Malaria Hope In Bacteria That Stop Mosquitoes Infecting Humans

Date: May-10-2013Malaria spreads in human populations because female Anopheles mosquitoes carrying malaria-inducing Plasmodium
parasites bite people and pass it into their bloodstream. Now a new US study shows it may be possible to use a bacterium that stops the parasite
developing in the mosquito and create a stable population where female mosquitoes pass this parasite immunity onto their
daughters.

In a sense, such an approach could use bacteria as a sort of vaccine, protecting mosquitoes from malaria parasites. The hope is that treating
mosquitoes with such a "vaccine" would stop them passing malaria to humans, a disease that in 2010 affected 219 million and killed an estimated
660,000 people worlwide.

Lead investigator Zhiyong Xi from Michigan State University (MSU), and colleagues, write about their work in a paper published in the journal
Science on 10 May.
Focus On Primary Malaria Carrier, Anopheles Stephensi
For some time scientists have been looking for a way to stop the spread of malaria by establishing a stable population of mosquitoes carrying
bacteria that render them immune to the malaria parasite. But they haven't been able ensure the bacterial infection gets passed on to new
generations of mosquitoes - until now.

In their study, Xi and colleagues infected the mosquitoes with a bacterium called Wolbachia, which commonly occurs in insects and is
already known to stop malaria-inducing Plasmodium parasites from developing in Anopheles mosquitoes.

They focused on Anopheles stephensi mosquitoes, the primary malaria carrier in the Middle East and South Asia.

In a statement, Xi, assistant professor of microbiology and molecular genetics at MSU, says:

"Wolbachia-based malaria control strategy has been discussed for the last two decades."

"Our work is the first to demonstrate Wolbachia can be stably established in a key malaria vector, the mosquito species Anopheles
stephensi, which opens the door to use Wolbachia for malaria control," he adds.
Study Shows Mosquito Carries and Passes Wolbachia Onto New Generations
First the researchers showed that Wolbachia can be carried by the mosquito and spreads throughout
their population, and then they showed the bacterium prevents the mosquitoes from passing the malaria-inducing parasites onto
humans.

"We developed the mosquito line carrying a stable Wolbachia infection. We then seeded them into uninfected populations and
repeatedly produced a population of predominantly Wolbachia-infected mosquitoes," Xi explains.

As often happens in research, success is the reward for painstaking hard work. The researchers had to identify the correct species of the
bacterium, then inject it into thousands of mosquito embryos to create one that developed into a female carrying Wolbachia.

The strain of Wolbachia they identified is called wAlbB.

The mosquito line they derived from the female mosquito carrying Wolbachia wAlbB has maintained the infection with 100% frequency
through 34 generations. Xi says the number of generations could be higher but this is where they stopped the study.

In another part of the study the team then introduced various ratios of Wolbachia-infected female mosquitoes into non-infected
populations. In all cases, within eight generations the whole population was carrying the bacterium.
Bacterium Kills Malaria Parasite in Mosquito Gut and Salivary Glands
In its examination of how the bacterium affects the parasite, the team found that Wolbachia kills Plasmodium both in the midgut of
the mosquito, where the parasites mature, and in the salivary glands, from where they pass into the bloodstream of humans via mosquito
bites.

The researchers suggest that the bacterium kills the parasites by forming unstable compounds known as reactive oxygen species (ROS), which
inhibit parasite growth.

Further studies are now needed to find out whether the parasite can develop resistance to ROS and to integrate Wolbachia-infected
mosquitoes with existing malaria control strategies, they note.
Discovery Could Open Door to Cheaper, Easier Malaria Control
A potential advantage of using Wolbachia infection to tackling malaria, could be the possibility that, once the bacterium infects a
mosquito population, it won't have to be reapplied. This would make it easier and cheaper to manage, unlike other methods such as pesticides or
human vaccine, which many poverty-stricken regions where malaria is endemic cannot easily afford.

In previous work, which created the basis for this latest study, Xi and his team used Wolbachia to halt Dengue fever. There they focused
on the mosquito species Aedes albopictus and Aedes aegypti. The work has led to a global effort to use Wolbachia to
eliminate Dengue and other diseases.

In a recent study led by the University of Oxford in the UK, researchers report how they used genetic fingerprints to identify new drug-resistant strains of the malaria-causing
parasite Plasmodium falciparum that are spreading rapidly in Cambodia.

Written by Catharine Paddock PhD

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