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. the effect of wolbachia infection on virus replication in insect hosts is complex and depends on the wolbachia strain and virus species. while several studies have indicated consistent refractory phenotypes of wolbachia infection on positive-sense rna viruses in drosophila melanogaster, the yellow fever mosquito aedes aegypti and the asian tiger mosquito aedes albopictus. this effect is not seen in dna virus infection and in some cases wolbachia infection has been associated or shown to increase single stranded dna and double-stranded dna virus infection. there is also currently no evidence that wolbachia infection restricts any tested negative-sense rna viruses indicating wolbachia would be unsuitable for restriction of negative-sense rna arthropod borne viruses. 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. deployments 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. on 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. effect on the sex-differentiation enzyme aromatase the enzyme aromatase is found to mediate sex-change in many species of fish. wolbachia can affect the activity of aromatase in developing fish embryos.