Mosquito-disseminated diflubenzuron and spinosad as alternatives to mosquito-disseminated pyriproxyfen: a proof-of-concept, blind, controlled comparison in experimental cagesFIRST REVIEW ROUND - REVIEWERS COMMENTSAUTHORS RESPONSE TO REVIEWERSREVIEWERS COMMENTSREVIEWERS COMMENTS.

BACKGROUND: Mosquito-disseminated pyriproxyfen (MD-PPF) is a promising novel tool for urban-mosquito control, yet resistance to PPF (a juvenile-hormone analogue) may arise in exposed mosquito populations. Alternative larvicide/pupicide molecules suitable for mosquito-driven dissemination, but with distinct modes of action, are therefore needed. OBJECTIVES: To provide a proof-of-concept evaluation of mosquito-disseminated diflubenzuron (MD-DFB, a chitin-synthesis inhibitor) and spinosad (MD-SPN, a biological neurotoxin composite) as potential alternatives to MD-PPF. METHODS: We studied Aedes aegypti-driven dissemination in 20 blind, controlled experiments run in 110 × 90 × 30-cm cages. Of primary interest was whether and how (a) mosquito-driven dissemination affected adult-mosquito emergence (1705 larvae in 40 open and 20 closed cups set inside cages; generalised linear mixed models) and (b) exposure to larvicide/pupicide-treated dissemination stations affected adult-female lifespan (400 females released inside cages; proportional-hazards mixed models). FINDINGS: Adult-mosquito emergence was similar across treatments in closed cups. In open cups, average emergence fell from ~90% [95% confidence interval (CI), 84-95%] in control cages to ~30% (20-43%), ~56% (42-69%), and ~75% (63-85%) in, respectively, MD-PPF, MD-DFB, and MD-SPN cages. Exposure to SPN, but not to DFB or PPF, clearly reduced adult-female lifespan (SPN death-hazard ratio 2.4; 1.2-5.0). CONCLUSION: Mosquito-disseminated diflubenzuron holds promise as a potential alternative to MD-PPF; further testing in field settings seems warranted.