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Infectious disease

How to contain the Zika virus

Pesticides: Chemistry plays a prominent role in strategies to control the mosquito-borne disease

by Marc S. Reisch
February 23, 2016 | A version of this story appeared in Volume 94, Issue 9

A picture of mosquito larvae in water.
Credit: Shutterstock
Mosquito larvae grow in water before emerging as adults.

For most people who catch it, the Zika virus isn’t so bad. Symptoms include achy joints, a rash, headache, and a slight fever. After a few days, the symptoms are gone.

But for pregnant women, Zika is a horror. The virus is the suspect behind an epidemic of more than 4,000 cases of children born in Brazil in the past year with abnormally small heads and brains, a rare condition known as microcephaly.

The mosquito-borne virus arrived in Latin America in 2015 from Africa and Southeast Asia. Today, Brazilian officials estimate the country has had up to 1.5 million cases.

As of Feb. 17, more than 80 cases of the disease have been brought to the U.S. by travelers, and a total of nine mosquito-borne infections have occurred in Puerto Rico and the U.S. Virgin Islands, according to the Centers for Disease Control & Prevention (CDC).

Now, alarm is growing over the potential for Zika to spread in the U.S. during the fast-approaching summer months, when mosquito populations swell. Some people also worry that travelers to the Olympics in Rio de Janeiro this summer will bring more cases of Zika back and aid its spread in the U.S.

Buzz off
Graphic showing the structures of different chemicals in insect repellents, adulticides, and larvicides.
Multiple chemical strategies are used to avoid mosquitos carrying Zika virus.

While scientists work to develop new diagnostic and immunization therapies for Zika, strategies that are already in place to control mosquito-borne viruses—including West Nile, dengue, and yellow fever—can be used to control Zika. Most experts recommend an integrated pest management approach in which chemical measures play a prominent role.

Limiting human contact with mosquitoes—in particular the two species of mosquitoes known to carry Zika, Aedes aegypti and Aedes albopictus—is no easy task. They tend to thrive in urban environments, breed in small pools of water, and bite primarily in the daytime but also at night.

Low-tech solutions are the first line of control. Government authorities such as the U.S. Environmental Protection Agency and CDC recommend that people wear long-sleeved shirts and pants, empty birdbaths and other outdoor containers regularly, and keep mosquitoes outside by using window screens.

To control mosquitoes before they mature into biting adults, water can be treated with larvicides. They include insect growth regulators such as pyriproxyfen and bacterial controls like Bacillus thuringiensis israelensis.

To knock down flying mosquito populations, adulticides are available. Among them are synthetic pyrethroids such as deltamethrin and the organophosphate naled. Consumers often turn to insect repellents formulated with N,N-diethyl-meta-toluamide, known as DEET, or icaridin.

However, the use of chemical controls does not come without public concern. Earlier this month, an Argentinian physicians group claimed that the use of pyriproxyfen to treat drinking water was responsible for the epidemic of microcephaly in Brazil.

Government authorities in Brazil disputed the relationship, as did the larvicide’s inventor, Sumitomo Chemical. Ian Musgrave, a pharmacology lecturer at the University of Adelaide, points out that the hormonal pathways of the growth regulator don’t exist in humans and thus the likelihood that pyriproxyfen could harm humans is low.

Still, authorities in some Brazilian states stopped adding the larvicide to drinking water after the physicians group’s report.

Without adequate controls, female mosquitoes are left to breed unchecked, sucking blood to nourish their eggs. And in seeking out that blood, “mosquitoes are very good at transmitting viruses to humans,” explains Catherine Hill, a professor of medical entomology at Purdue University.

When a mosquito bites a virus-infected person, the virus can invade, replicate in, and infect the insect’s salivary glands. “The next time the mosquito takes a human blood meal, it passes along the virus to other humans,” Hill says. A mosquito can take multiple bites before laying its eggs.

Because of concerns over Zika in the U.S., “there will be public pressure to increase spraying for mosquitoes,” predicts entomologist Joe Conlon, technical adviser for the American Mosquito Control Association, which represents mosquito control experts.

But Conlon says he doesn’t expect a big jump in spray programs, which in the long run could backfire by promoting resistance to overused chemicals. Instead, he expects an uptick in efforts by CDC to track cases in humans and an increase in efforts to trap and test mosquitoes for Zika throughout the roughly 1,800 government-run mosquito abatement districts in the U.S.

Randy Vaeth, assistant director for the district that covers 1,200 km2 in and around Baton Rouge, La., says vigilance is the key to keeping the threat from infected mosquitoes under control. Vaeth’s district regularly traps mosquitoes and sends them to a lab where they are tested for West Nile virus.

When five or six mosquitoes per thousand test positive, “that’s a threshold when we begin to see human cases,” Vaeth says, and the district begins an insect control program. To prepare for Zika, the district expects to purchase more traps.

Kathy Hall of consulting firm Kline & Co. estimates that mosquito districts across the U.S. spend a combined $80 million annually on mosquito control products, split about evenly between adulticides and larvicides. Adulticides, she notes, tend to be used more during an outbreak but can have unintended consequences. Organophosphates and pyrethroids, for instance, are toxic to bees.

Despite their drawbacks, organophosphates are valuable tools in controlling the spread of disease-carrying insects. Amvac Chemical, for instance, makes the organophosphate naled and sells it in formulations to make a fogging spray dispensed from planes, according to Jeff Alvis, a business manager at the firm.

Variables such as heat, rain, and humidity affect mosquito population growth, so it is too early to say how and where Zika will spread and whether the virus will have any impact on sales of naled, Alvis says.

Naled, which is a cholinesterase inhibitor that works by disrupting the insects’ nervous system, should be used as part of a program that includes other chemical and biological controls, Alvis recommends. “Resistance is always a potential in a living ecosystem,” he says.

Kurt Vandock, a vector biologist for Bayer CropScience, agrees that it is difficult to know whether the appearance of Zika in the U.S. will have much impact on chemical applications. But he does say that the pyrethroids Bayer supplies for mosquito control are also effective against the mosquitoes known to carry Zika.

The pyrethroids, synthetic molecules modeled on pyrethrins extracted from chrysanthemum flowers, kill adult mosquitoes by inhibiting sodium ion channels in the insects’ nervous system, according to Vandock. One of Bayer’s pyrethroid variants, deltamethrin, contains a single active isomer. As a result, it is effective at lower application rates than other pyrethroids, he says.

Larvicides such as Bt israelensis have a different mode of action, explains Steve Krause, public health business manager for Valent BioSciences, a manufacturer. When larvae ingest the bacterium, the bacteria “cleave cells in an insect’s gut, opening a hole in its stomach. The contents of the stomach spill into the insect’s body, causing sepsis and death,” he says.

Valent also sells a synthetic insect growth regulator, (S)-methoprene, alone or in combination with Bt israelensis. (S)-Methoprene is more effective in the later juvenile stage of the larvae, Krause says. It mimics mosquitoes’ natural hormones and keeps them from maturing into flying and biting adults, he says.

On their own, people can ward off mosquitoes by using repellents. Hall, the Kline consultant, estimates that U.S. retail sales of repellents approach $1 billion per year.

“We’re seeing an increase in demand for DEET, particularly from regions now affected by Zika,” says Brad Buehler, business director for Vertellus Specialties, a major supplier of DEET. The repellent does a good job of confusing the chemical signals mosquitoes use to home in on exposed human skin, Buehler says.

Icaridin, another repellent, has a similar mode of action. By working on mosquitoes’ odorant receptors, icaridin disables the insects’ ability “to recognize humans as blood donors,” says Dirk Sandri, marketing head at the Saltigo unit of Lanxess, a manufacturer. The firm says it expects sales of icaridin to grow by 50% this year compared with last year.

The trouble with repellents is they only last a few hours, and some people have allergic reactions to them. A drawback of insecticides, according to Hill, the Purdue entomologist, is that mosquitoes become resistant and the world constantly needs new ones (see page 31).

To aid that effort, Hill and colleagues at Purdue are developing an active molecule “that would make resistant mosquitoes nonresistant.” She explains that a goal of the research is to make pyrethroids, to which many mosquitoes are resistant, effective again.

“Because of mosquitoes’ rapid life cycle, they can mutate quickly and develop resistance to many chemistries we throw at them, particularly if they are overused,” Hill says. “We need to constantly develop new strategies.” There is no magic bullet, she adds, when it comes to keeping mosquito populations and the diseases they carry in check.  


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