,An inspection in Brazil to combat the Aedes aegypti mosquito (Joel Rodrigues/Agência Brasília)

 

Modified Mosquitoes: The Future for Controlling Vector-Borne Diseases?

The use of biologically modified Aedes aegypti mosquitoes to stop disease transmission is gaining traction as climate change and the ongoing El Niño event in the Pacific Ocean threaten an epidemic of mosquito-borne diseases in some regions.

By John Heilprin

March 1, 2024

A new epidemiological alert from the Pan American Health Organization urges all nations in the Americas to intensify efforts to control the Aedes aegypti, the main vector spreading dengue fever.

The idea of biologically modifying the mosquitoes to stop disease transmission and reduce their population is a solution that experts convened by GESDA have anticipated for several years.

PAHO’s mid-February alert stems from concerns about a significant increase in the number of reported cases of dengue during the first five weeks of 2024 – already 673,267 cases with 102 deaths – coming on the heels of the highest number of dengue cases ever recorded in the Americas last year: more than 4.5 million, with 2,340 deaths.

That’s a 225% increase over the five-year average, hitting hard in countries such as Argentina, Brazil, Colombia, Costa Rica, Guatemala, Guadeloupe, French Guiana, Martinique, Mexico, Paraguay and Peru. PAHO advises people to help reduce mosquito breeding sites and seek timely medical care.

Scientists can now modify the mosquitoes by adding the natural Wolbachia bacteria, which blocks diseases like dengue, Zika and chikungunya from growing in their bodies. The bacteria cause the mosquitoes to produce compounds in their guts that stunt the growth of parasites and reduce the ability to transmit arboviruses.

It also changes the reproductive ability of males, which don’t bite and are released to mate with the females. Because of the bacteria, the female mosquitoes’ eggs are unable to hatch, thinning the population of Aedes aegypti. It’s a clever bit of reproductive tinkering, but the counterintuitive idea of releasing more mosquitoes into the wild has met with some public resistance and social media misinformation in places such as Indonesia.

In other places, modifying Aedes aegypti to carry the natural Wolbachia bacteria has drawn praise as dengue rates drop. “It was like we were releasing hope,” Samu Tuidraki, the chief of Narewa, a village in Fiji, told the World Mosquito Program (WMP), which pioneered the Wolbachia method.

Diseases like dengue, Zika and chikungunya are global health emergencies while others such as yellow fever have re-emerged particularly with the acceleration of climate change, which moves or enlarges areas where Aedes aegypti are endemic. From his research in the 1980s, WMP’s CEO Scott O’Neill focused on Wolbachia, which was first described in the 1920s and occurs naturally in almost 50% of all insect species, but not in the Aedes aegpyti.

While researching Australian fruit flies, he found a strain of Wolbachia that could infect Aedes aegypti while protecting against the dengue virus. It is a common bacteria among insects and carries no potential to sicken humans or animals, according to findings from the US Centers for Disease Control and Prevention (CDC) and Singapore’s National Environment Agency (NEA).

 

‘A substantial public health challenge’

At GESDA’s 2022 Geneva Science and Diplomacy Anticipation Summit, O’Neill said the Wolbachia method already had protected more than 10 million people from dengue transmission in his homeland, Australia, and “we’re on the edge now of wanting to take it from 10.5 million at the present day to it being able to be scaled globally.”

What’s needed for that to happen, he said, is for big foundations to shell out more money, or for commercial start-ups to generate more revenue streams in places that can afford it. Either way, he added, more communication and community engagement will be needed to ensure that people will accept the idea.

“We grow in our laboratory or in a factory, if you like, mosquitoes that have this Wolbachia bacteria introduced into them,” he said. “We grow them up in the laboratory and then we release small numbers of them into communities where they mate with the wild mosquitoes and pass that Wolbachia into the mosquito community. It then gets transmitted into the mosquito population and maintains itself without having to be reapplied. And once the mosquitoes have it, they’re much less likely to give viruses to people when they bite them.”

Heatwaves, extreme drought and prolonged heavy rains and flooding enable greater transmission of mosquito-borne viruses such as dengue, chikungunya and Zika, which was linked to a surge in microcephaly cases — babies born with a very small head — in Brazil nearly a decade ago.

Dengue causes high fever, muscle pain and internal bleeding. Chikungunya is also spread by Aedes aegypti, which thrive in stagnant water. It has similar symptoms to dengue but is caused by a different virus with four serotypes. Infection by one does not create immunity from the others.

 

A car distributes insecticide against the Aedes aegypti mosquito (Lúcio Bernardo Jr./Agência Brasília)

Where the science and diplomacy can take us

The 2023 GESDA Science Breakthrough Radar®, distilling the insights of 848 scientists from 73 countries, tells us that the need to monitor, detect, contain and, above all, prevent new disease outbreaks is paramount as more people move into previously undisturbed ecosystems and climate change broadens areas where vector-transmitted diseases are present.

The threat grows. In December, the World Health Organization (WHO) reported a ten-fold surge in reported cases worldwide, up to 5.2 million in 2019, from 500,000 in 2000. The year 2019 marked an unprecedented peak, with reported instances spreading across 129 countries.

WHO said a “global incidence of dengue has markedly increased over the past two decades, posing a substantial public health challenge.” Health officials in Brazil, for instance, warned that dengue cases there could hit a record 5 million this year, more than triple from last year.

As WHO evaluates whether to officially endorse the use of biologically modified mosquitoes, the Radar also points to advances in synthetic biology and genetic engineering that could lead to new ways of constraining disease, such as modifying the human microbiome to resist viruses.

It notes that advances in these techniques – which enable modification and creation of living cells and organisms, and of their building blocks – could lead to major breakthroughs in fundamental biology and possible applications in fields ranging from nutrition to pharmaceuticals and engineering.

“The time may come when we can use these techniques to program functionality into living organisms in the same way that we can program a computer to perform specific tasks,” the Radar says. “However, this is profoundly challenging because of the extreme complexity of living organisms.”

The findings in the 2023 Science Breakthrough Radar®

Based on the Radar, here’s where we stand in several important areas:

3. Eco-Regeneration & Geoengineering

There can be no doubt the planet is experiencing some of the most pressing issues ever faced by humanity. Concerns about warming, pollution and biodiversity are only compounded by the forecasted rise in human population, which is expected to reach nearly 10 billion by 2050. Advances in science and technology will be vital for monitoring and mitigating problematic trends, and for establishing new ways for humanity to live on a changing planet.

Radar, page 124.

3.7 Infectious Diseases

The current disease load is only part of the problem. New diseases are continually emerging, with COVID-19 being the most dramatic recent example, as humans contact more novel pathogens and global transport networks facilitate their rapid spread. Environmental degradation is a potential contributor through human infiltration and destruction of natural habitats for increased trading of wildlife and intensive livestock farming, among other activities.

Radar, page 162.

3.7.3 Vector control

Around 80% of the world’s population is at risk of infection by viruses or parasites from vector organisms like mosquitoes, ticks and fleas that transmit disease directly to a person’s body, often by biting them. Gaining some control over these vectors could have major global health benefits.

Anticipation in a nutshell

5-year horizon: Success in mosquito control
10-year horizon: Synthetic biology harnessed
25-year horizon: Vector microbiomes put to work

Radar, page 166.

3.7.4 Outbreak prevention

A key research challenge is to understand and, ultimately, predict how outbreaks arise. It is, therefore, crucial to study diseases and track their movements from one species to another. Genomic data also must be gathered so outbreaks can be traced back to their sources, which can then be monitored.

Anticipation in a nutshell

5-year horizon: Drivers of disease emergence are tamed
10-year horizon: Public health systems strengthened
25-year horizon: Early warning system established

Radar, page 167.

Opportunities: Controlling vector-transmitted infectious disease

As people move into new ecosystems and climate change broadens areas with vector-transmitted diseases such as dengue fever, Zika, and chikungunya, the need to monitor, detect, contain and, above all, prevent new outbreaks is paramount. The opportunity to constrain disease transmitters with a new biological (non-genetic, hence possibly better accepted) method is within our grasp.

Radar, page 346.