Modified mosquitoes die before their malaria parasites become infectious

When it comes to keeping mosquitoes from spreading malaria, some proposed approaches involve killing the insects, or stopping them from acquiring malaria parasites. A new method, however, stunts the growth of the parasites once they're in the mosquito's gut.

Ordinarily, malaria is spread when a female mosquito bites someone who is already infected with the malaria-causing Plasmodium parasite. That parasite is carried with the sucked-up blood into the insect's gut, where it enters its next stage of development. Once it reaches that stage, it moves to the mosquito's salivary glands, so it can infect the next person the mosquito bites.

That said, according to scientists from the Transmission:Zero project at Imperial College London, only about 10% of parasite-carrying mosquitos live long enough for the parasite to reach the infectious stage. With that fact in mind, the researchers have set about slowing the growth of the parasite within the insect's gut, to the extent that the mosquito will simply die of old age before the parasite gets to its salivary glands.

In order to do so, the scientists genetically modified Anopheles gambiae mosquitoes – the main malaria-spreading variety – so that they produced two types of "antimicrobial peptide" molecules every time they ingested a blood meal. Obtained from African clawed frogs and honeybees, these molecules interfere with the parasite's energy metabolism, impairing its development.

As an added bonus, they also shorten the mosquito's lifespan, boosting the likelihood that the insect will die before the parasite becomes infectious. Ordinarily, adult female mosquitoes live for about six weeks.

In lab tests, the modified mosquitos were shown to be much less successful than regular mosquitos at transmitting the malaria parasite. The idea is that if released into the wild, the modified mosquitos would crossbreed with the others, gradually spreading their parasite-unfriendly genes throughout the population.

Unfortunately, however, their shorter lifespan would put them at a distinct disadvantage in this regard – the process of natural selection would quickly eliminate their unique trait from the gene pool. For that reason, the scientists are looking at further modifying the mosquitos by adding a "gene drive," which is a genetic component designed to force the spread of modified genes in a population.

Plans call for the modified mosquitos to be field-tested at a facility in Tanzania. In order to lower the risks of disrupting the ecosystem, two types of mosquitoes will be tested separately – one with only the parasite-stunting molecules, and one with only the gene drive. If neither appear to be ecologically harmful, they could then be combined into one strain.

"For many years, we have been trying to no avail to make mosquitoes that cannot be infected by the parasite or ones that can clear all the parasites with their immune system," said postdoctoral researcher Astrid Hoermann, co-author of a paper on the study. "Delaying the parasite’s development inside the mosquito is a conceptual shift that has opened many more opportunities to block malaria transmission from mosquitoes to humans."

The paper was recently published in the journal Science Advances.

Source: Imperial College London