1. Slow-release ivermectin formulations for malaria vector control Current status and prospects Carlos Chaccour MD MSc

2. Does IVM kill gambiae? Direct feedings 24 hours after 200mcg/kg JID 2010

3. How much IVM kills gambiae? The minimum insecticidal concentration 22.4 ng/ml (18-27 ng/ml) Kobylinski 2010 In vitro mixing + membrane 16 ng/ml (14-17 ng/ml) Kobylinski 2012 In vitro mixing + membrane 6 ng/ml (4-7 ng/ml) Bousema 2013 Volunteers + membrane

4. MIC + PK = The mosquitocidal window

5. 22 ng/ml 18 hours

6. 6 ng/ml 40 hours

7. Why is this important? A key factor for interrupting transmission would be the time IVM remains in blood above mosquito-killing levels (i.e the width of the window) (Slater et al 2014)

8. Widening the window Increase a single dose (mcg/kg) i.e. Higher Cmax Intermitent treatment i.e. Consecutive peaks Slow release ----> Alter the curve (!) Oral (bowel transit time) Parenteral

9. First attempt… Maeda 2003 Cunnigham 2006

10. 3 formulations: F – M - X I – II – III per subject Cuantifications Weekly (12 weeks) Monthly (12-24 weeks) Extensive toxicology study

13. Stable concentrations can be safely achieved modifying the formulation Slow release technology available today The modelled impact on transmission is very promising

14. Prospects, gaps and message New slow release formulations Slow release pill Transdermal patches Pill + patch approach Pegilated subcutaneous Knowledge gaps Joint work on TPP

15. Juliane Chaccour. Ángel Irigoyen, Ana G. Gil, Felix Hammann, Jose L Del Pozo. The MISSION Team: Santi, Chema, Rocio, Isa, Alberto. Campaign supporters and donnors