Researchers at the University of Arizona say they have succeeded for the first time in creating a genetically altered mosquito that cannot infect humans with malaria. Though efforts to develop such a mosquito have been underway for years, past efforts resulted in mosquitoes that were less virulent, but still capable of transmitting the disease.

Now for the first time, University of Arizona entomologists have succeeded in genetically altering mosquitoes in a way that renders them completely immune to the parasite, a single-celled organism called Plasmodium. Someday researchers hope to replace wild mosquitoes with lab-bred populations unable to transmit the malaria-causing parasite.

“If you want to effectively stop the spreading of the malaria parasite, you need mosquitoes that are no less than 100 percent resistant to it. If a single parasite slips through and infects a human, the whole approach will be doomed to fail,” says Michael Riehle, who led the research effort, the results of which were published in the journal Public Library of Science Pathogens. Riehle is a professor of entomology in the University of Arizona’s College of Agriculture and Life Sciences and is a member of the BIO5 Institute.

Of the estimated 250 million people who contract malaria each year, 1 million – mostly children – do not survive. Ninety percent of the number of fatalities, which Riehle suspects to be underreported, occur in Sub-Saharan Africa.

Malaria killed more soldiers in the Civil War than the fighting, according to Riehle. In fact, malaria was prevalent in most parts of the U.S. until the late 1940s and early 1950s, when DDT spraying campaigns wiped the vectors off the map. Today, a new case of malaria occurs in the U.S. only on rare occasions.

Each new malaria case starts with a bite from a vector – a mosquito belonging to the genus Anopheles. About 25 species of Anopheles are significant vectors of the disease.

Riehle's team designed a piece of genetic information capable of inserting itself into a mosquito's genome. This construct was then injected into the eggs of the mosquitoes. The emerging generation carries the altered genetic information and passes it on to future generations. For their experiments, the scientists used Anopheles stephensi, a mosquito species that is an important malaria vector throughout the Indian subcontinent.

The researchers targeted one of the many biochemical pathways inside the mosquito's cells. Specifically, they engineered a piece of genetic code acting as a molecular switch in the complex control of metabolic functions inside the cell. The genetic construct acts like a switch that is always set to “on,” leading to the permanent activity of a signaling enzyme called Akt. Akt functions as a messenger molecule in several metabolic functions, including larval development, immune response, and lifespan.

When Riehle and his co-workers studied the genetically modified mosquitoes after feeding them malaria-infested blood, they noticed that the Plasmodium parasites did not infect a single study animal.

“We were surprised how well this works,” said Riehle. “We were just hoping to see some effect on the mosquitoes' growth rate, lifespan or their susceptibility to the parasite, but it was great to see that our construct blocked the infection process completely.”

There are no effective or approved malaria vaccines. A few vaccine candidates have gone to clinical trials but they were shown to either be ineffective or provide only short-term protection. If an effective vaccine were to be developed, distribution would be a major problem, Riehle said.

Researchers and health officials put higher hopes into eradication programs, which aim at the disease-transmitting mosquitoes rather than the pathogens that cause it.

“The eradication scenario requires three things: A gene that disrupts the development of the parasite inside the mosquito, a genetic technique to bring that gene into the mosquito genome and a mechanism that gives the modified mosquito an edge over the natural populations so they can displace them over time,” Riehle says. “The third requirement is going to be the most difficult of the three to realize.”

At this point, the modified mosquitoes exist in a highly secured lab environment with no chance of escape. Once researchers find a way to replace wild mosquito populations with lab-bred ones, breakthroughs like the one achieved by Riehle's group could pave the way toward a world in which malaria is all but history.