Not only was last year the worst on record for severe outbreaks of dengue fever in Asia and South America, southern Europe even had an unprecedented outbreak of West Nile Virus in 2018. And, in 2016, an explosive outbreak of the Zika virus spread throughout South and Central America.
Remarkably, despite the enormous global health burden of viruses spread by mosquitoes – which cause hundreds of millions of infections and thousands of deaths each year – there are no drug treatments available that can stop the virus from spreading and causing disease. There are many reasons why an effective medicine hasn’t been developed, but one of the main challenges is the unpredictability of these often explosive outbreaks. And, with so many distinct viruses, being able to identify which virus might cause the next outbreak is almost impossible.
With few clues showing us what virus we need to prepare against, it’s hard to justify the resources and finances needed to develop virus-specific medicines. Not only that, but many of these infections can be hard to diagnose. Some of the most common mosquito-borne viruses, such as dengue and chikungunya, cause similar symptoms. Without an accurate diagnosis, it would be hard for doctors to prescribe the right medicine even if they were available.
But, our team of researchers has found a different approach that might be able to circumvent many of these issues. This solution is to target a common aspect of every single one of these infections: the body’s immune defence against viruses at the mosquito bite. Our research found that an immune-boosting skin cream can actually prevent infection from a wide range of these dangerous mosquito-borne viruses.
After being bitten by a mosquito, your immune system behaves a bit strangely. The cells in your skin focus mainly on the trauma caused by the puncturing and probing of these pesky insects. This response helps to repair the wounded tissue. However, the body largely ignores the virus – often until it’s too late. We found that the body’s immune defences against the virus failed to keep up with how quickly the virus replicated, which allowed it to spread throughout the body and cause disease.
Our team wondered whether it would be possible to prevent the virus’s attack if we were able to alert the skin’s cells to the lurking viral threat. This is the basis of a new treatment that uses an easily applied topical skin cream. This cream has been used for many years to treat other conditions, such as warts and some skin cancers. It contains an immune boosting agent, imiquimod. When the cream was applied to a mosquito bite, imiquimod alerts the skin’s immune cells, known as macrophages. The macrophages kick-start the immune system’s anti-viral state, stopping the virus in its tracks.
To understand how the cream could activate macrophage cells and whether this might protect the host, we infected mice with two genetically distinct viruses spread by mosquitoes: Semliki forest virus, which can be lethal in mice, and Bunyamwera virus, which causes a fever. Both of these viruses are spread by the Aedes mosquito, which is often the main culprit for transmitting viruses. Worryingly, these insects are rapidly moving from the tropics into more temperate climates.
Half of the infected mice were treated with the cream during the first few hours following infection. In the mice that received treatment, the cream stopped the virus from spreading to the blood and other sensitive tissues, such as the joints and brain. For the mice infected with Semliki forest virus, treatment improved the mice’s chance of survival from 0% to 65%. While for Bunyamwera virus infection, levels of virus in the blood were reduced by up to 10,000 times.
Boosting immune defence also worked for humans. Using skin samples donated by 16 volunteers, we infected them with either Zika or chikungunya virus in the lab. These viruses are also spread by Aedes mosquitoes. Only half of the samples were treated with the cream one hour after infection. In skin samples infected with Zika, the treatment reduced the amount of virus in the skin by more than 70 times. For chikungunya, the virus was reduced more than 600 times. Although more trials will be needed, our research shows that this treatment is effective on several genetically distinct viruses spread by mosquitoes.
Imiquimod-containing creams have been used for many years to treat other skin conditions. So we know it’s well tolerated by patients, and could be repurposed relatively easily compared to new medicines. And, because the cream has already been developed and is readily available, it could be an affordable treatment option in the meantime – until other, more specific, treatments have been developed. The next steps will be for researchers to start testing whether this is safe and effective to be used for routine treatment of these infections.
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