Department of Pathology and Laboratory Medicine, Brown University, Providence, Rhode Island, United States of America.
Department of Infectious Disease Epidemiology, Imperial College London, London, United Kingdom.
PLoS Comput Biol. 2023 Jun 9;19(6):e1010247. doi: 10.1371/journal.pcbi.1010247. eCollection 2023 Jun.
In malaria, individuals are often infected with different parasite strains. The complexity of infection (COI) is defined as the number of genetically distinct parasite strains in an individual. Changes in the mean COI in a population have been shown to be informative of changes in transmission intensity with a number of probabilistic likelihood and Bayesian models now developed to estimate the COI. However, rapid, direct measures based on heterozygosity or FwS do not properly represent the COI. In this work, we present two new methods that use easily calculated measures to directly estimate the COI from allele frequency data. Using a simulation framework, we show that our methods are computationally efficient and comparably accurate to current approaches in the literature. Through a sensitivity analysis, we characterize how the distribution of parasite densities, the assumed sequencing depth, and the number of sampled loci impact the bias and accuracy of our two methods. Using our developed methods, we further estimate the COI globally from Plasmodium falciparum sequencing data and compare the results against the literature. We show significant differences in the estimated COI globally between continents and a weak relationship between malaria prevalence and COI.
在疟疾中,个体通常会感染不同的寄生虫株。感染复杂性(COI)定义为个体中具有遗传差异的寄生虫株的数量。已经证明,种群中平均 COI 的变化可以提供有关传播强度变化的信息,现在已经开发了许多概率似然和贝叶斯模型来估计 COI。然而,基于杂合性或 FwS 的快速直接测量并不能正确代表 COI。在这项工作中,我们提出了两种新方法,这些方法使用易于计算的度量标准,直接从等位基因频率数据估计 COI。使用模拟框架,我们表明我们的方法在计算上效率高,并且与文献中的当前方法相当准确。通过敏感性分析,我们描述了寄生虫密度的分布、假设的测序深度以及采样基因座数量如何影响我们两种方法的偏差和准确性。使用我们开发的方法,我们进一步从恶性疟原虫测序数据中估计全球 COI,并将结果与文献进行比较。我们显示了全球范围内各大洲之间 COI 估计值存在显著差异,并且疟疾流行率与 COI 之间存在微弱关系。