Through grants from BMGF GCE Rd1, NIH (R21 & R01), the Foy lab has been documenting the effects of...
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Transcript of Through grants from BMGF GCE Rd1, NIH (R21 & R01), the Foy lab has been documenting the effects of...
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 2008August 2009
October 2009August 2012
June 2013
August 2013(August 2014)
We have been following SINGLE MDAs, given by HEALTH AUTHORITIES, during the RAINY SEASON for control of onchocerciasis or lymphatic filariasis
Senegal Aug. 2008Senegal Aug. 2009Senegal Oct. 2009Liberia Jun. 2013
Burkina Faso Aug. 2013
MDA coverages at all sites: 76-84%
Bednet coverages at all sites: 38-82%
Senegal Aug. 2012Burkina Faso Aug. 2013
Senegal Aug. 2012Liberia Jun. 2013
Burkina Faso Aug. 2013
Does IVM have an anti-sporogony effect in the field?...does it influence parasite genetics (in the
whole village?, in individual mosquitoes?)
What is the potential for mosquito resistance?...what would it look like?
Gene Description Fold change
No Description 81.75Niemann-Pick Type C-2 80.58
ornithine decarboxylase 45.30No Description 37.57No Description 31.81No Description 21.93
thioredoxin peroxidase 21.77Alkaline phosphatase 2 21.74
protease m1 zinc metalloprotease
21.09
• 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.
How does IVM MDA influence the microepidemiology of malaria transmission in a
village?
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***
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.”
VaccinesJ.O. antennae
brainthoracic ganglia
Other endectocidal drugs Livestock administration
Fritz et al. Ann Trop Med Parasit. 2009Fritz et al. J Med Entomol. 2012Butters et al. Acta Tropica. 2012
…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.
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).
Slater et al. PLoS1 2012 www.thiswormyworld.org
LF roundworm hookworms whipworm
ivermectin albendazole
Wuchereria bancrofti +++
Onchocerca volvulis +++
Ascaris lumbricoides +++ +++
Trichuris trichiura ++ ++
Strongyloides stercoralis +++
Nector americanus +/- ++
Ancyclostoma duodenale +/- ++
lice ++
scabies mites ++
Gnathostoma spp. ++ +
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)
2 or 3 arms:1)Active comparator: Standard treatment (& standard inclusion/exclusion criteria) IVM (150 µg/kg) + ALB (400 mg), 1X @ start of the rains
2)Experimental: Standard treatment + new bednets distributed to the community by the same CHW on the day of the MDA.3)Experimental: Standard treatment + new bednets + additional standard IVM (150 µg/kg) MDA every 3-4 weeks, ~6 times
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
SenegalSenegalDr. Massamba SyllaDr. Massamba Sylla
Dr. Moussa Dieng Sarr and APOCDr. Moussa Dieng Sarr and APOCMactar MansalyMactar Mansaly
AcknowledgmentsAcknowledgmentsFoy LabFoy Lab
Dr. Kevin KobylinskiDr. Kevin Kobylinski Dr. Kelsey DeusDr. Kelsey Deus
Ines Marques da SilvaInes Marques da SilvaMeg GrayMeg Gray
Matt ButtersMatt ButtersJake MeyersJake Meyers
Ben KrajacichBen KrajacichTim BurtonTim Burton
Wojtek NowakWojtek NowakJon SeamanJon Seaman
Jasmine DonkohJasmine DonkohDr. Haoues AloutDr. Haoues Alout
Other CollaboratorsOther CollaboratorsDr. Phillip ChapmanDr. Phillip Chapman
Dr. Jason RasgonDr. Jason RasgonDr. Kathryn PartinDr. Kathryn Partin
Dr. Jason RichardsonDr. Jason RichardsonDr. William Black IVDr. William Black IV
Dr. Saul Lozano-Fuentas Dr. Saul Lozano-Fuentas Dr. Floyd DowellDr. Floyd Dowell
Dr. Alvaro Molina-CruzDr. Alvaro Molina-CruzDr. Carolina Barillas-MuryDr. Carolina Barillas-Mury
Dr. Douglas BrackneyDr. Douglas BrackneyNathan GrubaughNathan Grubaugh
LiberiaLiberiaDr. Fatorma BolayDr. Fatorma Bolay
Dr. Joseph DiClaro IIDr. Joseph DiClaro IILawrence Fakoli IIILawrence Fakoli III
Burkina FasoBurkina FasoDr. Roch DabiréDr. Roch Dabiré
Dr. Abdoulaye DiabatéDr. Abdoulaye DiabatéDr. Rakiswendé YerbangaDr. Rakiswendé Yerbanga
Dr. Thierry LefevreDr. Thierry LefevreDr. Roland Bougouma and Dr. Roland Bougouma and
MoHMoH