Slow-release ivermectin formulations for malaria vector control Current status and prospects Carlos Chaccour MD MSc
Slow-release ivermectin formulations for malaria vector control
Current status and prospects
Carlos Chaccour MD MSc
Does IVM kill gambiae?
Direct feedings 24 hours after 200mcg/kgJID 2010
How much IVM kills gambiae?The minimum insecticidal concentration
22.4 ng/ml (18-27 ng/ml) Kobylinski 2010In vitro mixing + membrane
16 ng/ml (14-17 ng/ml) Kobylinski 2012In vitro mixing + membrane
6 ng/ml (4-7 ng/ml) Bousema 2013Volunteers + membrane
MIC + PK = The mosquitocidal window
22 ng/ml
18 hours
6 ng/ml
40 hours
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)
Widening the windowIncrease a single dose (mcg/kg)
i.e. Higher CmaxIntermitent treatment
i.e. Consecutive peaks
Slow release ----> Alter the curve (!)Oral (bowel transit time)Parenteral
First attempt…
Maeda 2003Cunnigham 2006
3 formulations: F – M - XI – II – III per subject
CuantificationsWeekly (12 weeks)Monthly (12-24 weeks)
Extensive toxicology study
1 2 3 4 6 7 8 9 10 11 12 16 20 240
102030405060708090
3F model
Weeks
IVM
levels
(n
g/m
l)
1 2 3 4 6 7 8 9 10 11 12 16 20 240
102030405060708090
3X model
Weeks
IVM
levels
(n
g/m
l)
Stable concentrations can be safely achieved modifying the formulation
Slow release technology available today
The modelled impact on transmission is very promising
Prospects, gaps and messageNew slow release formulations
Slow release pillTransdermal patchesPill + patch approachPegilated subcutaneous
Knowledge gaps
Joint work on TPP
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