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Unravelling the Measles Paradox in Children

— Observational MEASLES DISEASE

For patients and families

In plain language

An automatic summary of structured registry data. It is an orientation aid, not a substitute for the official protocol or a physician assessment.

What is being studied
This is an observational study: the protocol does not assign a study treatment.
Who it may be relevant to
Registry conditions: MEASLES DISEASE. Basic parameters: 4 years — 17 years · All.
What needs checking
Age, condition and sex are only basic indicators. Prior treatment, laboratory values and other mandatory requirements appear in the eligibility criteria below.
Where it takes place
Netherlands
Next step
Save the trial, show it to the treating physician, and confirm current recruitment with the study center. Costs, documents and travel →

Unsure about the terms? Read our patient guide →

Official title

Unravelling the Measles Paradox in Children: a Disease Associated With Both Immune Suppression and Immune Activation

Overview

Measles is caused by measles virus (MeV). The disease is associated with lymphopenia and immune suppression, which is an important cause of measles-associated morbidity and mortality. Measles-induced immune suppression can last several years, whereas measles lymphopenia is usually resolved within two weeks. At the same time, measles induces lifelong immunity. This apparent contradiction, known as the 'measles paradox', was partially solved when investigators demonstrated that MeV infects and depletes pre-existing memory cells, thereby causing 'immune amnesia'. This model is supported by observations in animal models and clinical studies, but several questions remain to be addressed, like the duration of measles-induced amnesia and changes in the immune repertoire after measles. to address the immunological questions regarding MeV infection.

Detailed description

Measles is caused by measles virus (MeV). The disease is associated with lymphopenia and immune suppression, which is an important cause of measles-associated morbidity and mortality. Measles-induced immune suppression can last several years, whereas measles lymphopenia is usually resolved within two weeks. At the same time, measles induces lifelong immunity. This apparent contradiction, known as the 'measles paradox', was partially solved when investigators demonstrated that MeV infects and depletes pre-existing memory cells, thereby causing 'immune amnesia'. This model is supported by observations in animal models and clinical studies, but several questions remain to be addressed, like the duration of measles-induced amnesia and changes in the immune repertoire after measles. Recently, investigators have acquired permission to address these remaining questions in 18-25 years old adults (MEC-2024-0230). However, investigators have reservations about the feasibility of including enough participants between 18 and 25 years old that have not been vaccinated against or infected with MeV; it is possible that investigators will not reach sufficient inclusions to address the immunological questions regarding MeV infection in that protocol. Therefore, investigators propose to additionally study these questions in children in the age of 4 up to and including 17.

Primary outcome measures

  • Compare measles-induced loss of pathogen-specific antibodies [Time frame: 36 months]
  • Compare measles-induced loss of pathogen-specific T-cells [Time frame: 36 months]

Eligibility criteria

Inclusion criteria

Group A

  • Aged 4 - 17 years old
  • Susceptible to measles
  • No pre-existing immunity against measles (vaccination or earlier infection)

Group B

  • Aged 4 - 17 years old
  • Protected against measles due to vaccination or earlier infection

Exclusion criteria

A potential subject who meets any of the following criteria will be excluded from participation in this study:

  • Diagnosed chronic disease that lasted over 3 months
  • Immune suppression (due to medication or underlying disease)
  • Group A; Detectable MeV-antibodies in the T1 blood sample

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: Yes

Study design

Observational model
Case-control

Study locations

Netherlands · 1 center
  • ErasmusMC — Rotterdam

Publications

  • van Velzen E, de Coster E, van Binnendijk R, Hahne S. Measles outbreak in an anthroposophic community in The Hague, The Netherlands, June-July 2008. Euro Surveill. 2008 Jul 31;13(31):18945. No abstract available. PMID 18761905
  • Mollema L, Harmsen IA, Broekhuizen E, Clijnk R, De Melker H, Paulussen T, Kok G, Ruiter R, Das E. Disease detection or public opinion reflection? Content analysis of tweets, other social media, and online newspapers during the measles outbreak in The Netherlands in 2013. J Med Internet Res. 2015 May 26;17(5):e128. doi: 10.2196/jmir.3863. PMID 26013683
  • Laksono BM, de Vries RD, Verburgh RJ, Visser EG, de Jong A, Fraaij PLA, Ruijs WLM, Nieuwenhuijse DF, van den Ham HJ, Koopmans MPG, van Zelm MC, Osterhaus ADME, de Swart RL. Studies into the mechanism of measles-associated immune suppression during a measles outbreak in the Netherlands. Nat Commun. 2018 Nov 23;9(1):4944. doi: 10.1038/s41467-018-07515-0. PMID 30470742
  • Knol M, Urbanus A, Swart E, Mollema L, Ruijs W, van Binnendijk R, Te Wierik M, de Melker H, Timen A, Hahne S. Large ongoing measles outbreak in a religious community in the Netherlands since May 2013. Euro Surveill. 2013 Sep 5;18(36):pii=20580. doi: 10.2807/1560-7917.es2013.18.36.20580. PMID 24079377
  • Van Den Hof S, Smit C, Van Steenbergen JE, De Melker HE. Hospitalizations during a measles epidemic in the Netherlands, 1999 to 2000. Pediatr Infect Dis J. 2002 Dec;21(12):1146-50. doi: 10.1097/00006454-200212000-00012. PMID 12488666
  • Mina MJ, Kula T, Leng Y, Li M, de Vries RD, Knip M, Siljander H, Rewers M, Choy DF, Wilson MS, Larman HB, Nelson AN, Griffin DE, de Swart RL, Elledge SJ. Measles virus infection diminishes preexisting antibodies that offer protection from other pathogens. Science. 2019 Nov 1;366(6465):599-606. doi: 10.1126/science.aay6485. PMID 31672891
  • Rennick LJ, de Vries RD, Carsillo TJ, Lemon K, van Amerongen G, Ludlow M, Nguyen DT, Yuksel S, Verburgh RJ, Haddock P, McQuaid S, Duprex WP, de Swart RL. Live-attenuated measles virus vaccine targets dendritic cells and macrophages in muscle of nonhuman primates. J Virol. 2015 Feb;89(4):2192-200. doi: 10.1128/JVI.02924-14. Epub 2014 Dec 3. PMID 25473055
  • de Vries RD, Lemon K, Ludlow M, McQuaid S, Yuksel S, van Amerongen G, Rennick LJ, Rima BK, Osterhaus AD, de Swart RL, Duprex WP. In vivo tropism of attenuated and pathogenic measles virus expressing green fluorescent protein in macaques. J Virol. 2010 May;84(9):4714-24. doi: 10.1128/JVI.02633-09. Epub 2010 Feb 24. PMID 20181691

Identifiers

NCT: NCT06923631 · NL-009458

Primary sources (government registries)

View this study on ClinicalTrials.gov ↗