July 23, 2024

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Existing Malaria Diagnostic Process Found to Have “Concerning” Flaws

Existing Malaria Diagnostic Process Found to Have “Concerning” Flaws


Existing Malaria Diagnostic Process Found to Have “Concerning” Flaws

A new report suggests that current methods may significantly overestimate the reproduction rate of malaria parasites in human blood. This overestimation has significant implications for assessing the harm these parasites may cause to their hosts.

Furthermore, the findings contribute to understanding the evolution of traits leading to drug resistance, the speed of parasite transmission within populations, and the evaluation of new vaccines.


Existing Malaria Diagnostic Process Found to Have "Concerning" Flaws

This research was recently published in the journal “Trends in Parasitology.”



Researchers created a dynamic mathematical model of infection to identify biases in blood sampling and errors in previous computer models, which led to substantial overestimations.

Megan Greischar, Assistant Professor of Ecology and Evolutionary Biology at the College of Agriculture and Life Sciences and the lead author of the paper, stated, “The inability to measure these rates accurately is concerning.”


Lauren Childs, Associate Professor of Mathematics at Virginia Tech and a co-author of the paper, explained, “We used to have a very simple model to infer multiplication rates, but that model didn’t work, so now we know we need a more powerful model. She said this research sheds light on how the issue of accurately measuring reproduction rates arose.”


Existing Malaria Diagnostic Process Found to Have "Concerning" Flaws



Some candidate malaria vaccines act during the lifecycle stage when the parasite replicates in the bloodstream, making understanding the parasite’s reproduction rate crucial for assessing vaccine efficacy.


Infected mosquitoes transmit malaria parasites to human hosts through blood meals.

The parasites first replicate in liver cells and then enter red blood cells. There, the parasites replicate synchronously within red blood cells and burst into the bloodstream, killing the red blood cells.

The offspring parasites then proceed to the next cycle by invading new red blood cells. This cycle repeats approximately every 48 hours.


When measuring reproduction rates, clinicians collect blood samples from infected patients and calculate the observed number of parasites.

Timing is crucial because young parasites that burst from red blood cells are easily detectable in the early stages of their lifecycle.

However, as they age, in the later stages of their lifecycle, parasites become viscous and adhere to blood vessel walls, making them undetectable. Since this cycle continually repeats, the timing of sampling determines whether a higher or lower number of parasites in the blood can be observed.


Existing Malaria Diagnostic Process Found to Have "Concerning" Flaws Existing Malaria Diagnostic Process Found to Have "Concerning" Flaws



Previous models used to estimate parasite reproduction rates attempted to correct for this sampling bias by inferring the number of parasites that might exist in the later stages of the parasite’s lifecycle when they cannot be directly observed. This research suggests that these methods are insufficient in determining the actual reproduction rate of the parasites.


Prior studies measured the maximum number of offspring produced by a human malaria parasite (Plasmodium falciparum) during a 48-hour replication cycle in laboratory cultures. Greischar stated, “They could only replicate up to 32 times, which is quite a lot already, meaning a single parasite could produce a maximum of 32 offspring parasites, with a median around 15 to 18.”


Using mathematical models combined with modern and historical data from malaria-infected individuals, researchers were able to determine that inferences made by previous parasite quantity models resulted in reproduction rates orders of magnitude higher than what is likely.


“We’ve seen increases in the thousands,” Greischar said. “This means parasites would repeatedly produce over 1000 parasites from a single red blood cell, which doesn’t align with our understanding of the biology of these parasites.”


Now that Greischar and Childs have identified the issue, future work may involve developing techniques to infer the hidden portions of parasite populations to accurately calculate their reproduction rates.




Existing Malaria Diagnostic Process Found to Have “Concerning” Flaws

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