Symptomatic illness and treatment of Plasmodium falciparum malaria in African children

Plasmodium falciparum malaria is a major cause of morbidity and mortality globally, with a disproportionate fraction of cases and deaths in children under five years of age in sub-Saharan Africa. Estimating the proportion of infected individuals and symptomatic cases that receive effective antimalarial treatment is essential for assessing effectiveness of response efforts to reduce the malaria burden and for identifying coverage gaps for interventions. This thesis aims to provide new insights into the clinical malaria burden, and provides estimates of the proportion of malaria-infected children in sub-Saharan Africa that receive antimalarial treatment. The first major theme of this thesis was to develop a framework for estimating the prevalence of paediatric fever in sub-Saharan Africa, distinguishing between malaria-attributable fevers (MAF), and non-malarial febrile illness (NMFI) with and without an asymptomatic P. falciparum infection. Using household survey data and Bayesian geostatistical methods, continental cartographic estimates of paediatric fever prevalence were produced, separated by underlying cause. The second research focus was to develop an essential adjustment to household survey data to assess the duration a P. falciparum-infected individual remains positive via rapid diagnostic test after being treated with antimalarial medication. This adjustment was used in subsequent chapters, allowing for more accurate assessment of the likelihood of a febrile individual in the household survey datasets having experienced a MAF or NMFI in the two weeks preceding the survey. Current malaria burden estimation approaches typically enumerate the total number of malaria- positive fevers expected at a national-level. This approach systematically overestimates the clinical burden of malaria, as many of these malaria-positive fevers are causally attributable to NMFI (and the malaria infection is asymptomatic). In the third research chapter, estimates were produced of the proportion of paediatric malaria-positive fevers that are causally attributable to either malaria or NMFI that present at public health facilities in sub-Saharan African countries. The results presented in this chapter provide estimates of the potential scale of overestimation of the P. falciparum malaria burden using conventional burden estimation approaches. Finally, estimates of effective antimalarial coverage amongst children under 5 residing in 41 country-years with a household survey were presented, and individual-, community-, clinic-, and national-level coverage gaps for effective antimalarial coverage were identified. The results and conclusions from these studies are presented alongside recommendations and implications for both caregivers in malaria-endemic countries implementing paediatric fever management policy, and for epidemiologists studying the burden of malaria and non-malarial febrile illnesses.