Combating Malaria with mosquitoes

A possible novel strategy

There have been a lot of mixed results on the malaria control front. Simple and effective measures such as executing public malaria prevention campaigns, spraying against mosquito larvae, disseminating anti-malarial medications and mosquito netting have been slow to take hold due to a constellation of frustrating problems. The sad scourge of political corruption, extreme poverty and socio-cultural prejudice are but a few of the barriers that impede progress towards bringing down the death toll of this ancient protozoal disease that kills in the area of one million people a year.

This is why it is still worth perusing alternative strategies against the malaria parasite. Any measure that can help impact the effects of this disease should be considered and if found to be effective, added to the existing known strategies. This doesn’t include opening ones mind until your brains fall out and embracing implausible measures that just don’t work such as homeopathy and nutritional supplement “treatments”. Alternative efforts like these reflect -at best- a stunning dissonance between reality and belief or -at worst- complete and utter stupidity and a morbid disregard for human life.

However, among the more interesting possible anti-malarial strategies that might bypass some of the problems of other programs are biological approaches for combating malaria. For example, approaches that could cut its life cycle could dramatically reduce the prevalence of this parasite using a completely novel angle.

Actually, the idea itself isn't really new. Scientists have been trying for years to develop a malaria resistant mosquito that could survive in the wild. Until recently, the idea of combating malaria through biological mechanisms involving its life cycle has been a nice but impractical theory. It made sense but has been very difficult to make work- the devils been in the details. The good news is that recent developments in this area might breathe new life to this approach making it, at the very least, a promising avenue worth pursuing.

An interesting article in the January 2008 issue of Scientific American touches on some of the hopeful developments in this field. In summary, it mentions various lines of research on the malarial parasite life cycle, genetically engineered mosquitoes (Anopheles) and their capacity to survive in the wild that are coming together to perhaps create an viable and effective instrument for combating the malaria organism (Plasmodium falciparum).

In 2007, researchers found that the midgut environment of the anopheline mosquito, where the malaria parasite is transported and becomes infectious, plays an important role in the development of the malaria parasite. By genetically manipulating the mosquito to produce a substance found in Sea Cucmbers (CEL-111) in this midgut region, these researcher have been able to significantly inhibit the sporogenic development of Plasmodium falciparum.

The authors in this study note that “To our knowledge, this is the first demonstration of stably engineered anophelines that affect the Plasmodium transmission dynamics of human malaria. Although our laboratory-based research does not have immediate applications to block natural malaria transmission, these findings have significant implications for the generation of refractory mosquitoes.” These researchers basically have managed to create a viable mosquito resilient to the malaria parasite- an important piece of the puzzle.

Other threads of research are probing alternative mechanisms that alter the parasite life cycle within the mosquito and offer intriguing bits of information adding to the development of a robust data base for discovering more anti-malarial bio-mechanisms. For example, in the same year it was discovered that a capsule protein PbCap380 an ingredient of the malarial oocyst outer wall was critical for malarial survival inside the mosquito. The oocyst stage of the malarial life cycle is key to this parasites ability to infect humans and without this particular protein component the parasites were gradually eliminated from the mosquitoes reducing their capacity to transmit the disease.

Another study found they were able to reduce the adherence of the ookinate stage of the parasite to the lining of the mosquito midgut; an important part of eventual oocyst development by RNA interference. In essence they were able to reduce the level of a “ligand” – a glycoaminoglycans structure on the gut lining- that acts like Velcro.

Having a mechanism or mechanisms to inhibit plasmodium inside altered mosquitoes and maintaining a viable population of these insects are crucial steps toward a larger active bio-engineered anti-malarial program. However, one of the biggest steps in this area is to translate these successes to the field. If one or more of these mechanisms can be spread throughout the wild gene pool of mosquitoes then a whole new front against malaria could be established.

In fact, another recent study offers tantalizing evidence that transgenic malaria resistant mosquitoes can in fact survive in the wild. These authors note that “The introduction of genes that impair Plasmodium development into mosquito populations is a strategy being considered for malaria control. The effect of the transgene on mosquito fitness is a crucial parameter influencing the success of this approach.”

The study found that transgenicaly altered mosquitoes actually had a survival advantage in the lab when compared to non- transgenically altered mosquitoes. The authors conclude that the result of their findings “suggest that when feeding on Plasmodium-infected blood, transgenic malaria-resistant mosquitoes have a selective advantage over non-transgenic mosquitoes. This fitness advantage has important implications for devising malaria control strategies by means of genetic modification of mosquitoes.” On a related note, another important study in fruit flies reveals that it is possible to spread genetically modified insect genes in the wild.

Taken as a whole, one begins to see that several vital steps are being made to close the circle on a novel biological mechanism that can be used to reduce malaria in its natural environment. Each of these studies provides a brick of knowledge that begin to form a wall against malaria transmission. This fascinating activity may indeed be the genesis of a true “bio-weapon” against malaria and add to the greater effort in combating a deadly human disease.