PROJECT SUMMARY/ABSTRACT
Malaria causes high morbidity and mortality globally with 247 million cases and 619,000 deaths in 2021, >90%
of which occurred in children living in sub-Saharan Africa. Children who survive repeated episodes of
symptomatic malaria caused by the Plasmodium falciparum parasite still do not thrive. Repeated malaria
exposures eventually confer clinical immunity whereby these children can be “asymptomatically” infected with
the parasite. These asymptomatic P. falciparum infections, while not clinically apparent, have significant
individual and public health consequences, including chronic anemia, increased susceptibility to bacterial sepsis,
and maintenance of onward malaria transmission by serving as parasite reservoirs. Prior studies suggest that
asymptomatic infections can also adversely impact cognitive performance in school-aged children. In
asymptomatic malaria infections, parasite density directly correlates with markers of systemic inflammation.
Systemic inflammation, as measured by circulating inflammatory cytokines, has been proposed to
mechanistically alter brain development. Despite the potential mechanistic links, it remains unknown whether
systemic inflammation mediates the relationship between asymptomatic P. falciparum infections and cognitive
performance. Based on this prior evidence and our preliminary data, we hypothesize that 1) asymptomatic P.
falciparum parasitemia reduces cognitive performance; 2) treatment of microscopy-detectable asymptomatic
parasitemia can reverse such reductions in cognition; and 3) subclinical inflammation, as measured by pro-
inflammatory plasma cytokines, partially mediates the effect asymptomatic P. falciparum parasitemia on
cognitive performance in young schoolchildren. To test these hypotheses, we will conduct a 10-week
interventional trial in asymptomatic children aged 7-9 years (n=300, 50% female) residing in western Kenya
whereby those with microscopy-positive P. falciparum parasitemia are treated at baseline. Parasitemia,
hemoglobin, plasma cytokines, plasma metabolites, and inflammatory markers will be measured at baseline and
at follow-up. Successful completion of this project will determine whether treatment of asymptomatic P.
falciparum infections leads to improvements in cognitive performance and whether systemic inflammation
mediates this relationship. Understanding these relationships is essential for developing public health programs
that reduce the impact of malaria and its sequelae.
