1. Impact of the combination of LLIN and IRS versus LLIN alone on vector density and malaria transmission in Northern Tanzania: A community randomized Controlled Trial Natacha Protopopoff, Alex Wright, Reginald Kavishe, Philippa West, Robinson Tigererwa, Franklin W. Mosha, William Kisinza, Immo Kleinschmidt, Mark Rowland Kilimanjaro Christian Medical College

2. Background ITN and IRS have been shown to be individually effective in preventing malaria. Scale-up over the past decade in Africa Is there an additional benefit to using both simultaneously? Evidence so far is ambivalent: Randomized control trial in Sudan/Gambia/Benin no added effect Other trial e.g. Bioko added impact

3. Rural district on west shore of lake Victoria, Tanzania Altitude ranging from 1100-1600m Population of 425,000 IRS since 2007 yearly round with pyrethroid Lambda-cyhalothrin and bendiocarb in 2012 Prevalence 23% varying between 1% to 62% in June 2011 Two malaria transmission seasons November/December and June/July Study area

4. Two arms clusters randomized control trial (50 clusters) Objective: To assess whether IRS with bendiocarb plus LLINs provide added protection against malaria Outcomes – Malaria prevalence and aneamia – Entomological Inoculation Rate (EIR) – Mosquito density Year 1: BaselineYear 2: Intervention Arm AIRS +LLINs Arm BIRS +LLINsLLINs Study design

5. Trial timetable Baseline 2011Intervention year 2012 JanFebMarAprMayJunJulAugSepOctNovDecJanFebMarAprMayJunJulAugSepOctNovDec LLIN XS 1 XS 2 XS A XS B XS C Monthly Entomological XS = 7 roundsMonthly Entomological XS = 12 rounds IRS 1 LLIN LLIN+ IRS XS 1 XS 2 XS A XS B XS C Monthly Entomological XS = 7 roundsMonthly Entomological XS = 12 rounds IRS 1 LLIN IRS 2 IRS: Intervention - 2 bendiocarb IRS: Baseline - 1 lambdacyhalothrin Net distribution to all population

6. Material & Methods CDC monthly light trap collection – Each month 40 clusters (20 LLIN arm-20 LLIN+IRS arm) 8 houses randomly selected/cluster/month One night collection Laboratory testing – Detection of Sporozoite in Anopheles collected (ELISA) – Real time PCR Taq Man assay for species identification

7. Coverage was assessed with household questionnaire IRS coverage Intervention arm (LLIN + IRS)Control arm (LLIN) IRS % [95% CI], (N) Baseline IRS 201196.4% [94.2-97.8], (1120)92.7% [89.6-95.0], (1062) Post Intervention IRS (Dec11-Jan12)89.3% [85.0-93.6], (634) IRS (Apr12)86.9% [80.9-93.0], (1271)

8. ITN coverage post Control arm (LLIN) % [95% CI], (N) Intervention arm (LLIN + IRS) % [95% CI], (N) Baseline Ownership (at least one net own/household) 95.0% [92.5-96.7], (1060)97.3% [96.2-98.1], (1119) Post intervention Ownership (at least one net own/household) 92.0% [89.8-94.3], (1917)94.0% [91.6-96.3], (1914) Houses with all bed covered51.9% [46.3-57.5], (1917)59.5%[55.6-63.4], (1914) Houses with all bed covered decrease from 61.3% [95%CI: 56.9-65.6] (Jan-Marc 2013) to 41.9% [95%CI: 36.6-47.1] (Oct-Dec 2013)

9. Post intervention results LLIN arm LLIN + IRS arm OutcomeN% / Mean N Ratio95%CIPvalue Mean Culex/HH19043.419092.7RR*=0.660.37-1.190.163 Mean gambiae s.l/HH18921.718930.4RR*=0.160.06-0.440.001 Sporozoite rate30592.5%7171.8%OR=0.730.21-2.540.607 EIR/month/hh 1.2 0.2RR*=0.010.00-0.01<0.001 15,480 mosquitoes collected during these 12 rounds. 26.1% were identified as Anopheles Sporozoite rate 0.4% in Anopheles arabiensis (1/239) * Adjusted for baseline Anopheles density

10. Baseline results 15,860 mosquitoes collected during the seven baseline rounds 45.3% were Anopheles 98.3% Anopheles gambiae s.l. and 0.2% Anopheles funestus. 81.4% (95%CI: 76.0-86.7) An.gambiae s.s. and 18.6% (95%CI: 13.3- 23.9) An.arabiensis. Sporozoite rate in An.arabiensis 0% (N=187) LLIN arm LLIN + IRS arm OutcomeHH no.% / Mean HHno.% / Mean Ratio95%CIPvalue Mean Culex/HH10553.811202.7RR=0.70.4-1.40.301 Mean Ano gambiae s.l/HH10553.111202.2RR=0.70.1-4.40.708 Sporozoite rate13591.7%14662.9%OR=1.71.0-2.80.048 EIR/month/hh 1 1 1.3RR=1.20.3-5.90.803

11. Post intervention result per round IRS

12. Discussions & conclusion This trial shows that using IRS with Bendiocarb combined with pyrethroid ITNs is beneficial compared to using ITNs alone on anopheles density and EIR. Moderate coverage of LLIN High pyrethroid resistance observed in the area (mortality 11% in Anopheles exposed to permethrin) Difference in density observed over all the collection round Arabiensis does not seems to have an important role in malaria transmission

13. Thank you! People of Muleba Project team RTI International Muleba District Medical Office Thank you for listening Kilimanjaro Christian Medical College