1. The Importance of Insecticide Resistance Monitoring to Maintain IRS Program Effectiveness PMI Experiences in Northern Ghana CDC Resident Advisor for President’s Malaria Initiative, Ghana Annual Conference of the American Society for Tropical Medicine and Hygiene October 26, 2015 Philip Ricks, PhD

2. Insecticide Resistance (IR) Monitoring in President’s Malaria Initiative (PMI) IRS Districts, Northern Ghana  Outline Background on Ghana and malaria History of PMI IRS in Northern Ghana IR Monitoring in original and new districts o Methods, insecticide selection/changes, and impact of changes Challenges and lessons learned

3.  IRS program effectiveness depends on: Initial selection of an effective insecticide prior to IRS in naïve areas Early IR detection Developing an appropriate IR management strategy Why is IR Monitoring Important?

4. Malaria Prevalence (microscopy) Among Children <5 Years Ghana by Region, 2014  ~25 million pop  10 Regions  ~240,000 km 2  An. gambiae s.I.  National parasitemia prevalence: 28% * Ashanti 17% Northern 40% Western 39% Central 38% Upper West 38% Upper East 12% Brong Ahafo 27% Eastern 29% Volta 25% Greater Accra 11% * Demographic Health Survey, 2014 Ghana Statistical Services

5. The Northern Region  Savannah climate/semi-arid, Sahel One rainy season, May/June-Sep/Oct One peak malaria transmission season, 3-4 months, Aug-Nov Main malaria vector: An. gambiae s.l.  Savannah climate/semi-arid, Sahel One rainy season, May/June-Sep/Oct One peak malaria transmission season, 3-4 months, Aug-Nov Main malaria vector: An. gambiae s.l.  30% of Ghana’s land area but only 10% of national pop.  Chosen for PMI-supported IRS Focus region for Government of Ghana Lower socio-economic development High malaria rate (>40%)  30% of Ghana’s land area but only 10% of national pop.  Chosen for PMI-supported IRS Focus region for Government of Ghana Lower socio-economic development High malaria rate (>40%)

6. PMI-supported IRS in Ghana Geography and Population Coverage  5 Northern Region districts selected for initial IRS, 2008  9 districts covered by 2012, last one added in 2011 Average coverage rate of targeted structures (2008-2015): 91% o Annual range: 83% - 97% Avg. annual population protected by IRS (2008-2015): 710,778 people o Annual range: 534,060 - 941,240

7. PMI IRS in Northern Region 7

8.  Entomological surveillance sites, 4 districts 2 original IRS districts 1 control district 1 new IRS district  Entomological monitoring Vector behavior Malaria transmission Insecticide resistance o WHO tube assay o Molecular analyses PMI-supported IRS in Ghana Entomological Monitoring

9. PMI-supported IRS in Ghana Insecticide Selection & Transition  Pyrethroid-based insecticide (alphacypermethrin) used exclusively 2008-2011 Transition to long-lasting organophosphates (OP), pirimiphos-methyl, began in 2012/13 due to IR Number of sprayed districts reduced from 9 to 5, due to cost OP used in all 5 PMI-supported NR districts by 2013

10. An. gambiae s.l. Susceptibility to WHO-recommended Insecticides Original PMI IRS Districts, 2009 – 2011 * Group of InsecticideType of insecticide 2009 Mean Mortality (%) 24hr 2010 Mean Mortality (%) 24hr 2011 Mean Mortality (%) 24hr Organophosphate Fenitrothion (1%)97.3 95.0 100.0 Malathion (5%)96.3 98.3 95.0 Carbamate Propoxur (0.1%)98.6 98.3 - Bendiocarb (0.1%)88.8 96.7 Pyrethroid Alphacypermethrin (0.4%)100 88.5 96.7 Deltamethrin (0.05%)95.0 86.7 84.6 Lambda- cyhalothrin (0.05%)88.870.076.7 * Excludes Bunkprugu-Yunyoo 10

11. An. gambiae s.l. Susceptibility to WHO-recommended Insecticides Original PMI IRS Districts, 2013-2014

12. Limitations of 2008 Insecticide Selection  Large amount of data from Obuasi (>600 km south) Different climate Bi-modal transmission season IRS and other vector control measures since 2004  Gaps in IR mapping, sparse data from Northern Region  High agricultural insecticide use in Ghana

13. Community Parasitemia Surveys in Bunkpurugu Yunyoo District (BYD) 2010-2014 An IRS Impact Assessment

14. An. gambiae s.l. Susceptibility to WHO-recommended Insecticides BYD, 2011-13 Group of InsecticideType of insecticide 2011 Mean Mortality (%) 24hr 2012 Mean Mortality (%) 24hr 2013 Mean Mortality (%) 24hr Organophosphate Fenitrothion (1%)-95.3100.0 Pirimiphos-methyl100.0 Carbamate Propoxur (0.1%)-95.0 Bendiocarb (0.1%)100.090.293.5 Pyrethroid Alphacypermethrin (0.4%)95.094.389.0 Deltamethrin (0.05%100.085.061.0 Lambda- cyhalothrin (0.05%)95.0

15.  Cross-sectional community survey among children under 5 Years to measure prevalence of parasitemia, pre and Post IRS Finger stick Fever Questionnaire administered to caregiver BYD Community Parasitemia Survey: Methods

16. BYD Community Parasitemia Survey Timeline 2010 Baseline Survey 2010 Ento Monitoring 2011 IRS started 2011-2014 Follow-up Surveys

17. BYD Community Parasitemia Surveys Enthusiastic Participation?

18. Prevalence of Children <5 Years with Parasitemia in BYD, 2010-2014 18

19. Susceptibility Status of Local An. gambiae s.l. against WHO-recommended Insecticides in PMI IRS Districts, 2014

20. Challenges (1)  Implications of insecticide changes Cost Geographic coverage  epidemiological, socio-economic, political impacts  Limitations of IR monitoring Time/geographic coverage Insecticides monitored: past and present Yearly variations

21. Challenges (2)  Other variables Case management and malaria in pregnancy Bed net coverage and insecticide used in bed nets

22. Summary of IRS in Northern Region  IR monitoring crucial to maintain effectiveness of IRS Limited data for initial insecticide selection (2008) Informed decision to switch insecticides (2012) Complemented knowledge from community parasitemia prevalence surveys (2010-2014)

23. Lessons Learned (1)  IR monitoring needs to encompass: Appropriate time frames, including pre-IRS Appropriate geographic coverage Information on current and past agricultural insecticide use Testing of proposed and potential insecticides/insecticide classes

24. Lessons Learned (2)  IR monitoring needs to be a central part of national vector control program Capacity-building for NMCP  IR data need to be properly weighed against other factors

25. Acknowledgments  Noguchi Memorial Institute for Medical Research  Ghana National Malaria Control Program  Abt/AIRS  Participants in AP monitoring and their families  AP Survey Interviewers & Lab technicians  Community Volunteers  District Health Directorates  Regional Health Directorate for Northern Ghana  Peace Corps Volunteers  Ghana Field Epidemiology and Lab Training Program students

26. Thank You Philip Ricks, PhD ( pmricks@cdc.gov)

27. Back Up Slides

28. Using Data for Decision-making (1) When to Change IRS Target Area/District  IRS discontinued in Savelugu Nanton District due to low structure coverage

29. Using Data for Decision-making (2) When to Change IRS Target Area/District 2014 IRS discontinued in SND, coverage and resistance 2013-2014 IR monitoring showed 100% susceptibility to OPs in Kumbungu 2015 IRS re-started in Kumbungu District

30. Distribution of Ace-1 Resistance Allele among An coluzzi, 2013 30

31. Bunkprugu Yunyoo District (BYD) AP Monitoring 2010-2014 Results 31

32. Change in Infective Bites/Person/Night (EIR) Bunkpurugu-Yunyoo District, 2010-2014

33. Control district: No IRS, 2010-2014 Change in Infective Bites/Person/Night (EIR), 2010-2014 (1)

34. Insecticide changed from PYR to OP Change in Infective Bites/Person/Night (EIR), 2010-2014 (2)

35. Pyrethroid-based IRS IRS withdrawn from Tolon- Kumbungu District Change in Infective Bites/Person/Night (EIR), 2010-2014 (3)

36. DistrictStart IRSStopChange to OP West Mamprusi20082012 Savelugu Nanton2008post-20142012 Karaga2008post-2012Stopped Gushiegu2008post-2012Stopped Tolon-Kumbugu2008post-2012 Stopped\ Restarted in Kumbungu 2105 East Mamprusi20092012 Saboba2010post-2012Stopped Chereponi2010post-2012Stopped Bunkprugu-Yunyoo20112013 History of IRS in Northern Region, Ghana 2008 - present

37. Prevalence of Parasitemia among Children < 5 Years and EIR (infective bites/person/year), BYD (2010-2014)

38. Distribution of Entomological Inoculation Rate (EIR) in IRS and non-IRS areas, 2010 - 2014

39. EIR Prevalence Association Between EIR and Malaria Prevalence 0.25 0.50 0.75 1.00

40. 2013 Susceptibility Status of Local An. gambiae s.l. against WHO-recommended Insecticides for IRS, by District

41. Evolution of PMI IRS in Ghana’s Northern Region Year Number of Districts SprayedInsecticide Used Coverage Rate of Targeted Structures Total Population Protected 20085Pyrethroids> 85%601,973 20096Pyrethroids94%708,103 20108Pyrethroids97%849,620 20119*Pyrethroids92%926,699 20129 6 Pyrethroids 2 Organophosphates 1 Both insecticides93%941,240 20134Organophosphate91%534,060 20144Organophosphates83%570,572 2015 5Organophosphates92%553,954 * Last/Newest district added in 2011, Bunkprugu-Yunyoo

42. Susceptibility Status of Local An. gambiae s.l. against WHO-recommended Insecticides for IRS, Northern Region, February 2008 Group of insecticideType of insecticideMean # tested Mean KD (%) 60min Mean Mortality (%) 24hr Corrected Mortality (%) OrganophosphateMalathion20100 100.0 OrganochlorineDDT2041.27062.5 CarbamatePropoxur2096.291.290.3 PyrethroidDeltamethrin2098.796.295.3 Permethrin (0.75%)2091.286.285.5 Cyfluthrin2098.7 98.6 Lambdacyhalothrin24.594.898.9 Deltamethrin19.598.796.1 Permethrin (0.05%)25939089.4

43. Susceptibility Status of Local An. gambiae s.l. against WHO-recommended Insecticides for IRS, Northern Region, 2010 Groupof InsecticideType of insecticide Mean # tested Mean KD (%) 60min Mean Mortality (%) 24hr Corrected Mortality (%) OrganophosphateFenitrothione (1%)2012.5 95.0 97.3 Malathion (5%)2072.5 98.3 96.3 OrganochlorineDieldrin (4%)201.25 - 26.3 DDT (4%)205 - 28.6 CarbamatePropoxur (0.1%)2093.7 98.3 98.6 Bendiocarb (0.1%)2045.0 96.7 88.8 PyrethroidAlphacypermethrin (0.4%)2033.8 88.5 100 Deltamethrin (0.05%2090.5 86.7 95.0 Lambda- cyhalothrin (0.05%) 20 6.3 70% 88.8

44. Susceptibility Status of Local An. gambiae s.l. against WHO-recommended Insecticides for IRS, Northern Region, 2009 Groupof InsecticideType of insecticide Mean # tested Mean KD (%) 60min Mean Mortality (%) 24hr Corrected Mortality (%) OrganophosphateFenitrothione (1%)2012.597.3 Malathion (5%)2072.596.3 OrganochlorineDieldrin (4%)201.2526.3 DDT (4%)20528.6 CarbamatePropoxur (0.1%)2093.798.798.6 Bendiocarb (0.1%)2045.088.8 PyrethroidAlphacypermethrin (0.4%)2033.8100 Deltamethrin (0.05%2090.595.0 Lambda- cyhalothrin (0.05%) 20 6.3 88.8 88.8

45. Monthly Trends in Cone Bio Assay Mortalities in IRS Districts, August 2009 – April 2010

46. Bunkpurugu-Yunyoo (IRS) 2010 (Pre-IRS) 2011 (Pyrethroid) 2012 (Pyrethroid) 2013 (Organo-phosphate, OP) 2014 (Organo-phosphate, OP) 1 Annual Entomological Inoculation Rate (EIR)127.087.16.06.83.3 2 Mosquito Parity74.5%64.7%43.1%28.2%24.3% 3 Mosquito indoor resting densityN/A3.01.50.20.1 Savelugu-Nanton (IRS) 2010 (Pyrethroid) 2011 (Pyrethroid) 2012 (OP) 2013 (OP) 2014 (OP) Annual EIR7.09.210.30.0 Mosquito ParityN/A44.8%37.4%27.5%28.1% Mosquito indoor resting densityN/A1.21.60.40.7 Tolon-Kumbungu (Partial IRS) 2010 (Pyrethroid) 2011 (Pyrethroid) 2012 (Pyrethroid) 2013 (No IRS) 2014 (No IRS) Annual EIR21.024.0102.893.3166.9 Mosquito ParityN/A53.3%46.6%50.4%68.5% Mosquito indoor resting density0.90.80.90.70.9 Tamale (Non-IRS) 2010 (No IRS) 2011 (No IRS) 2012 (No IRS) 2013 (No IRS) 2014 (No IRS) Annual EIR110.0135.0104.8160.9113.9 Mosquito ParityN/A68.6%65.8%64.3%72.3% Mosquito indoor resting density3.12.61.61.72.3 1 Mosquito Annual Entomological Inoculation Rate (EIR): no. infective bites/person/year 2 Mosquito Parity: % of mosquitoes that had laid eggs 3 Mosquito indoor resting density: no. mosquitoes/person/room/night Selected Entomological Variables, IRS and non-IRS Districts, 2010-2014

47. PMI Entomological Monitoring Sites, 2015  Original IRS Districts Kumbungu (2 sites), withdrawn 2012 and restarted 2015 Savelugu Nanton (3 sites), withdrawn 2014 Tolon District (2 sites), withdrawn 2012  New IRS District Bunkpurugu-Yunyoo (4 sites), started 2011  Control District (Never sprayed) Tamale (3 sites)

48. West Africa Climate