Wolbachia bacteria can reduce Dengue viral infection spread
Promising results suggest that the use of Wolbachia bacterium are key to targeting endemic infections of Dengue virus. More than 100 countries have been reported to suffer from the burden of the disease and 70% of severe dengue is prevalent in Latin American and Asian countries (Cogan, 2021). A. aegypti act as vehicles for several mosquito-borne viral diseases as viruses are spread through mosquito bites, allowing infection through blood; therefore, intercepting this relationship is critical to prevent transmission of Dengue. As mentioned in a previous blog post, bacteria that reside within and on another organism can influence cellular processes within that host. It was suspected that Wolbachia (that are typically found on Drosophila melanogaster/Fruit flies) would possess beneficial effects; and so, A. aegypti cells were infected with the bacteria. Subsequently, scientists concluded that the presence of the bacterium alters the mosquitos’ immune system and makes the environment inhospitable for the virus to replicate. Henceforth, this prompted further investigation to understand how this relationship can affect epidemiology.
Studies demonstrated that the presence and density of Wolbachia strains affect the amount of virus detected within mosquitos, following exposure. Albert Joubert et al (2016) established this by superinfecting mosquitos with two different strains and measured how this altered the infectivity and transmissibility of Dengue. The lines that were superinfected showed significantly less viral matter in comparison to those infected with just one strain of Wolbachia.This is in line with the work of Ant et al (2018) who generated lines of infected mosquitos to compare how the strains (wMel, wAlbA, wAlbB and wAu) differed in its protective role against the standard mosquito. Not only does this show a causal effect but it was concluded that strain wAu was highly efficient at staggering the infectivity of Dengue, compared to those infected with wAlb and wMel. This information is imperative for future research to develop a strategy.
Since then, research has continued to test the possibility of deploying Wolbachia as a defence mechanism and controlling the arbovirus. Tantowijoyo et al (2020) and Gesto et al (2021) have contributed to this with their trials by releasing A. aegypti lines that were pre-infected with wMel into Yohyakarta (Indonesia) and Niteroi (greater Rio de Janerio, Brazil), correspondingly. Both studies were successful in sustaining the release of the mosquitos and ensured that Wolbachia established long-term infection in the native A. aegypti. These results were more hopeful compared to that of Garcia et al (2019). Traditionally, chemical insecticides are used in pest control and thus, naturally, A. aegypti develop resistance overtime. The insecticide resistance profile of the laboratory colonies was much lower than that of native A. aegypti, replicating this was key to allow the released mosquitos to spread amongst the population. By introducing resistant genes, the mosquito lines released by Tantowijoyo et al (2020) and Gesto et al (2021) permitted the stable invasion of Wolbachia. 14–16 months post-release, a sample of mosquito eggs were for analysis, and it was found that Wolbachia density was high, and this corresponded with the low viral titre of Dengue present.
More recent work that contributes to the field by Utarini et al (2021) reported that the integration of wMel-infected A. aegypti saw the significant reduction of Dengue-related hospitalisation. The researchers also highlighted that the positive aspect to this trial was that the successful invasion meant that it was not necessary to keep releasing wMel-infected A. aegypti, making it a cost and time effective solution.
Though this provides hope for relieving the burden of viral-borne diseases, it is plausible that Dengue can adapt to the Wolbachia-associated selective pressure. Therefore, this flaws the approach as we cannot completely rely on nature to not take its course. The next steps would be to monitor the mosquito population for any signs of resistance developing and further measure the long-term stability of this solution –in order to ensure that this success can be replicated in other regions.
References
Albert Joubert, D., Walker, T., Carrington, L., De Bruyne, J., Kien, D., Hoang, N., Chau, N., Iturbe-Ormaetxe, I., Simmons, C. and O’Neill, S., 2016. Establishment of a Wolbachia Superinfection in Aedes aegypti Mosquitoes as a Potential Approach for Future Resistance Management. PLOS Pathogens, 12(2), p.e1005434.
Ant, T., Herd, C., Geoghegan, V., Hoffmann, A. and Sinkins, S., 2018. The Wolbachia strain wAu provides highly efficient virus transmission blocking in Aedes aegypti. PLOS Pathogens, 14(1), p.e1006815.
Cogan, J.E. 2021. Dengue and severe dengue. [Online]. [Accessed on 27 December 2021]. Available from: https://www.who.int/news-room/fact-sheets/detail/dengue-and-severe-dengue
Garcia, G., Sylvestre, G., Aguiar, R., da Costa, G., Martins, A., Lima, J., Petersen, M., Lourenço-de-Oliveira, R., Shadbolt, M., Rašić, G., Hoffmann, A., Villela, D., Dias, F., Dong, Y., O’Neill, S., Moreira, L. and Maciel-de-Freitas, R., 2019. Matching the genetics of released and local Aedes aegypti populations is critical to assure Wolbachia invasion. PLOS Neglected Tropical Diseases, 13(1), p.e0007023.
Gesto, J., Ribeiro, G., Rocha, M., Dias, F., Peixoto, J., Carvalho, F., Pereira, T. and Moreira, L., 2021. Reduced competence to arboviruses following the sustainable invasion of Wolbachia into native Aedes aegypti from Southeastern Brazil. Scientific Reports, 11(1).
HealthWire | Wellness at a click. 2021. The mosquito that fight dengue | HealthWire. [online] Available at: <https://www.healthwire.co/the-mosquito-that-fight-dengue/> [Accessed 28 December 2021].
Tantowijoyo, W., Andari, B., Arguni, E., Budiwati, N., Nurhayati, I., Fitriana, I., Ernesia, I., Daniwijaya, E., Supriyati, E., Yusdiana, D., Victorius, M., Wardana, D., Ardiansyah, H., Ahmad, R., Ryan, P., Simmons, C., Hoffmann, A., Rancès, E., Turley, A., Johnson, P., Utarini, A. and O’Neill, S., 2020. Stable establishment of wMel Wolbachia in Aedes aegypti populations in Yogyakarta, Indonesia. PLOS Neglected Tropical Diseases, 14(4), p.e0008157.
Utarini, A., Indriani, C., Ahmad, R., Tantowijoyo, W., Arguni, E., Ansari, M., Supriyati, E., Wardana, D., Meitika, Y., Ernesia, I., Nurhayati, I., Prabowo, E., Andari, B., Green, B., Hodgson, L., Cutcher, Z., Rancès, E., Ryan, P., O’Neill, S., Dufault, S., Tanamas, S., Jewell, N., Anders, K. and Simmons, C., 2021. Efficacy of Wolbachia-Infected Mosquito Deployments for the Control of Dengue. New England Journal of Medicine, 384(23), pp.2177–2186.
