National Control Programme

Does indoor residual spraying provide additional protection against clinical malaria over best practice? An A randomised controlled trial in The Gambia

Margaret Pinder, Musa Jawara, Lamin BS Jarju, Ballah Kandeh, David Jeffries, Kolowola Salami, Kalifa Bojang, Umberto D’Alessandro, David J Conway and Steve W Lindsay Trial site

Study conducted in the Upper River Region Basic study design

35 villages-clusters 35 village-clusters with with LLINs DDT-IRS & LLINs Study Plan

• Child cohort of 7,858 children aged 6 months to 14 years • Passive case detection carried out over 2 rainy seasons • X-sectional surveys before & after the rains • Entomology carried out over 2 rainy seasons Study plan

X-sectional Rains X-sectional 2010 survey survey PCD

LLINs IRS

2011 Rains X-sectional survey PCD

Jan Dec

LLINs IRS Quality of IRS 1. Coverage of rooms by village-cluster (n=35) Year Mean 95% CI coverage

2010 86% 82.8-90.2

2011 83% 79.3-86.3

2. DDT was analysed by an independent WHO certified laboratory and found satisfactory 3. Concentration sprayed measured by HPLC Target dose 2.0g/m2 : Mean sprayed 1.7g/m2 Residual activity – WHO cone tests with susceptible colony An. gambiae s.s. 1. On house walls Weeks post- % 95% CI IRS mortality

1 99 97.9-100

6 94 89.3-99.3 LLIN Coverage (Olyset Nets)

Surveys of Child Cohort (6m-14 yrs)

Baseline End of rains End of rains 2010 2011

Children 7474 7032 6807

LLINs 46% 93% 96% Residual activity – WHO cone tests with susceptible colony An. gambiae s.s.

2. On LLIN Months in % mortality 95% CI use

LLIN 0 93 90.9-94.5

LLIN 3 87 82.9-90.1

LLIN 16 91 87.8-93.4

non-LLIN 0 10 7.3-14.1 Baseline characteristics of the cohort

Measure LLIN IRS-LLIN N=3896 N=3949

Female 50% 49%

Mean age (yrs) 6.11 6.18 (6.07-6.23) (6.07-6.29) Children using 45% 46% LLIN Pf parasite rate 1.6% 1.6%

Moderate 4.4% 3.5% anaemia (<80g/L) Haemoglobin g/L 112 113 Primary outcome measure: Passive Case Detection

Case definition Temperature >37.5 ◦C OR history of fever in last 2 days PLUS Positive RDT

CHN training VHWs Malaria in child cohort by PCD I

Outcome Year 1 Year 2

LLIN IRS-LLIN LLIN IRS-LLIN N=3942 N=3887 N=3837 N=3820 Complete data 98% 99% 99% 99% 1 malaria 11% 11% 14% 14% attack >1 malaria 1.4% 0.9% 1.5% 1.3% attack Incidence malaria 0.0468 0.0442 0.0321 0.0341 /child / month Malaria in child cohort PCD III Malaria & anaemia at X-sectional surveys

Outcome Year 1 Year 2

LLIN IRS-LLIN LLIN IRS-LLIN N=3942 N=3887 N=3837 N=3820 Pf parasite 14% 17% 17% 16% rates Moderate 6% 6% 5% 5% anaemia Severe 0.2% 0.2% 0.2% 0.2% anaemia Haemoglobin 113 114 113 112 g/L Entomology – densi ty 6 rooms in 32 clusters sampled monthly Mean An gambiae s.l. n= 672

Year Light traps Exit traps

LLIN IRS-LLIN LLIN IRS-LLIN

1 4.92 3.70 0.54 0.40

(3.05-6.79) (2.03-5.37) (0.18-0.89) (0.15-0.66)

2 1.96 1.27 0.46 0.59

(0.69-3.24) (0.39-2.15) (0-1.15) (0.01-0.10) Entomology: mosquito rates

Outcome Year Light traps

LLIN IRS-LLIN 0.32 0.19 Sp Rate 1 (9/2829) (4/2131) 0.09 0.68 2 (1/1131) (5/773) EIR 1 2.44 1.08

2 0.29 1.45 Implications

Our data indicates that susceptibility of the vectors to DDT and permethrin used in the SANTE study was high over most of the trial area

However we found increasing resistance in 2011 and a foci of high resistance Conclusion

In an area of seasonal malaria with high LLIN coverage, the addition of IRS with DDT did not reduce malaria in children aged 6 months to 14 years.

If LLIN coverage can be maintained at high levels there is no need to conduct IRS Firstly the Field staff National Malaria Control Programme The Gambia NMCP MRC, The Gambia Adam Jagne-Sonko Field Assistants and Nurses Balla Kandeh Musa Jawara Lamin Jarju Kolawole Salami / Anselme Sanou RHT David Conway Sherif Jammeh Umberto DAlessandro Mbye Njie Davies Nwakanma Baba Jeng Lamin Manneh CHN Data Management Team VHW LSHTM FUNDING MRC, UK Steve Lindsay Harpakesh Kaur LLINs donated by Lucy Tusting Sumitomo Chemicals Kate Buck and Terri O’Halloran Susceptibility WHO bioassays tube tests on An. gambiae s.l. raised from larvae caught in the 4 Study Areas Paper % Year Area Exposed Dead 95% C I impregnated mortality

4 DDT 39 39 100 91-100 2010 Control 40 0 0 0-9 1 DDT 118 105 89 82-94 2 DDT 94 83 88 80-94 2011 3 DDT 121 110 91 84-95 Control 228 1 0.4 0-2 4 DDT 72 33 46 34-58 2011 Control 56 1 2 0-10