Tuesday, December 3, 2019

Fighting Diseases With… Bacteria?

Dengue Fever is a worldwide rising health problem that is especially exacerbated by global warming. Dengue fever is a viral disease that is spread via mosquitoes, specifically the species Aedes aegypti. It affects populations in over 100 countries and costs about USD 9Billion annually to treat all cases (Ranjit & Kissoon, 2011; Shepard et al., 2016). In 2013 alone, there were approximately 60 million symptomatic cases and 13,600 deaths due to Dengue infections (Shepard et al., 2016). In the past few years, scientists have come up with a clever way to combat the spread of disease by infecting Aedes aegypti with Wolbachia pipientis, a bacterial species which competes with the dengue virus and blocks its replication. W. pipientis is an intracellular symbiotic bacterium that is maternally inherited in insects (Moreira et al. 2009). It is present in over 60% of all insect species; Most notably, it is present in mosquito species that do not transmit human pathogens, and absent in those (specifically, A. aegypti) that are considered infection vectors (Moreira et al. 2009).


Mechanism of Infection
Dengue fever is transmitted via female mosquitos through their saliva when they bite a human. The virus binds to Langerhans cells (a type of dendritic cells in the skin that binds to pathogens and moves them to the lymph system) and enters into the cells via membrane proteins. Once in the cell, the virus’s RNA can be replicated in the cytoplasm and translated into proteins on the endoplasmic reticulum. It is then transported to the Golgi apparatus, where it receives the necessary glycoproteins to become a mature virus, and is released from the cell via exocytosis and can bind to other cells, such as macrophages. (Rodenhuis-Zybert et al. 2010).

The Efficacy of Infecting A. aegypti with W. pipientis
Researchers have been infecting mosquito populations worldwide with Wolbachia species since 2011, and some preliminary results regarding the effects on human disease transmission have been reported. A city in Australia reported only four locally acquired dengue cases in four years; previously, the same area had no less than 69 cases over a similar period since 2001 (O’Neil et al. 2019). The World Mosquito Program (WPM), reported that some studies had shown a 76% reduction in dengue infections in release areas used as study sites (Servick, 2019). This success is especially remarkable when compared to control sites, such as areas around Yogyakarta, Indonesia, which reported 76% fewer dengue cases in the 2.5 years since W. pipientis infected A. aegypti release than surrounding control areas (“Indonesia | World Mosquito Program,” 2019)


Results are still in the early stages and are mainly dependent on public health surveillance data, but these results are giving researchers confidence. This innovative prevention technique is more cost-effective than population-reducing approaches; and could be used in addition to traditional methods such as insecticides, which are often ineffective at controlling the spread of diseases. Researchers have faced some hurdles, such as the longevity of Wolbachia in A. aegypti and tolerance of the bacterium to different climates. Despite these difficulties, if incoming results support the preliminary evidence later this year, the World Health Organization could approve it for broader use. 

References

Indonesia | World Mosquito Program. (2019). Retrieved November 29, 2019, from https://www.worldmosquitoprogram.org/en/global-progress/indonesia


Moreira, L. A., Iturbe-Ormaetxe, I., Jeffery, J. A., Lu, G., Pyke, A. T., Hedges, L. M., ... & Hugo, L. E. (2009). A Wolbachia symbiont in Aedes aegypti limits infection with dengue, Chikungunya, and Plasmodium. Cell, 139(7), 1268-1278.


O'Neill SL, Ryan PA, Turley AP et al. Scaled deployment of Wolbachia to protect the community from dengue and other Aedes transmitted arboviruses [version 3; peer review: 2 approved]. Gates Open Res 2019, 2:36


Ranjit, S., & Kissoon, N. (2011). Dengue hemorrhagic fever and shock syndromes. Pediatric Critical Care Medicine, 12(1), 90-100.


Rodenhuis-Zybert, I. A., Wilschut, J., & Smit, J. M. (2010). Dengue virus life cycle: viral and host factors modulating infectivity. Cellular and molecular life sciences, 67(16), 2773-2786.


Servick, K. (2019). Mosquitoes armed with bacteria beat back dengue virus. Science. https://doi.org/10.1126/science.aba3223


Shepard, D. S., Undurraga, E. A., Halasa, Y. A., & Stanaway, J. D. (2016). The global economic burden of dengue: a systematic analysis. The Lancet infectious diseases, 16(8), 935-941.

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