next morning to find his right arm covered in bites; a wrong turn in his sleep had left the arm pressed up against the netting.

"I must have fed 25 mosquitoes that night," says Poinar, now a paleo-entomologist at Oregon State University.

A week or so later, Poinar experienced a severe bout of fever and chills. He struggled to hold a cup of tea steady. "I really thought I would die and never make it home to the States to see my family again," he told The Huffington Post.

At least one of his blood-sucking visitors apparently carried malaria. With a double dose of the antimalarial drug he'd already been taking to prevent infection, Poinar recovered enough that summer to continue his infectious disease research with the World Health Organization.

He was one of the lucky ones. More than 2 percent of all worldwide deaths, around 800,000 per year, are attributable to the disease.

ANCIENT ADVERSARY

Humanity has long battled the malaria-transmitting Anopheles mosquito. In fact, as Poinar explains in a recent paper published in American Entomologist, mosquitoes trapped and preserved in amber suggest that malaria parasites were already hijacking the insect's insides to reproduce some 100 million years ago.

"My goodness, these are old," Poinar recalls thinking when he first made the discovery inside the rare Burmese fossils. "They give us insight into how co-evolution has led malaria to be very well adapted."

The malaria parasite, Plasmodium, has evolved over the last couple of decades to withstand not only the preventative chloroquine Poinar took in 1976 -- at which time Plasmodium had already built up enough resistance that he needed a double dose to fight off the infection -- but also newer drugs, as evidenced by the recent emergence of artemisinin resistance in western Cambodia. And the malaria-carrying mosquitoes, too, are increasingly unyielding to the insecticides used in sprays and bed nets.

"That's what makes it so hard to control," says Poinar.

Malaria's long list of victims includes popes and poets, emperors and explorers, infants and infantry. Recent studies even suggest the disease may have contributed to the death of King Tut and to the fall of the Roman Empire. Still today, malaria is a constant threat for more than three billion people and takes the lives of thousands of children every day, mostly in sub-Saharan Africa.

But public health officials are now declaring that humanity's parasitic nemesis may have finally met its match. "In this day and age, no one should be dying from a disease that is entirely preventable and treatable," Margaret Chan, Director-General of the World Health Organization, told attendees at the 2011 Malaria Forum, hosted by the Bill & Melinda Gates Foundation in Seattle this October. "This time we are staying one step ahead of malaria."

This echoes the overly optimistic pronouncement of the U.S. Surgeon General in 1969: "The war against diseases has been won." More than four decades later, infectious disease remains the number one killer of children worldwide.

Our disease-fighting weaponry has certainly improved in recent years, from the widespread distribution of insecticide-treated bed nets to hopeful progress towards a malaria vaccine. But Poinar and other experts suggest that getting ahead of the disease, let alone maintaining a lead, is far easier said than done. It doesn't help that the parasite leads such a complicated life both inside the mosquito and the human host. As Nathan Myhrvold, founder and CEO of Intellectual Ventures, explained at the forum, Plasmodium is unlike most other infectious organisms: "The damn thing has sex, so it evolves much faster."

When a female Anopheles mosquito draws blood from a person (or, in some cases, an animal) infected with malaria, male and female sex cells of the parasite head to the insect's gut where they fuse, sparking a complex reproduction process. Depending on the strain of the parasite, new generations can develop in about a month; the ability to exchange genetic material sexually maximizes the adaptive changes each time around.

James McCann, director ad interim of the Pardee Center for the Study of the Longer-Range Future at Boston University, warns that drugs and vaccines alone are not likely to win the arms race against such a fast and resilient foe. "We need to look at malaria as an ecology disease, as distinct from a disease of biomedicine," he tells HuffPost. "And we need to be clever and multidisciplinary in how we address it."

That might mean the help of economists, ecologists, social scientists and engineers. It might also mean thinking about malaria from the perspective of the parasite or mosquito. Like humans, Plasmodium and its winged carrier have basic needs, including food, water, sun and sex. How humans alter its access to these requirements -- by manipulating a landscape or the flow of a river, for example -- may help or hinder the spread of disease. And all of this may be influenced by the context of the place, including its social, political and economic conditions.

"New medical interventions, bed net programs, trials of a malaria vaccine -- these are all wonderful developments," Jonathan Patz, director of global environmental health at the University of Wisconsin, Madison, tells HuffPost. "But too often we ignore the root causal factors for why we even have malaria in a location."

NATURAL SECURITY

Those underlying factors are still not completely clear. When Patz recently visited the Dalai Lama at his home in India, Patz described (among other ecological challenges) the difficulty in understanding why and how mosquitoes pick and choose different spaces. The Dalai Lama's response: "You should have just asked the mosquito."

Patz's current theories center around the problem of deforestation. Two to three percent of the world's forests are lost each year as trees make way for more people. Fewer trees, of course, means more open, sun-drenched land -- a welcome change for certain malaria mosquitoes. Several Anopheles species, including the most prevalent and deadly in Africa, seem to prefer to lay their eggs where the sun shines.

After accounting for the size of local human populations and other possible variables that influence mosquito abundance, Patz found a nearly 200-fold increase in malaria risk when he compared the most and least degraded rainforest sites in the Peruvian Amazon.

"Preserved forests provide many different benefits, from serving as a carbon dioxide sink for the problem of greenhouse gases to protecting biodiversity," he says. "Now, as our work is showing, it also has fairly direct benefits to public health."

The indirect benefits themselves may not be insignificant. Slight changes in temperature or precipitation patterns can alter the ability of both the cold-blooded mosquito and the parasite to survive and reproduce. At 64 degrees Fahrenheit, for example, malaria parasites reproduce too slowly to mature during the lifetime of a mosquito; but at 68 degrees, they can reproduce in plenty of time to get passed along by the flying syringe.

Destroying forests also puts at risk potential future medicines, including those that might someday help prevent or treat malaria (many antimalarials, past and present, derive from botanical sources).

One of the major efforts underway to save rainforests is the United Nation's Reducing Emissions from Deforestation and Forest Degradation (REDD) program, which offers financial incentives for developing countries to keep their trees standing. However, as Patz notes, only carbon dioxide emissions are currently considered when putting a value on an intact forest. If REDD could incorporate a broader range of benefits, the program might go even further to benefit both the environment and public health.

People inadvertently provide mosquitoes with moist breeding grounds through other means as well: by building new roads that change the flow of water run-off or by creating fish ponds to serve as a source of protein. "Unfortunately, the fish are probably not eating the larvae," says Patz, adding that particular mosquito-eating fish could be enlisted.

"Using environmental approaches where appropriate makes a lot of sense," says Dyann Wirth, chair of immunology and infectious diseases at the Harvard School of Public Health. "The challenge in Africa is that Anopheles mosquitoes can adapt quite readily. So changes you make may have unanticipated effects."

One telling example dates back to the 1950s: The WHO sprayed large amounts of DDT to counter a malaria outbreak in Borneo, successfully killing off malaria mosquitoes, as well as some pesky cockroaches. "Everything was wonderful," says Patz. But then thatched roofs began falling on peoples' heads. The pesticide, it turned out, had also killed off wasps that ate thatch-eating caterpillars. What's more, the pesticide moved up the food chain, poisoning lizards, which were then eaten by cats. And as cats died, rats flourished, spreading new diseases, including typhus. WHO responded by parachuting in more cats.

"We can't solve one problem in isolation without considering the interconnections," says Patz. "Otherwise, you may cause more harm than good."

SICKNESS vs. HUNGER

There are often trade-offs, too. Strategies to combat infectious diseases and address food insecurity, for instance, aren't always compatible.

When Boston University's McCann arrived in Burie, Ethiopia, in 2005, it was very different from what he remembered from his two-year stay in the 1970s. Back then, the area was malaria-free. "There were no mosquitoes," McCann recalls. "There was no reason to be awake at night from buggers buzzing around."

But sometime in the subsequent decades, mosquitoes moved in and brought malaria with them. McCann's former landlord and other townspeople shared horror stories of entire schools abandoned and of houses simply locked up because no one inside had survived.

McCann, an agricultural expert, noticed something else that had changed: widespread planting of a new variety of corn.

Lacking food security, Africans have embraced just about any opportunity to squeeze more sustenance from the earth. The new maize, which grows faster and more abundantly than traditional varieties, had "spread like wildfire," McCann says.

The locals call it "Silsa Sidist," or 66, short for BH660. While the varietal is a powerful example of agricultural technology's potential, McCann feared that the product may have a serious drawback: The plant sheds pollen at the same time that mosquitoes lay their eggs. And this particular pollen is perfect food for the larvae. As McCann puts it, the right temperature and right humidity come together to create the "perfect storm."

Curious to see if this explained the local surge in malaria, McCann worked with an Ethiopian malaria expert to study where farmers were growing the super corn and where people were getting malaria. They found 10 times the rate of malaria associated with the new corn as compared to other crops.

McCann shared their results with a local agriculture manager. "I just got this look of, 'Yes, you've convinced me,'" recalls McCann.

"And then he said, 'Don't tell anyone.'" Farmers weren't about to give up their prize crop.

Agriculture represents the largest driver of landscape change around the world, accounting for at least 40 percent of the global land surface. With strategic management of this land, McCann suggests that there need not be a choice between keeping communities fed and disease-free: Farmers could plant other lucrative crops, such as red peppers, in the most malaria-prone areas, while researchers could pursue a high-yield variety of maize that sheds its pollen earlier in the season.

Mark Wilson, a malaria expert at the University of Michigan, notes that since water is also a necessary component for breeding mosquitoes, farmers could plant the corn on a slight slope or cultivate it in a way that doesn't leave furrows for rain to fill.

"You can't ask people to stop growing maize," says Wilson. "You've got to consider all the interactions: economic, nutritional and parasitological."

In many African settings, the shift from livestock herding to another agricultural activity can also expose humans to more malaria mosquitoes. Gerry Killeen of the Ifakara Health Institute in the United Republic of Tanzania notes that when people in the Demerara River Estuary of Guiana removed livestock from the landscape to plant more profitable rice fields, mosquitoes switched their food source from cows to humans.

MALARIA FORECASTS

McCann's work highlights the fact that the number of people who are hungry or sick can vary significantly by the season, as well as year to year. Could forecasts of climate conditions inform disease prevention, like an epidemiological farmer's almanac?

Mercedes Pascual, a professor of disease ecology at the University of Michigan, is testing such a strategy in East Africa and northwest India with the goal of helping local people better control the mosquito vector and be ready to treat imminent cases of malaria that, for example, might be triggered by a monsoon or heavy rainfall. This might prove particularly useful as extreme weather events increase with climate change.

"We are using climate as an early warning to anticipate outbreaks months in advance," she told HuffPost.

The trick, says Pascual, is to have as much lead time as possible. So her team is looking at outlying sea surface temperatures, which are known to drive weather patterns. Using computer models, they combine this information with historical records of disease and rainfall, as well as local irrigation use, population size and estimated levels of immunity.

Improved surveillance, including the rising use of rapid diagnostic tests, could be "brutally important" in helping drugs and other interventions reach the people and places where they are needed most, notes Killeen. In previous years, if someone showed up at a clinic with the symptoms of malaria -- chills, fever, fatigue -- they were simply treated with antimalarials. But malaria symptoms mimic many other diseases. As a result, precious medicine can be wasted, patients' true conditions left untreated and the emergence of drug-resistant parasites hastened.

Basic knowledge about the connections between natural disasters and disease can also inform protective measures and responses. After a tsunami hit southeast Asia in 2004, the threat of malaria rose sharply. Fresh water from seasonal rains mixed with the saltwater pools left from the tsunami to create a haven for breeding mosquitoes. Similarly, after a three-year drought ravaged sub-Saharan Africa several years ago, lowered water levels in Lake Victoria left stagnant pools around the shoreline -- another prime breeding ground for malarial mosquitoes.

DAMS AND DEVELOPMENT

Periods of heavy rains, droughts and land development by a growing human population are to be expected in malaria-prone regions. But experts advocate some strategies that could at least minimize how much mosquitoes benefit from these phenomena.

Many African countries are eager to develop their river basins, says William Jobin, an irrigation and drainage engineer and director of Blue Nile Associates. A proposed hydroelectric dam on the Congo River is anticipated to provide electricity for all of central Africa. Meanwhile, Ethiopia is responding to its catastrophic drought with new dams.

"I see this as an opportunity to develop water resources, agriculture and hydropower in a healthy way," says Jobin. He harkens back to the success of the Tennessee Valley Authority in the U.S. During 1930s through 1950s, the TVA developed systems that raised and lowered reservoirs to stem the breeding of malaria mosquitoes. During the dry season, instead of a steady drop, they fluctuated the water levels -- alternately flushing mosquitoes into the middle of lakes where fish feasted on the bugs and stranding them on shore where ants could pick them off.

A variety of strategies, including playing with water and deploying pesticides, helped the U.S. eradicate malaria in 1951.

Jobin sought the same success for the Sudan. In the early 1980s, Jobin helped negotiate a $100 million loan from the World Bank to install drainage pumps and other improvements for the Gezira irrigation system, which frequently overflowed during the rainy season to create massive mosquito breeding areas.

He left the Sudan when a civil war started in 1984, but the project continued with "marked success in controlling all the diseases, including malaria," he says. Then in 1989, the same year that the military dictator Omar Al-Bashir overthrew the parliamentary government and cancelled the drainage program, heavy rains returned, along with an explosive outbreak of malaria.

Jobin says he learned a lesson from that experience: "The dictators are almost as bad as the mosquitoes."

He hopes that the new projects will draw more support and success. "The smart thing to do is invest in water and food security, and do it in a way that reduces malaria," says Jobin. "That will make an impact far beyond anything that the health sector could."

Further, by eradicating malaria, not only will people in the developing world suffer less disease, but they are also likely to enjoy an improved quality of life, thanks to fewer missed days of school and work and less money spent on health care. Overall, malaria is estimated to cost Africa $12 billion a year in lost productivity.

The battle against malaria is part of the wider development agenda, says Elizabeth Juma, head of the Division of Malaria Control for the Kenya National Malaria Control Program: "Controlling malaria can pull people out of the cycle of poverty."

LOOKING HIGH AND LOW

While hydroelectric dams can benefit human health and development, researchers in the Netherlands hope to harness another renewable energy to control malaria. The Solarmal project uses bated poison-free traps, powered by rooftop solar panels, that lure mosquitoes away from homes and trap and kill them via dehydration.

Today's standard antimalarial arsenal has relied largely on the use of insecticide-treated bed nets. Some research now suggests, however, that the use of bed nets could actually be coming back to bite antimalarial efforts.

"Last year, we saw an explosion of resistance in Senegal that was certainly linked with the mass distribution of bed nets," Jean-Francois Trape of the Institute for Development Research in Dakar, Senegal, told HuffPost.

A study, led by Trape and published this August in leading medical journal The Lancet, found that a combination of drug treatments, insecticide-impregnated bed nets and the spraying of homes with a chemical concoction proved highly efficacious in the short-term for the Senegalese. But the results also showed that malaria quickly fought back, reaching even higher infection rates than before the introduction of the deterrents.

Bed nets and indoor residual spraying rely primarily on a single class of insecticides called pyrethroids. Unfortunately, as the chemicals succeed in killing off large numbers of weak mosquitoes, the stronger insects -- or those that are resistant to the concoction -- survive and reproduce. This evolution can occur quickly. Between 2007 and 2009, Malawi went from having no evidence of resistance among anopheles mosquitoes to "huge levels," says Janet Hemingway, director of the Liverpool School of Tropical Medicine in the UK.

More strategies are in the works to minimize or even eliminate the need for insecticides, from tools as low-tech as stinky socks that attract and kill malarial mosquitoes to high-tech mosquito-zapping lasers and light barriers.

Meanwhile, scientists are looking to manipulate the same adaptable mosquito genes that have evolved in tandem with humans over millions of years. Luke Alphey, chief scientist at Oxitec, the UK start-up behind the work, and a visiting professor at Oxford University, is engineering a way to make male insects infertile.

"If we can get enough of the wild females in with engineered sterile males," he tells HuffPost, "then the target population will decline and collapse."

As opposed to insecticides that may become less efficient over time, Alphey suggests his strategy actually works increasingly well: When malarial mosquito populations drop, the proportion of genetically-modified males grows.

Still, there is no "magic bullet," says Alphey. He and other experts agree that the goal of swatting away malaria for good is a long way off, despite the billions of dollars invested by the Gates Foundation and other private and public funds over the last decade. What's more, that flow of money could taper off, warns Jobin. The WHO and Global Fund to Fight AIDS, Tuberculosis and Malaria appear to face substantial cutbacks in the coming months. (The latter agency provides about two-thirds of all global anti-malaria funding.)

"Here we are, inadvertently destroying ecosystems and killing off species," says Patz. "Yet when we try to eradicate a species like the mosquito, we can't do it."

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