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Background  Poor knowledge on the afebrile  Plasmodium falciparum  biology limits elimination approaches to target asymptomatic malaria. Therefore, the association of parasite factors involved in cytoadhesion, parasite multiplication and gametocyte maturation with afebrile malaria was assessed.    Methods   Plasmodium falciparum  isolates were collected from febrile (axillary temperature ≥ 37.5 °C or a reported fever in the previous 24 h) and afebrile (fever neither at the visit nor in the previous 24 h) individuals residing in Southern Mozambique.  var ,  PfSir2a  and  Pfs25  transcript levels were determined by reverse transcriptase quantitative PCRs (RT-qPCRs) and compared among 61 pairs of isolates matched by parasite density, age and year of sample collection.    Results  The level of  varC  and  PfSir2a  transcripts was higher in  P. falciparum  isolates from afebrile individuals (P ≤ 0.006), while  varB  and  DC8  genes (P ≤ 0.002) were higher in isolates from individuals with febrile infections. After adjusting the analysis by area of residence, doubling the relative transcript unit (RTU) of  varC  and  PfSir2a  was associated with a 29.7 (95% CI 4.6–192.3) and 8.5 (95% CI 1.9–32.2) fold increases, respectively, of the odds of being afebrile. In contrast, doubling the RTU of  varB  and  DC8  was associated with a 0.8 (95% CI 0.05–0.6) and 0.2 (95% CI 0.04–0.6) fold changes, respectively, of the odds of being afebrile. No significant differences were found for  Pfs25  transcript levels in  P. falciparum  isolates from afebrile and febrile individuals.    Conclusions   var  and gametocyte-specific transcript patterns in febrile and afebrile infections from southern Mozambique matched by age, parasite density and recruitment period suggest similar transmissibility but differential expression of variant antigens involved in cytoadhesion and immune-evasion.

Differential expression of var subgroups and PfSir2a genes in afebrile Plasmodium falciparum malaria: a matched case–control study