RESUMO
BACKGROUND: Outdoor, early-biting, zoophagic behaviours by Anopheles farauti (s.s.) can compromise the effectiveness of bed nets for malaria control. In the Western Pacific region, pigs and dogs represent significant alternative blood sources for mosquitoes. Treating these animals with endectocides may impact mosquito survival and complement control measures. This hypothesis was explored using membrane feeding assays (MFAs), direct feeds on treated pigs, pharmacokinetic analyses and a transmission model. RESULTS: Ivermectin was 375-fold more mosquitocidal than moxidectin (24 h LC50 = 17.8 ng/ml vs 6.7 µg/ml) in MFAs, and reduced mosquito fecundity by > 50% at ≥ 5 ng/ml. Treatment of pigs with subcutaneous doses of 0.6 mg/kg ivermectin caused 100% mosquito mortality 8 days after administration. Lethal effects persisted for up to 15 days after administration (75% death within 10 days). CONCLUSION: The application of these empirical data to a unique malaria transmission model that used a three-host system (humans, pigs and dogs) predicts that the application of ivermectin will cause a significant reduction in the entomological inoculation rate (EIR = 100 to 0.35). However, this is contingent on local malaria vectors sourcing a significant proportion of their blood meals from pigs. This provides significant insights on the benefits of deploying endectocides alongside long-lasting insecticide-treated nets (LLINs) to address residual malaria transmission.
Assuntos
Anopheles/efeitos dos fármacos , Inseticidas/administração & dosagem , Ivermectina/administração & dosagem , Macrolídeos/administração & dosagem , Malária/prevenção & controle , Administração Cutânea , Animais , Comportamento Alimentar , Feminino , Fertilidade/efeitos dos fármacos , Inseticidas/sangue , Inseticidas/farmacocinética , Inseticidas/farmacologia , Ivermectina/sangue , Ivermectina/farmacocinética , Ivermectina/farmacologia , Macrolídeos/sangue , Macrolídeos/farmacocinética , Macrolídeos/farmacologia , Malária/transmissão , Modelos Biológicos , Controle de Mosquitos/métodos , Papua Nova Guiné , Distribuição Aleatória , SuínosRESUMO
Proteomic investigations in Anopheles gained momentum following the sequencing of the Anopheles gambiae genome, allowing peptide data from mass spectrometry to be searched against large datasets of predicted protein sequences. Exhaustive discovery proteomics investigations have improved the annotation of genomic datasets and catalogued proteins from mosquito tissues, including the salivary glands, midgut, and sensory appendages. These efforts have revealed protein constituents that define the unique biological functions of these organs. Quantitative proteomics investigations have begun to characterise the molecular basis of mosquito behaviour and immune responses. With a current trend towards increasing sensitivity of mass spectrometers and simpler workflows, proteomics is set to accelerate the development of antiparasite interventions through the identification of new targets for parasite or vector control and diagnostic biomarkers.