Science

Mosquitoes intentionally infected with bacteria reduced dengue fever cases by 77%

Dengue fever is rife in all provinces of Indonesia and is endemic in many cities. To try to eradicate this disease transmitted by mosquitoes Aedes aegypti, the World Mosquito Program and its partners conducted a randomized controlled trial in the city of Yogyakarta. This three-year trial consisted of releasing mosquitoes carrying the Wolbachia, a bacterium that prevents them from transmitting arboviruses such as the dengue or Zika virus. The results of these trials are particularly encouraging: the deployment of mosquitoes has reduced the incidence of dengue fever by 77%.

In 2019, the World Health Organization named dengue as one of the top 10 threats to global health. Each year, an upsurge in cases is observed during the rainy season in South Asia; nearly 8 million cases occur in Indonesia each year. But the disease tends to spread in more temperate countries: the WHO estimates that 40% of the world population is now exposed to the risk of dengue.

Certain measures – such as the chemical or biological targeting of mosquitoes and the elimination of their breeding sites – have been put in place to combat this disease, which can be fatal, but have proved in vain. However, it turns out that mosquitoes Aedes aegypti infected with the bacteria Wolbachia pipientis are less susceptible to infection with dengue virus (and other arboviruses). To limit the spread of dengue fever in Indonesia, researchers therefore set out to exploit this bacterium, which is not naturally present in the species A. aegypti.

Hospitalizations reduced by 86%

This approach requires the introduction of mosquitoes infected with Wolbachia into populations of wild mosquitoes, over a period of several months; mating between these two populations indeed generates offspring also infected by the bacteria. To test the effectiveness of this method, scientists from World Mosquito Program, in collaboration with the Tahija Foundation and Gadjah Mada University, carried out field tests in the city of Yogyakarta.

Twelve areas were randomly selected for the deployment of infected mosquitoes; twelve other sites, not affected by the release, served as control areas. Mosquitoes carrying Wolbachia were released in the form of eggs between March and December 2017. Natural boundaries (roads, rivers, non-residential areas) were used to define the boundaries of the different areas as much as possible, in order to limit the spread. of Wolbachia in untreated areas. Mosquito traps, disseminated in the homes, made it possible to monitor the evolution of individuals carrying the bacteria.

The city of Yogyakarta is particularly affected by dengue fever. As part of the trials, mosquitoes infected with Wolbachia were released in twelve areas of the city (here in dark blue). © World Mosquito Program

The results of this full-scale test have just been published in The New England Journal of Medicine. The release of infected mosquitoes led to a 77% reduction in the incidence of dengue fever, as well as an 86% reduction in hospitalizations due to the disease. More specifically, only 67 cases of dengue were detected in the treated areas, against 318 in the areas which did not benefit from the deployment of infected mosquitoes. At the same time, only 13 hospitalizations were recorded in the treated areas (against 102 for the other sites).

In total, four serotypes of the dengue virus were identified among the inhabitants who exhibited typical symptoms of the disease, but the effectiveness of the approach remained almost the same for all: the highest effectiveness was observed for serotype 2 (84%) and the lowest concerns serotype 1 (71%).

A promising approach to fight against all arboviruses

This technique induces a long-term reduction in the incidence of dengue fever. Today, more than three years after the mosquito releases, Wolbachia bacteria remain at a very high level in the local mosquito population. Since the trial, the method has been implemented in all districts of the city. ” It is a great success for the people of Yogyakarta.[…] We believe there is a possible future where people in Indonesian cities can live dengue free. », Enthuses Professor Adi Utarini of the University of Gadjah Mada, co-principal investigator of the trial.

mosquito populations evolution
Evolution of mosquito populations infected with Wolbachia bacteria, from January 2017 to January 2020, in the areas where they were introduced (A) and in the control areas (B). © World Mosquito Program

The results obtained are also consistent with those of previous studies carried out in Indonesia, northern Australia and Brazil. For Professor Scott O’Neill, director of the World Mosquito program, they are proof that this approach based on mosquitoes infected with Wolbachia is not only safe and sustainable, but that it can be replicated in different epidemiological settings. A similar experiment was carried out in New Caledonia, in Nouméa, from July 2019 to December 2020; here again, tests made it possible to ensure the fertility, fertility and longevity of the mosquitoes to guarantee its lasting establishment in the city.

According to scientists, only differences in climate, altitude and complexity of the urban environment are likely to affect the settlement dynamics of Wolbachia and therefore the timing of its impact on the spread of dengue. But this approach remains in any case the most effective to date to contain the disease; and it could be just as effective for other arboviruses such as Zika, chikungunya or yellow fever virus.

Sources: The New England Journal of Medicine, AWED Study Group

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