The end of dengue fever? Mosquito experiment in Indonesia sees huge reduction in cases (South China Morning Post)

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Recently concluded trial that involved mosquitoes with an inhibited ability to transmit viruses saw dengue cases drop 77 per cent after two years. World Mosquito Programme says the method has great potential for cities across Asia and Latin America and aims to reach 75 million people in five years

I published this article in the South China Morning Post

Mosquitoes injected with a natural bacterium called Wolbachia, which hinders the insect’s ability to transmit viruses including dengue, were released to breed and infect local populations in Yogyakarta, Indonesia, in a recently concluded trial. Photo: Getty Images/EyeEm

Dengue in Indonesia

Australian and Indonesian scientists have been conducting trials on a technique they believe has the potential to eradicate the deadly dengue virus in its strongholds in Southeast Asia and other parts of the world.

Cases of disease caused by the virus have been steadily on the rise in recent decades, according to the World Health Organisation (WHO), and 2019 recorded the highest number of cases to date.

The scientists have been injecting the Aedes aegypti mosquito – the main species responsible for transmitting dengue to humans – with a natural bacterium called Wolbachia, which hinders the insect’s ability to transmit viruses including dengue without suppressing mosquito populations and potentially affecting ecosystems.

Researchers from Australia’s Monash University involved in the World Mosquito Programme (WMP) and counterparts at their Indonesian partners, the Tahija Foundation and Gadjah Mada University, have been infecting mosquitoes with Wolbachia for the past three years, and in August released the results of a trial carried out in the Indonesian city of Yogyakarta.

Mosquito samples being tested for Wolbachia levels in a laboratory at Gadjah Mada University in Yogyakarta.

Mosquito samples being tested for Wolbachia levels in a laboratory at Gadjah Mada University in Yogyakarta.

The results showed a significant reduction in the number of confirmed dengue cases in areas of Yogyakarta where the trials were conducted compared to areas that are subject only to routine dengue control measures. Routine methods include monitoring by local government officials to remove waste water – reducing the number of places where mosquitoes can lay their eggs – and fogging and spraying to remove the insects.

To carry out the Wolbachia project, 12 areas of Yogyakarta were randomly selected. Wolbachia-carrying mosquitoes were released over a period of seven months with the help of the local community. These insects bred with the local populations, infecting large majorities of mosquitoes in each area with the bacterium.

The scientists then monitored the number of dengue cases throughout the city. Consenting patients who showed signs and symptoms of dengue provided details of where they lived and where they had travelled, and were tested to determine whether they had contracted the disease.

Two years later, the scientists found a 77 per cent reduction in the incidence of dengue in areas where the Wolbachia-infected mosquitoes had been released. Detailed results of the trial will be presented at an international scientific conference in November and published in a peer-reviewed journal.

The WMP says Wolbachia is naturally found within the cells of 60 per cent of the planet’s insect species, including moths, butterflies and some species of mosquitoes. However, this bacterium is not usually found in the Aedes aegypti mosquito.

Dr Adi Utarini from Gadjah Mada University at a mosquito release point in the community.

Dr Adi Utarini from Gadjah Mada University at a mosquito release point in the community.

The worldwide incidence of dengue fever has increased dramatically over the last decade, from 2.4 million cases in 2010 to 4.2 million in 2019, according to the WHO. Around half of the world’s population is at risk of contracting the disease in the future, the organisation says.

There are two main reasons for this, the WMP says. First, the Aedes aegypti mosquito tends to live close to urban areas, and as city populations have grown, so have opportunities for the mosquito to feed and reproduce. Second, climate change is expanding the mosquito’s range further north, which means there are now cases of dengue in regions that had until quite recently been free of the disease.

Other factors, including poor urban planning; inadequate public services and infrastructure, such as lack of access to tap water; and growing travel and trade, are increasingly creating environmental conditions for mosquitoes to breed in areas that were previously unaffected. That’s according to Rachel Lowe, an associate professor and the Royal Society Dorothy Hodgkin Fellow based at the London School of Hygiene and Tropical Medicine.

“The global increase in greenhouse gas concentrations is raising surface temperatures,” Lowe says. “Increased temperatures increase the replication speed of the virus, vector survival, reproduction and biting rates, which could lead to longer transmission seasons, allowing spread to higher altitudes and latitudes.”

A programme member gathers mosquito samples from the community to test for Wolbachia levels.

A programme member gathers mosquito samples from the community to test for Wolbachia levels.

Climate change is also driving changes in average rainfall, and in the frequency and magnitude of extreme climate-related events, including floods and droughts, which can alter the timing of disease outbreaks, Lowe adds.

It is difficult to produce a definitive figure for total annual dengue infections globally, since the vast majority of cases are asymptomatic and therefore go unreported or misclassified, according to the WHO. A recent estimate by the organisation points to 390 million dengue infections a year, of which 96 million are symptomatic cases.

Symptoms of dengue range from nausea and vomiting to rashes, aches and pains. Although less common, some victims develop severe dengue, which can result in complications such as severe bleeding, organ impairment or even death when not managed appropriately.

Severe dengue was first recognised in the 1950s during epidemics in the Philippines and Thailand, and today is present in most Asian and Latin American countries. It has become a leading cause of hospitalisation and death among children and adults in these regions.

In Indonesia, dengue is an endemic and highly problematic disease. From January to June this year, the country registered at least 68,000 dengue cases and 349 deaths, according to Siti Nadia Tarmizi, director of prevention and control for zoonotic diseases and vector transmission at the country’s Ministry of Health.

The trial carried out by the WMP is the largest of its kind targeting the Aedes aegypti mosquito and the team is proud of its result, saying the 77 per cent reduction in cases is “significant and important”.

A programme member trains local community members to use mosquito release containers.

A programme member trains local community members to use mosquito release containers.

Releasing mosquitoes in communities requires a great deal of trust on the part of residents, especially after many years of campaigning to raise awareness that it is precisely the mosquito that is responsible for spreading dengue. The WMP only releases Wolbachia-infected mosquitoes with locals’ support and collaboration, so building trust is a fundamental part of their work, says Professor Cameron Simmons, director of WMP in Oceania and lead investigator for the trial.

“The communities where we work are used to living with dengue. Many of our community group members and volunteers have either themselves or had family members contract dengue. The traditional dengue control measures have been performed every year for years, and dengue cases keep rising,” he says.

“We find that once they understand our Wolbachia method and what we’re trying to achieve, community members are our most passionate and powerful advocates.”

Ayu Rahayu from WMP’s Yogyakarta diagnostic laboratory team prepares a tray of mosquitoes for DNA extraction.

Ayu Rahayu from WMP’s Yogyakarta diagnostic laboratory team prepares a tray of mosquitoes for DNA extraction.

The goal is to reach 75 million people worldwide over the next five years, says Janina Khayali, director of WMP for the Americas.

Now that the researchers have shown that their Wolbachia method can be deployed across a city, they think “it has great potential for cities across Latin America and Asia”. The WMP is currently working on projects in cities in three countries in Latin America: Mexico, Colombia and Brazil.

The scientists released the first batch of mosquitoes in the northern Australian state of Queensland 10 years ago, and last year the region was declared “essentially dengue free” by local health authorities.

Other methods are being deployed elsewhere in the world in an attempt to eradicate the scourge of dengue. In June, an experimental project by UK-based biotechnology company Oxitec to release more than 750 million genetically modified mosquitoes between 2021 and 2022 was approved in the Florida Keys, in the United States. The pilot project is designed to test whether a genetically modified mosquito can be a viable alternative to insecticide application to control the spread of Aedes aegypti.

The modified insect produces female offspring that die in the larval stage, long before they can bite and spread disease. Only the female mosquito bites for blood, using the protein to produce eggs, while the males feed on nectar and are therefore not dengue carriers.

The Oxitec proposal has received complaints from environmental advocacy groups that have warned of unexpected consequences, such as damage to the ecosystem and the potential creation of hybrid and insecticide-resistant mosquitoes – something the company insists will not be a problem.