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bioRxiv · 10.1101/2025.02.26.640285

Optimal cues for transmission investment in malaria parasites

Wang, A.·Greischar, M. A.·Mideo, N.
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Abstract

The timing of investment into reproduction is a key determinant of lifetime reproductive success (fitness). Many organisms exhibit plastic, i.e., environmentally-responsive, investment strategies, raising the questions of what environmental cues trigger responses and why organisms have evolved to respond to those particular cues. For malaria parasites (Plasmodium spp.), investment into the production of specialized transmission stages (versus stages that replicate asexually within the host) is synonymous with reproductive investment and also plastic, responding to host- and parasite-derived factors. Previous theory has identified optimal plastic transmission investment strategies for the rodent malaria parasite, Plasmodium chabaudi, as a function of the time since infection, implicitly assuming that parasites have perfect information about the within-host environment and how it is changing. We extend that theory to ask which cue(s) should parasites use? Put another way, which cue(s) maximize parasite fitness, quantified as host infectiousness during acute infection? Our results show that sensing a parasite-associated cue, e.g., the abundance of infected red blood cells or transmission stages, allows parasites to achieve fitness approaching that of the optimal time-varying strategy, but only when parasites perceive the cue non-linearly, responding more sensitively to changes at low densities. However, no single cue can recreate the best time-varying strategy or allow parasites to adopt terminal investment as the infection ends, a classic expectation for reproductive investment. Sensing two cues--log-transformed infected and uninfected red blood cell abundance--enables parasites to accurately track the progression of the infection, permits terminal investment, and recovers the fitness of the optimal time-varying investment strategy. Importantly, parasites that detect two cues more efficiently exploit hosts, resulting in higher virulence compared with those sensing only one cue. Finally, our results suggest a potential tradeoff between achieving an optimal transmission investment strategy in a given host environment and robustness in the face of environmental or developmental fluctuations.

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Wang, A., Greischar, M. A., Mideo, N.. 2025-03-01. Optimal cues for transmission investment in malaria parasites. https://doi.org/10.1101/2025.02.26.640285

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