Diagnostics to support malaria elimination: Choosing an appropriate biomarker to target the subclinical Plasmodium falciparum transmission reservoir

As national malaria control programs contemplate their options for shifting tactics and tools to support malaria elimination, it is useful to review the basic characteristics of target analytes commonly used for malaria diagnosis. We identify several epidemiological nuances that impact choice of target analytes for Plasmodium falciparum transmission and we review key concepts such as parasite biomass concentration, circulating parasite density, infectiousness, sequestration, analyte deletions, and persistence. We then define key requirements for the selection of appropriate target analytes that could serve as Plasmodium falciparum proxy indicators of transmission risk. We focus on the intrinsic themes and attributes of malaria biomarkers and deliberately separate those properties from the detection technologies because if a biomarker does not have the appropriate intrinsic properties to meet elimination needs, no amount of heroic engineering can overcome this shortcoming.