Mapping the Immune Response to P. Falciparum Explains How Malaria Evades Treatment

Over the years, scientists have learned that Plasmodium falciparum (P. falciparum) is tricky. This parasite, which causes the deadliest type of malaria in humans (falciparum malaria), is transmitted through the bite of infected female Anopheles mosquitoes. Once in the body, the parasite changes rapidly: a single-celled worm in the bloodstream that later multiples in the liver before multiplying even further in the circulatory system. This parasite also has hundreds of proteins that help it to evade the immune system and thrive. So it’s no wonder that, historically, it has been difficult to find ways to prevent or treat falciparum malaria. While a vaccination is available, it requires multiple shots and still remains only minimally effective in preventing severe disease. Finding ways to overcome this will help those in areas of the world where malaria is endemic. 

Immune Evasion: P. Falciparum’s Tool

According to Medical XPress, scientists from UCSF and the CZ Biohub SF began finding ways to characterize the ways in which malaria interacts with and escapes from the immune system. To begin, the research team sourced blood samples from 198 individuals from Uganda. The samples were sourced from both adults and children. Next, the research team cleaved and chopped up P. falciparum’s proteome, or the 5,400 proteins made by the parasite, and engineered viruses to showcase these proteins. 

Finally, the team introduced these engineered viruses to the blood samples. A tool called PhIP-Seq allowed for a deeper examination of how the blood reacted to the P. falciparum proteins. If anybody from the sample had ever been exposed to malaria prior, the researchers expected their body to react and be better prepared to react. 

A paper from this study, published in eLife, found that the blood most commonly produced antibodies for repeat elements – or repetitive amino acid sequences within the protein. In fact, people living in areas where they were heavily exposed to malaria showed 2x more reaction to these amino acid sequences than those in other areas. 

The issue, scientists say, is that the body focuses on these repeat elements – while ignoring the more functional, harmful elements of P. falciparum proteins. In a sense, malaria protects itself by tricking the immune system into attacking lesser important parts of the parasite. Though this confers a slight protective response, it fails to enact durable, long-term, sustained responses, allowing for increased susceptibility to more severe responses – and allowing malaria to escape from vaccinations or other intended preventative measures. 

Moving forward, developing a vaccine that targets non-repeat elements may be more beneficial than current offerings.

Malaria: The Details

An estimated 1,500-2,000 cases of malaria occur in the United States each year, though this mosquito-borne illness is more common in South Asia and sub-Saharan Africa. In rarer cases, malaria may be transmitted through sharing needles, blood transfusions, or from mother to child. Symptoms typically appear between 7-30 days following infection. In some individuals, the symptoms are constant; others experience “attacks,” or intensely symptomatic periods with periods of remission. Symptoms include:

  • High fever and shaking chills
  • Nausea and vomiting
  • Muscle pain
  • Fatigue and general weakness
  • Headache
  • Drenching sweats
  • Chest and abdominal pain
  • Enlarged liver and spleen
  • Cough
  • Anemia (low red blood cell count – complication)
  • Cerebral malaria (complication)
  • Organ failure (complication)

Antimalarial treatments work to kill the parasite. If you believe that you may have malaria, please speak with your physician immediately to work out a plan of care.

Jessica Lynn

Jessica Lynn

Jessica Lynn has an educational background in writing and marketing. She firmly believes in the power of writing in amplifying voices, and looks forward to doing so for the rare disease community.

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