title: Impact of pyrethroid resistance on operational malaria control in Malawi.
abstract: The impact of insecticide resistance on insect-borne disease programs is difficult to quantify. The possibility of eliminating malaria in high-transmission settings is heavily dependent on effective vector control reducing disease transmission rates. Pyrethroids are the dominant insecticides used for malaria control, with few options for their replacement. Their failure will adversely affect our ability to control malaria. Pyrethroid resistance has been selected in Malawi over the last 3 y in the two major malaria vectors Anopheles gambiae and Anopheles funestus, with a higher frequency of resistance in the latter. The resistance in An. funestus is metabolically based and involves the up-regulation of two duplicated P450s. The same genes confer resistance in Mozambican An. funestus, although the levels of up-regulation differ. The selection of resistance over 3 y has not increased malaria transmission, as judged by annual point prevalence surveys in 1- to 4-y-old children. This is true in areas with long-lasting insecticide-treated nets (LLINs) alone or LLINs plus pyrethroid-based insecticide residual spraying (IRS). However, in districts where IRS was scaled up, it did not produce the expected decrease in malaria prevalence. As resistance increases in frequency from this low initial level, there is the potential for vector population numbers to increase with a concomitant negative impact on control efficacy. This should be monitored carefully as part of the operational activities in country.
authors.affiliation: Liverpool School of Tropical Medicine, Liverpool L3 5QA,  United Kingdom.
authors.forename: Charles S
authors.initials: CS
authors.lastname: Wondji
authors.forename: Michael
authors.initials: M
authors.lastname: Coleman
authors.forename: Immo
authors.initials: I
authors.lastname: Kleinschmidt
authors.forename: Themba
authors.initials: T
authors.lastname: Mzilahowa
authors.forename: Helen
authors.initials: H
authors.lastname: Irving
authors.forename: Miranda
authors.initials: M
authors.lastname: Ndula
authors.forename: Andrea
authors.initials: A
authors.lastname: Rehman
authors.forename: John
authors.initials: J
authors.lastname: Morgan
authors.forename: Kayla G
authors.initials: KG
authors.lastname: Barnes
authors.forename: Janet
authors.initials: J
authors.lastname: Hemingway
mesh_terms: D000110:Acetylcholinesterase / Q000235:genetics; D000818:Animals; D000852:Anopheles / Q000187:drug effects / Q000235:genetics; D002675:Child, Preschool; D003433:Crosses, Genetic; D005260:Female; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation / Q000187:drug effects; D017344:Genes, Insect / Q000235:genetics; D056726:Genetic Association Studies; D005843:Geography; D006239:Haplotypes / Q000235:genetics; D006801:Humans; D007223:Infant; D007305:Insecticide Resistance / Q000187:drug effects*; D008288:Malaria / Q000453:epidemiology / Q000469:parasitology* / Q000517:prevention & control*; D008295:Malawi / Q000453:epidemiology; D008297:Male; D008969:Molecular Sequence Data; D009032:Mosquito Control; D009154:Mutation / Q000235:genetics; D011110:Polymorphism, Genetic / Q000187:drug effects; D011722:Pyrethrins / Q000633:toxicity*; D017422:Sequence Analysis, DNA; D015222:Sodium Channels / Q000235:genetics; D014158:Transcription, Genetic / Q000187:drug effects
chemical_list: D011722:Pyrethrins; D015222:Sodium Channels; D000110:Acetylcholinesterase