One Health

The Centre for Virus Research's (CVR) work to control the spread of dengue fever takes a ‘molecules to populations’ approach. The goal is to save lives by blocking transmission of the virus.

Our researchers discovered that transmission of dengue fever can be blocked when mosquitoes carry Wolbachia, a common bacteria found in many insect species.

Molecular

CVR researchers identified the molecular changes caused by Wolbachia bacteria that inhibit dengue virus replication.

Wolbachia infection dysregulates many mosquito proteins, including those that control lipid metabolism and storage. These changes reduce the replication of dengue virus.

A risk of bacterial control is that the virus may mutate and circumvent Wolbachia’s inhibiting effect. Understanding the molecular basis of the interaction enables the design of strategies which counteract these mutational risks.

Cell

Our researchers explored which strains of Wolbachia inhibit dengue virus replication.

They transferred a range of Wolbachia strains into Aedes aegypti mosquito cell lines. This revealed wide variation in the efficiency with which different strains inhibit dengue. Different Wolbachia strains also affect the mosquito cells in different ways.

This combination of variation in the effectiveness and method of disruption of dengue replication points to the possibility of enhancing the bacterial control of dengue. Effectiveness could be maximised via strain switching strategies.

Host

In the lab, researchers identified which strains of Wolbachia perform best in vivo, under realistic conditions.

Tests revealed variation in the ability of different strains to spread, in their dengue transmission-blocking efficiency and in the effects of different environmental conditions, particularly temperature.

Researchers identified Wolbachia wAlbB as the optimal strain for use in the hot tropical climates where dengue is most prevalent. This knowledge increased the chances of successful field-based trials of the control strategy.

Population

CVR researchers tested the effectiveness of Wolbachia-based dengue control in high-transmission urban areas.

They collaborated with partner institutes in Malaysia and Australia to pilot the approach. Wolbachia-infected mosquitoes were released at nine residential sites in Greater Kuala Lumpur. Dengue incidence reduced at all release sites vs. control sites. A 40-80% reductions in cases was observed.

At some sites, around 95% of wild mosquitoes carry Wolbachia more than three years later.

The field tests showed Wolbachia to be an effective, safe, sustainable, cost-effective and eco-friendly approach to dengue control. The Malaysian Government has stopped using insecticides at the trial sites and is rolling out releases at many further sites. Plans for Wolbachia interventions are underway in other countries.