Biomedical Sciences Program, School of Medicine, University of California, San Diego, La Jolla, California, United States of America; Department of Pediatrics, School of Medicine, University of California, San Diego, La Jolla, California, United States of America.
Scripps Genomic Medicine, The Scripps Translational Science Institute, La Jolla, California, United States of America; Department of Molecular and Experimental Medicine, The Scripps Research Institute, La Jolla, California, United States of America.
PLoS Negl Trop Dis. 2014 Jun 5;8(6):e2882. doi: 10.1371/journal.pntd.0002882. eCollection 2014 Jun.
Plasmodium vivax infects a hundred million people annually and endangers 40% of the world's population. Unlike Plasmodium falciparum, P. vivax parasites can persist as a dormant stage in the liver, known as the hypnozoite, and these dormant forms can cause malaria relapses months or years after the initial mosquito bite. Here we analyze whole genome sequencing data from parasites in the blood of a patient who experienced consecutive P. vivax relapses over 33 months in a non-endemic country. By analyzing patterns of identity, read coverage, and the presence or absence of minor alleles in the initial polyclonal and subsequent monoclonal infections, we show that the parasites in the three infections are likely meiotic siblings. We infer that these siblings are descended from a single tetrad-like form that developed in the infecting mosquito midgut shortly after fertilization. In this natural cross we find the recombination rate for P. vivax to be 10 kb per centimorgan and we further observe areas of disequilibrium surrounding major drug resistance genes. Our data provide new strategies for studying multiclonal infections, which are common in all types of infectious diseases, and for distinguishing P. vivax relapses from reinfections in malaria endemic regions. This work provides a theoretical foundation for studies that aim to determine if new or existing drugs can provide a radical cure of P. vivax malaria.
间日疟原虫每年感染 1 亿人，威胁着全球 40%的人口。与恶性疟原虫不同，间日疟原虫寄生虫可以在肝脏中以休眠状态（称为休眠体）持续存在，这些休眠形式可以在初次蚊叮咬数月或数年后引起疟疾复发。在这里，我们分析了一名患者血液中的寄生虫全基因组测序数据，该患者在非流行地区经历了连续 33 个月的间日疟复发。通过分析初始多克隆和随后的单克隆感染中身份、读取覆盖率和次要等位基因存在或缺失的模式，我们表明这三种感染中的寄生虫可能是减数分裂的兄弟姐妹。我们推断这些兄弟姐妹来自于一个单四分体样形式，该形式在受精后不久在感染蚊子的中肠中发育。在这种自然交叉中，我们发现间日疟原虫的重组率为每 10kb 1 个厘摩，并且我们进一步观察到主要耐药基因周围存在不平衡区域。我们的数据为研究多克隆感染提供了新的策略，多克隆感染在所有类型的传染病中都很常见，并且为区分疟疾流行地区的间日疟复发和再感染提供了依据。这项工作为旨在确定新的或现有的药物是否可以根治间日疟提供了理论基础。
