Brazil taps biotech to counter dengue epidemic


Elementary school student looks at Wolbachia bacteria-infected mosquito larvae suspended in water. (Photo by courtesy of WMP Brazil.)

As they fight their country’s unprecedented epidemic of dengue fever, Brazilian health authorities are promoting nationwide use of biotech tools that go beyond the more conventional approaches of spraying insecticides, cleaning up mosquito breeding sites, and, more recently, administering vaccines.

Specifically, the government has partnered with a nonprofit on the deployment of mosquitos infected with a dengue-blocking bacteria, and has permitted a private company to release male mosquitos that it has genetically engineered to ensure their female offspring die shortly after hatching.

Brazil has the world’s greatest number of cases of dengue, an Aedes aegypti mosquito-borne disease whose symptoms can include incapacitating abdominal pain, vomiting, fatigue and muscle and joint aches so intense that the malady is sometimes called “breakbone fever.”

The Brazilian Health Ministry says that from Jan. 1 to April 28 of this year, the country registered 3.92 million probable cases of dengue, far surpassing the 1.65 million reported during all of 2023. Deaths from dengue totaled 1,888 from January to April 28, a number that might increase when authorities finish investigating the causes of 2,218 additional deaths.

By early April, high numbers of probable dengue cases had been recorded in nine of Brazil’s 26 states and in the federal district of Brasília, the country’s capital. Experts note that the bulk of the states with elevated numbers were in eastern, southeastern and southern Brazil, where most of the large population centers are located. But by the end of the month, high dengue counts were also being registered in a growing number of states elsewhere in the country as well.

Dengue also surged in neighboring Argentina, Uruguay, and Paraguay, and increased its presence in Peru and Colombia during the austral summer, which runs from December to April. Summer heat and rain in these and other countries spur breeding of the Aedes aegypti mosquito, which, aside from spreading dengue, is also a vector for a variety of other illnesses including zika and chikungunya.

Experts say dengue has broadened its reach worldwide and within Brazil because warming from climate change has created conditions for the mosquito to extend its range. Though they acknowledge the disease is not new to Brazil, they point out that it has spread into areas of the southern part of the country where they wouldn’t have imagined finding it 10 to 20 years ago.

That means dengue is reaching populations with no natural immunity to it, a problem compounded by the fact that none of the four strains of the disease leaves those who recover from it with natural immunity to the other strains.

Brazil is tackling prevention with traditional methods such as cleaning up construction sites, tire-disposal dumps and other areas where mosquitos breed in stagnant water; using fog machines to spray insecticides in low concentrations; and running public-information campaigns.

It is also conducting a nationwide rollout of a dengue vaccine, the first country in the world to do so. The two-dose vaccine, imported from Japan, has been shown to be 80% effective, but it is in short supply. Currently, it is only being used to vaccinate children aged 10 to 14 in cities that have at least 100,000 residents or are experiencing severe outbreaks of the disease.

Against that backdrop, Brazilian public health specialists are also pursuing biotech solutions—two in particular. One of these, called the Wolbachia method, is being implemented under a decade-long partnership of the World Mosquito Program (WMP)—an international nonprofit association formed to combat mosquito-borne diseases—and Fiocruz, a Brazilian government public-health research institute affiliated with the Health Ministry.

The Wolbachia method, pioneered by WMP in Australia in 2011, is named for a type of bacteria found in most insects but not naturally present in Aedes aegypti mosquitos. When Aedes aegypti mosquitos are infected with the bacteria, dengue and other arboviruses are blocked from propagating in their bodies.

In Brazil, the method is being carried out by preparing containers of water mixed with Wolbachia-mosquito eggs and hanging them on trees in Aedes aegypti-infested communities, or by releasing Wolbachia-infected adult mosquitos from vehicles moving through those communities.

As these Wolbachia mosquitos become a growing presence in the local Aedes aegypti population, that population’s overall ability to transmit dengue to humans declines. Female mosquitos carrying Wolbachia bacteria pass it on to their descendants, multiplying the method’s impact. Further, males with Wolbachia make their female mates infertile.

Brazil conducted its first releases of Wolbachia-infected mosquitos in 2014 in Rio de Janeiro, following controlled trials. Larger-scale deployments of the method began three years later. Since then, the Wolbachia method has been used in five cities in southeastern, northeastern and western Brazil in a bid to protect 3.2 million people.

Under a planned R$30 million (US$5.7 million) expansion of the program slated to begin in July, six other cities in southeastern, northeastern and southern Brazil will become part the program, covering a further 1.7 million people by the end of the year.

The WMP-Fiocruz partnership operates a plant in Rio de Janeiro to produce Wolbachia-infected mosquito eggs. Called the WMP/Fiocruz Egg Production Center, it is currently turning out 10 million eggs per week. The egg output is expected to expand significantly soon, as Fiocruz recently finished building a second plant in Belo Horizonte, Minas Gerais state, and has begun construction of a third in the southern city of Curitiba.

“Brazil needs more than the usual tools used to fight dengue because it has reached epidemic proportions,” says Diogo Chalegre, biologist and coordinator of governmental relations for the WMP in Brazil. “Wolbachia is safe for humans and the environment because it naturally exists in 50% to 60% of all insects without genetic modification, and when an infected mosquito dies, so does Wolbachia.”

Experts appear to agree that the approach does not pose ecological or human health concerns.

Julio Croda, an independent epidemiologist and infectious-disease specialist at western Brazil’s Federal University of Mato Grosso do Sul, points out that the Wolbachia method has undergone clinical tests. These tests, which were conducted in Yogyakarta, Indonesia, and whose results were published in the New England Journal of Medicine in June 2021, “show [the bacterium] to be safe and effective,” he says.

Notes Croda: “When Wolbachia-infected mosquitos were introduced into one part of the city from January 2017 to January 2020, it reduced dengue cases by 77% compared to another area of the city where Wolbachia was not introduced.”

Niterói, a city of 500,000 people that lies across Guanabara Bay from Rio de Janeiro, took part in a Wolbachia pilot project in 2015, in the process becoming the first city in Brazil with full Wolbachia coverage. From 2015 to 2021, dengue cases in the city declined by 70%; and during the latest surge, Niterói has not experienced a spike in dengue infections as Rio de Janeiro has, Niterói’s health secretariat told EcoAméricas.

From Jan. 1 to April 28 of this year, Niterói registered 1,311 cases of dengue. That compares with 94,262 cases in Rio de Janeiro, whose population is 13 times greater than Niterói’s and where the Wolbachia method has been attempted in areas that are home to less than one-sixth of the city’s population.

The other biotech solution Brazil is pursuing to combat dengue involves Oxitec, a private, U.S.-owned, U.K.-based company that has developed a genetically modified male mosquito whose female offspring die before they reach adulthood. Since it is female mosquitos that bite and transmit disease, the presence of the gene-altered male mosquitos helps suppress mosquito-borne illness by effectively reducing the number of vectors.

Called Aedes do Bem (which means “Good Aedes” in English) and sold abroad as Friendly Aedes, Oxitec’s gene-altered male mosquitos are released in regions of high dengue risk to mate with wild females. Their impact is enhanced by the fact that their surviving male offspring also transmit the bioengineered gene when they mate, thereby ensuring that in yet another generation, only males survive.

The Oxitec system involves the placement outdoors of containers holding gene-altered Aedes aegypti eggs, which are activated by adding water. In 2015, a four-year pilot of the technology was launched in partnership with municipal authorities in Piracicaba, a city in São Paulo state with a high incidence of dengue.

According to Oxitec, the Aedes aegypti population decreased by 98% in treated areas. In the first year, the area hardest hit by dengue—a neighborhood of 5,000 people—saw dengue cases decline by 91% compared to the previous 12-month period, the Piracicaba health secretariat has reported.

Oxitec says studies it has conducted have shown its genetically modified mosquitos are non-toxic and do no harm to animals that eat them. A company-sponsored pilot project in Panama showed that in suppressing Aedes aegypti mosquitos there, populations of other urban mosquito species did not increase to fill the void.

CTNBio, Brazil’s biosafety regulatory authority, gave Oxitec biosafety approval in 2020 to release the second generation of its transgenic mosquitos nationwide. The approval, a copy of which Oxitec sent to EcoAméricas, says the methodology “complies with CTNBio standards and relevant legislation that aim to guarantee the biosafety of the environment, agriculture, human and animal health.”

“We’re driven by the belief that the fight [against dengue] will be won not with more chemical pesticides, but by making a new generation of safe, environmentally friendly products accessible to everyone,” says Natalia Ferreira, managing director of Oxitec’s Brazil unit. “Results from our [mosquito] releases in Brazil validate our solution as an effective and—now, importantly—scalable mosquito control tool.”

Julio Croda of the Federal University of Mato Grosso do Sul says that Oxitec’s data indicate the technology “probably poses no risks to humans or the environment.”

But Croda adds that the company must conduct and publish clinical trials and long-term follow-up research to confirm this conclusion, something it has yet to do. He says a study of this type might determine, for instance, whether mutations in future generations of Oxitec mosquitos pose environmental or human-health risks.

Anthony Shelton, an emeritus professor of entomology at Cornell University, takes a somewhat different view. Shelton has studied efforts to develop moth-control technology that is similar to the dengue approach in that it involves bioengineering adult male moths to carry a gene that causes their female offspring to die shortly after they hatch.

“Several approaches to control the spread of dengue are needed,” Shelton says. “However, the most common approach, using insecticides, has been problematic because Aedes aegypti mosquitoes develop resistance to them and because of the negative environmental and human health impacts of these insecticides.”

Adds Shelton: “Oxitec’s GM [genetically modified] mosquito technology is safer for the environment and for human health than most insecticides because it only affects this species of mosquito and not organisms such as beneficial insects, fish or other organisms in the environment. Also, it would be extremely difficult for an Oxitec GM mosquito to change genetically and become a problem to human health or the environment because the offspring of the females die before they can reproduce.”

The CTNBio greenlight of Oxitec’s technology allowed the company to launch commercial sales of its boxed kits in November 2021. Oxitec has created a network of distributors throughout Brazil to serve individuals and small businesses. It has also signed contracts with municipal authorities and private companies in the federal district of Brasília and nearly all of the country’s 26 states.

How the Oxitec and Wolbachia approaches fare will no doubt be a focus of attention within Brazil as well as internationally given the increased prevalence of dengue worldwide.

At a Brazilian Health Ministry meeting in February, World Health Organization Director-General Tedros Adhanom said Brazil’s dengue outbreak is “part of a large global increase in dengue fevers.”

The outbreak, he said, featured “over 500 million cases and over 5,000 deaths reported last year from 80 countries in every region of the world except Europe.”

- Michael Kepp

In the index: Water is added to an "ovitrap" cup where female mosquitos lay eggs, which are then collected by Oxitec for monitoring purpose.

Diogo Chalegre
Governmental Relations
World Mosquito Program in Brazil
Rio de Janeiro, Brazil
Tel: +(55 21) 3865-9264
Julio Croda
Epidemiologist and infectious-disease specialist
Federal University of Campo Grande
Mato Grosso do Sul, Brazil
Tel: +(55 67) 3345-7223
Natalia Ferreira
Managing Director
Oxitec Brazil
Campinas, São Paulo state, Brazil
Anthony Shelton
International Professor of Entomology Emeritus
Cornell University
Ithaca, NY
Tel: (607) 255-3605 (Debra Warfield)
Fax: (607) 255-3760
Documents & Resources
  1. Health Ministry statistics on dengue in Brazil (in Portuguese): link