Following Plasmodium falciparum infection, individuals can remain asymptomatic, present with mild fever in uncomplicated malaria cases, or show one or more severe malaria symptoms. Several studies have investigated associations between parasite transcription and clinical severity, but no broad conclusions have yet been drawn. Here, we apply a series of bioinformatic approaches based on P. falciparum’s tightly regulated transcriptional pattern during its ~48-hour intraerythrocytic developmental cycle (IDC) to publicly available transcriptomes of parasites obtained from malaria cases of differing clinical severity across multiple studies. Our analysis shows that within each IDC, the circulation time of infected erythrocytes without sequestering to endothelial cells decreases with increasing parasitaemia or disease severity. Accordingly, we find that the size of circulating infected erythrocytes is inversely related to parasite density and disease severity. We propose that enhanced adhesiveness of infected erythrocytes leads to a rapid increase in parasite burden, promoting higher parasitaemia and increased disease severity.

恶性疟原虫感染后，个体可能没有症状，在无并发症的疟疾病例中出现轻度发烧，或表现出一种或多种严重的疟疾症状。几项研究调查了寄生虫转录与临床严重程度之间的关联，但尚未得出广泛的结论。在这里，我们应用了一系列基于恶性疟原虫的生物信息学方法在其约 48 小时的红细胞内发育周期 (IDC) 中严格调节的转录模式到从多项研究中临床严重程度不同的疟疾病例中获得的寄生虫的公开可用转录组。我们的分析表明，在每个 IDC 中，没有隔离到内皮细胞的受感染红细胞的循环时间随着寄生虫血症或疾病严重程度的增加而减少。因此，我们发现循环感染红细胞的大小与寄生虫密度和疾病严重程度成反比。我们提出受感染的红细胞粘附性增强会导致寄生虫负担迅速增加，从而促进更高的寄生虫血症和疾病严重程度的增加。