Transmission and Age Impact the Risk of Developing Febrile Malaria in Children with Asymptomatic Plasmodium falciparum Parasitemia

Abstract

Background: Plasmodium falciparum infections lead to febrile illness unless the host has sufficient immunity, in which case infection may cause no immediate symptoms (ie, "asymptomatic parasitemia"). Previous studies are conflicting on the role of asymptomatic parasitemia in determining the risk of developing febrile malaria.

Methods: We monitored 2513 children (living in Kilifi, Kenyan Coast) by blood smears in 17 cross-sectional surveys to identify asymptomatic parasitemia and used active surveillance over 11325 child-years of follow-up to detect febrile malaria. We evaluated the interaction between transmission intensity, age, and asymptomatic parasitemia in determining the risk of developing febrile malaria.

Results: In the moderate and high transmission intensity settings, asymptomatic parasitemia was associated with a reduced risk of febrile malaria in older children (> 3 years), while in the lower transmission setting, asymptomatic parasitemia was associated with an increased risk of febrile malaria in children of all ages. Additionally, the risk associated with asymptomatic parasitemia was limited to the first 90 days of follow-up.

Conclusions: Asymptomatic parasitemia is modified by transmission intensity and age, altering the risk of developing febrile episodes and suggesting that host immunity plays a prominent role in mediating this process.

Keywords: Plasmodium falciparum; age; asymptomatic; immunity; transmission.

Figure 1.

A flow chart showing the total number of children recruited in the cohorts and the numbers of children that met the case definitions for this study.

Figure 2.

Risk of developing febrile malaria in uninfected children versus children with asymptomatic infections across the 3 malaria transmission settings. This plot compares the time to first febrile malaria episode between uninfected children versus children with asymptomatic infections across the different malaria transmission settings. The risk table shows the number of participants under observation at every 30-days interval for both the uninfected (blue) and asymptomatic (red) groups. The log-rank test was used compare the survival distributions between the 2 groups (P < .0001).

Figure 3.

Risk of developing febrile malaria between asymptomatic and uninfected children, stratified by malaria transmission intensity and age. The plots compare the time to first febrile malaria episode between the uninfected children versus children with asymptomatic infections across the different malaria transmission settings, stratified by 3 age groups: 0–3, >3–7 and >7 years old. The risk table shows the number of participants under observation at every 100-day interval for both the uninfected (blue) and asymptomatic (red) groups. The log-rank test was used compare the survival distributions.