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.

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