title: Vectorial capacity and vector control: reconsidering sensitivity to parameters for malaria elimination.
abstract: BACKGROUND
  Major gains have been made in reducing malaria transmission in many parts of the world, principally by scaling-up coverage with long-lasting insecticidal nets and indoor residual spraying. Historically, choice of vector control intervention has been largely guided by a parameter sensitivity analysis of George Macdonald's theory of vectorial capacity that suggested prioritizing methods that kill adult mosquitoes. While this advice has been highly successful for transmission suppression, there is a need to revisit these arguments as policymakers in certain areas consider which combinations of interventions are required to eliminate malaria.
  
  
  RESULTS
  Using analytical solutions to updated equations for vectorial capacity we build on previous work to show that, while adult killing methods can be highly effective under many circumstances, other vector control methods are frequently required to fill effective coverage gaps. These can arise due to pre-existing or developing mosquito physiological and behavioral refractoriness but also due to additive changes in the relative importance of different vector species for transmission. Furthermore, the optimal combination of interventions will depend on the operational constraints and costs associated with reaching high coverage levels with each intervention.
  
  
  CONCLUSIONS
  Reaching specific policy goals, such as elimination, in defined contexts requires increasingly non-generic advice from modelling. Our results emphasize the importance of measuring baseline epidemiology, intervention coverage, vector ecology and program operational constraints in predicting expected outcomes with different combinations of interventions.
authors.affiliation: The Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, UK oliver.brady@well.ox.ac.uk.
authors.forename: Oliver J
authors.initials: OJ
authors.lastname: Brady
authors.affiliation: Department of Zoology, University of Oxford, Oxford, UK.
authors.forename: H Charles J
authors.initials: HC
authors.lastname: Godfray
authors.affiliation: Department of Geography and Environment, University of Southampton, Southampton, UK Fogarty International Center, NIH, Bethesda, MD, USA Flowminder Foundation, Stockholm, Sweden.
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Tatem
authors.affiliation: Spatial Ecology and Epidemiology Group, Department of Zoology, Oxford University, Oxford, UK.
authors.forename: Peter W
authors.initials: PW
authors.lastname: Gething
authors.affiliation: Clinton Health Access Initiative, Boston, MA, USA.
authors.forename: Justin M
authors.initials: JM
authors.lastname: Cohen
authors.affiliation: Fogarty International Center, NIH, Bethesda, MD, USA.
authors.forename: F Ellis
authors.initials: FE
authors.lastname: McKenzie
authors.affiliation: Fogarty International Center, NIH, Bethesda, MD, USA Department of Biological Sciences & Eck Institute for Global Health, University of Notre Dame, Notre Dame, IN, USA.
authors.forename: T Alex
authors.initials: TA
authors.lastname: Perkins
authors.affiliation: Fogarty International Center, NIH, Bethesda, MD, USA Department of Epidemiology & Biostatistics, Indiana University, Bloomington, IN, USA.
authors.forename: Robert C
authors.initials: RC
authors.lastname: Reiner
authors.affiliation: Department of Disease Control, London School of Hygiene and Tropical Medicine, London, UK.
authors.forename: Lucy S
authors.initials: LS
authors.lastname: Tusting
authors.affiliation: The Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, UK Department of Zoology, University of Oxford, Oxford, UK.
authors.forename: Marianne E
authors.initials: ME
authors.lastname: Sinka
authors.affiliation: The Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, UK.
authors.forename: Catherine L
authors.initials: CL
authors.lastname: Moyes
authors.affiliation: Institute for Disease Modeling, Bellevue, WA, USA.
authors.forename: Philip A
authors.initials: PA
authors.lastname: Eckhoff
authors.affiliation: Fogarty International Center, NIH, Bethesda, MD, USA Department of Entomology and Nematology, University of California, Davis, CA, USA.
authors.forename: Thomas W
authors.initials: TW
authors.lastname: Scott
authors.affiliation: School of Biological & Biomedical Sciences, Durham University, Durham, UK.
authors.forename: Steven W
authors.initials: SW
authors.lastname: Lindsay
authors.affiliation: The Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, UK Fogarty International Center, NIH, Bethesda, MD, USA Institute for Health Metrics and Evaluation, University of Washington, Seattle, WA, USA.
authors.forename: Simon I
authors.initials: SI
authors.lastname: Hay
authors.affiliation: Department of Zoology, University of Oxford, Oxford, UK Fogarty International Center, NIH, Bethesda, MD, USA Institute for Health Metrics and Evaluation, University of Washington, Seattle, WA, USA Sanaria Institute for Global Health and Tropical Medicine, Rockville, MD, USA.
authors.forename: David L
authors.initials: DL
authors.lastname: Smith
mesh_terms: D000818:Animals; D000852:Anopheles / Q000469:parasitology*; D060740:Disease Eradication / Q000379:methods*; D006291:Health Policy; D006801:Humans; D007306:Insecticides; D008018:Life Cycle Stages; D008288:Malaria / Q000517:prevention & control* / Q000635:transmission; D009032:Mosquito Control / Q000379:methods; D062486:Public Health Surveillance
chemical_list: D007306:Insecticides
keywords: Elimination; Malaria; Modelling; Operational research; Policy; Vector control
references.citation: Malar J. 2014;13:125
references.pmid: 24678587
references.citation: Trends Biotechnol. 2013 Mar;31(3):185-93
references.pmid: 23395485
references.citation: PLoS Pathog. 2012;8(4):e1002588
references.pmid: 22496640
references.citation: Elife. 2015;4. pii: e09672. doi: 10.7554/eLife.09672
references.pmid: 26714109
references.citation: PLoS Med. 2007 Jul;4(7):e229
references.pmid: 17608562
references.citation: Trans R Soc Trop Med Hyg. 2014 Apr;108(4):185-97
references.pmid: 24591453
references.citation: Malar J. 2004 Jun 4;3:13
references.pmid: 15180900
references.citation: Adv Parasitol. 2014;84:151-208
references.pmid: 24480314
references.citation: PLoS One. 2012;7(5):e37661
references.pmid: 22701527
references.citation: Nat Commun. 2015;6:8170
references.pmid: 26348689
references.citation: Lancet. 2010 Nov 6;376(9752):1592-603
references.pmid: 21035841
references.citation: J R Soc Interface. 2013 Apr 6;10(81):20120921
references.pmid: 23407571
references.citation: Trans R Soc Trop Med Hyg. 2007 Sep;101(9):867-80
references.pmid: 17631372
references.citation: Malar J. 2011;10:133
references.pmid: 21592366
references.citation: Am J Trop Med Hyg. 2015 May;92(5):903-12
references.pmid: 25778501
references.citation: PLoS Med. 2011;8(1):e1000401
references.pmid: 21311587
references.citation: J Med Entomol. 1978 Jun 7;14(6):603-26
references.pmid: 357723
references.citation: Malar J. 2007;6:10
references.pmid: 17254339
references.citation: Parasit Vectors. 2014;7:276
references.pmid: 24946878
references.citation: Elife. 2015;4:e08347
references.pmid: 26126267
references.citation: PLoS Biol. 2007 Mar;5(3):e42
references.pmid: 17311470
references.citation: Parasit Vectors. 2011;4:153
references.pmid: 21798055
references.citation: Malar J. 2014;13:338
references.pmid: 25168421
references.citation: Soc Sci Med. 1998 Feb-Mar;46(4-5):523-32
references.pmid: 9460831
references.citation: Cochrane Database Syst Rev. 2013;8:CD008923
references.pmid: 23986463
references.citation: Philos Trans R Soc Lond B Biol Sci. 2014;369(1645):20130431
references.pmid: 24821917
references.citation: Malar J. 2013;12:124
references.pmid: 23577656
references.citation: Science. 2011 Jun 17;332(6036):1384-5
references.pmid: 21680828
references.citation: Bull World Health Organ. 1956;15(3-5):613-26
references.pmid: 13404439
references.citation: Science. 2014 Jun 13;344(6189):1230-2
references.pmid: 24926005
references.citation: Parasit Vectors. 2012;5:69
references.pmid: 22475528
references.citation: Trends Parasitol. 2009 Nov;25(11):511-6
references.pmid: 19744887
references.citation: Biol Lett. 2012 Oct 23;8(5):874-7
references.pmid: 22647930
references.citation: World Health Organ Tech Rep Ser. 1957;38(123):3-84
references.pmid: 13496805
references.citation: Parasit Vectors. 2013;6:351
references.pmid: 24330720
references.citation: Trop Dis Bull. 1952 Sep;49(9):813-29
references.pmid: 12995455
references.citation: Trop Med Int Health. 2007 Jan;12(1):75-88
references.pmid: 17207151
references.citation: Science. 2013 Feb 22;339(6122):909-10
references.pmid: 23430640
references.citation: Philos Trans R Soc Lond B Biol Sci. 2013 Aug 5;368(1623):20120137
references.pmid: 23798686
references.citation: Malar J. 2014;13:330
references.pmid: 25149656
references.citation: Parassitologia. 2000 Jun;42(1-2):149-66
references.pmid: 11234325
references.citation: Proc Natl Acad Sci U S A. 2015 Mar 10;112(10):3014-9
references.pmid: 25605894
references.citation: Int Health. 2015 Mar;7(2):121-9
references.pmid: 25733562
references.citation: PLoS One. 2013;8(8):e71247
references.pmid: 23951118
references.citation: Malar J. 2013;12:329
references.pmid: 24044424
references.citation: Philos Trans R Soc Lond B Biol Sci. 2013 Aug 5;368(1623):20120145
references.pmid: 23798693
references.citation: Malar J. 2012;11:122
references.pmid: 22531245
references.citation: Nature. 2015 Oct 8;526(7572):207-11
references.pmid: 26375008
references.citation: PLoS Med. 2010;7(8). pii: e1000324. doi: 10.1371/journal.pmed.1000324
references.pmid: 20711482
references.citation: Am J Trop Med Hyg. 2013 May;88(5):809-16
references.pmid: 23589532
references.citation: Trop Dis Bull. 1952 Jun;49(6):569-86
references.pmid: 14958825
references.citation: Malar J. 2011;10:356
references.pmid: 22165904
references.citation: Parasit Vectors. 2010 Dec 03;3:117
references.pmid: 21129198
references.citation: Lancet Infect Dis. 2008 Jun;8(6):369-78
references.pmid: 18387849
references.citation: Parasit Vectors. 2010 Dec 31;3:122
references.pmid: 21192834
references.citation: Bull World Health Organ. 1964;30:241-61
references.pmid: 14153413
references.citation: Bull World Health Organ. 1956;15(3-5):369-87
references.pmid: 13404426
references.citation: Parasit Vectors. 2014;7:338
references.pmid: 25052008
references.citation: PLoS One. 2011;6(9):e25137
references.pmid: 21980386
references.citation: Science. 1905 Dec 1;22(570):689-99
references.pmid: 17729473
references.citation: Parasit Vectors. 2010 Aug 16;3:72
references.pmid: 20712879
references.citation: Parasit Vectors. 2011;4:89
references.pmid: 21612587
references.citation: Malar J. 2011;10:378
references.pmid: 22185615