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

Lynette Isabella Ochola-Oyier,Kevin Wamae,Faith Osier,Juliana Wambua,Francis Ndung’U,George Nyangweso,Philip Bejon,Gabriel Mwambingu

doi:10.1093/infdis/jiy591

Abstract

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. 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. 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. 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.

Highlights

Plasmodium falciparum infections lead to febrile illness unless the host has sufficient immunity, in which case infection may cause no immediate symptoms
Plasmodium falciparum infections are characterized by disease manifestations that range from asymptomatic infection, mild febrile episodes, through to severe malaria
Asymptomatic parasitemia is widespread, affecting 24% of the population in sub-Saharan Africa [2], and might indicate that the host is at risk of developing febrile malaria at a later date, or that the host is immune and is at a reduced risk of febrile malaria

Summary

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 11 325 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. The data were prospectively collected between 1998 and 2014 for Ngerenya, 2005 and 2010 for Junju, and 1999 and 2001 for Chonyi In these cohorts children were recruited at birth for weekly clinical malaria monitoring until the age of 15 years [27]. We used data from the active weekly surveillance to determine malaria episodes and annual cross-sectional surveys to define asymptomatic parasitemia and uninfected children. The cross-sectional surveys are conducted before the long rains that occur in May to July, with the short rains occurring in October to November [30]

Results

Discussion

Conclusion