Abstract

Observational data over 15 years of rotavirus vaccine introduction in Belgium have indicated that rotavirus hospitalisations in children aged <5 years plateaued at a higher level than expected, and was followed by biennial disease peaks. The research objective was to identify factors influencing these real-world vaccine impact data. We constructed mathematical models simulating rotavirus-related hospitalisations by age group and year for those children. Two periods were defined using different model constructs. First, the vaccine uptake period encompassed the years required to cover the whole at-risk population. Second, the post-uptake period covered the years in which a new infection/disease equilibrium was reached. The models were fitted to the observational data using optimisation programmes with regression and differential equations. Modifying parameter values identified factors affecting the pattern of hospitalisations. Results indicated that starting vaccination well before the peak disease season in the first year and rapidly achieving high coverage was critical in maximising early herd effect and minimising secondary sources of infection. This, in turn, would maximise the reduction in hospitalisations and minimise the size and frequency of subsequent disease peaks. The analysis and results identified key elements to consider for countries initiating an optimal rotavirus vaccine launch programme.

Highlights

  • Development and implementation of an appropriate vaccination programme with high vaccine coverage should help to control transmissible infections in a population [1]

  • Newer vaccines developed against diseases caused by rotavirus, Streptococcus pneumoniae, human papillomavirus or meningococci were subject to similar issues around optimum implementation to reach maximum disease control benefit as quickly as possible [5,6]

  • When the new rotavirus vaccines first came onto the market in high-income countries (HICs) in 2006, there was confidence that these vaccines, with their mode of action generating an ‘infection-like’ reactivity that does not lead to severe health outcomes, would move to disease elimination [8,9], as predicted by the first published dynamic models based on results from testing the vaccine in Phase III studies in HICs [10,11]

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Summary

Introduction

Development and implementation of an appropriate vaccination programme with high vaccine coverage should help to control transmissible infections in a population [1]. When the new rotavirus vaccines first came onto the market in high-income countries (HICs) in 2006, there was confidence that these vaccines, with their mode of action generating an ‘infection-like’ reactivity that does not lead to severe health outcomes, would move to disease elimination [8,9], as predicted by the first published dynamic models based on results from testing the vaccine in Phase III studies in HICs [10,11]. These promising modelling [8,9], as predicted by the first published dynamic models based on results from testin2gotfh2e3 vaccine in Phase III studies in HICs [10,11]. Tpoareexdpwlaiinthtthheeceaaurslyesmoofdthelepdriesdcircetpioannsc,iwesebceotnwsetreunctthede raeaml-awthoermldadtiactaal omnordoetlavfoirrutshveaecacrilnyatyieoanrscoamfteprarveadccwinitehinthtreoedaurclytiomnoidnecllupdreindgictvioarnisa,bwlees cthoantstcrouucltdedafafemctatthheemouattciocaml em[o1d8]e,lbfaosretdheoneaorblyseyrevaerds dafattearfvroamccitnheeicnoturondtruyctwiointhinthceluldoninggveastridaebtlaeislethdaotbcsoeurlvdaatifofencst othf erootuatvciormusev[a1c8c],inbaatsieodn oimn pobacset rovveedr dtiamtaef(rtohme RthoetacBoIuSnsttruydwyitihn tBheelgloiunmge)s[t1d9]e.tIaniltehdeoabnsaelryvsaistiponressoenf treodtahveirueswveahccaivneateixotnenimdepdactht iosvreersetiamrceh(tbhyedReovtealBoIpSsintugdaysiencBoneldgimumat)h[e1m9]a.tIicnatlhme oadnaelycsoisveprriensgenlatetedr hyeeraersw. eTheavaeneaxlytesnisdaeldsothdiissrceussesaerschdabtya dfreovmeloopthinegr Ha IsCecsotnhdatminaitthiaetmedataicaUlMmVodcealmcopvaeigrinngsulcahtearsyFeainrsla. nTdh,eUaniatleydsiKs ianlsgoddomisc(uUssKe)s, dAautsatrfriao,mAoutshtrearliHa,ICansdthtahteinUit.Sia.,tefodracUomMpVarciasomnpwaiigthn sthuechanaaslFyisnislafnindd, iUngnsit.eTdhKesiengcdooumn(tUrieKs),wAeurestsreiale, cAteudstbralsiead, aonndatchceesUsStAo ,afdoerqcuoamtepapruisbolinshwedithdtahtae a[1n7a,2ly0s–i2s4fi].nTdhinegds.ifTfehresnet csotruantetrgiieesswanedreesxepleecrtieedncbeasseinddoinffaecrecenstsctoouandtreiqeus aintedpicuabtelisthaedt idt awtas[1n7o,2t0o–b2v4i]o. uTshtehdaitfftehreeimntpsatrcattoefgrioestaavnidruesxvpaecrcieinacteisoinnwdoifufelrdenbet caoffuenctreidesbiyndthiceadteetahialst iotfwthaes vnaoctcoinbveiporuosgtrhaamt tmhe ilmaupnaccht.oTf hroetraeviisruasnveaecdcintoatuionndewrostualnddbtehaefffeacctteodrsbydrtihveindgettahielsroefatlh-we ovralcdciinmepparcotgoraf mromtaelvaiurunschv.aTchcienraetisona ntoeeidetnotuifnydaenrsotapntidmtahlesftaractoergsydfroirvivnagccthineereinatlr-wodourlcdtiiomn.pact of rotavirus vacciTnhatiisornetsoeaidrcehntsihfyoualndohpetlipmaHlIsCtrsathegayt hfoarvveancoctinyeeitnitnrotrdoudcutcioend. rotavirus vaccination but nTohwis wreissehartcohbsehgoiunlda vhaeclpciHnaItCiosnthcaatmhpavaeignnostuyceht ianstrSowduitczeedrlraontdav, iFrruasnvcaec, ctihneatNioenthbeurtnlaonwdsw, oisrhDtoenbmegairnka[2v5a]ctcoiniadteinotnifcyamanpoapigtinmsaulcvhaacsciSnwe iitmzeprleamnde,nFtaratinocne,ptahtehwNaeyth. eInrlapnrdins-, ocirpDlee,nomuarrrkec[2o5m] mtoeinddenatiofynsancooupltdimaalslovabcecianpepilmicpablelme etontvaaticocninpaatitohnwagy.aIinsptrointhcieprlein, foeucrrteiocnosmtmhaetnmdaatyiofnosllcoowulsdimalislaorbeexappopsulirceabrloeuttoesvaanccdinvaatciocninaagtiaoinnsetffoetchtesr. infections that may follow similar exposure routes and vaccination effects

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