Global plan for insecticide resistance management in malaria vectors

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Annex 7 Implications ofdiscriminating doses ofinsecticide on detectionof resistanceThe dosage of insecticide used in susceptibility testing plays arole in determining how long insecticide resistance can remainhidden before a detectable percentage of survivors is identifiedin the test. For a semi-dominant gene, the ‘lethal dose 50’(LD 50, dose required to kill exactly 50% of exposed insects) isdifferent for homozygous susceptible, heterozygous or homozygousresistant (Figure A7.1).Figure A7.1: Diagram illustrating the LD 50of semi-dominant homozygous susceptible, heterozygous or homozygous resistant fora semi-dominant gene (illustrative data only)Frequency10090SusceptibleHeterozygousHomozygousresistant80706050403020Approximate location ofdiscriminating dose on thespectrum. Resistance must behigh before it can be detected.100LD 50for SSLD 50for RSLD 50for RRConcentrationrequired to killvectorsFrom the WHO Global Malaria ProgrammeDepending on where the discriminating dose is on this spectrum,the estimate of susceptibility will be different, even with the samegene frequency. If the dose is too high, heterozygous mosquitoeswill remain undetected, and resistance will not be detected untilhomozygous resistant mosquitoes are firmly established in thepopulation, at which point it is extremely difficult to slow the spreadof resistance as IRM options will be very limited.116GLOBAL PLAN FOR INSECTICIDE RESISTANCE MANAGEMENT IN MALARIA VECTORS (GPIRM)
Annex 8 Main hypotheses usedto model the impact ofinsecticide resistanceon malaria burdenSeveral experts were consulted in designing modelling for theGPIRM. These included teams from the MRC Centre for OutbreakAnalysis and Modelling, Imperial College London, and TulaneUniversity School of Public and Tropical Medicine.Inputs.The model is based on data on current populations at risk in eachcountry, malaria incidence rates (1), coverage rates with indoorresidual spraying (IRS) and long-lasting insecticidal nets (LLINs), theprotective efficacy 1 of IRS and LLINs, and estimates of insecticideuse for IRS and LLINs (pyrethroids and non-pyrethroids).In the case of full protective efficacy, malaria-related mortality ofchildren under 5 years of age is assumed to be reduced by 55%when LLINs or IRS are used (2), whereas malaria transmissionincidence is assumed to be reduced by 50% with LLINs (3) andby 55% with IRS (as found in a randomized controlled trial in theUnited Republic of Tanzania) (4). There is limited evidence for theprotective efficacy of IRS and LLINs in adults, and it is assumed tobe half that in children. 2In the case of failure of pyrethroids, the protective efficacy of anLLIN is assumed to be 25% (close to that of an untreated net [5])and that of pyrethroid-based IRS to be 10%. Sensitivity analysesshow an efficacy of 15–35% for LLINs and 0–20% for pyrethroidbasedIRS. For the estimates of child mortality, antimalarialtreatment is assumed to be constant at current levels. Theseassumptions are summarized in Table A8.1.1 ‘Protective efficacy on cases’: reduction in malaria incidence with a given control tool; ‘protectiveefficacy on mortality’: reduction in mortality from malarial episodes with a given control tool2 Based on the assumption that adults are not directly protected by nets and IRS to the same extent aschildren because they spend less time under an LLIN or in a sprayed house.117
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WHO Global Malaria ProgrammeGLOBAL
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Navigating the GPIRMExecutive summa
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ContributorsThe Global Plan for Ins
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Elissa Jensen, United States Presid
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ForewordThe past decade has seen un
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1.3 Potential effectof resistance o
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2.2 Country activitiesPillar I. Pla
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PART 3 TECHNICALRECOMMENDATIONSFOR
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PART 1THE THREAT OFINSECTICIDE RESI
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Attributes of the four classes of i
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1.2 Status ofinsecticideresistance1
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1.2.2 Resistance is widespread and
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Figure 7: Insecticide-resistance me
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The operational impact of resistanc
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Case study 2. Experimental hut tria
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Figure 12: Genetic heritability dri
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Figure 14: kdr West and kdr East mu
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Monitoring of insecticide resistanc
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Figure 15: Impact of insecticide re
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Figure 16: Potential applications o
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PART 2COLLECTIVE STRATEGYAGAINST IN
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Overview of the strategy against in
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2.2.1 Pillar I. Plan and implement
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Step 2: Design an IRM strategy.Prin
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Figure 20: Recommendations for moni
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Examples of regional entomological
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Establish a strong intersectoral bo
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Standardized data format and timely
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Page 75 and 76: 2.5.3 Financial cost of monitoring
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Page 80 and 81: Part 3Technical recommendations for
Page 89 and 90: PART 4NEAR-TERMACTION PLAN4.1 Role
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Page 95 and 96: Technical support to countries• P
Page 97 and 98: Global database• Malaria-endemic
Page 99 and 100: Within 1-2 years.Accelerated fundin
Page 101 and 102: 24. Ranson H et al. Pyrethroid resi
Page 103 and 104: First steps in malaria vector contr
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Page 107 and 108: Annex 2 Long-lastinginsecticidal ne
Page 109 and 110: Annex 3 History of insecticideresis
Page 111 and 112: in many countries, will improve und
Page 113 and 114: Annex 5 Example of ‘tippingpoint
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Page 119 and 120: Figure A8.2: Estimated impact of in
Page 121 and 122: Combinations.How do combinations wo
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Page 125 and 126: Annex 10 Genetic researchagendaBack
Page 127 and 128: Table A11.1: Cost of indoor residua
Page 129 and 130: References.1. United States Preside
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Global plan for insecticide resistance management in malaria vectors

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