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Effects of Ivermectin/Albendazole MDAs on Malaria Transmission in West Africa

This study examines the effects of single Mass Drug Administrations (MDAs) of ivermectin/ivermectin+albendazole on malaria transmission in West Africa. The study evaluates the potential for mosquito resistance, the influence on parasite genetics, and the impact on the microepidemiology of malaria transmission. The study also explores the broader concept of making vector blood meals toxic to control malaria transmission.

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Effects of Ivermectin/Albendazole MDAs on Malaria Transmission in West Africa

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  1. Through grants from BMGF GCE Rd1, NIH (R21 & R01), the Foy lab has been documenting the effects of single MDAs of ivermectin/ivermectin + albendazole in West Africa since 2008. Evaluation of ivermectin mass drug administration for malaria transmission control across different West African environments. Alout H, Krajacich BJ, Meyers JI, Grubaugh ND, Brackney DE, Kobylinski KC, DiClaro JWII, Bolay FK, Fakoli LS, Diabate A, Dabire RK, Bougma RW, Foy BD. Malaria Journal. In press. & Alout H et al, Poster Session C, #1635 August 2013 (August 2014) August 2008 August 2009 October 2009 August 2012 June 2013

  2. We have been following SINGLE MDAs, given by HEALTH AUTHORITIES, during the RAINY SEASON for control of onchocerciasis or lymphatic filariasis Senegal Aug. 2008 Senegal Aug. 2009 Senegal Oct. 2009 Liberia Jun. 2013 Burkina Faso Aug. 2013 MDA coverages at all sites: 76-84% Senegal Aug. 2012 Burkina Faso Aug. 2013 Bednet coverages at all sites: 38-82% Senegal Aug. 2012 Liberia Jun. 2013 Burkina Faso Aug. 2013

  3. What is the potential for mosquito resistance?...what would it look like? • Initial observations of stronger ivermectin effects against the A. gambiae RSP strain (Kdr 1014S and elevated GSTe2 and CYP6Z1) compared to the A. gambiae G3 strain (LC50 = 22.4 ng/mL). • Wild A. gambiae collected from treatment villages in W. Africa had a high prevalence of the Kdr 1014F mutation (between 67-98%), yet they all showed susceptibility to ivermectin. • We are currently blood feeding a mixed allele strain on ivermectin in attempt to select for resistance. Does IVM have an anti-sporogony effect in the field?...does it influence parasite genetics (in the whole village?, in individual mosquitoes?) How does IVM MDA influence the microepidemiology of malaria transmission in a village?

  4. This broader concept for malaria transmission control is NOT really about ivermectin per se…. Rather, it is about making a relatively high proportion of vector blood meals over their adult life span toxic, because vectors’ require blood for survival and reproduction, and at least 2 human blood meals to transmit*** Vaccines Other endectocidal drugs Livestock administration J.O. antennae Fritz et al. Ann Trop Med Parasit. 2009 Fritz et al. J Med Entomol. 2012 Butters et al. Acta Tropica. 2012 thoracic ganglia brain Meyers et al, Poster session B, #755 NIH R21 submission: “Antibody targeting of mosquito insecticide antigens” IVCC submission being considered: “Control of outdoor malaria transmission by repeated ivermectin administration to people and livestock in Burkinabé villages.”

  5. …on the other hand, ivermectin is the ‘only game in town’ for the near future, because of its long-term use in MDA and excellent safety profile in humans, and its effects against so many other NTD parasites that are commonly co-endemic in communities afflicted with malaria. Thus, it is ideal for integrated infectious disease control at both the personal and community level. LF hookworms whipworm roundworm Slater et al. PLoS1 2012 www.thiswormyworld.org Kobylinski et al. AJTMH 2014 BMGF GCE Rd. 13 funded trial: Dry-to-rainy season integrated control of NTDs and malaria -the plan is for a modest interventional trial (Phase 3, RCT [villages], parallel assignment). • 2 or 3 arms: • Active comparator: Standard treatment (& standard inclusion/exclusion criteria) IVM (150 µg/kg) + ALB (400 mg), 1X @ start of the rains • Experimental: Standard treatment + new bednets distributed to the community by the same CHW on the day of the MDA. • Experimental: Standard treatment + new bednets + additional standard IVM (150 µg/kg) MDA every 3-4 weeks, ~6 times Primary outcome measures: Time to first malaria episode and malaria incidence over the treatment period in enrolled 0-5 yr old children (active case surveillance) Secondary outcome measures: Monitoring for AEs, molecular force of infection, entomological indices (vector density, parity, sporozoite rates, EIR, W. bancrofti infections), STH prevalence & intensity, questionnaire survey of the CHWs

  6. Acknowledgments Foy Lab Dr. Kevin Kobylinski Dr. Kelsey Deus Ines Marques da Silva Meg Gray Matt Butters Jake Meyers Ben Krajacich Tim Burton Wojtek Nowak Jon Seaman Jasmine Donkoh Dr. HaouesAlout Other Collaborators Dr. Phillip Chapman Dr. Jason Rasgon Dr. Kathryn Partin Dr. Jason Richardson Dr. William Black IV Dr. Saul Lozano-Fuentas Dr. Floyd Dowell Dr. Alvaro Molina-Cruz Dr. Carolina Barillas-Mury Dr. Douglas Brackney Nathan Grubaugh Senegal Dr. Massamba Sylla Dr. MoussaDiengSarr and APOC MactarMansaly Burkina Faso Dr. RochDabiré Dr. AbdoulayeDiabaté Dr. Rakiswendé Yerbanga Dr. Thierry Lefevre Dr. Roland Bougouma and MoH Liberia Dr. FatormaBolay Dr. Joseph DiClaro II Lawrence Fakoli III

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