The race against time to defeat mosquito-borne diseases

Deep in the bowels of Imperial College London’s main campus is a facility known as the insectary. The journey to it, via basement corridors and an entrance that sounds an alarm upon opening, feels like something out of a horror film.

Beyond two sets of double doors lies the reason for the security: thousands of the Anopheles mosquito that has long been humanity’s deadliest animal threat. The insects in these temperature-controlled chambers are central to pioneering efforts to use genetic engineering to stop them passing on life-threatening malaria.

Federica Bernardini, a research associate, places a hand close to the white mesh sides of a box housing the biting bugs. “I am not going to put it there for long,” Bernardini says, quickly pulling back from the tiny creatures.

The Imperial work is part of a global struggle against the intensifying threat of mosquitoes and the destructive pathogens they carry. The first malaria vaccination campaign is being rolled out this year, while researchers are exploring ways to stem disease that are both ingenious and — in the case of genetic engineering — controversial to some.

It is part of a wider public health battle against various infectious diseases that have surged in recent years due to environmental change, the Covid-19 pandemic and other factors.

The mosquito campaign is a race against the clock. The insects are becoming more resistant to traditional prevention methods, while the climate crisis has opened up new regions where they can thrive.

The great question now is whether humanity can control malaria and other illnesses spread by mosquitoes before their growing prevalence makes that goal impossible.

“The further out we push the move into the malaria eradication era, the harder it’s going to get,” says Helen Jamet, deputy director for the disease in the global health division of the charitable Gates Foundation. “Because we’ll have a lot more of these climate-based events — and we’ll have a lot more of the problems around insecticide resistance, drug resistance and invasive species that will become harder and harder to tackle.”

Mosquitoes are great survivors whose ubiquity and menace has long given them an outsize presence in the human imagination. The oldest amber fossils found of what one researcher brands “flying needles” date back to the days of the dinosaurs.

The winged arthropod is an “incredibly durable beast”, says Yesim Tozan, assistant professor of global and environmental health at New York University. “The mosquito evolves with us and our living styles,” she says. “That agility and flexibility makes it quite intractable.”

The sobering baseline today is that mosquitoes are threatening more people in more places than ever. The dangerous species of the insect are what are known as disease vectors — carriers of pathogens that they pass among human populations by sucking people’s blood. The economic costs of mosquito-borne diseases have been estimated at $12bn a year.

Poorer countries fare much worse, which is why the problem has historically been under-addressed by private healthcare investment. Now, richer nations are increasingly endangered.

Dengue has spread dramatically and about half the world’s population is now at risk of catching it, according to the World Health Organization. The disease is rarely fatal, but its common name of “breakbone fever” suggests how debilitating severe cases can be. The number of infections reported to the UN health body climbed from just over 500,000 in 2000 to 5.2mn in 2019 and probably misses many asymptomatic cases. WHO modelling puts the number at closer to 400mn cases annually, driven by urbanisation, rising rainfall and humidity, and increased population mobility.

The dengue-transmitting Aedes albopictus mosquito, known as the Asian tiger because of its striped, white markings, is flourishing in more places globally. It has established itself in 13 EU countries compared with eight in 2013, according to the European Centre for Disease Prevention and Control (ECDC). The 130 cases of locally acquired dengue reported in 2023 were almost double the number from 2010 to 2021 combined. The past seven years have seen reported local transmission of Zika, which can cause grave birth defects, in France and chikungunya — a viral disease with symptoms similar to dengue — in Italy.

“Trade, travel, climate change — all of these are really drivers of [this] emergence,” says Céline Gossner, the ECDC’s principal expert in emerging and vector-borne diseases. “We will see more cases of dengue and more outbreaks, that’s very sure.”

Malaria deaths worldwide have risen since the Covid-19 pandemic, after years of decline. Prevention efforts helped bring the number down from an estimated 897,000 in 2000 to 568,000 in 2019, but it climbed to 608,000 in 2022, mostly among children under five in African countries.

The US saw its first homegrown malaria cases for 20 years last year, with infections reported in Florida, Texas and Maryland. This expansion is in some ways a reversion to historical trends. Malaria used to be endemic in the US and Europe, known by names such as “marsh fever” and “ague”. Dengue, chikungunya and Zika virus outbreaks have also occurred recently in US states and territories, according to the US Centers for Disease Control and Prevention.

There is reason to think climate change and other environmental trends will widen mosquito ranges still further. Higher temperatures can increase biting frequency and the reproduction rates of both the insect and the pathogens it bears. Flooding made more frequent by climate change creates new stagnant pools for the insects to lay eggs, as do expanded water storage efforts in areas stricken by drought.

Continued urbanisation will provide mosquito females — the only ones that bite — with more bodies for feasting. Invasive species, such as the malarial Anopheles stephensi, thrive in cities — and may bite during the day time, making traditional protections such as bednets less useful.

“We are in a more vulnerable world,” says John-Arne Røttingen, chief executive of the Wellcome philanthropic foundation, of the growing mosquito threat. “Some countries are more fragile than ever and, in those contexts, it will be more challenging.”

The evident dangers are driving a new age of research. In Paris, France’s Institut Pasteur is building a new centre devoted to vector-borne diseases.

“Mosquitoes can adapt more easily and quicker than us,” says Anna-Bella Failloux, head of insect vector research at the institute. “But we will not give up. We can limit the burden.”

One development that is both momentous and exemplary of the difficulties of the task ahead is the launch this year of the first malaria vaccination campaign. Two jabs, devised by Oxford university and the pharmaceutical company GSK, target the deadly P. falciparum strain of malaria. Both are “safe and effective in preventing malaria in children”, says the WHO.

The worry is that the rollout is patchy. Indian malaria vaccine makers called in May for multilateral agencies to order more doses to boost the campaign and drive down costs. Gavi, the global vaccine alliance, has said it needs not only to provide the doses, but to ensure the necessary logistics are in place to deliver the jabs.

Both vaccines seem to be good rather than great, reducing malaria cases in trials by more than half during the first year after vaccination. Both are most effective after four doses: a big ask in countries where health services may be thin and hard for patients to access.

Another problem is the limited reach of the vaccination. Malaria will continue to spread from unjabbed people who carry the parasite with no symptoms, says Professor Faith Osier, co-director of Imperial College’s Institute of Infection. “Unless you target vaccinating [the] entire population, you don’t actually get rid of it,” she adds.

A promising emerging area of anti-malaria efforts uses monoclonal antibody technology, which stimulates the human immune system. The antibodies disrupt the Plasmodium parasite that causes malaria, by binding to it to stop its transmission to other people. One dose was up to 88.2 per cent effective in preventing infection over a 24-week period, according to a US National Institutes of Health clinical trial in Mali published in 2022.

The approach is being improved all the time, says Dr Jeanne Marrazzo, director of the US government’s National Institute of Allergy and Infectious Diseases. The latest monoclonal antibodies show an even greater ability to kill Plasmodium before it reaches the human liver, where it reproduces. “The second generation ones are even more potent and, importantly, last longer,” Marrazzo says. “So you can imagine a malaria programme where you think about protecting people seasonally.”

Methods of preventing malaria are the more urgently needed because long-standing treatments for the disease are becoming less effective. The standard modern therapy based on artemisinin, a plant extract used in Chinese traditional medicine, is suffering from growing pathogen resistance. Partial resistance has spread from south-east Asia to Rwanda, Uganda and the Horn of Africa, according to research published this year.

A parallel quest is under way to deal with growing mosquito resistance to human-made pyrethroid insecticides historically used to treat bed nets. A chemical called chlorfenapyr has shown encouraging results when used alongside pyrethroids. The combination cut the prevalence of malaria in children aged six months to 14 years by 43 per cent in the year after application, according to study in Tanzania published in 2022.

As tried and tested methods start to falter, scientists are making crucial advances in other approaches, such as the practice of setting “good” bugs against bad.

This nature-based technique harnesses bacteria called Wolbachia that occur naturally in many insects, including some mosquitoes. Introducing Wolbachia into eggs from the Aedes aegypti species can curb the growth of viruses in the adult insect, including those that cause dengue, chikungunya and Zika.

The Wolbachia method is being rolled out by the World Mosquito Program, a non-profit initiative of Australia’s Monash university. It is currently working in 14 countries in the Latin America and Asia-Pacific regions. Dengue cases in Colombia’s Aburrá Valley region fell to a 20-year low after a release of Wolbachia insects there, research has suggested. In 2025, WMP and Fiocruz, a foundation under Brazil’s ministry of health, expect to open a factory in the country to turn out 5bn disease-blocking mosquito eggs a year.  

The Wolbachia approach appears to have some limitations. These include its vulnerability to environmental factors, temperature and host diet, according to research published in 2020. The WMP counters that it has shown Wolbachia can establish itself in insect populations in hot countries — although it acknowledges high temperatures can reduce maternal transmission of the bacteria.

The most revolutionary technique to stop mosquito-borne diseases is genetic engineering.

Oxitec, a US-owned biotechnology company, released modified Anopheles stephensi mosquitoes to combat malaria in Djibouti in the Horn of Africa in May. A release of Aedes aegypti insects in Brazil suppressed wild mosquito populations by up to 96 per cent, according to a 2022 paper by company researchers. The insect eggs are sold in supermarkets in Brazil under the brand name Aedes do Bem, which translates roughly as “good Aedes”. Customers add water, hatch and release the insects.  

Without additional tools we will never be able to cross the last mile of malaria elimination, no matter how much money we put in . . . We absolutely need to innovate

Oxitec’s method involves releasing batches of male mosquitoes, which are trademarked “Friendly” — but prove anything but for their mates. The engineered insects carry a gene that causes female offspring to die before reaching maturity. This company describes the approach as “self-limiting” because fewer of the edited genes are passed on with each successive insect generation. This has the environmental advantage of not permanently altering the ecosystem — but it does mean repeated “Friendly” releases will be required.

The gene drive techniques being worked on by Imperial College London, its partners and others aims for an even more radical solution. The approach can work by disrupting genes crucial for female fertility, or by causing the sex ratio of the insect population to distort in favour of male offspring. The technology can potentially cut mosquito populations to levels at which malaria cannot be transmitted.

But the speed and efficiency with which these engineered traits can spread have raised concerns that they could have damaging biodiversity effects. So far, however, there is no evidence to support the idea that this would be the case, proponents argue. Organisations including the African Union are promoting the managed use of gene drive mosquito technology to improve public health.

A 2019 genetically modified sterile male mosquito release in Burkina Faso, west Africa, showed they successfully mixed with wild counterparts, although their survival rates were lower. Gene drive could be an essential tool in the fight against malaria, according to Professor Abdoulaye Diabaté, principal investigator at Target Malaria Burkina Faso, which oversaw the release.

“There is a general consensus that without additional tools we will never be able to cross the last mile of malaria elimination, no matter how much money we put in there and time we devote to it,” he said in October. “We absolutely need to innovate.”

Over at Imperial’s underground London mosquito vault, Bernardini hopes technological advances born there will be a potent new weapon in the fight to save lives.

But Bernardini argues that, rather than seeking one single “magic tool”, humankind will need the combined power of simultaneous breakthroughs to subdue its ancient insect foe.

“You are going to have a synergistic effect that is going to use advances in all the aspects — whether that is a new insecticide, a new vaccine or transgenic technology,” Bernardini says. “Collectively, that will give us a better chance.”

Graphic illustration by Ian Bott. Cartography by Steven Bernard