Unleashing a New Weapon on the Mosquito: A Mosquito

It is lunchtime in a laboratory located in the heart of Medellin. A technician dressed in white carries a tray filled with blood into a humid nursery. She slides a tray of blood between each of the rows of cages. Each one is about the size of a small refrigerator. Her charges, all 100,000, start to whirr and emit a excited hum in response.

This is a factory that produces mosquitoes. It produces more than 30,000,000 adult Aedes Aegypti Mosquitoes each week, which are easily identifiable by their white polka-dots on their black legs. The females' broodstock is fed discarded blood blanks and horse blood. Some of the progeny from these females will eventually be released in Medellin, Cali, and other cities and towns along Colombia's lush river valleys. Some insects will be chilled to a stupor before they are transported up to Honduras.

The World Mosquito Program laboratory.

Anggy Aldana at the World Mosquito Program laboratory in Medellin.

This elaborate effort is part an experiment that has made encouraging progress in the long-term fight against mosquito-borne diseases.

Aedes aegypti can spread arboviruses such as dengue or yellow fever. These viruses can cause severe illness or death. These Aedes are different: They carry bacteria that neutralizes the deadly viruses.

Entomologists began considering a new solution to the suffering caused by mosquitoes five decades ago. Instead of killing them (a futile proposition in many places), what if you could disarm the mosquitoes? What if, even if they couldn't stop biting humans, you could prevent them from spreading disease? What if you could actually use an infectious microbe to stop a second?

Scientists began to study a parasitic bacterium called Wolbachia that lives in the intestines of all insect species. The female mosquito that carries Wolbachia will pass the bacteria on to her eggs, which she then passes on to her offspring.

Wolbachia does not naturally occur in mosquitoes that are the biggest threat to humans - the Aedes Aegypti which is the carrier of the virus, or the Anopheles Subspecies carrying malaria. It could eventually make those mosquito species harmless.

How do you infect the mosquito with Wolbachia bacteria?

After a lot of trial and error, researchers discovered that they could insert bacteria into mosquito eggs with tiny needles. Infected mosquitoes grew out of those eggs.

A looping video shows a thin needle injecting liquid into a row black mosquito eggs. Each egg is about a half-millimeter long and oblong.

Source: World Mosquito Program

Eleanor Lutz

The Aedes Aegypti mosquitoes, which hatched with Wolbachia and lived there, did fine. As hoped for, Wolbachia largely blocked viruses. The mosquito that bit someone with dengue and caught the virus didn't spread it to the next person.

Researchers wondered: What if they could infect

You can find out more about it here.

The disease might be stopped if they eliminate the mosquitoes from a city or village. This method is not harmful to the ecosystem, unlike truckloads sprayed on every street, which run into water systems.

How can you infect all the mosquitoes of a city as large as Medellin with Wolbachia?

Three illustrations showing the results of breeding between wild and Wolbachia-infected mosquitoes. No offspring will be produced when a Wolbachia infected male mates with a wild female. All offspring of a male wild and a female Wolbachia infected will carry Wolbachia. When two mosquitoes infected with Wolbachia mate, their offspring will all carry Wolbachia.

All offspring

Wolbachia

All offspring

Wolbachia

All offspring

Wolbachia

All offspring

Wolbachia

Source: World Mosquito Program

Eleanor Lutz

Scientists needed to test their theory in the field once they had proven they could infect mosquitoes. The method was tested first in small towns of northern Australia where females that had been released with Wolbachia mated wild males, and spread Wolbachia throughout the mosquito population.

The team, led by an Australian named Scott O'Neill, then tried a few towns in Vietnam and a small town in Indonesia. After three years there, the areas where Wolbachia was released were still present.

Dengue hospitalizations were down 86 percent and reported cases decreased by 77 percent.

.

The results were astounding -- a relief to a public health system that had been accustomed to dengue seasons of misery. Even a'mild case' of dengue can cause intense pain and suffering. It is commonly known as 'breakbones fever'. Five percent of all cases progress to hemorrhagic dengue, which causes uncontrolled bleeding. If they don't have the treatment necessary to control bleeding, half of those who suffer from hemorrhagic disease will die. The dengue virus is not killed by antiviral drugs, and there has been a long search for an effective vaccine.

Fraught

.

Dengue is a virus that kills and infects over 400 million people each year. It's also spreading rapidly. Dengue is an endemic virus in Indonesia. Every outbreak season, it overwhelms hospitals, just as Covid-19 did during the peak of the pandemic.

Aegypti's range is expanding due to climate change. Dengue has been introduced with it. Last year, France experienced its first dengue outbreak. The virus has been found in Florida and Texas. Last year, Brazil experienced the worst dengue epidemic ever recorded -- nearly 1,000 deaths and 2.3 million cases.

Map of the world showing recent dengue transmission in orange. This group includes 110 countries and territories, most of which are in the Americas. A large part of Africa and Southeast Asia is also included.

Americas

Two U.S. States and

45 countries and territories

Oceania

11 Countries

Or Territories

Americas

Two U.S. States and

45 Countries or Areas

The following are the most recent and relevant territories

Oceania

11 Countries

Or Territories

Americas

Two U.S. States and

45 Countries

Or Territories

Oceania

11 Countries

Or Territories

Source:

Leta et al.

International Journal of Infectious Diseases

Please note that data in the United States are shown at the state-level. All other areas will be shown at the national level. Only countries reporting dengue infection due to travel are highlighted.

Eleanor Lutz

Insecticides are becoming less effective against mosquitoes. The Wolbachia results from the trial in Indonesia showed that the bacteria could be permanently established if mosquitoes carrying Wolbachia supplanted local mosquitoes.

Dr. O'Neill's team took their tests to Brazil from Indonesia. A second group called WolBloc, led by Steven Sinkins, an entomologist at the University of Glasgow, and his colleagues, started a trial using a strain of Wolbachia in Kuala Lumpur.

Medellin with its three-million population is the most challenging test yet.

One of the neighbourhoods in Medellin.

In a city of this size you will need many mosquitoes. They must be millions and millions.

Dr. O'Neill's team -- now called the World Mosquito Program - set up the production. The process of creating conditions that maximize mosquito reproduction is tricky.

The females in the factory feed on the blood trays placed at the top, and then fly to the bottom, where they lay their eggs on the filter paper that is placed inside the little cups of water. The technicians remove the paper that is covered with hundreds of tiny egg-like structures. After nine to 10 days, the eggs hatch into tiny larvae that look like worms.

Then they are pupae. They are then poured into mesh cages and sorted by gender (females grow bigger).

In a tray with water, you can see mosquito pupae.

In a shallow tray of water, mosquito pupae swarm and wiggle around.

The adults are sent to the world in boxes. Some are kept for breeding, like battery hens. Staff members of the program release them into neighborhoods on motorbikes or on foot. Researchers in Cali are using a blue drone to spit out 150 mosquitoes at every 50 meters. The drone flies over roofs and high-rise buildings.

The eggs for the other group are packed into capsules, which are about the size of a vitamin. They also contain all nutrients that they require to grow. The eggs are distributed to the people of the community who then drop them into a cup with water and can grow mosquitoes that are resistant to dengue on their patios.

The World Mosquito Program released 2 million Wolbachia infected mosquitoes in three months at its first target in Medellin.

Researchers waited to see if they would successfully mate with the locals. Then researchers waited: would they successfully mate with locals?

The program collected mosquitoes from the neighborhood in traps after four weeks. In the lab, the team ground up the insects and tested them for Wolbachia DNA. In the months that followed, the number of samples with Wolbachia RNA increased.

Anatomy of a mosquito on a dry-erase board in the lab.

The program eventually found Wolbachia bacteria in two-thirds (or more) of mosquitoes, enough to consider it established in the neighborhood. Staff members then spread out across the city, slowly blanketing it with Wolbachia.

The project was expanded to Cali a few years back, where dengue and Chikungunya rates were on the rise. Marlon Vico, 33, a resident of Siloe neighborhood, located on a hilltop above the city of Cali, contracted chikungunya last year. He was aching and feverish, and could not get out of bed. He said, 'I was unable to work for over two months and this had a major impact on the family's finances.

Marlon Victoria & family

Marlon Victoria and his family.

When the researchers asked for assistance, Mr. Victoria agreed. He hung boxes with mosquito eggs on the trees and assured skeptics this would help the dengue cases which were sending their children to the hospital. He said, 'We told people we would be bringing in more mosquitoes but they were good mosquitoes.'

Was it effective? Dengue rates are difficult to measure. Outbreaks usually occur in cycles lasting four, five, or six years. The Covid pandemic, during which people avoided public transport, markets, and schools -- all of which were major transmission sites -- further complicates things.

The Colombian national dengue surveillance system, however, recorded the lowest dengue rate in Medellin for more than 20 years in 2021 - which was supposed to be a dengue peak year.

A graph showing the peaks of dengue infections and the missing peak for 2021, after mosquito releases started in 2017.

Monthly Payments of 120

Dengue is a disease that can be contracted.

per 100,000

Mosquito Release

Start August 2017

2021 is the year

Expected to be

A peak year

Dengue monthly cases of 120

per 100,000

Mosquito Release

Start August 2017

2021 is the year

Expected to be

A peak year

Source: Medellin Health Secretariat & the World Mosquito Program

Eleanor Lutz

Fans such as Dr. O'Neill claim that the experiences of Colombia and Indonesia should be enough to prove that Wolbachia should be released in all areas with an arbovirus issue. This is a big proposition.

The cost of mass producing mosquitoes and dispersing them across a city or country is not cheap. The Colombian program is a busy technical operation with a large staff. The mosquito factory in Colombia took seven years to reach a production of over one million insects per week. Personnel costs are the biggest cost. Automatization, such as using the drone to control the releases Mr. Victoria performed by hand, streamlines the process.

The World Mosquito Program drone takes off from an empty parking space.

A World Mosquito Program drone.

The program claims that the project will be paid for in seven years through reduced health care expenses, reduced expenditures on insecticide spraying, and other control methods, and reclaimed wages.

Racks of eggs of mosquitoes and a tray with chilled mosquitoes.

A tray of mosquitoes and mosquito eggs at the World Mosquito Program laboratory.

Does it work everywhere? It's not certain. Dr. O'Neill said that they do not know why the World Mosquito Program mosquitoes did not establish themselves in certain areas where they were released in Vietnam. In some parts of Medellin, the establishment process has taken longer than in other areas. The Wolbachia strain used in Malaysia appears to be more resistant to higher temperatures, and may therefore be better suited to some countries.

Laura Harrington is a professor at Cornell University and an expert in mosquito mating. (What makes a good mosquito match? In her research, she has found that in all climate zones, lab-reared insects do not compete with wild mosquitoes for mates. She says, 'They are not as sexy'. She said that while the potential of Wolbachia for dengue control is exciting, it is too early to set a price or timeline for its use, as it's not clear how many mosquitoes would be needed to launch a city-wide program.

There is also the evolution battle that's going on inside each infected mosquito. Arboviruses must spread to survive so they are trying to find ways to defeat Wolbachia, which can disarm them. They will eventually, said Dr. O'Neill, but not soon.

He said that it could happen in an evolutionary timescale of a few decades or even 10,000 years. "But I would be satisfied with a few years, so that other technologies can develop.

Arboviruses can spread to other mosquito species. This is a different problem. Wolbachia can also spread to other mosquito species: the WolBloc team is already seeing some success.

preventing malaria transmission

Wolbachia-infected mosquitos. This is a huge opportunity for countries like West Africa, which has a high burden of arboviruses as well as malaria.

In Medellin mosquitoes are no longer a threat, but an irritation. 'You don’t hear much about dengue anymore,' said Mr. Victoria. If people could just forget about dengue, that would be an incredible thing.