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Saturday, May 18, 2024

Column: Of mosquitoes and microbes

Dengue fever, which also goes by the more striking name “break-bone fever,” is considered by the World Health Organization to be one of the most neglected tropical diseases. The illness, as its nickname suggests, causes high fever and intense muscle and joint aches.

Most attempts through medical history at eradicating mosquito-borne diseases like dengue fever involved finding insecticides that killed mosquitoes most efficiently without devastating crops or helpful insects. More recently, scientists have tried killing or sterilizing the mosquitoes through bacterial infections.

Though initially promising, these methods have not had much success in keeping dengue fever at bay. Michael Turelli, a population biologist at UC Davis, is very familiar with the decades-long frustration of trying to control the spread of dengue fever with bacteria.

“It’s not my idea; many people had suggested several different ways of using [bacteria],” Turellia said. “I had shown why most of those methods wouldn’t work.”

Turelli and his colleague Scott O’Neill had tried using the common insect bacterium Wolbachia pipientis to shorten mosquito lifespan. Like many bacteria, Wolbachia has many strains that differ in how they impact infected mosquitoes. O’Neill received money from the Gates Foundation to introduce a life-shortening strain of Wolbachia.

However, they had to make some calculations. For a population to change from one form to another (uninfected to infected), the population has to get over a point called the unstable equilibrium threshold. Like a runner jumping over a hurdle, a low point is easier to clear than a high one.

“In order for these strategies to work … the unstable point has to be below 0.5,” Turelli said.

For the life-shortening strain of Wolbachia, that wasn’t the case. Infected female mosquitoes produced half as many eggs as uninfected mosquitoes, making it impossible for the infection to efficiently spread through the population.

“I thought our project had failed,” Turelli said. “I held a meeting in Australia where I went through the mathematics and biology of the thing and why this would never spread in nature, and we had better look for something else.”

That something else came, as it often does in science, from a different researcher in a different field. Michael Ashburner, a genetics professor at the University of Cambridge in the United Kingdom, was studying fruit fly resistance to viruses that they would naturally encounter.

Ashburner found that resistance was purely maternally transmitted every time, which doesn’t make sense genetically. He was able to show that it was Wolbachia infection, not fruit fly genes, that were spreading maternally and causing the resistance to the viruses.

Wolbachia infections spreads maternally because, while an infected female mating with an infected male results in healthy offspring, an uninfected female doing the same results in the death of nearly all of the offspring.

Ashburner then found that the same thing happened when mosquitoes were infected with Wolbachia; they are unable to transmit dengue fever, and the infection spreads from mother to offspring.

Their work wasn’t finished yet, however. They had to find the right strain.

“The strain that really shortens life and reduces fecundity [of the mosquitoes], it blocks dengue infection much more completely than the one that has smaller fitness consequences,” Turelli said.

In other words, as the harm that Wolbachia inflicts upon the mosquito increases (bad), the ability it has to block dengue fever also increases (good). The key is to balance these traits for the most beneficial strain.

After carefully teasing out which strains best balance these traits, Turelli and his colleagues were finally ready to release lab-grown, infected mosquitoes into the field. They chose two tiny towns in far north Queensland in Australia, Yorkey’s Knob and Gordonvale, which are both surrounded by sugar cane fields that the mosquitoes can’t penetrate without straying far from access to bloodmeals.

The first results look very promising; the infection rate in the mosquitoes increased dramatically in both towns, from nearly zero percent to 81 percent in Gordonvale and 95 percent in Yorkey’s Knob.

After a year or two, Turelli, investigators from the Gates Foundation and international experts in population biology will meet to discuss the latest results and the next steps.

“We view it as the first attempt at biocontrol of human disease without any genetic engineering,” Turelli said.

Over the next year, we’ll find out if the attempt turns into success.

AMY STEWART can be reached at science@theaggie.org.

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