Effort to eliminate dengue faces biggest test

A new study in the journal Nature Microbiology has found that, thanks to climate change, nearly half the world’s population could be at risk of catching mosquito-borne diseases like zika, dengue, chikungunya, and yellow fever by 2050.

But thankfully, scientists led by entomologist Scott O’Neill from Australia’s Monash University, backed by the Bill and Melinda Gates Foundation, have been working for years on a novel concept to eliminate such diseases with a counter-intuitive notion: instead of trying to kill mosquitoes, they are instead breeding and releasing thousands of them. 

The latest battleground is the city of Medellin in Colombia.

The Aedes aegypti mosquito is a carrier of dengue – which infects 390 million people annually and kills tens of thousands. The insect also carries chikungunya, yellow fever and the zika virus, which has been linked to birth defects across the world.

Originally from Africa but now found in other tropical and subtropical zones around the world, A. aegypti was for years controlled with spray pesticides or by limiting its breeding grounds – both strategies devastating to the environment and people. The effects of global climate change have also ramped up the threat. 

But O’Neill, head of the World Mosquito Program (WMP), dusted off an old concept and turned it into a viable way to fight disease.

Karen Robles, an entomologist at the WMP’s base in Medellin, showed Cosmos around the hot, humid labs where mosquitoes are continuously bred. 

She explained that O’Neill’s research focused on Wolbachia, a species of bacteria naturally present in up to 60% of insect species, including some mosquitoes. They aren’t usually found in A. aegypti, but when they are, they suppresses viruses by boosting the insects’ immune system and competing for key molecules such as cholesterol. These two factors drastically lower the probability of viruses growing successfully and being transmitted to humans.

The other useful quality of Wolbachia is that it spreads through the mosquito population in a self-sustaining way. If a male with Wolbachia mates with a female without it, her eggs won’t hatch, but if a female with Wolbachia mates with a male without it, she will still pass on the bacteria.

Combined, these quirks of biology mean that over time the overall number of mosquitoes and the rates of virus transmission of these viruses will both decrease.

Unlike a chemical or genetic intervention, research shows that it is difficult for viruses such as dengue to quickly develop resistance to the Wolbachia intervention.

O’Neill is these days based in Vietnam, but he sat down with Cosmos in Medellin while on one of his periodic visits to the operations there and explained the long road from a university project to a global public health NGO operating in a dozen countries.  

He says he started working with Wolbachia during a PhD project at a time when the bacteria were looked at more as a way to shorten mosquito lifespan. It was only later that it was shown to stop virus transmissions.

“As a scientist, most things fail, so we were very fortunate to have this drop into our lap,” he explains, “but we still talked to communities for two years before the first release.”

After trial releases in Cairns, in the Australian state of Queensland, in 2011, the first project to cover an entire human settlement was in the nearby city Townsville in 2014.

There were six outbreaks of dengue in northern Queensland between 2003 and 2004, with a combined total of nearly 900 cases reported, resulting in two deaths – the first recorded in Australia in many decades.

According to a 2018 paper authored by O’Neill and colleagues, Wolbachia populations have remained stable since deployment and in the past five years, no local dengue transmission has been confirmed in any area of Townsville where Wolbachia had been established. This is impressive because there had been annual local dengue transmission for every one of the previous 13 years, and an increasing number of cases being imported into the zone from other regions.

“We’ve now expanded to 12 different locations around the world, and in each one of them we are seeing how the technology adapts in each,” O’Neill says. 

But Townville is a city of only about 187,000 people. To really prove how well the Wolbachia method works, the WMP has expanded its work to Medellin, a municipality containing nearly two and a half million people in the country’s mountainous Andean region.

Iván Darío Vélez, Colombia’s WMP director, says researchers at the University of Antioquia, a large public institution in the city, already had their own tropical disease projects, but saw great value in becoming a local program partner – especially because the technology had already been tested in Australia.

Now, after successful small-scale trials, the infected mosquitoes are being produced on an industrial scale: thousands are bred in the lab, then teams spread them throughout the city by driving, riding motorbikes or simply walking around.

One of the reasons why Medellin is a key experiment is because it is a tropical city, about 1.5 kilometres above sea level – home to a wet, dense and urban environment.

Epidemiologist Moritz Kraemer from the UK’s University of Oxford was lead author of the Nature Microbiology study that mapped where mosquitoes are expected to spread in the next 30 years

He says currently the majority of A. aegypti live below 1600 metres, but in the next three decades they are expected to be found in places previously thought too high or cold.

“We expect that there will be changes, especially in areas of Colombia and Mexico where established populations are close by,” Kraemer says.

The success of the Medellin Wolbachia deployment, of course, remains to be seen, but based on results in other WMP outposts, Vélez is feeling confident.

He is glowing in his praise for O’Neill. “If things go the way we hope, he deserves a Nobel Prize,” he says.