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Malaria: Round two

POSTED 5 APRIL 2007

Malaria: Signs of hope at last?
On March 21, researchers announced the development of a mosquito with genetic resistance to malaria. Enlisting the insect's immune system in the bitter battle against Small African child with an IV line extending from her forehead is cuddled by a womanthis deadly infection has intrigued scientists since about the time they realized that mosquitoes had immune systems. Still, once you create a skeeter that would not carry the malaria parasite, you would need to "drive" its unusual genes through the population of malarial mosquitoes, which one bean-counter tallied at 100 billion in Africa alone.

Baby with malaria at Garki General Hospital in Abuja, Nigeria. Photo: WHO/PIERRE VIROT

Big continent. Big job. But the Johns Hopkins researchers reported that their malaria- resistant mosquitoes had more young, and lower death rates, and so soon started to saturate the skeeter scene. After nine generations, the percentage of bugs in the laboratory experiment rose from 50 percent resistant to 70 percent (see # in the bibliography).

The bad news: this increase happened only in the presence of malaria. When the mosquitoes did not feed on malarial blood, the inserted gene gave them no advantage. And since not all mosquitoes get a "blood meal," even in areas where malaria is rampant, it's not clear how well the inserted genes would spread. Furthermore, the research was done not with the human malaria parasite, but rather with Plasmodium berghei, which infects mice.

But the fact that the genes for resistance did not disappear was cause for headlines, since it indicated that the genes could spread, and that having genetic immunity to malaria was, to the mosquito, all gain, and no pain.

Life cycle of the malaria parasite

Graphic shows various stages of the malaria parasite, inside mosquitoes and humans.

This complex life cycle has been honed by evolution for maximum survival, but it also offers many opportunities for interference, once you understand the complicated series of biological interactions. Graphic: CDC

Needed: Some new ideas!
The news got us to thinking: As malaria continues to kill an estimated 700,000 to 2.7 million each year, mainly poor young Africans, and as the disease continues to evade drugs, are some new tactics emerging?

Malaria is a complex parasitic disease that moves between humans and mosquitoes in the genus Anopheles. Malaria parasites, members of the genus Plasmodium, infect and kill red blood cells, which transport our oxygen. Malaria can cause fever, chills, sweating, headaches and muscle pains. Severe cases can kill by damaging the brain, blood or kidneys. Many survivors build up some immunity, which explains why children face the highest death toll.

Starting around World War II, the weapon of choice against malaria was DDT, a persistent pesticide that was eventually banned due to environmental side-effects. The insecticide broke down slowly, built up in fat and in people who ate predator animals, and killed large birds, including the bald eagle. Malaria rates jumped as the parasite evolved resistance to drugs, mosquitoes evolved resistance to DDT and spraying was curtailed for environmental reasons. In recent years, anti-malaria campaigners have restored DDT to the picture, but the insecticide is sprayed inside houses, rather than wholesale from airplanes.

Black and white photo         of two men in military garb, one sticking a sinister looking insecticide         sprayer down other’s shirt.A U.S. soldier demonstrates DDT spraying equipment. The use of DDT soared after World War II, due to its effectiveness against the mosquitoes that spread malaria and the lice (as shown here) that carry typhus. The World Health Organization claims DDT saved 25 million lives. Photo: CDC

In the 1990s, rising malaria rates attracted attention and serious research money. As researchers probed the biochemical cues involved in each stage of this life cycle, they pondered strategies that would be more sophisticated -- and perhaps also more promising -- than insecticides and bed nets.

Underpinning these advances is detailed information about the genetics of the three organisms involved: The human genome was reported in 2001, and the Anopheles mosquito and the human malaria parasite genomes were both reported in 2002.

It's unclear whether high-tech approaches will work better than old-fashioned mosquito control and parasite killing, but what is clear from the death toll is that more options and more effort are sorely needed in the struggle against malaria.

Ready to check out some new biotech strategies against malaria.

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Megan Anderson, project assistant; Terry Devitt, editor; S.V. Medaris, designer/illustrator; David Tenenbaum, feature writer; Amy Toburen, content development executive

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