Outside of insects, Wolbachia infects a variety of isopod species, spiders, mites, and many species of filarial nematodes (a type of parasitic worm), including those causing onchocerciasis (river blindness) and elephantiasis in humans, as well as heartworms in dogs. Not only are these disease-causing filarial worms infected with Wolbachia, but Wolbachia also seems to play an inordinate role in these diseases.
A large part of the pathogenicity of filarial nematodes is due to host immune response toward their Wolbachia. Elimination of Wolbachia from filarial nematodes generally results in either death or sterility of the nematode. Consequently, current strategies for control of filarial nematode diseases include elimination of their symbiotic Wolbachia via the simple doxycycline antibiotic, rather than directly killing the nematode with far more toxic antinematode medications.
Indonesian research minister Mohamad Nasir during a visit to a Wolbachia mosquito lab of the Eliminate Dengue Project.
Further information: Biological pest control
Naturally existing strains of Wolbachia have been shown to be a route for vector control strategies because of their presence in arthropod populations, such as mosquitoes. Due to the unique traits of Wolbachia that cause cytoplasmic incompatibility, some strains are useful to humans as a promoter of genetic drive within an insect population. Wolbachia-infected females are able to produce offspring with uninfected and infected males; however, uninfected females are only able to produce viable offspring with uninfected males. This gives infected females a reproductive advantage that is greater the higher the frequency of Wolbachia in the population. Computational models predict that introducing Wolbachia strains into natural populations will reduce pathogen transmission and reduce overall disease burden. An example includes a life-shortening Wolbachia that can be used to control dengue virus and malaria by eliminating the older insects that contain more parasites. Promoting the survival and reproduction of younger insects lessens selection pressure for evolution of resistance.
Adi Utarini, research lead of the Wolbachia trial in Yogyakarta, Indonesia
In addition, some Wolbachia strains are able to directly reduce viral replication inside the insect. For dengue they include wAllbB and wMelPop with Aedes aegypti, wMel with Aedes albopictus. and Aedes aegypti. A trial in an Australian city with 187,000 inhabitants plagued by dengue had no cases in four years, following introduction of mosquitoes infected with Wolbachia. Earlier trials in much smaller areas had been carried out, but the effect in a larger area had not been tested. There did not appear to be any environmental ill-effects. The cost was A$15 per inhabitant, but it was hoped that it could be reduced to US$1 in poorer countries. The "strongest evidence yet" to support the Wolbachia technique was found in its first randomized controlled trial, conducted between 2016 and 2020 in Yogyakarta, an Indonesian city of about 400,000 inhabitants. In August 2020, the trial's Indonesian lead scientist Adi Utarini announced that the trial showed a 77% reduction in dengue cases compared to the control areas.
Wolbachia has also been identified to inhibit replication of chikungunya virus (CHIKV) in A. aegypti. The Wmel strain of Wolbachia pipientis significantly reduced infection and dissemination rates of CHIKV in mosquitoes, compared to Wolbachia uninfected controls and the same phenomenon was observed in yellow fever virus infection converting this bacterium in an excellent promise for YFV and CHIKV suppression.
Wolbachia also inhibits the secretion of West Nile virus (WNV) in cell line Aag2 derived from A. aegypti cells. The mechanism is somewhat novel, as the bacteria actually enhances the production of viral genomic RNA in the cell line Wolbachia. Also, the antiviral effect in intrathoracically infected mosquitoes depends on the strain of Wolbachia, and the replication of the virus in orally fed mosquitoes was completely inhibited in wMelPop strain of Wolbachia.
Wolbachia infection can also increase mosquito resistance to malaria, as shown in Anopheles stephensi where the wAlbB strain of Wolbachia hindered the lifecycle of Plasmodium falciparum.
However, Wolbachia infections can enhance pathogen transmission. Wolbachia has enhanced multiple arboviruses in Culex tarsalis mosquitoes. In another study, West Nile Virus (WNV) infection rate was significantly higher in Wolbachia-infected mosquitoes compared to controls.
Wolbachia may induce reactive oxygen species-dependent activation of the Toll (gene family) pathway, which is essential for activation of antimicrobial peptides, defensins, and cecropins that help to inhibit virus proliferation. Conversely, certain strains actually dampen the pathway, leading to higher replication of viruses. One example is with strain wAlbB in Culex tarsalis, where infected mosquitoes actually carried the west nile virus (WNV) more frequently. This is because wAlbB inhibits REL1, an activator of the antiviral Toll immune pathway. As a result, careful studies of the Wolbachia strain and ecological consequences must be done before releasing artificially-infected mosquitoes in the environment.
In 2016 it was proposed to combat the spread of the Zika virus by breeding and releasing mosquitoes that have intentionally been infected with an appropriate strain of Wolbachia. A contemporary study has shown that Wolbachia has the ability to block the spread of Zika virus in mosquitoes in Brazil.
In October 2016, it was announced that US$18 million in funding was being allocated for the use of Wolbachia-infected mosquitoes to fight Zika and dengue viruses. Deployment is slated for early 2017 in Colombia and Brazil.
In July 2017, Verily, the life sciences arm of Google's parent company Alphabet Inc., announced a plan to release about 20 million Wolbachia-infected Aedes aegypti mosquitoes in Fresno, California, in an attempt to combat the Zika virus. Singapore's National Environment Agency has teamed up with Verily to come up with an advanced, more efficient way to release male Wolbachia mosquitoes for Phase 2 of its study to suppress the urban Aedes aegypti mosquito population and fight dengue.
In November 3, 2017, the US Environmental Protection Agency (EPA) registered Mosquito Mate, Inc. to release Wolbachia-infected mosquitoes in 20 US states and the District of Columbia.