Extraordinary parasite multiplication rates in human malaria infections

• Published in: Trends in parasitology 2023-08, Vol.39 (8), p.626-637
• Main Authors: Greischar, Megan A., Childs, Lauren M.
• Format: Article
• Language: English
• Subjects: Animals; controlled human infection trial; Humans; Malaria - parasitology; malaria therapy; Malaria, Falciparum - parasitology; Parasites; Plasmodium falciparum; replication rates; within-host dynamics
• ISSN: 1471-4922; 1471-5007
• DOI: 10.1016/j.pt.2023.05.006

Theory assumes that multiplication rates of pathogenic organisms have substantial influence on disease severity and spread.Malaria infections represent one of the most straightforward systems in which to measure parasite multiplication rates (PMRs), but PMRs have proven difficult to link to health outcomes.Applied to human infection data, standard methods for estimating PMRs yield extraordinarily large values, far exceeding the maximum expansion rate (i.e., burst size) established in vitro.Spurious multiplication rates appear when some ages of parasites are more difficult to sample and when the age distribution of the parasite population changes through time, problems that are likely common among pathogenic organisms.Small changes in age distributions can lead to estimates of extraordinarily high multiplication rates that may explain why PMRs often fail to predict disease severity. For pathogenic organisms, faster rates of multiplication promote transmission success, the potential to harm hosts, and the evolution of drug resistance. Parasite multiplication rates (PMRs) are often quantified in malaria infections, given the relative ease of sampling. Using modern and historical human infection data, we show that established methods return extraordinarily – and implausibly – large PMRs. We illustrate how inflated PMRs arise from two facets of malaria biology that are far from unique: (i) some developmental ages are easier to sample than others; (ii) the distribution of developmental ages changes over the course of infection. The difficulty of accurately quantifying PMRs demonstrates a need for robust methods and a subsequent re-evaluation of what is known even in the well-studied system of malaria.