Imiquimod May Stop Mosquito-Borne Viruses in their Tracks

The key to controlling the next mosquito-borne disease outbreak may lie in a well-known, widely available topical skin cream.

Investigators from the University of Leeds, in the United Kingdom, say applying imiquimod following a bite from an virus-infected mosquito can inhibit the spread of the virus in a patient. Imiquimod is indicated for use against skin cancer, external genital warts, and actinic keratosis.

Clive McKimmie, PhD, who leads the virus host interactions team at the University of Leeds School of Medicine, told Contagion^® that a previous study by his team showed that the body’s natural response to an inflammatory mosquito bite doesn’t arrest replication of a virus, but actually enhances it. In their new study, published this month in Science Translational Medicine, McKimmie and colleagues found the body initially ignores the virus in mosquito bites, giving the virus a head start before the immune response kicks in.

“Because of this, we asked whether it is possible to pre-empt the virus attack by alerting the skin’s cells to the lurking viral threat at the mosquito bite,” said McKimmie, the study’s corresponding author. “This is the basis of our new treatment strategy that comes in the form of an easy to apply cream that contains an immune boosting agent, imiquimod.”

The cream works by activating skin macrophages and creating a heightened antiviral state. McKimmie said the strategy appears to be effective against a number of viruses, making its potential impact broad.

The study is based on tests in mouse and human models. The mice were infected with one of three viruses—Semliki Forest, chikungunya and Bunyamwera—at the sites of mosquito bites. Half of the mice were treated with imiquimod an hour after the infection. In the cases of all 3 viruses, the imiquimod-treated mice had substantially improved outcomes. In the case of Semliki Forest virus, all of the mice who did not receive imiquimod were dead within 2 weeks, but the survival rate among those receiving the topical medication was 65%.

For the human tests, McKimmie and colleagues took skin samples from 16 healthy volunteers. Each sample was cut in half and both samples were infected with a virus, in this case Zika or chikungunya. After an hour, 1 of each volunteer’s skin samples was given the topical treatment.

When investigators calculated viral replication in the skin samples 2 days later, they found untreated Zika-infected samples had 70 times more virus compared to samples that received the imiquimod treatment. In the case of chikungunya, untreated samples had 600 times the viral replication. They found the treated skin didn’t release any virus, implying that the virus wouldn’t spread into the body of a person treated with imiquimod.

McKimmie said they also tried applying the topical therapy to mouse models 5- and 10-hours post-infection. At 5 hours, the cream still had a notable effect, but no significant effect was observed when they waited 10 hours to apply the cream. He noted that these studies were based only on mice, and the virus typically takes longer to replicate in the human body than it does in mice.

“This in turn may mean that the window available for post-exposure intervention in humans is conveniently longer than that observed in our model,” he said. “Because the mosquitoes responsible are day-biting and their bites are typically visible within minutes, it is possible that there is a sufficient time to notice a bite and apply the cream.”

Still, McKimmie said he doesn’t envision the cream becoming the primary method of infection control. He said the strategy is probably ideal only in cases of specific outbreaks, particularly for immunosuppressed patients. And even though imiquimod is well-tolerated and widely available in generic form, McKimmie said it shouldn’t replace precautions that can prevent bites in the first place.

“The best defense against mosquito-borne infections is to wear clothes that protect the skin from biting mosquitoes and wear insect repellent,” he said. “For those mosquitoes that still bite, our new strategy of treating bites with imiquimod cream may be useful.”