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Malaria, Thy Name Is Shapeshifter: Malaria Vaccine Part 1

The Chinese Nei Ching text dating back more than 4000 years (2700 BCE), attributes malaria to the machinations of three demons: one carrying a hammer, another a bucket of water, and one, a stove. While this helped explain the headaches, chills, and fevers then, today, vaccine researchers might be tempted to count a higher number of demonic forces at work. The Plasmodium parasite, which causes malaria, undergoes ten morphologic changes across five tissues in two different hosts. To make matters worse, multiple Plasmodium species infect humans. For these reasons and more, malaria has eluded vaccination attempts for more than fifty years.

Podcast: Free Audio File

If you prefer to listen to podcasts, feel free to play the audio version of this blog by clicking on the player above.

Podcast: Malaria, Thy Name Is Shapeshifter: Malaria Vaccine Part 1
Length: 4 minutes 54 seconds
Written and read by the author

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Malaria Infected Thousands During the US Civil War

Malaria has claimed the lives of hundreds of millions of people, and the disease has shaped history. Among other infectious agents, malaria accelerated the decimation of the indigenous people of South America during the European colonization, and it hastened the fall of the Roman empire. As two of the Horsemen of the Apocalypse, War and Pestilence ride side by side. Even in North America, this disease impacted history. Malaria infected thousands of soldiers during the Civil War and claimed more US lives than battle during the early days of the Pacific campaign in World War II.

While no longer endemic to the United States since 1951, malaria still resides in over 100 countries, and by the time you finish listening to this podcast, more than eight children in Africa will have died from the disease. The WHO released 2015 data supporting over 200 million Plasmodium infections and over 400,000 deaths, children being largely overrepresented.

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Anopheles Mosquitoes Transmit Malaria

When infected, mosquitoes of the genus Anopheles transmit the Plasmodium parasite into people while obtaining their blood meal. From here, the parasites work their way to the liver and then creep intracellularly. There they replicate. The affected liver cells rupture and all of the new parasites now move to the bloodstream where they infect red blood cells. Once inside the red blood cells, the parasite replicates again and on an exponential level. Here the clinical manifestations occur, and death becomes a risk.

So far, the parasite’s reproduction has been asexual. Plasmodium likes to save sex for when they are inside the mosquito. Go figure! Dirty-minded little parasites. Thus, some of the organisms, while inside the human red blood cell, will differentiate into male and female versions. When these cells are slurped up by the mosquito, then the mosquito’s midgut becomes a Plasmodial sex palace. If the mosquito survives this parasitic orgy, yes, they are negatively affected by the disease too (although I trust this will garner little sympathy), then the cycle continues.

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Plasmodium Hides Inside Cells

Within this weird life cycle with multiple stages of asexual and sexual reproduction lies the challenges with vaccination. Typically, pathogens don’t change this much within hosts. That is crucial because, from an antigenic perspective, these little guys shapeshift during these stages. They also often reside intracellularly, be it liver or blood cells. As a result, typical humoral vaccine stimulation, that is the formation of free-floating, extracellular antibodies, does not work well alone.

For a malaria vaccine to work, researchers have needed to focus on various proteins at specific stages of infection. They have targeted the infectious stage that isolates the liver in eleven different vaccine attempts. For the later blood infection, over twenty vaccines have made it to clinical trials. Most have failed. The need for a robust cell-mediated response has further complicated research. In the next podcast, we’ll peak into the innovation of the current malaria vaccine – Mosquirix and tackle a few common veterinary vaccine terms along the way.

References and Further Reading

  1. Arama, C., & Troye-Blomberg, M. (2014). The path of malaria vaccine development: Challenges and perspectives. Journal of Internal Medicine, 275(5), 456-466. doi:10.1111/joim.12223
  2. Center for Disease Control. (2019, January 4). CDC - Malaria - About Malaria - FAQs. Retrieved May 12, 2019, from https://www.cdc.gov/malaria/about/faqs.html
  3. Crompton, P. D., Pierce, S. K., & Miller, L. H. (2010). Advances and challenges in malaria vaccine development. The Journal of clinical investigation, 120(12), 4168–4178. doi:10.1172/JCI44423
  4. Hill AV (2011). "Vaccines against malaria". Philos. Trans. R. Soc. Lond. B Biol. Sci. 366 (1579): 2806–14. doi:10.1098/rstb.2011.0091. PMC 3146776. PMID 21893544
  5. Institute of Medicine (US) Committee on the Economics of Antimalarial Drugs; Arrow KJ, Panosian C, Gelband H, editors. Saving Lives, Buying Time: Economics of Malaria Drugs in an Age of Resistance.
  6. KrishnaswamySep, D. J., FrittsMay, R., KaiserMay, J., CohenMay, J., PennisiMay, E., & CohenMay, J. (2017, December 10). How Mosquitoes Fight Malaria. Retrieved May 12, 2019, from https://www.sciencemag.org/news/2010/09/how-mosquitoes-fight-malaria
  7. National Institutes of Health. (2017, October 31). Engineering malaria resistance in mosquitoes. Retrieved May 12, 2019, from https://www.nih.gov/news-events/nih-research-matters/engineering-malaria-resistance-mosquitoes
  8. Washington (DC): National Academies Press (US); 2004. 5, A Brief History of Malaria. Available from: https://www.ncbi.nlm.nih.gov/books/NBK215638/
  9. World Health Organization. (2016, December 13). 10 facts on malaria. Retrieved May 12, 2019, from https://www.who.int/features/factfiles/malaria/en/

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