Moving in for the kill

An estimated 390 million dengue infections occurring each year across 150-odd countries is proof that the current mosquito control measures are grossly inadequate to keep the Aedes species, the vector that transmits dengue, chikungunya and Zika, under check. In Brazil, more than 1.5 million people were affected by Zika last year. That the virus has now spread to more than 20 countries in Latin America and the Caribbean only serves to augment the failure on the Aedes front.

In spite of several challenges, insecticide-treated bed nets have helped in cutting down the number of malaria cases in Africa. But they are of little use in keeping the Aedes mosquito species, which are aggressive daytime biters, at bay. Urbanisation has allowed the Aedes aegypti mosquitoes, found in tropical and sub-tropical countries, to breed in diverse waterbodies and even indoors in nearly any sort of water-filled container.

A major constraint in the fight against Aedes aegypti has been the vector’s resistance to widely used insecticides such as organophosphates and pyrethroids. Developing an effective vaccine against Zika may take years but there’s hope in the case of dengue: Sanofi has recently launched the first-ever vaccine against it. It, however, has several limitations as of now, including lower efficacy against the DENV-2 serotype (dengue has four serotypes in all) that is prevalent in India and vaccine-generated antibodies that facilitate the entry of the dengue virus into human cells. Even when a cheap, safe and effective vaccine against dengue becomes available, the compulsion to reduce the mosquito population will remain a top priority as A. aegypti transmits Zika and chikungunya as well.

Novel strategies
Two novel strategies have shown promise in recent years. One involves the use of genetically modified male Aedes aegypti mosquitoes that carry a dominant lethal gene. The gene is passed down to offspring when they mate with wild female mosquitoes that are not genetically altered. The lethal gene in the offspring produces a protein that stops their cells from functioning normally by producing more of itself and prevents other genes essential for survival from turning on. This prevents the mosquito larvae from growing properly and causes them to die before adulthood, essentially breaking the insect’s life cycle. The dominant lethal gene is kept under check while breeding in labs by using tetracycline drug. But due to the absence of tetracycline in sufficient quantities in nature, the larvae end up dying due to overproduction of the protein. As male mosquitoes do not bite humans, the release of genetically modified males will not increase the risk of dengue.

The biggest advantage of using this technique is its species-specificity; mutant Aedes aegypti released into the wild will not breed with another species of Aedes. Also, field studies carried out in West Panama have shown that short-term suppression of Aedes aegypti population did not lead to abundance of Aedes albopictus (Asian tiger mosquito), notes a paper published in September 2015 in the journal Pest Management Science. But more data may be needed to confirm this.

Since the modified insects disperse and actively seek wild female unaltered mosquitoes for mating, targeting the difficult-to-reach pest populations like Aedes aegypti becomes easier and more efficient than conventional control measures.

To be effective, genetically altered male mosquitoes need to be released in large quantities at regular intervals so they compete with the wild normal male insects for mating. Since the offspring do not live long enough to reproduce and the release can be stopped at any time, the Release of Insects carrying Dominant Lethal genes (RIDL) is a “self-limiting approach (the genetic modifications are not perpetuated in wild populations)”, notes a piece in The Lancet (February 1, 2016).

The first open field trial carried out in 2010 in the Caribbean island of Grand Cayman without much publicity by Oxitec, a British company founded and part-owned by the University of Oxford, was reported to be a success. An 80 per cent reduction in adult dengue-causing mosquitoes was registered in a 16-hectare plot.

The key performance parameters for genetically modified male mosquitoes released into the wild are longevity, dispersal capacity and mating competitiveness. According to an August 2012 paper in PLOS ONE, a field study done between 2010 and 2011 in an uninhabited forested area of Pahang, Malaysia showed that longevity of released males was similar to the wild ones but the mean distance travelled by the genetically sterile males was lower (52 m against 100 m for wild mosquitoes).

Similar trials have been carried out in several countries including Brazil (Itaberaba suburb of the city of Juazeiro, Bahia) with great success. The release of sterile male mosquitoes led to 80-95 per cent suppression of the target wild population in Brazil (PLOS Neglected Tropical Diseases, July 2015).

Radiation too can produce sterile males and has been successfully used for controlling certain agricultural pests. But in the case of mosquitoes, several field trials carried out using radiation- or chemically-sterilised mosquitoes have been hit by “poor performance of irradiated mosquitoes”.

Blocking dengue transmission
Another novel approach successfully tested in the northern Australian city of Cairns is to block dengue transmission to humans by greatly reducing the replication of the dengue virus and its spread inside the body of the mosquito. This is achieved by introducing a life-shortening Wolbachia (a diverse group of intracellular bacteria) bacteria strain into male and female Aedes aegypti mosquitoes. While embryos from uninfected wild females fertilised by sperm from Wolbachia-infected males fail to develop, embryos from infected females fertilised by infected or uninfected wild males survive. Since Wolbachia is maternally inherited, infected females pass on the bacteria to offspring immaterial of which male mosquito it mated with. As a result, when male and female mosquitoes carrying Wolbachia are released spatially apart to breed with wild mosquitoes in an area, the bacteria spreads rapidly in the mosquito population there.

Unlike in the case of mosquitoes carrying the dominant lethal gene, the release of even a single female mosquito infected with Wolbachia bacteria could “potentially lead to the alien Wolbachia spreading in the target population”, warns a paper published in June 2013 in the journal Pathogens and Global Health. “This is likely to be seen as an undesirable outcome and therefore a significant risk, unless species-wide invasion is the intent of the release.”

The release of Wolbachia-infected Aedes aegypti mosquitoes is “ongoing in dengue-endemic countries such as Indonesia, Vietnam and Brazil”, The Lancet paper notes.

As the field trials showed, the ability of wild Aedes aegypti’s ability to spread dengue virus can be greatly reduced, if not eliminated, as it tends to be a population-replacement approach. Though Wolbachia’s ability to cut Zika transmission is not known, studies have indicated that it can be effective against chikungunya, yellow fever and West Nile disease transmitted by the Aedes aegypti mosquito.

None of these novel approaches should be looked upon as silver bullets. Only an integrated pest management programme can help reduce the mosquito population and sustain the gains. Even a less effective vaccine can then become a great complementary tool.