title: Mosquito-Disseminated Insecticide for Citywide Vector Control and Its Potential to Block Arbovirus Epidemics: Entomological Observations and Modeling Results from Amazonian Brazil.
abstract: BACKGROUND
  Mosquito-borne viruses threaten public health worldwide. When the ratio of competent vectors to susceptible humans is low enough, the virus's basic reproductive number (R0) falls below 1.0 (each case generating, on average, <1.0 additional case) and the infection fades out from the population. Conventional mosquito control tactics, however, seldom yield R0 < 1.0. A promising alternative uses mosquitoes to disseminate a potent growth-regulator larvicide, pyriproxyfen (PPF), to aquatic larval habitats; this kills most mosquito juveniles and substantially reduces adult mosquito emergence. We tested mosquito-disseminated PPF in Manacapuru, a 60,000-inhabitant city (~650 ha) in Amazonian Brazil.
  
  
  RESULTS
  We sampled juvenile mosquitoes monthly in 100 dwellings over four periods in February 2014-January 2016: 12 baseline months, 5 mo of citywide PPF dissemination, 3 mo of focal PPF dissemination around Aedes-infested dwellings, and 3 mo after dissemination ended. We caught 19,434 juvenile mosquitoes (66% Aedes albopictus, 28% Ae. aegypti) in 8,271 trap-months. Using generalized linear mixed models, we estimated intervention effects on juvenile catch and adult emergence while adjusting for dwelling-level clustering, unequal sampling effort, and weather-related confounders. Following PPF dissemination, Aedes juvenile catch decreased by 79%-92% and juvenile mortality increased from 2%-7% to 80%-90%. Mean adult Aedes emergence fell from 1,077 per month (range 653-1,635) at baseline to 50.4 per month during PPF dissemination (range 2-117). Female Aedes emergence dropped by 96%-98%, such that the number of females emerging per person decreased to 0.06 females per person-month (range 0.002-0.129). Deterministic models predict, under plausible biological-epidemiological scenarios, that the R0 of typical Aedes-borne viruses would fall from 3-45 at baseline to 0.004-0.06 during PPF dissemination. The main limitations of our study were that it was a before-after trial lacking truly independent replicates and that we did not measure mosquito-borne virus transmission empirically.
  
  
  CONCLUSIONS
  Mosquito-disseminated PPF has potential to block mosquito-borne virus transmission citywide, even under adverse scenarios. Our results signal new avenues for mosquito-borne disease prevention, likely including the effective control of Aedes-borne dengue, Zika, and chikungunya epidemics. Cluster-randomized controlled trials will help determine whether mosquito-disseminated PPF can, as our findings suggest, develop into a major tool for improving global public health.
authors.affiliation: Laboratório de Triatomíneos e Epidemiologia da Doença de Chagas, Centro de Pesquisa René Rachou, Fundação Oswaldo Cruz, Belo Horizonte, Minas Gerais, Brazil.|Laboratório de Ecologia de Doenças Transmissíveis na Amazônia, Instituto Leônidas e Maria Deane, Fundação Oswaldo Cruz, Manaus, Amazonas, Brazil.
authors.forename: Fernando
authors.initials: F
authors.lastname: Abad-Franch
authors.affiliation: Laboratório de Ecologia de Doenças Transmissíveis na Amazônia, Instituto Leônidas e Maria Deane, Fundação Oswaldo Cruz, Manaus, Amazonas, Brazil.
authors.forename: Elvira
authors.identifier: http://orcid.org/0000-0001-5674-8278
authors.initials: E
authors.lastname: Zamora-Perea
authors.affiliation: Laboratório de Ecologia de Doenças Transmissíveis na Amazônia, Instituto Leônidas e Maria Deane, Fundação Oswaldo Cruz, Manaus, Amazonas, Brazil.
authors.forename: Sérgio L B
authors.initials: SL
authors.lastname: Luz
mesh_terms: D000330:Aedes; D000818:Animals; D001102:Arbovirus Infections / Q000453:epidemiology / Q000517:prevention & control*; D001938:Brazil / Q000453:epidemiology; D002947:Cities; D058872:Epidemics / Q000517:prevention & control*; D005260:Female; D006801:Humans; D007306:Insecticides / Q000008:administration & dosage*; D008297:Male; D008962:Models, Theoretical; D009032:Mosquito Control / Q000379:methods*; D011159:Population Surveillance; D011725:Pyridines / Q000008:administration & dosage*
chemical_list: D007306:Insecticides; D011725:Pyridines; C055613:pyriproxyfen