In the late 1800s, scientists definitively linked mosquitoes with epidemic diseases like malaria. In the years that followed, popular public health responses included draining wetlands, covering water supply tanks, and spraying petroleum products like kerosene on pools and puddles where mosquitoes bred. The discovery of synthetic pesticides – including DDT in the 1930s – shifted the war.
Due to the indiscriminate toxicity of many of these substances – not to mention adaptations by the pests themselves – research into more effective chemical responses continues. Insecticide-treated bed nets have become a mainstay of disease prevention. Vaccine development, a decadelong endeavor, continues with promising results. And advances in microbiology and genetics are allowing epidemiologists to expand the possibilities of mosquito control in ways unimaginable just a few decades ago.
Vaccinations
While malaria can be cured with proper treatment if recognized early enough, no vaccine exists to prevent the disease despite a century of research. There is also no vaccine, much less a cure, for dengue and West Nile virus.
The genetic complexity of the malaria-causing parasite, for instance, is one reason the disease continues to kill an estimated 1 million people every year. Critical discoveries and successful field trials in the last few years, though, suggest a reliable malaria vaccine may be close at hand. In one case, the discovery of an antibody that “cages” the parasite inside red blood cells has raised expectations considerably.
Researchers have long been baffled by the complexity of dengue. “They’ve been working on vaccines since the 1960s but there’s nothing in [vaccine] trials right now that I know of,” said Luke Alphey, a visiting professor in zoology at the University of Oxford. “It’s pretty amazing, actually. The libraries on this disease are pretty large, but for whatever reason, nothing seems to have come out of that.”
Part of the issue is the complexity of the illness, Alphey said. Dengue occurs in four closely related microorganisms, or serotypes. The first infection may result in a heavy fever, followed by the development of natural immunity to that particular serotype. Yet subsequent infections by one of the other three serotypes could prove fatal. “It’s very difficult to develop a multiserotype vaccine,” said Alexander S. Raikhel, a professor of entomology at the University of California, Riverside. “Although I’m not aware that even a one-seratype vaccine has been successful so far.”
Better pesticides
Unlike modern medicines, the use of pesticides dates back thousands of years – to the ancient Sumerians, who used sulfur compounds in an effort to control crop pests. The Chinese followed with concoctions derived from arsenic and mercury. The Romans, meanwhile, used seawater.
After industrialization, large amounts of petroleum-derived substances like coal-sourced creosote and naphthalene began to be spread in farm fields. Unfortunately, these treatments proved to be indiscriminate killers, and soon a search was underway for a substance that would knock out pests while leaving beneficial insects unscathed.
One of the most powerful synthetic pesticides, DDT, was discovered in the late 1800s but didn’t come into widespread use until the second world war. Some people called DDT the atomic bomb of pesticides. Soon, serious concern over its damage to beneficial insects, birds, fish and humans, along with mosquitoes’ increasing resistance that was first observed in the 1930s, sidelined the treatment option in much of the developed world.
“Resistance is very fast with malaria [parasites],” University of California’s Raikhel said. In Cambodia, parasites have evolved to resist treatment by a progression of chemical interventions – most recently, the widely used artemisinin, one of the most effective malaria-targeting compounds known. “At least in Asia it’s been a last resort, so we’re very concerned,” Raikhel said.
Engineering sterility
While pesticides and bed nets are some of the most effective interventions for mosquito-borne disease, there is a long way to go to eliminating the threat altogether. A more recent approach to mosquito control making impressive strides involves infecting dengue-carrying Aedes aegypti with a bacteria known as wolbachia, one of the world’s most common parasitic microbes carried by insects like fruit flies and dragonflies.
Researchers with the Eliminate Dengue program in Australia have found that when infected male mosquitoes breed with females, the eggs produced don’t hatch. Infected females will pass along the bacterium to their offspring, thereby increasing sterility across local mosquito populations. Field trials in Australia, Indonesia, Brazil and Colombia are showing positive results, according to Scott O’Neill, the ED program leader and a professor at Monash University in Melbourne.
“As a sustainable, long-term approach, we believe our wolbachia method has the potential to greatly reduce the global burden of dengue,” he said. “Our approach is compatible and complementary with existing dengue control methods, and it will support future methods such as a dengue vaccine once available.”
While the approach only impacts the individual species targeted, O’Neill expects a similar approach will be effective when expanded to address other species. For instance, O’Neill said the team has already demonstrated that wolbachia can reduce the ability of mosquitoes to transmit chikungunya and yellow fever as well as parasites that cause malaria. West Nile, however, is a bit trickier. In fact, recent research suggests that the wolbachia efforts may actually increase the transmission of West Nile.
“Our results point to a previously unforeseen complication – the possibility that mosquitoes rendered resistant to one pathogen by wolbachia infection might become better vectors of an alternative pathogen,” Jason Rasgon, associate professor of entomology at Penn State University, said in a prepared release.
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