Malaria, Zika and Dengue Could Meet Their Match in Mosquito-Borne Bacteria

A common bacteria that infects mosquitoes seems to prevent them from carrying more deadly diseases.

A female mosquito in the process of feeding on a human host. James Gathany, Centers for Disease Control

Scientists are grooming an unlikely ally in the fight against mosquitoes and the deadly diseases they carry. Infecting mosquitoes with strains of a common bacteria can curb the insects' ability to carry and spread scourges like dengue, yellow fever and Zika, lab studies show.  

And now it appears these bacterial infections, from a genus of microbes known as Wolbachia, are already at work in nature reducing the spread of malaria, at least in West Africa, something that hadn't been seen before in the real world.     

Wolbachia appears to be acting as a natural malaria control agent,” says molecular entomologist Flaminia Catteruccia, of Harvard University. “The true extent of this effect is still unknown as we only tested a small proportion of mosquitoes. It's still early days but it's a promising new tool that may provide an important contribution to our fight for malaria eradication.”  

Catteruccia and colleagues examined 221 Anopheles female mosquitoes, the major vectors of African malaria, which were collected from homes in Burkina Faso. They found malaria parasites in 12 of them, a five percent ratio consistent with past studies. A whopping 116 of the mosquitoes, on the other hand, were infected with Wolbachia bacteria, which had been unknown in the species before the group spotted it in 2014.

But just a single mosquito was found to test positive for both Wolbachia and malaria, suggesting that the bacteria is effectively preventing malaria parasites from establishing themselves in mosquitoes where the bacteria is present, they report today in Nature Communications

Female mosquitoes infected with Wolbachia also laid eggs and reproduced more rapidly than their counterparts, likely aiding the spread of the infection and its anti-malarial benefits throughout local populations. A sample of 602 mosquitoes showed that from 19 to 46 percent (depending on the sample year) carried the Wolbachia strain wAnga.

“Others have put Wolbachia into mosquitoes and have been able to show that when it's present it has an effect on limiting malaria parasites. But that was all done in a lab,” says biologist Luciano Moreira, of Brazil's Oswaldo Cruz Foundation and the global non-profit Eliminate Dengue.

“This group has found a population in Africa that was naturally infected, which is very interesting. In many parts of Africa, for example, malaria is a huge problem while in other places it doesn't seem to be as big of a problem. Maybe that's because mosquitoes in those areas are infected with Wolbachia. Here they found a situation where that might be happening in the real world and that's very important and exciting.” 

The stakes are high. Mosquitoes are among the deadliest enemies of our own species. Because of the diseases they carry, these pests account for some 725,000 deaths every year. About 60 percent of those deaths are due to malaria.

Wolbachia is a common bacterium with many different strains. It infects millions of invertebrate species and more than half of all insects, but until recently wasn't known to occur in the major disease-carrying mosquito species. 

Wolbachia isn't contagious like a cold virus.  It's passed down only from mother to offspring, and the bacterium has some interesting ways of ensuring its own future. 

The bacteria hijack the mosquito reproductive system. When males mate with females not carrying the same strain, their offspring aren't viable. The bacteria effectively sterilize the male's sperm.

Infected females can reproduce with males carrying a matching Wolbachia strain, or uninfected males, and will pass on Wolbachia to their offspring in either case. This gives infected females a reproductive advantage that allows them to invade a population if introduced and spread the infection widely.

It's not entirely clear what physiological methods the bacteria use to thwart other diseases that would crowd into their mosquito hosts. “These bacteria may somehow stimulate the mosquito immune system and render it more effective at killing malaria parasites; or alternatively they may compete for resources [perhaps critical fatty acids like cholesterol] that are also needed by Plasmodium,” says Catteruccia.

Whatever the reason, it's becoming increasingly clear that those methods can be effective.

Earlier this month Moreira co-authored a study in Cell Host & Microbe showing that Wolbachia blocked the spread of the Zika virus. His group fed human blood infected with Zika to mosquitoes, some with Wolbachia infections and some without. Those with Wolbachia ended up with far fewer Zika infections.

 Catteruccia and colleagues also collected saliva from Zika-infected mosquitoes and injected it into others. Among the 80 mosquitoes without Wolbachia, 68 of them (85 percent) acquired a Zika infection. Of the 80 who did carry Wolbachia, none contracted Zika.

This preliminary work was promising but not surprising. Other projects have shown significant impacts on dengue, another disease spread by the same mosquito species.

Over a ten-week period in 2011, Scott O’Neill of Monash University (Australia) unleashed swarms of Wolbachia-infected mosquitoes into two northern Australian towns as part of Eliminate Dengue.

Not only did the insects survive, they thrived. And even today, most of the Aedes aegypti mosquitoes in the region carry Wolbachia.

“Now five years later the populations are still 85 or 90 percent positive for Wolbachia, so it's really been maintained and they've seen no local transmission of dengue in those areas,” Moreira says.

Eliminate Dengue is now operating similar projects in Indonesia, Vietnam, and Columbia. Moreira is running one in two small locations in Rio de Janeiro, Brazil.  

“We did releases from August of last year to January of this year and are now in a monitoring phase,” he explains. “Every week we collect mosquitoes and our numbers show that at least 80 percent are infected with Wolbachia, so the infection is sustainable and that's very promising.”

Scott O'Neill adds that Eliminate Dengue is now working to expand the scale with much larger, randomized trials in Indonesia and Vietnam.

“At the same time we are preparing for large deployments over 1 to 3 million people in South America with the goal of learning how to undertake large deployments logistically as well as reduce the cost of deployment to under US $1 per person,” he adds. 

Meanwhile, the first commercial use of the bacterium to fight mosquito-borne disease might occur right here in the United States on a backyard scale. The EPA is currently reviewing an application from MosquitoMate, a biotech company which hopes to market Wolbachia as a targeted pesticide against Asian tiger mosquito (Aedes albopictus). 

The MosquitoMate method is to breed males with Wolbachia, then release them into the wild (or a homeowner's backyard) to breed with local females. Because none of the females naturally carry the bacteria, all these matings should be sterile and hopefully populations will plunge. The company, which was incubated at the University of Kentucky, has tested the approach in three different states over the past three years and reported some success.

The public comment period on the proposal ended May 31, and a decision is forthcoming.

Of course bacteria isn't the only intriguing option for controlling mosquito-borne disease—there are plenty of other deterrents and battling the bugs will likely take every weapon in the human arsenal. As this month's Smithsonian Magazine cover story details, gene editing techniques could be used to create disease-free mosquitoes—or even wipe out the insects entirely. But that method is sure to be controversial, and likely won't be practical for perhaps a decade.

Meanwhile the largely unsung Wolbachia bacteria may already be at work in the wild, and might be more easily co-opted for further gains.

“If we can find natural populations of mosquitoes that have Wolbachia we can try to put those mosquitoes into other areas where malaria is a huge problem,” Moreira says. “This is the final goal, many people are trying to find solutions for malaria and the other diseases and I think that Wolbachia is a very promising approach.”   

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