Asexual stage synchronicity in symptomatic and asymptomatic falciparum malaria

Andrade et al have reported that P. falciparum parasitised erythrocytes circulate for longer in persistent asymptomatic infections than in symptomatic malaria. This radical suggestion, attributed to in-vivo adaptation by the parasite population to reduced cytoadherence, is based largely on in-vivo transcriptomic data from 24 Malian children: 12 with acute falciparum malaria and 12 with asymptomatic parasitaemia. We show that the reported analysis generated erroneous results because of data formatting issues. We also show that the algorithm used to estimate the average asexual parasite developmental stage (hours post-invasion) from in-vivo transcriptomic data breaks down when applied to asynchronous infections. We argue that comparisons between asymptomatic and symptomatic malaria of asexual parasite developmental stage distributions are confounded by differences in synchronicity and gametocytaemia, and also by selection bias (because schizogony often precipitates clinical presentation). There is no convincing evidence of an adaptive delayed cytoadherence phenotype in chronic P. falciparum infections.