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 HygieneOctober 26, 2015

Philip Ricks, PhD

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

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?

Malaria Prevalence (microscopy) Among Children <5 Years Ghana by Region, 2014

~25 million pop 10 Regions ~240,000 km2

An. gambiae s.I. National parasitemia

prevalence: 28% *Ashanti

17%

Northern40%

Western39% Central

38%

Upper West38%

Upper East12%

Brong Ahafo27%

Eastern29%

Volta25%

Greater Accra11%

* Demographic Health Survey, 2014Ghana Statistical Services

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.

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%)

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

PMI IRS in Northern Region

7

Entomological surveillance sites, 4 districts

• 2 original IRS districts

• 1 control district

• 1 new IRS district

Entomological monitoring

• Vector behavior

• Malaria transmission

• Insecticide resistanceo WHO tube assayo Molecular analyses

PMI-supported IRS in GhanaEntomological Monitoring

PMI-supported IRS in GhanaInsecticide 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

An. gambiae s.l. Susceptibility to WHO-recommended InsecticidesOriginal PMI IRS Districts, 2009 – 2011 *

Group of Insecticide Type of insecticide2009Mean

Mortality (%) 24hr

2010Mean

Mortality (%) 24hr

2011Mean

Mortality (%) 24hr

Organophosphate

Fenitrothion (1%) 97.3 95.0 100.0Malathion (5%) 96.3 98.3 95.0

Carbamate

Propoxur (0.1%) 98.6 98.3 -Bendiocarb (0.1%) 88.8 96.7 96.7

Pyrethroid

Alphacypermethrin (0.4%) 100 88.5 96.7Deltamethrin (0.05%) 95.0 86.7 84.6Lambda- cyhalothrin (0.05%) 88.8 70.0 76.7

* Excludes Bunkprugu-Yunyoo 10

Alp

ha-c

yper

met

hrin

0.5

%

Piri

mip

hos-

met

hyl 0

.25%

Bend

ioca

rb 0

.1%

DD

T 4%

Alp

ha-c

yper

met

hrin

0.5

%

Piri

mip

hos-

met

hyl 0

.25%

Bend

ioca

rb 0

.1%

DD

T 4%

2013 2014

0%10%20%30%40%50%60%70%80%90%

100%SND (IRS 2008-2014) TKD (IRS 2008-2012) TML (No IRS)

Per

cent

age

Mor

tali

ty (%

)

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

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

Community Parasitemia Surveys in Bunkpurugu Yunyoo District (BYD)

2010-2014

An IRS Impact Assessment

An. gambiae s.l. Susceptibility to WHO-recommended InsecticidesBYD, 2011-13

Group of Insecticide Type of insecticide2011Mean

Mortality (%) 24hr

2012Mean

Mortality (%) 24hr

2013Mean

Mortality (%) 24hr

Organophosphate Fenitrothion (1%) - 95.3 100.0Pirimiphos-methyl 100.0

Carbamate Propoxur (0.1%) - 95.0Bendiocarb (0.1%) 100.0 90.2 93.5

PyrethroidAlphacypermethrin (0.4%) 95.0 94.3 89.0Deltamethrin (0.05% 100.0 85.0 61.0Lambda- cyhalothrin (0.05%) 95.0

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

BYD Community Parasitemia Survey Timeline

2010 Baselin

e Survey

2010 Ento

Monitoring

2011 IRS

started

2011-2014

Follow-up

Surveys

BYD Community Parasitemia SurveysEnthusiastic Participation?

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

18

52%50%

48%

21% 22%

0%

10%

20%

30%

40%

50%

60%

2010 (N=1,923) 2011 (N=2,040) 2012 (N=2,026) 2013 (N=1,311) 2014 (N=1,408)

No IRSPyrethroids Organophosphates

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

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

Challenges (2)

Other variables

• Case management and malaria in pregnancy

• Bed net coverage and insecticide used in bed nets

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)

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

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

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

Thank You

Philip Ricks, PhD ( pmricks@cdc.gov)

Back Up Slides

Using Data for Decision-making (1)When to Change IRS Target Area/District

IRS discontinued in Savelugu Nanton District due to low structure coverage

Using Data for Decision-making (2)When to Change IRS Target Area/District

2014IRS

discontinued in SND, coverage and resistance

2013-2014IR monitoring showed 100%

susceptibility to OPs in

Kumbungu

2015IRS re-started in

Kumbungu District

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

30

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

31

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

Control district: No IRS, 2010-2014

Change in Infective Bites/Person/Night (EIR), 2010-2014 (1)

Insecticide changed from PYR to OP

Change in Infective Bites/Person/Night (EIR), 2010-2014 (2)

Pyrethroid-based IRS

IRS withdrawn from Tolon-Kumbungu

District

Change in Infective Bites/Person/Night (EIR), 2010-2014 (3)

District Start IRS Stop Change to OP

West Mamprusi 2008 2012

Savelugu Nanton 2008 post-2014 2012

Karaga 2008 post-2012 Stopped

Gushiegu 2008 post-2012 Stopped

Tolon-Kumbugu 2008 post-2012Stopped\

Restarted in Kumbungu 2105

East Mamprusi 2009 2012

Saboba 2010 post-2012 Stopped

Chereponi 2010 post-2012 Stopped

Bunkprugu-Yunyoo 2011 2013

History of IRS in Northern Region, Ghana 2008 - present

2010 - No IRS 2011 - Pyrethroids 2012 - Pyrethroids 2013 - OPs 2014 - OPs0%

10%

20%

30%

40%

50%

60%

0

20

40

60

80

100

120

140

Parasitemia Prevalence EIR

EIR

(in

fec

tiv

e b

ite

s/p

ers

on

/ye

ar)

Perc

ent

Par

asit

e P

reva

lenc

e

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

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

EIR

Pre

vale

nce

Association Between EIR and Malaria Prevalence

0.25

0.50

0.75

1.00

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

Evolution of PMI IRSin Ghana’s Northern Region

Year

Number of DistrictsSprayed Insecticide Used

CoverageRate of

Targeted Structures

Total Population Protected

2008 5 Pyrethroids > 85% 601,973

2009 6 Pyrethroids 94% 708,103

2010 8 Pyrethroids 97% 849,620

2011 9* Pyrethroids 92% 926,699

2012 9

6 Pyrethroids2 Organophosphates 1 Both insecticides 93% 941,240

2013 4 Organophosphate 91% 534,060

2014 4 Organophosphates 83% 570,572

2015 5 Organophosphates 92% 553,954

* Last/Newest district added in 2011, Bunkprugu-Yunyoo

Susceptibility Status of Local An. gambiae s.l. against WHO-recommended Insecticides for IRS, Northern Region, February 2008

Group of insecticide Type of insecticide Mean # tested

Mean KD (%) 60min

Mean Mortality (%) 24hr

Corrected Mortality (%)

Organophosphate Malathion 20 100 100  100.0

Organochlorine DDT 20 41.2 70 62.5

Carbamate Propoxur 20 96.2 91.2 90.3

Pyrethroid Deltamethrin 20 98.7 96.2 95.3

  Permethrin (0.75%) 20 91.2 86.2 85.5  Cyfluthrin 20 98.7 98.7 98.6

  Lambdacyhalothrin 24.5 94.8 98.9 98.9

  Deltamethrin 19.5 98.7 96.1 96.1

  Permethrin (0.05%) 25 93 90 89.4

Susceptibility Status of Local An. gambiae s.l. against WHO-recommended Insecticides for IRS, Northern Region, 2010

Group ofInsecticide Type of insecticide

Mean # tested

Mean KD (%)

60min

Mean Mortality (%)

24hrCorrected

Mortality (%)Organophosphate Fenitrothione (1%) 20 12.5 95.0 97.3

  Malathion (5%) 20 72.5 98.3 96.3Organochlorine Dieldrin (4%) 20 1.25 - 26.3

  DDT (4%) 20 5 - 28.6Carbamate Propoxur (0.1%) 20 93.7 98.3 98.6

  Bendiocarb (0.1%) 20 45.0 96.7 88.8

Pyrethroid Alphacypermethrin (0.4%) 20 33.888.5

100  Deltamethrin (0.05% 20 90.5 86.7 95.0

  Lambda- cyhalothrin (0.05%) 

20 

6.3

 

70% 

88.8

Susceptibility Status of Local An. gambiae s.l. against WHO-recommended Insecticides for IRS, Northern Region, 2009

Group ofInsecticide Type of insecticide

Mean # tested

Mean KD (%)

60min

Mean Mortality (%)

24hrCorrected

Mortality (%)Organophosphate Fenitrothione (1%) 20 12.5 97.3 97.3

  Malathion (5%) 20 72.5 96.3 96.3Organochlorine Dieldrin (4%) 20 1.25 26.3 26.3

  DDT (4%) 20 5 28.6 28.6Carbamate Propoxur (0.1%) 20 93.7 98.7 98.6

  Bendiocarb (0.1%) 20 45.0 88.8 88.8

Pyrethroid Alphacypermethrin (0.4%) 20 33.8 100 100  Deltamethrin (0.05% 20 90.5 95.0 95.0

  Lambda- cyhalothrin (0.05%) 

20 

6.3 

88.8 

88.8

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

Bunkpurugu-Yunyoo (IRS) 2010(Pre-IRS)

2011(Pyrethroid)

2012 (Pyrethroid)

2013 (Organo-phosphate, OP)

2014 (Organo-phosphate,

OP)

1 Annual Entomological Inoculation Rate (EIR) 127.0 87.1 6.0 6.8 3.3

2 Mosquito Parity 74.5% 64.7% 43.1% 28.2% 24.3% 3 Mosquito indoor resting density N/A 3.0 1.5 0.2 0.1

Savelugu-Nanton (IRS) 2010(Pyrethroid)

2011(Pyrethroid)

2012 (OP)

2013 (OP)

2014 (OP)

Annual EIR 7.0 9.2 10.3 0.0 0.0Mosquito Parity N/A 44.8% 37.4% 27.5% 28.1%Mosquito indoor resting density N/A 1.2 1.6 0.4 0.7

Tolon-Kumbungu (Partial IRS) 2010(Pyrethroid)

2011(Pyrethroid)

2012 (Pyrethroid)

2013 (No IRS)

2014 (No IRS)

Annual EIR 21.0 24.0 102.8 93.3 166.9Mosquito Parity N/A 53.3% 46.6% 50.4% 68.5%Mosquito indoor resting density 0.9 0.8 0.9 0.7 0.9

Tamale (Non-IRS) 2010(No IRS)

2011(No IRS)

2012 (No IRS)

2013 (No IRS)

2014 (No IRS)

Annual EIR 110.0 135.0 104.8 160.9 113.9Mosquito Parity N/A 68.6% 65.8% 64.3% 72.3%Mosquito indoor resting density 3.1 2.6 1.6 1.7 2.31 Mosquito Annual Entomological Inoculation Rate (EIR): no. infective bites/person/year2 Mosquito Parity: % of mosquitoes that had laid eggs3 Mosquito indoor resting density: no. mosquitoes/person/room/night

Selected Entomological Variables, IRS and non-IRS Districts, 2010-2014

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)

West Africa Climate