New evidence suggests malaria cycles are innate to the organism

May 14, 2020

Scientists from the Walter Reed Army Institute of Research joined partners at Duke University, Florida Atlantic University and Montana State University to publish a study providing clear evidence that malaria's characteristic cycle of fever and chills is a result of the parasite's own influence--not factors from the host.

What regulated that cycle, the result of parasites bursting out of infected red blood cells in sync then re-colonizing new red blood cells, has been studied since at least the 1920s. In the current study, evidence challenges the central dogma that a cyclic pattern of parasite growth is solely dependent on cues from the host.

Though the specific signals utilized remain to be elucidated, these findings raise the exciting possibility of disrupting this cycle as an antimalarial strategy.

"The malaria parasite contains an intrinsic biological oscillator that controls growth and development. Understanding the complex network that controls this oscillator could lead the development of novel antimalarials that may either kill the parasite or interfere with the growth cycle giving the host immune system the upper hand" said Colonel Norman Waters, an author on the paper.

In this study researchers studied four strains of Plasmodium falciparum, the deadliest and most prevalent of the five malaria species that infect humans, using in vitro cultures away from any host's circadian signals.

Using high-density time-series transcriptomics--techniques that measure the products of genes to gain insight into their activity--and microscopy, they found that the majority (87-92%) of tracked genes were cyclical--strong evidence that the cycle's primary regulator is intrinsic.

Malaria, infecting approximately 228 million individuals in 2018, remains a meaningful threat to public health and global stability. One of the top five infectious disease threats to deployed Service Members, WRAIR has participated in the development of most FDA-approved malaria prevention and treatment drugs as well as the world's most advanced malaria vaccine, RTS,S.

WRAIR and its partners remain committed to developing novel interventions to prevent the transmission of malaria, including mosquito repellents, chemoprophylaxis, biologics and more in order to eliminate the threat towards Service Members.
The opinions or assertions contained herein are the private views of the author, and are not to be construed as official, or as reflecting true views of the Department of the Army or the Department of Defense. The investigators have adhered to the policies for protection of human subjects as prescribed in AR 70- 25.

Headquartered in Silver Spring, Maryland, the Walter Reed Army Institute of Research provides unique research capabilities and innovative solutions to a range of force health and readiness challenges currently facing U.S. Service Members, along with threats anticipated during future operations.

Walter Reed Army Institute of Research

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