How to fight the deadly Dengue virus? Make your own mosquito

Freeing mosquitoes into the corridors of apartments may seem like an unusual strategy for cities where mosquitoes fight the worst outbreak of dengue, a painful disease that spreads among humans. But the thousands of small insects released last week were not the average mosquito.

They were bred in the laboratory to carry a bacterium called Wolbachia, a substance not commonly found in this type of mosquito. When a male mosquito containing bacteria is released and mated with a naturally born female, the resulting egg will not hatch.

As a result, Singapore’s government has reduced the number of cases of dengue fever in areas where laboratory-raised insects have been released.

Scientists and governments are expanding these high-tech solutions as the threat of the Dengue virus increases. Some people use genetically modified mosquitoes. Others are zapping them with an x-ray beam to sterilize them.

The World Health Organization states that about half of the world’s population is at risk of dengue fever and viral infections that cause a potentially fatal, intense flu-like illness. Growing urbanization and raised cities give mosquitoes a huge human population. The number of reported cases of this disease increased from approximately 500,000 in 2000 to 4.2 million in 2019, particularly in tropical countries such as Brazil, Indonesia and the Philippines.

Both mosquitoes that carry dengue fever and the virus itself propagate in warm climates, and global warming can further spread the disease.

Dengue fever is transmitted by the Aedes aegypti mosquito, which, when infected in pregnant women, can cause severe birth defects and other diseases such as chikungunya that cause fever and joint pain. Public health campaigns have traditionally focused on simple solutions, such as encouraging people to empty stagnant water from household items such as vases, buckets, and watering cans where mosquitoes spawn. .. Pesticides are also used in areas where dengue fever is likely to occur.

However, mosquitoes have developed immunity to common pesticides and dengue cases are increasing worldwide. That is why scientists have modified or modified the mosquitoes themselves.

In Singapore, which has long suffered from dengue fever, professional mosquito breeding began with mosquito eggs shipped from Michigan. A team led by Zhiyong Xi, a professor of microbiology and molecular genetics at Michigan State University, used long thin glass needles to inject Wolbachia into mosquito eggs. When hatched, the larvae also contained bacteria.

Its first generation passed the Wolbachia bacterium to its offspring, producing a new strain of mosquito infused with the bacterium, whose eggs were shipped to Singapore to discover a city-state colony.

Females need to be separated from males before their offspring are released and they do not bite or transmit the Dengue virus. Gender selection is important because the Singapore program involves mating males with bacteria and females without them. If both sexes carry the bacteria, the mosquitoes will reproduce normally, hindering the program’s goal of reducing local mosquito populations.

A machine developed by Verily, a life sciences-focused company of Alphabet Inc., uses an automated mechanical sieve to separate female mosquito pupae (typically large) from male mosquitoes. .. According to the company, this step eliminates about 95% of women.

Use a computer vision system to identify women who the sieve may have missed. The system looks for female prominent prongs or mouths, antennas, and other anatomical cues and flags them for removal. Less than 1 in 1 million mosquitoes are released by women, preventing Wolbachia from passing on to wild mosquito populations.

Not all Wolbachia mosquitoes released in Singapore are screened by Alphabet machines. Others receive low-dose x-rays using a specific methodology developed by Singapore in collaboration with the International Atomic Energy Agency. Irradiation renders female mosquitoes infertile, so inadvertently released mosquitoes cannot reproduce and prevent the spread of Wolbachia to future generations.

The Singapore government says that in some of the cities where men were released, there were 65% to 80% fewer cases of dengue compared to areas where mosquitoes were not released. Currently, 5% of public housing blocks in the city emit mosquitoes. Releases will be expanded to 15% by 2022.

Other programs hope Wolbachia will be widely inherited in wild populations. That’s because these programs have discovered another characteristic of bacteria: it strongly reduces the ability of Aedes aegypti mosquitoes to transmit dengue to humans.

The Global Mosquito Program is a non-profit organization operating in dozens of countries in Asia, the Pacific, and Latin America in the city of Yogyakarta, Indonesia, which contains laboratory-bred mosquitoes (male and female). Both) have been released. It relied on the fact that female mosquitoes give rise to offspring that also carry bacteria, ie the dengue blocking function is inherited.

According to an August non-profit organization, the study found a 77% reduction in dengue cases in areas where mosquitoes were released compared to areas where it was not.

This method is much easier than the Singapore method, which involves complex gender classification. However, some scientists say that liberating women in Wolbachia is potentially irreversible. If Wolbachia turns out to have unintended consequences, they say it’s very difficult to extract bacteria from a population of mosquitoes.

A laboratory study found that carrying Wolbachia increased the transmission of West Nile virus in the Culex pipiens mosquito species endemic to North America. “It’s a large black box,” said Jason Rasgon, a professor of disease epidemiology at the State University of Pennsylvania, who needs to do more research on the impact of Wolbachia on the transmission of other diseases before it can make larger releases. Insisted that there was.

Cameron Simmons, director of the World Mosquito Program, said many governments are conducting risk assessments of that approach. “Overall, Wolbachia was a negligible risk compared to doing nothing,” he said.

A company is going in a completely different direction. Genetic engineering. Oxitec, a US-owned biotechnology company with research bases in the United Kingdom and Brazil, inserts a new gene into the egg that causes female mosquitoes to die shortly after hatching, during larval development.

Last year, Oxitec tested the latest genetically modified version (OX5034) in Indaiatuba, Brazil near São Paulo. For the trial, the company produced OX5034 eggs in a Brazilian factory and distributed them at release points around the municipality. When the eggs hatched, the female died before becoming an adult who could fly and bite.

Oxitec said the grown-up man crossed with a local wild woman and passed down the gene that killed the woman, reducing the number of Aedes aegypti mosquitoes by about 95%.

The company received US federal approval for a pilot release in Florida in May. It is scheduled to start next year.

Oxitec says the genes they add are self-limiting. This means that after a few generations (about 3-4 months), the gene targeting women will be bred from the seed. Municipalities wishing to continue their approach say they will continue to release OX5034 eggs to control mosquito populations, and those that do not will not be off-ramp yet.

Jeffrey Powell, a biology professor at Yale University, sees the genetic modification approach as flawed. The need for regular re-emissions becomes expensive, and in the wild mosquitoes may adapt to avoid mating with Oxitec genetically destined males, he said. “There’s no evidence that it’s doing anything wrong,” he said about the gene Oxytech introduced into mosquitoes, “it’s completely unknown.” He found naturally in many mosquito species. He said he felt more comfortable with the use of Wolbachia.

Oxitec says it has released about 1 billion mosquitoes over the last decade and there is no evidence of female mosquitoes selectively mating with non-Oxitec males.

“There is no ecological footprint. There is no sustainability,” said Kevin Gorman, head of field operations at Oxitec. “It will never change the environment forever.”

Email Jon Emont at [email protected]