From: Ivermectin to reduce malaria transmission II. Considerations regarding clinical development pathway
 | Outcome measure | Rationale | Method | Advantages | Disadvantages |
---|---|---|---|---|---|
In Humans | Clinical incidence | Of primary importance for the target population | Clinical case definition and laboratory confirmation | Unequivocal and tangible reflection of benefit for the population The earliest measurable clinical end-point reflecting transmission reduction | Requires robust baseline data Must reflect seasonal variations |
Parasite prevalence | Directly related to the EIR and VC | Consensus needed Options include: microscopy RDT PCR RT-PCR QT-NASBA [75] LAMP [76] | Robust measure Used across many settings Tangible reflection of benefit at population level | Laborious. Requires robust baseline data Must reflect seasonal variations Some methods are not suitable for the field. Method must be tailored according to the local prevalence | |
Gametocytaemia | A measure of infectiousness to mosquitoes (k) [63] | Consensus needed Options include: RT-PCR (RNA vs DNA) LAMP QT-NASBA | Robust measure of transmission | Must collect baseline data May not reflect population benefit May not reflect the independent effect of ivermectin | |
Variations in population level serology [77] | Indirect measure of transmission | Consensus needed on mosquito and parasite antigens | Direct reflection of exposure to malaria vectors and parasites Most useful in very low-transmission settings Useful without baseline data | May not reflect clinical benefit Must reflect seasonal variations | |
Molecular force of infection [78] | Indirect measure of transmission | PCR | Reliable and easier to determine than FOI | May not reflect clinical benefit Seasonality Inter-cluster variations | |
Entomological | Entomological inoculation rate [66] | A direct measure of transmission intensity. Likely to reflect the additional effect of ivermectin | Human landing catches vs light traps for biting rate Dissection, ELISA or PCR for sporozoite rate | Most useful in high transmission settings | Requires extensive knowledge of the local vectors. Very laborious. Minimum EIR of 5-10 needed for reliability [64] Ethics of human landing catches Must avoid contamination from control sites |
Vectorial capacity | Would additionally reflect the daily survival of vectors, a more direct effect of ivermectin | As above plus determination of the daily survival and assessment of the extrinsic incubation period | The most direct assessment of transmission | Requires extensive knowledge of the local vectors. Very laborious. Minimum EIR of 5-10 needed for reliability [64] Ethics of human landing catches Must avoid contamination from control sites |