Brazil is fighting dengue with bacteria-infected mosquitos

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As dengue cases continue to rise in Brazil, the country is facing a massive public health crisis. The viral disease, spread by mosquitoes, has sickened more than a million Brazilians in 2024 alone, overwhelming hospitals.

The dengue crisis is the result of the collision of two key factors. This year has brought an abundance of wet, warm weather, boosting populations of Aedes aegypti, the mosquitoes that spread dengue. It also happens to be a year when all four types of dengue virus are circulating. Few people have built up immunity against them all.   

Brazil is busy fighting back.  One of the country’s anti-dengue strategies aims to hamper the mosquitoes’ ability to spread disease by infecting the insects with a common bacteria—Wolbachia. The bacteria seems to boost the mosquitoes’ immune response, making it more difficult for dengue and other viruses to grow inside the insects. It also directly competes with viruses for crucial molecules they need to replicate. 

The World Mosquito Program breeds mosquitoes infected with Wolbachia in insectaries and releases them into communities. There they breed with wild mosquitoes. Wild females that mate with Wolbachia-infected males produce eggs that don’t hatch. Wolbachia-infected females produce offspring that are also infected. Over time, the bacteria spread throughout the population. Last year I visited the program’s largest insectary—a building in Medellín, Colombia, buzzing with thousands of mosquitoes in netted enclosures— with a group of journalists. “We’re essentially vaccinating mosquitoes against giving humans disease,” said Bryan Callahan, who was director of public affairs at the time.

The World Mosquito Program first began releasing Wolbachia mosquitoes in Brazil in 2014. The insects now cover an area with a population of more than 3 million across five municipalities: Rio de Janeiro, Niterói, Belo Horizonte, Campo Grande, and Petrolina.

In Niterói, a community of about 500,000 that lies on the coast just across a large bay from Rio de Janeiro, the first small pilot releases began in 2015, and in 2017 the World Mosquito Program began larger deployments. By 2020, Wolbachia had infiltrated the population. Prevalence of the bacteria ranged from 80% in some parts of the city to 40% in others. Researchers compared the prevalence of viral illnesses in areas where mosquitoes had been released with a small control zone where they hadn’t released any mosquitoes. Dengue cases declined by 69%. Areas with Wolbachia mosquitoes also experienced a 56% drop in chikungunya and a 37% reduction in Zika.

How is Niterói faring during the current surge? It’s early days. But the data we have so far are encouraging. The incidence of dengue is one of the lowest in the state, with 69 confirmed cases per 100,000 people. Rio de Janeiro, a city of nearly 7 million, has had more than 42,000 cases, an incidence of 700 per 100,000.

“Niterói is the first Brazilian city we have fully protected with our Wolbachia method,” says Alex Jackson, global editorial and media relations manager for the World Mosquito Program. “The whole city is covered by Wolbachia mosquitoes, which is why the dengue cases are dropping significantly.”

The program hopes to release Wolbachia mosquitoes in six more cities this summer. But Brazil has more than 5,000 municipalities. To make a dent in the overall incidence in Brazil, the program will have to release millions more mosquitoes. And that’s the plan.

The World Mosquito Program is about to start construction on a mass rearing facility—the biggest in the world—in Curitiba. “And we believe that will allow us to essentially cover most of urban Brazil within the next 10 years,” Callahan says.

There are also other mosquito-based approaches in the works. The UK company Oxitec has been providing genetically modified “friendly” mosquito eggs to Indaiatuba, Brazil, since 2018. The insects that hatch—all males—don’t bite. And when they mate, their female offspring don’t survive, reducing populations. 

Another company, Forrest Brasil Tecnologia, has been releasing sterile male mosquitoes in parts of Ortigueira. When these males mate with wild females, they produce eggs that don’t hatch.  From November 2020 to July 2022, the company recorded a 98.7% decline in the Ades aegypti  population in Ortigueira. 

Brazil is also working on efforts to provide its citizens with greater immunity, vaccinating the most vulnerable with a new shot from Japan and working on its own home-grown dengue vaccine. 

None of these solutions are a quick fix. But they all provide some hope that the world can find ways to fight back even as climate change drives dengue and other infections to new peaks and into new territories. ““Cases of dengue fever are rising at an alarming rate,” Gabriela Paz-Bailey, who specializes in dengue at the US Centers for Disease Control and Prevention, told the Washington Post. “It’s becoming a public health crisis and coming to places that have never had it before.”

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We’ve written about the World Mosquito Program before. Here’s a 2016 story from Antonio Regalado that looked at early excitement and Bill Gates’ backing of the project. 

That same year we reported on Oxitec’s early work in Brazil using genetically modified mosquitoes. Flavio Devienne Ferreira has the story. 

And this story from Emily Mullin looks at Google’s sister company, Verily. It built a robot to create Wolbachia-infected mosquitoes and began releasing them in California in 2017. (The project is now called Debug). 

From around the web

The FDA-approved ALS drug Relyvrio has failed to benefit patients in a large clinical trial. It was approved early amidst questions about its efficacy, and now the medicine’s manufacturer has to decide whether to pull it off the  market. (NYT)

Wegovy: it’s not just for weight loss anymore. The FDA has approved a label expansion that will allow Novo Nordisk to market the drug for its heart benefits, which might prompt more insurers to cover it. (CNN)

Covid killed off one strain of the flu and experts suggest dropping it from the next flu vaccine. (Live Science) 

Scientists have published the first study linking microplastic pollution to human disease. The research shows that people with plastic in their artery tissues were twice as likely to have a heart attack, stroke, or die than people without plastic. (CNN)

The many uses of mini-organs

This article first appeared in The Checkup, MIT Technology Review’s weekly biotech newsletter. To receive it in your inbox every Thursday, and read articles like this first, sign up here.

This week I wrote about a team of researchers who managed to grow lung, kidney, and intestinal organoids from fetal cells floating around in the amniotic fluid. Because these tiny 3D cell clusters come from the fetus and mimic some of the features of a real, full-size organ, they can provide a sneak peek at how the fetus is developing. That’s something nearly impossible to do with existing tools.

An ultrasound, for example, might reveal that a fetus’s kidneys are smaller than they should be, but absent a glaring genetic defect, doctors can’t say why they’re small or figure out a fix. But if they can take a small sample of amniotic fluid and grow a kidney organoid, the problem might become evident, and so might a potential solution.  

Exciting, right? But organoids can do so much more!

Let’s do a roundup of some of the weird, wild, wonderful, and downright unsettling uses that researchers have come up with for organoids.

Organoids could help speed drug development. By some estimates, 90% of drug candidates fail during human trials. That’s because the preclinical testing happens largely in cells and rodents. Neither is a perfect model. Cells lack complexity. And mice, as we all know, are not humans.

Organoids aren’t humans either, but they come from humans. And they have the advantage of having more complexity than a layer of cells in a dish. That makes them a good model for screening drug candidates. When I wrote about organoids in 2015, one cancer researcher told me that studying cells to understand how an organ functions is like studying a pile of bricks to understand the function of a house. Why not just study the house?

Big Pharma appears to agree. In 2022, Roche hired organoid pioneer Hans Clevers to head its Pharma Research and Early Development division. “My belief is that human organoids will eventually complement everything we are currently doing. I’m convinced, now that I’ve seen how the whole drug development process runs, that one can implement human organoids at every step of the way,” Clevers told Nature.

Organoids are trickier to grow than cell lines, but some companies are working to make the process automated. The Philadelphia-based biotech Vivodyne has developed a robotic system that combines organoids with organ-on-a-chip technology. The system grows 20 kinds of human tissue, each containing 200,000 to 500,000 cells, and then doses them with drugs. These “lab-grown human test subjects” provide “huge amounts of complex human data—larger than you could get from any clinical trial,” said Andrei Georgescu, CEO and cofounder of Vivodyne, in a press release.

According to Viodyne’s website, the proprietary machines can test 10,000 independent human tissues at a time, “yielding vivarium-scale output.” Vivarium-scale output. I had to roll this phrase around my brain quite a few times before I understood what they meant: the robot provides the same amount of data as a building full of lab mice.

Organoids could help doctors make medical decisions for individual patients. These mini organs can be grown from stem cells, but they can also be grown from adult cells that have been nudged into a stem-like state. That makes it possible to grow organoids from anyone for any number of uses. In cancer patients, for instance, these patient-derived organoids could be used to help figure out the best therapy.

Cystic fibrosis is another example. Many cystic fibrosis therapies are approved to treat people with specific mutations. But for people who have rarer mutations, it’s not clear which therapies will work. Enter organoids.

Doctors take rectal biopsies from people with the disease, use the cells to create personalized intestinal organoids, and then apply different drugs. If a given treatment works, the ion channels open, water rushes in, and the organoids visibly swell. The results of this test have been used to guide the off-label use of these medications. In one recent case, the test allowed a woman with cystic fibrosis to access one of these drugs through a compassionate use program. 

Organoids are also poised to help researchers better understand how our bodies interact with the microbes that surround (and sometimes infect) us. During the Zika health emergency in 2015, researchers used brain organoids to figure out how the virus causes microcephaly and brain malformations. Researchers have also managed to use organoids to grow norovirus, the pathogen responsible for most stomach flus. Human norovirus doesn’t infect mice, and it has proved especially tricky to culture in cells. That’s probably part of the reason we have no therapies for the illness.  

I’ve saved the weirdest and arguably creepiest applications for last. Some researchers are working to leverage the brain’s unparalleled ability to learn by developing brain organoid biocomputers. The current iterations of these biocomputers aren’t doing any high-level thinking. One clump of brain cells in a dish learned to play the video game Pong. Another hybrid biocomputer maybe managed to decode some audio signals from people pronouncing Japanese vowels. The field is still in extremely early stages, and researchers are wary of overhyping the technology. But given where the field wants to go—full-fledged organoid intelligence—it’s not too early to talk about ethical concerns. Could a biocomputer become conscious? Organoids arise from cells taken from an individual. What rights would that person have? Would the biocomputer have rights of its own? And what about rodents that have had brain organoids implanted in them? (Yes, that’s happening too). 

Last year, researchers reported that human organoids implanted in rat brains expanded into millions of neurons and managed to wire themselves into the animal’s brain. When they blew a puff of air over the rat’s whiskers, they could record an electrical signal zipping through the human neurons.

In a 2017 Stat story on efforts to implant human brain organoids into rodents, the late Sharon Begley talked to legal scholar and bioethicist Hank Greely of Stanford University. During their conversation, he invoked the literary classic Frankenstein as a cautionary and relevant tale: “it could be that what you’ve built is entitled to some kind of respect,” he told her.

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In 2023, scientists reported that brain organoids  hitched to an electronic chip could perform  some very basic speech recognition tasks. Abdullahi Tsanni has the story.

Saima Sidik tells us how organoids created from the uterine lining might reveal the mysteries of menstruation. Here’s her report. 

When will we be able to transplant mini lungs, livers, or thyroids into people? Ten years …  maybe, said my colleague Jess Hamzelou in this past issue of The Checkup. 

From around the web

An Alabama bill passed on Wednesday creates a “legal moat” around embryos. Under the new law, providers and recipients of IVF could not be prosecuted or sued for damaging or destroying embryos. But the law doesn’t answer the central question raised by Alabama courts last week: Are embryos people? (NYT)

More legal news. The Senate homeland security committee passed a bill this week that would block certain Chinese biotechs from conducting business in the US. The aim is to keep them from accessing Americans personal health data and genetic information. But some critics have raised supply chain concerns. (Reuters)

Some scientists have expressed concern that too many covid shots could fatigue the immune system and make vaccination less effective. But a man who got a whopping 217 covid vaccines showed no signs of a flagging immune response. (Washington Post)

Buckle up. Norovirus is coming for you. (USA Today).Small studies showing that ibogaine, a psychedelic derived from tree bark, can treat opioid addiction have renewed interest in this illegal drug. But some researchers question whether it could ever be a feasible therapy (NYT)