Wolbachia infection program shows early results in dengue fight
Field trials of a biological control program to subdue dengue have shown some promise in reducing the spread of the disease.
Presenting the initial results at the National Dengue and Arboviruses Conference 2017 held in Kuala Lumpur recently, Dr. Nazni binti Wasi Ahmad, medical entomologist from the Institute for Medical Research (IMR), Kuala Lumpur, said that the efforts to disseminate large numbers of Aedes aegypti mosquito adults—infected with Wolbachia bacteria—had led to a noticeable reduction in weekly dengue cases in one of two suburban areas in Selangor.
Nazni, who is also a member of Wolbachia Malaysia, the project team responsible for the field trials, cautiously noted that while it remained too early to definitively confirm the effectiveness of the program—due to known fluctuations in dengue infection rates—the reduction in cases recorded to date could point to the Wolbachia proliferation method as a self-sustaining and cost-effective method for dengue control.
According to Wolbachia Malaysia, a minimum of two to three female mosquitoes in a population of 100 people are needed to spread dengue. Conventional integrated mosquito control strategies have been unsuccessful at sustainably suppressing mosquito populations below this threshold, due to a mostly cryptic “last 10 percent” of breeding sites—e.g. discarded receptacles, roof gutters, flower pots—that evade destruction efforts.
Before the field trials commenced, public engagement efforts (i.e. local seminars, public tours of the Wolbachia Malaysia facility, media releases) were conducted by the Ministry of Health (MOH)’s Institute of Health Behaviour Research (IPTK), with up to 98.7% of residents in one area agreeing to the release. Approximately 50 adults were released per house; over 1,062 houses and 52 apartment blocks were involved in the trials. Effectiveness was measured using ovitraps to determine the spread of Wolbachia through the mosquito population, as well as dengue cases reported per week pre- and post-release.
The research team found an 80 to 100% spread of Wolbachia in the wild Aedes aegypti population in several sections of the trial zones; however, population numbers fluctuated over time, possibly due to small collection sample size, or influxes of Wolbachia-uninfected mosquitoes from hatched eggs and from outside the release sites.
Turning mosquito against mosquito
Wolbachia species have been a recognized natural pathogen of insects for over 80 years, but recent research has found direct evidence that various strains act as effective inhibitors of viral replication in A. aegypti—a species which is not naturally infected by the bacteria, but can be artificially infected via microinjection of eggs. As Wolbachia are unable to survive outside a cellular environment, they cannot be naturally transmitted between insect species, but only vertically from infected parent to offspring. [Nature 2011;476:450–453]
Two strategies for Wolbachia use in vector control are population suppression (in which the wild-type population is gradually eliminated) and population replacement (in which wild-type population is gradually substituted with the infected.) Suppression—currently used in Wolbachia initiatives in Singapore and China—relies on the fact that infected males do not produce viable offspring after mating with uninfected females, while replacement relies on the production of viable but infected offspring when infected females mate with infected or uninfected males.
According to Nazni, suppression strategies require releasing large numbers of Wolbachia-infected male mosquitoes over a sustained period of time, reducing viable egg production and therefore mosquito population size. In comparison, replacement strategies require the release of smaller numbers of both male and female infected mosquitoes, which gradually spread Wolbachia into the population, but do not reduce it. However, as Wolbachia-infected females cannot support replication of the dengue virus, viral transmission between generations of mosquitoes is interrupted as a result.
Wolbachia Malaysia is a replacement-strategy Wolbachia initiative under the advisement of Dato’ Dr. Fadzilah Kamaludin, director of IMR, and works in collaboration with the MOH, the University of Glasgow, Scotland, the University of Melbourne, Australia, with funding from the Wellcome Trust UK. Under the recommendations of Professors Steven Sinkins of the University of Glasgow and Ary Hoffman of the University of Melbourne, the wAlbB strain was employed by Wolbachia Malaysia due to the strain’s heat tolerance ability and suitability to the local climate, rather than the wMel strain used in similar initiatives elsewhere.
More information about the initiative can be found at www.imr.gov.my/wolbachia.