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Review of the relation of parasite density and symptomatic disease in malaria infections








Review of the relation of parasite density and symptomatic disease in malaria infections


Jane Cunningham


World Health Organization






15 February 2023


In malaria-endemic areas, asymptomatic carriage of malaria parasites occurs frequently and the detection of malaria parasites in blood films from a febrile individual does not necessarily indicate clinical malaria. The parasite density is a measure of the amount of parasites detected in a peripheral blood sample and is associated with the risk of presenting malaria symptomatology. A case definition for symptomatic malaria that is used widely in endemic areas requires the presence of fever together with a parasite density above a specific cutoff.The current threshold for the performance of Rapid Diagnostic Tests (RDT) (200 p/uL) has been defined adequate for detecting the majority of clinical malaria ( Parasitological Confirmation of Malaria Diagnosis: Report of a WHO Technical Consultation, Geneva, 6-8 October 2009. Geneva: World Health Organization, 2010). The Malaria Advisory Committee of the Global Malaria Program would like to investigate if those thresholds should be maintained.Aim:To evaluate different thresholds of parasitemia density that defines clinical malaria.Specific Objectives:- To describe the distribution of parasitemia density on patients with malaria disease present to the health facility, in different epidemiological settings and age groups.- To describe the distribution of the parasitemia density in symptomatic and asymptomatic subjects in cross-sectionals, in different epidemiological settings and age groups, in order to determine what is the attributable fraction of fever due to malaria, sensitivity and specificity of different cut-off points.Methodology:For the data from outpatient clinics, the distribution of the parasitemia density, allowing to evaluate what is the proportion of the Plasmodium falciparum positive samples above a certain cutoff point, i.e. what is the proportion of the clinical malaria cases that present to the health facility with a parasitemia level greater than 200 parasites/ul.For the cross-sectional data, a model will evaluate the risk of being febrile given a parasitemia level and based on that relationship will estimate what is the attributable fraction of the fevers due to malaria and hence will estimate what is the sensitivity and specificity using different parasitemia density cut-off points.Expected Outcomes:The analysis will be presented to the Malaria Policy Advisory Committee (MPAC) of the Global Malaria Program (GMP) at World Health Organization (WHO) and will help on the consideration if the currently recommended thresholds for RDT performance should be maintained. RDT is currently the most used methodology for diagnosis malaria worldwide and the recommendation would have an ample impact on global public health.



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Statistical Analysis Plan