{"id":11832,"date":"2026-04-20T07:28:17","date_gmt":"2026-04-20T07:28:17","guid":{"rendered":"https:\/\/dodo.proefschriftmaken.nl\/portfolio\/joukje-willemsen\/"},"modified":"2026-05-04T09:51:34","modified_gmt":"2026-05-04T09:51:34","slug":"joukje-willemsen","status":"publish","type":"us_portfolio","link":"https:\/\/dodo.proefschriftmaken.nl\/en\/portfolio\/joukje-willemsen\/","title":{"rendered":"Joukje Willemsen"},"content":{"rendered":"","protected":false},"excerpt":{"rendered":"","protected":false},"author":7,"featured_media":11833,"comment_status":"closed","ping_status":"closed","template":"","meta":{"_acf_changed":false,"footnotes":""},"us_portfolio_category":[45],"class_list":["post-11832","us_portfolio","type-us_portfolio","status-publish","has-post-thumbnail","hentry","us_portfolio_category-new-template"],"acf":{"main_text":"","naam_van_het_proefschift":"Collaborating with Mother Nature","samenvatting":"Het respiratoir syncytieel virus (RSV) is een belangrijke oorzaak van sterfte bij jonge baby\u2019s, vooral in lage- en middeninkomenslanden. Nieuwe manieren om baby\u2019s te beschermen, zoals vaccinatie van zwangere vrouwen, zijn daar vaak nog niet beschikbaar. Dit proefschrift is geschreven met als doel beleidsmakers te ondersteunen bij hun besluitvorming door inzicht te geven in de potenti\u00eble reductie van kindersterfte door RSV-vaccinatie tijdens de zwangerschap.\n\nWe onderzochten eerst op welke leeftijd kinderen overlijden aan RSV en zagen dat verschillen in dataverzameling een grote invloed hebben op deze schattingen. Studies die achteraf gegevens verzamelen laten een hogere leeftijd bij overlijden zien en onderschatten daarmee de mogelijke impact van vaccinatie tijdens de zwangerschap.\n\nVervolgens hebben we een bestaand wiskundig model verbeterd met recente gegevens over ziektelast, afweerreacties en data uit klinische studies. Daarbij hielden we rekening met verschillen tussen landen in het gebruik van gezondheidszorg tijdens de zwangerschap en de acceptatie van vaccinatie in deze periode. We vonden dat vaccinatie tijdens de zwangerschap een aanzienlijk deel van de RSV-gerelateerde sterfte kan voorkomen, vari\u00ebrend van 33% tot 83% per land, met een gemiddeld effect van 55\u201363%.\n\nTot slot bekeken we hoe antistoffen in de eerste levensmaanden afnemen en hoe klinische studies beter kunnen aansluiten bij beleidsbeslissingen. De snelheid waarmee antistoffen afnemen bleek afhankelijk van de hoeveelheid bij de geboorte, wat suggereert dat verschillen tussen te vroeg en op tijd geboren baby\u2019s kleiner zijn dan eerder gedacht. Al met al laat dit proefschrift zien dat betere schattingen van ziektelast, inzicht in bescherming en de uitvoerbaarheid van verschillende strategie\u00ebn essentieel zijn om RSV-vaccinatie tijdens de zwangerschap zo effectief mogelijk in te zetten.","summary":"RSV is one of the leading causes of death among young children worldwide. Although most children experience only mild symptoms, the virus can lead to severe lower respiratory tract infections such as bronchiolitis or pneumonia. Annually, an estimated 100,000 children die from RSV, the vast majority (97%) of whom live in low- and middle-income countries (LMICs), and nearly half of these deaths occur in the first six months of life.\n\nThis thesis investigates the potential impact of maternal vaccination\u2014where pregnant women are vaccinated to transfer antibodies to their unborn child via the placenta\u2014on reducing RSV-related mortality in LMICs.\n\nPart I focuses on the age distribution of children who die from RSV. In Chapter 2, we compare children who die in the hospital with those who die outside the hospital (in the community). We find that children in the community die at a younger age (median 1.5 months) than those in the hospital (median 2.4 months). In Chapter 3, we present the first detailed age distribution of RSV mortality specifically for Gavi-eligible countries. This shows that the burden of mortality is concentrated at a very young age, peaking around one month.\n\nPart II describes the development of a mathematical model to predict the impact of vaccination. In Chapter 4, we use this model to calculate how many deaths in 51 Gavi countries can be prevented. It is estimated that maternal vaccination can prevent 55% to 63% of hospital deaths among children under six months of age. In Chapter 5, we show that small policy differences between the US FDA and the European EMA\u2014such as limiting the vaccination window to 32-36 weeks of pregnancy to minimize the risk of preterm birth\u2014can have major consequences. Such a restriction could lead to an estimated 3,300 additional deaths per year in LMICs.\n\nPart III tests and refines the immunological assumptions in the maternal vaccination model, such as how quickly antibody levels decline in young children and how placental health affects the transfer of maternal antibodies. In Chapter 6, we investigate the half-life of antibodies in preterm and term-born children. Further analysis shows that the difference in protection between preterm and term-born children is likely smaller than previously thought. In Chapter 7, we examine whether placental abnormalities affect the transfer of antibodies from mother to child. We find no clear link.\n\nPart IV reflects on how clinical research can be better designed so that results are more useful for impact models and policy decisions. Chapter 8 describes a meeting on the design of clinical trials for RSV prevention, which revealed that there is often a gap between evidence required for approval and evidence required for effective implementation in LMICs. In Chapter 9, we introduce a new statistical method to analyze the effectiveness of interventions with multiple endpoints.\n\nIn the General Discussion, we combine the key insights from this thesis and conclude that models combining improved disease burden estimates with immunologically informed protection and realistic implementation assumptions are essential to optimally shape the use of RSV vaccination and other prevention strategies.","auteur":"Joukje Willemsen","auteur_slug":"joukje-willemsen","publicatiedatum":"22 mei 2026","taal":"NL","url_flipbook":"https:\/\/ebook.proefschriftmaken.nl\/ebook\/joukjewillemsen?iframe=true","url_download_pdf":"https:\/\/ebook.proefschriftmaken.nl\/download\/9b95ab60-d12a-427a-9869-296156da7e6d\/optimized","url_epub":"","ordernummer":"18827","isbn":"978-90-393-8051-2","doi_nummer":"","naam_universiteit":"Universiteit Utrecht","afbeeldingen":11834,"video_url":"","podcast_url":"","naam_student:":"","binnenwerk":"","universiteit":"Universiteit Utrecht","cover":"","afwerking":"","cover_afwerking":"","design":""},"_links":{"self":[{"href":"https:\/\/dodo.proefschriftmaken.nl\/en\/wp-json\/wp\/v2\/us_portfolio\/11832","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/dodo.proefschriftmaken.nl\/en\/wp-json\/wp\/v2\/us_portfolio"}],"about":[{"href":"https:\/\/dodo.proefschriftmaken.nl\/en\/wp-json\/wp\/v2\/types\/us_portfolio"}],"author":[{"embeddable":true,"href":"https:\/\/dodo.proefschriftmaken.nl\/en\/wp-json\/wp\/v2\/users\/7"}],"replies":[{"embeddable":true,"href":"https:\/\/dodo.proefschriftmaken.nl\/en\/wp-json\/wp\/v2\/comments?post=11832"}],"version-history":[{"count":1,"href":"https:\/\/dodo.proefschriftmaken.nl\/en\/wp-json\/wp\/v2\/us_portfolio\/11832\/revisions"}],"predecessor-version":[{"id":11835,"href":"https:\/\/dodo.proefschriftmaken.nl\/en\/wp-json\/wp\/v2\/us_portfolio\/11832\/revisions\/11835"}],"wp:featuredmedia":[{"embeddable":true,"href":"https:\/\/dodo.proefschriftmaken.nl\/en\/wp-json\/wp\/v2\/media\/11833"}],"wp:attachment":[{"href":"https:\/\/dodo.proefschriftmaken.nl\/en\/wp-json\/wp\/v2\/media?parent=11832"}],"wp:term":[{"taxonomy":"us_portfolio_category","embeddable":true,"href":"https:\/\/dodo.proefschriftmaken.nl\/en\/wp-json\/wp\/v2\/us_portfolio_category?post=11832"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}