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A new dawn for fighting mosquito-borne diseases

Over recent decades many mosquito-borne diseases have resurfaced or emerged and spread rapidly. From Zika, dengue to West Nile fever and chikungunya. Even malaria, which has had long-term global efforts to eradicate it, has recently shown signs of increasing.

Many of these diseases have no specific treatment and the limited medicines available for some are facing resistance. Insecticides used to control mosquitoes are also facing resistance. On many fronts, innovations are urgently needed to control old diseases and prevent new ones from spreading.

Help is at hand, however, as governments worldwide have accepted that efforts need to be increased and cooperation improved. New vaccines and medicines are under development but have
had limited success. So Scientists in fields as diverse as biochemistry, genomics, entomology, computing, remote sensing, avionics, artificial intelligence, robotics and aerospace engineering are combining their resources to develop new ways to fight diseases.

Here are a some recent scientific developments that are bringing a new dawn in the global fight against mosquito-borne diseases.

New global strategies to fight diseases

Petri dish

Millions of lives have been saved by vector-control techniques. It is estimated that between 2000 and 2015, for malaria alone 663 million cases were prevented by distributing insecticide treated
bednets and indoor spraying of insecticides in sub-Saharan Africa. By 2015, however, Global efforts for eliminating malaria had stalled and malaria cases and deaths had started to increase in some regions.

The WHO initiated a new strategy that was endorsed by the World Health Assembly in 2015: the Global Technical Strategy for Malaria 2016-2030. As part of this strategy, WHO is working with 21 countries in five regions to eliminate malaria by 2020. Called the E-2020 initiative, the countries were identified by WHO on the basis of their downward trend in malaria incidence from 2000-2016 and their capabilities to carry out the necessary measures to achieve elimination.

Global vector-borne disease strategy

Tape worm

Zika, dengue, yellow fever and Chikungunya also have had serious outbreaks due to neglect of vector control in many countries. Yellow fever is the only one with a widely available vaccine.

Other neglected diseases spread by mosquitoes include Japanese encephalitis, lymphatic filariasis and West Nile fever. In addition, other important vector-borne diseases that need attention include Chagas disease transmitted by triatomine bugs, onchocerciasis  by blackflies, leishmaniasis by blackflies, Lyme borreliosis and encephalitis by ticks, human African trypanosomiasis by tsetse flies, and schistosomiasis by snails.

WHO developed a comprehensive approach to improve the capability of countries to manage all vector-borne diseases. In 2017 the World Health Assembly adopted the WHO Global Vector Control Response (GVCR) 2017-2030. The new strategy aimed to engage multiple sectors, including healthcare, environment, urban planning and education.

It also included a drive to boost innovation to develop new techniques and products for disease and vector control. WHO said the GVCR “promises a new dawn for the control and elimination of vector-borne diseases”.

Fighting insecticide resistance with next-generation insecticides

Mosquito fumigation

In recent decades Anopheles and Aedes mosquitoes populations in various parts of the world have built up resistance to many of the available insecticides and larvicides used for vector control. DDT had spectacular success in eradicating mosquito-borne diseases up to the 1980s, but as early as the 1950s resistance was noticed in areas where it had been used for several years.

The early successes led to complacency and lack of development of new products. Added to that, organochlorine and organophosphate pesticides were banned in many countries due to their toxicity to other animals, including humans, and their persistence in the environment. Pyrethroids are the only insecticide available for treating bed nets, so resistance is bound to occur. Without new products vector control is “doomed to failure”, according to IVCC.

Global initiatives are having success in developing new products. Two new-generation insecticides were approved by WHO in 2017 and are being distributed in malaria areas for use in IRS programmes by the NgenIRS project. This is being carried out by the Innovative Vector Control Consortium (IVCC), the US President’s Malaria Initiative, Abt Associates, PATH and The Global Fund. Since 2016 the project has supported operations in 12 African countries and bought over 4.5 million bottles of the new insecticides.

New odours to attract and repel mosquitoes

Mosquitoes find human hosts by sensing the carbon dioxide we breathe out. But when they get close they can locate exposed skin sites for feeding on blood by detecting volatile chemicals given off by human skin.

Mosquitoes have several means of sensing their environment: the antennae, the maxillary palps and labial palps (both mouth parts). Researchers at the University of California Riverside found that the same receptor neuron in the maxillary palps that detects carbon dioxide also responds to skin odours. They are also more sensitive to these odours.

When the researchers chemically blocked this receptor in Aedes aegypti mosquitoes they stopped being attracted to human odour. Using modern chemical screening techniques they screened half a million compounds in a chemical database for potential to activate the receptor neuron, based on the chemical structure.

The screening identified 138 compounds based on smell, cost, safety and whether they were natural compounds. About 85% were already approved for use as flavouring, fragrances or cosmetics, so they could avoid costly safety tests and be used straight away. Of these, they chose two compounds to study further:

  • ethyl pyruvate, which is a food flavouring with a fruity flavour:  this was found to reduce Aedes aegypti attraction to a human arm
  • cyclopentanone, a minty-smelling flavour and fragrance: this was a powerful attractant for Culex quinquefasciatus mosquitoes   

The University of California Riverside filed patents for their discoveries and licenced some for commercialisation.

Robotics, gene sequencing and cloud computing to detect diseases early

Using drones to detect mosquito borne diseases

Project Premonition is developing a high-tech system to identify potential disease outbreaks before they happen by capturing and analysing mosquitoes. Many animal species are reservoirs of human diseases and mosquitoes feeding on their blood can be exploited as sample collectors for diseases present in the locality.

The project began in 2015 and is a collaboration between Microsoft Research (MSR), University of Pittsburgh, Johns Hopkins University, University of California Riverside, and Vanderbilt University.

The project is developing autonomous drones that can locate mosquito hotspots in complex environments containing trees and buildings, robotic traps to collect and identify mosquito specimens, and genomics, cloud computing and machine learning algorithms to analyse the DNA and RNA in the mosquitoes.

In 2016 a robotic trap was set up in Harris County, Texas and was able to detect over 22,000 mosquito encounters from nine species of mosquito. It was also used to evaluate the chemical lures discovered by the University of California Riverside (described earlier).

The DNA and RNA collected from the mosquitoes can identify the mosquito species, the mosquito-borne diseases and the animal that the mosquito fed on. The genomics part of the project can already identify the genetic makeup of the samples with 99.9% accuracy.

Releasing mosquitoes infected with Wolbachia bacteria

In July this year, CSIRO announced the successful results of a project that released millions of sterile male Aedes aegypti mosquitoes on the Cassowary coast in Queensland, Australia. The project uses new techniques developed by Verily (owned by Alphabet the parent company of Google) for large-scale rearing, sorting out the males and releasing large numbers of the mosquitoes.

Verily is also developing software, monitoring tools, sensors and traps to indicate the mosquito hotspots where the treatment is most effective.  

Wolbachia is a bacteria that naturally occurs in large proportion of insects and is thought to be one of the most common parasitic microbes. It has complex relationships with its host insects. Some cannot reproduce or survive without it and some only reproduce by parthenogenesis. When male mosquitoes are infected with Wolbachia, the females they mate with that are not infected with the bacteria cannot produce viable eggs.

The project, which also involved James Cook University, released around two million infected male Aedes aegypti  into the wild. The early results show that local Aedes mosquito populations were reduced by 80%. The project has tested its sterile insect technique in several sites worldwide.

The World Mosquito Program is working in 12 countries across Asia, the Americas and Pacific islands releasing Aedes mosquitoes infected with Wolbachia to reduce the ability of wild populations to spread viruses.

A gut feeling to blocking diseases

Rentokil's research into mosquito control

The midgut of mosquitoes is the initial site of infection for a range of diseases, therefore finding a way to block infections there will also block transmission to humans. Many research projects in multiple disciplines are looking at novel ways to do this, including:

Preventing fungal infections

Researchers at Johns Hopkins University in the US found that a common fungus, Talaromyces, can infect Aedes aegypti mosquitoes and make them more susceptible to the dengue virus. The researchers also found that a Penicillium fungus made Anopheles mosquitoes more susceptible to infection with the malaria parasite.

Thinking that the fungi were affecting a digestive process, they blocked trypsin, a protein-digesting enzyme, from the Aedes mosquito gut and found it had the same effect. This showed the fungi could be protecting the virus or parasite from being digested or inactivated by trypsin. The research suggests that antifungal solutions are a potential alternative to insecticide spraying to protect the mosquitoes from diseases they might spread to humans.

Biochemical modification of the mosquito gut

Another study at Colorado State University has made the first comprehensive analysis of the complex biochemical interactions that occur in a mosquito when a dengue virus infects the cells lining its gut. From there it invades the cells lining the gut and adjusts the biochemical processes in the cells to suit its own nutrition requirements.

Using high-resolution mass spectrometry the researchers identified the chemical changes during the early, mid and late infection periods. This showed several biochemical pathways in the mosquito that are required for the virus to replicate. These are now targets for further research to find ways to block them.

Knocking out mosquito genes

DNA of mosquitoes

The malaria parasite has to complete a complex journey through the Anopheles mosquito to be able to infect a human. It interacts with the mosquito midgut, hemolymph (equivalent to blood) and salivary glands, giving numerous biochemical targets for developing malaria control.

Until recently there were no effective gene-editing tools for Anopheles mosquitoes. However, new gene editing technology, called CRISPR/Cas9, has been developed and used to genetically alter AedesAnopheles and Culex mosquitoes in the lab.

Another team of researchers at Johns Hopkins University developed a new gene-editing procedure for Anopheles mosquitoes using a tool called CRISPR/Cas9. Their procedure knocks out the Anopheles mosquito gene FREP1 that enables the Plasmodium parasite to infect the cells lining the midgut. The mutant mosquitoes showed a significant decrease in infection with the parasite. Further work is needed, however, before they can be released to breed with the wild population and their prospective impact in reducing the threat of malaria can be examined.

New antimalarials

Using science for mosquito control

Medicines for Malaria Venture (MMV) has a partnership network of over 400 pharmaceutical, academic and endemic-country partners in 55 countries developing drugs to protect against malaria.

Since its foundation in 1999, the network has brought seven new medicines to market that are already being used to prevent and treat the disease. As recently as July this year the US FDA endorsed tafenoquine, another medicine produced under the programme. This targets the dormant liver stage of Plasmodium vivax and is the first new medicine for 60 years for this type of treatment.

The future

The future for controlling mosquito-borne diseases is looking more promising than in recent years. The examples described above show that developments in many scientific disciplines are providing new ways of treating diseases and controlling mosquitoes.

As part of our commitment to fighting mosquito-borne diseases, Rentokil Initial is establishing a new global centre of excellence for mosquito control, the only commercial pest control company to have such a facility.

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