How Can Malaria Be Prevented? The Creation of Genetically Modified Mosquitoes to Combat Malaria

How Can Malaria Be Prevented? The Creation of Genetically Modified Mosquitoes to Combat Malaria
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Malaria Prevention

Malaria prevention takes a number of different forms including insect repellent, nets, development of vaccines, using antimalarial drugs prophylactically, and the creation of transgenic mosquitoes.

Malaria

Malaria infections are spread by five species of Plasmodium (a parasitic protozoa), and they are transmitted by about 50 mosquito species. The protozoa develop in the gut of the mosquito and move to the saliva where they are passed onto a host every time the mosquito enjoys a blood meal.

The majority of malaria deaths in sub-Saharan Africa are caused by Plasmodium falciparum.

Genetically Modified Mosquitoes

Genetically modified mosquitoes can be of benefit in two ways - 1) reduce the size of mosquito populations and 2) replace populations with mosquitos that are unable to transmit the disease.

It is worth noting that not every mosquito can transmit the malaria parasite, and of those that can, many are actually incapable of doing so. They are said to be refractory. And so finding the genes that permit malaria infection will give scientists an understanding of how they can silence them or replace them in such a way that mosquitoes become a refractory to the parasite. And there are a number of ways that this can be achieved:-

  • Scientists at Johns Hopkins University have genetically engineered mosquitoes that confer resistance to rodent malaria. This was achieved by identifying receptors that the parasite uses in the mosquito gut and then producing proteins that bound to these receptors to prevent the parasite from taking hold. Could this approach be adapted to confer resistance to human malaria?

  • Boosting antibodies that will kill the parasite within the mosquito

  • Finding the gene or genes that confer refractiveness

  • Discovering genes that confer resistance to human vector-borne diseases

Malaria Prevention Using Genetically Modified Mosquitoes

For a genetically modified mosquito project to be successful at malaria prevention, refractory genes will have to be spread quickly and deeply through a mosquito population. It is one thing to be able to create a genetically modified mosquito in the laboratory, it’s quite another to be able to drive it into a wild type population.

One possible way that is being worked on is to attach a gene of interest (one that confers resistance or one for refractiveness) to a construct known as Medea - it stands for maternal-effect dominant embryonic arrest, and in part was named after the Greek mythological character Medea who killed her children when her husband left her for another woman.

So how does Medea help?

Media is a selfish gene construct consisting of a toxin and an antidote. A mother carrying Medea will produce the toxin that kills her progeny. However, those expressing Medea will be saved by the antidote. In this way a population ratio can be skewed in favour of those with Medea-bearing alleles and the gene of interest attached to it.

Medea has been shown to change populations in Drosophila, but many issues will have to be addressed before genetically engineering mosquitos can be released into the wild, including the concerns that people have over the release of genetically modified animals, as well as informing the inhabitants of malaria endemic regions about the technology, its impact and implications.

Malaria parasites

Malaria is one of the world’s biggest killers. If diagnosed quickly, the prognosis is very good indeed. But in countries where resources for treatment and diagnosis are few, it’s a major cause of death.

Malaria is caused by the infection of red blood cells by a parasite known as Plasmodium. There are several species; Plasmodium falciparum, Plasmodium vivax, Plasmodium ovale, Plasmodium malariae and Plasmodium knowlesi. They are carried by anopheles mosquitoes and are transferred to humans when the bugs have a little nibble on us. The parasites multiply in the liver and then spread rapidly through the body in our blood.

According to the World Health Organisation, more than one million people were killed by the disease in 2006.

Genome map and how malaria can be prevented

Now the big guns are coming out and scientists have revealed the genome map of two parasites known to carry Malaria; Plasmodium vivax and Plasmodium knowlesi. Such detailed knowledge of the enemy is a big boost in the battle against this killer disease.

Two separate teams of researchers revealed detailed genome maps of the malaria parasites in a recent edition of Nature.

Although P. vivax is rarely fatal, the scientists discovered that it shares many genes with P. falciparum. Only 150 genes were specific to P. Vivax. The genome of P. falciparum, (which is responsible for the majority of malaria infections) was elucidated several years ago.

P. vivax can lie dormant in the liver for several months and is known to recur long after the primary infection has been eradicated.

P. knowlesi is more commonly known as a parasite of some monkeys, but increasingly during recent years, more humans have become infected by them, particularly in southeast Asia.

Genes and malaria parasites

The researchers revealed some intriguing findings. They located genes in P. vivax that help it to invade red blood cells. An understanding of the genetics of malarial parasites provides potential targets for future therapies. Up until now P. vivax has been largely ignored by researchers and little has been known about it. This is primarily because P. falciparum has been the focus of much of the research attention. But now its genome has been laid bare a comparison of the genetic details of both may shed further light on the underlying genetic mechanisms guiding these parasitic infections.

References

Marshall JM, Taylor CE (2009) Malaria Control with Transgenic Mosquitoes. PLoS Med 6(2): e1000020. doi:10.1371/journal.pmed.1000020

Ito J, Ghosh A, Moreira LA, Wimmer EA, Jacobs-Lorena M (2002) Transgenic anopheline mosquitoes impaired in transmission of a malaria parasite. Nature 417: 452–455.