Can Treatment of Malaria be Restricted to Parasitologically Confirmed Malaria? A School-Based Prospective, Exposed/Non Exposed to Fever, Study in Benin.

This study was designed to measure the incidence of malaria attacks during a 2-week follow-up period in 2 populations of patients. First, an index group (IG, exposed to fever) constituted by schoolchildren attending the school nursery for fever and not diagnosed malaria, based on a negative HRP2-based RDT. Second, a control group (CG, not exposed to fever) constituted of apparently healthy schoolchildren paired with index cases on gender, age, week of inclusion and malaria status (ie: negative HRP2-based RDT).

In a pragmatic purpose, the subjects were selected for inclusion if no malaria diagnosis was made by the means accessible to a clinician in routine practice, i.e., RDT and body temperature assessment. During the follow-up, malaria was defined as the association of fever and parasitemia, using any malaria diagnostic method, whatever its availability on the field: (blood smear and/or PCR).

Hence, the primary objective of the study was to show that applying the algorithm of management of fevers in the school setting is safe, in the way it does not lead to an excessive number of undiagnosed (and thus untreated) malaria attacks, by comparing the number of malaria attacks between the two groups (exposed and non exposed to fever).

The secondary objective was to compare malaria incidence between children at high risk for malaria during follow-up in the IG and CG respectively. Children at high risk for malaria in these 2 groups were defined by the detection of Plasmodium falciparum infection at enrollment, using the most sensitive diagnostic tool currently available (i.e., PCR). Based on data from the literature, we estimated to about 15% the proportion of children attending for fever with a negative RDT and a positive PCR for malaria, and we assumed this proportion to be roughly the same in apparently healthy children. Twenty-eight children at high risk for malaria in each group (corresponding to187 children in each group) are needed to detect an 8% difference in proportion between the 2 groups (α = 0.05 and β = 0.8). Assuming a maximum of 5% in the dropout rate, we aimed at including a minimum of 200 children in each group.

Study site: This study was performed from February through June 2008 in 4 schools, located at Allada, Southern-Benin, where malaria transmission is intense and perennial. Altogether, the 4 study schools received about 2600 schoolchildren of 5 years-old and above.