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Table 3 Potential primary outcome measures for clinical trials of an ivermectin-based vector control tool

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
  1. EIR entomological inoculation rate, FOI force of infection, LAMP loop-mediated isothermal amplification, PCR polymerase chain reaction, QTNASBA real-time quantitative nucleic acid sequence-based amplification, RDT rapid diagnostic test, RT-PCR real-time PCR