HackingEpidemics:UnlockingtheDriversofTransmissionSeasonalitytoBattleVaccine-Preventable Diseases TheUNestimatesthat94.4millionchildrenunder5willdiebetween2016and2030iftheunder-5 mortalityrateisnotdecreased.Currently,infectiousdiseasesthatarepreventableortreatablecause abouthalfofchildhooddeaths.Iworkonchildhoodinfectiousdiseasesbecausemajorimprovements canbeachievedbyoptimizingtheadministrationofexistingvaccinesandtreatments.Thereisa needforsmartervaccinationstrategiesthatareadaptabletochangingepidemiologyand groundedfromanunderstandinginhumanimmunobiology.Wehavethreestudiesthatseekto fulfillthisneed.First,wewilldevelopastatisticaltoolsettomeasurevaccineefficacyinreal-time usingbothtraditionalandnewdatastreams(internetquerydata).Byapplyingourtoolset,wewill evaluatetheimpactofthechickenpoxvaccineintheUS.Second,weaimtoquantifythetransmission andreactivationdynamicsofherpesvirusesinordertomakerecommendationsregardingvaccination effortsandtiming,whileanticipatingtreatmentneeds.Todoso,wewillusedataonhospitalized chickenpox,shingles,herpessimplex,andcytomegaloviruscasesfromCalifornia,spanning3 decades.Hospitaldata,vaccinecoverage,demographydata,anddynamicmathematicalmodelswill becombinedtoestimatetransmissionandreactivationratesforeachofvirus.Wewilldetermineif reactivationisseasonal,whichwehypothesizeisamanifestationofseasonalimmunity.Third,wewill conductahumanclinicalstudytodetermineifimmunityundergoesfunctionalchangesthroughoutthe yearthataffectsusceptibilitytoinfection.Wewillcharacterizebothcircadian(24-hr)andseasonal rhythmsintheimmunesystemandinteractionsamongrhythms.Weproposeaninnovativesampling schemeinvolvingmulti-dayclinicalsessionsinwinter,spring,summer,andfall,whichwouldprovide snapshotsofimmunecellactivityaroundthe24-hrcycle,andacrossseasons.Thisstudywould advanceourknowledgeoftheinseparableinterplaybetweenhumanimmunobiologyandinfectious diseasedynamics.

Public Health Relevance

Thisprojectwillhaveamajorimpactonpublichealthbyachievingtwogoals.First,wewilldevelop statisticaltoolsandmathematicalmodelstoquantifythetransmissionimpactofnewvaccinesinreal- timeastheyarerolled-outintocommunities,leadingtoabetterunderstandingoflong-termprotective effectsofimmunization.Second,wewillconductaclinicalinvestigationtoadvancethefieldofhuman immunology,todetermineifseasonalchangesinimmunityinfluencesusceptibilitytodiseaseswhich wouldaidinthepreventionandtreatmentofdiseases.

Agency
National Institute of Health (NIH)
Institute
Office of The Director, National Institutes of Health (OD)
Type
Early Independence Award (DP5)
Project #
1DP5OD023100-01
Application #
9212533
Study Section
Special Emphasis Panel (ZRG1-RPHB-W (53)R)
Program Officer
Basavappa, Ravi
Project Start
2016-09-19
Project End
2021-08-31
Budget Start
2016-09-19
Budget End
2017-08-31
Support Year
1
Fiscal Year
2016
Total Cost
$372,822
Indirect Cost
$115,768
Name
Princeton University
Department
Biology
Type
Schools of Arts and Sciences
DUNS #
002484665
City
Princeton
State
NJ
Country
United States
Zip Code
08543
Winter, Amy K; Martinez, Micaela E; Cutts, Felicity T et al. (2018) Benefits and Challenges in Using Seroprevalence Data to Inform Models for Measles and Rubella Elimination. J Infect Dis 218:355-364