In the war on malaria, a new tactic on mosquitoes

A developing strategy to defend against malaria neither aims to kill the insect nor uses drugs against the malarial parasite

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Reducing cases of malaria worldwide involves a scientific conundrum: How do humans control pervasive mosquitoes that are evolving a resistance to insecticides and also carrying an infective parasite that's showing a resistance to antibiotics?

Natural adaptation continues countering defensive measures people take to control the world's most infectious disease, which plagues people living in or traveling to Africa, Central and South America, the Middle East and southern Asia, particularly India.

But a research team including Duquesne biologist David Lampe, who holds a doctoral degree in entomology, is developing a "substantially improved strategy" to defend against malaria that neither opts to kill the insect nor uses drugs against the malarial parasite.

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The alternative approach involves genetically engineering bacteria to control the parasite inside the mosquito.

In its study, "Fighting malaria with engineered symbiotic bacteria from vector mosquitoes," published in the Proceedings of the National Academy of Sciences, the team has focused on a bacterium that lives in the Anopheles mosquito's mid-gut alongside the malaria-causing parasite, Plasmodium falciparum.

The team made a genetic change in the bacterium (Pantoea agglomerans) that has a symbiotic relationship with the parasite so the bacterium will secrete proteins toxic to the parasite. In rodent studies, the team succeeded in reducing a rodent parasite -- a parasite from the same family of Plasmodium parasites as the one that causes malaria -- by 98 percent.

If this were a movie, the plot would involve the recruitment of an insider to kill the world terrorist.

The study says five potent proteins that the bacterium is programmed to secrete all worked to inhibit the parasite, each with a different mechanism. The multi-gun approach would help reduce the chance of the parasite developing resistance to the deadly proteins.

A current line of the research is using species of bacterium that can be permanently altered to spread through generations of mosquitoes, rather than requiring they be reintroduced in each new generation.

Controlling the spread of malaria has seen a success but remains a puzzle.

Of 460 species of Anopheline mosquitoes, 100 are suitable vectors for human malaria and about 40 are important vectors. Mr. Lampe said several of these mosquito species enjoy biting humans and are skilled in entering houses in Africa. People living in hot zones for malaria can receive hundreds of mosquito bites a year, making it difficult to avoid malarial infection.

For now, more complete control of mosquitoes isn't feasible without using environmentally dangerous pesticides such as DDT. But Mr. Lampe said studies show the new research strategy is effective against African and Asian mosquitoes, suggesting it's likely to be effective against the parasite in all vector mosquitoes.

The strategy also is compatible with malarial-control tools used to reduce mosquito populations and drugs used to treat the infection.

"However, more work lies ahead before this approach can be implemented in the field," the study states. "One key issue is how to effectively introduce engineered bacteria into mosquitoes in the field."

Clay jars containing cotton balls soaked in sugar and the genetically altered bacteria could be placed in baiting stations around malaria-prone villages. The major challenge involves resolving regulatory, ethical and social issues that arise with any proposal to release genetically modified organisms into the environment.

The World Health Organization's 2011 malaria report says malaria killed 655,000 in 2010, including more than 380,000 in Nigeria and most involving African children, with 216 million total infections worldwide. Eighty-one percent of the infections and 91 percent of the deaths occurred in Africa.

Successful prevention and control measures over the past decade include widespread use of bed nets, better diagnostic tools and wider availability of effective medicines to treat malaria. The result has been a 25 percent reduction in mortality rates since 2000 and 33 percent decline in key areas of Africa, the World Health Organization states in its 2011 malaria report.

But the report also says the mortality figures "are still disconcertingly high for a disease that is entirely preventable and treatable."

"One child still dies every minute from malaria, and that is one child and one minute too many," Raymond G. Chambers, the United Nations Secretary General's Special Envoy for Malaria, states in the report. "The toll taken by the current economic crisis must not result in our gains being reversed or progress slowed."

He described the goal of a near-zero death rate by the end of 2015.

Malaria is not a major health concern in the United States, although it was widespread historically, and the vectors for it still remain here.

The U.S. Centers for Disease Control and Prevention reported 1,691 domestic cases of malaria in 2010, virtually all of them involving people who traveled overseas and "imported" the disease upon their return home. Domestic infections no longer occur.

But many areas of the world remain high risk for malaria, prompting the CDC in its 2011 malaria report to warn that "the use of appropriate prevention measures by travelers is still inadequate."

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