Vaccinations in High-Income Populations – Netherlands Study


A recent study explored the nonspecific effects of measles, mumps and rubella, as well as diphtheria, tetanus and pertussis vaccinations in youth from high-income populations.

Vaccinations for diphtheria, tetanus, and pertussis (DTP), measles, and polio confer protection against these infections but are also believed to confer protection against other infections. Factors such as the order of receipt of the vaccinations have been shown to influence these nonspecific effects. In high-income populations, such as in countries like the Netherlands where infant morbidity and mortality due to infectious disease are not prevalent, these nonspecific effects are not widely investigated. Previous studies have shown measles, mumps and rubella (MMR) and DTP vaccines affect the rate of hospital admissions, albeit in opposite ways, as well as affect mortality and morbidity beyond targeting their intended diseases. These studies, however, were observational in nature and thus more susceptible to biases such as the healthy vaccine bias. To further explore the nonspecific effects of MMR and DTP vaccines, researchers examined the rates of hospitalization due to infectious disease in Danish children.

Collecting Data on Vaccinations

Using Praeventis, the national immunization register, researchers collected data on vaccinations among Dutch youth who were born and received vaccinations from January 1, 2005 until December 31, 2012. Following the Dutch national immunisation program, children are recommended to receive inactive DTaP-IPV-Hib vaccines (diphtheria, tetanus and acellular pertussis, DTaP, inactivated polio vaccine, IPV, and Haemophilus influenza type b, Hib) concurrently with a pneumococcal vaccination (PCV) at 2,3,4 and 11 months, and a live MMR vaccine concurrently with a meningococcal disease serogroup C (MenC) vaccination at 14 months. This data was then coordinated with hospital admission data from the national medical register to examine the occurrence of upper and lower respiratory tract infections, gastrointestinal infections and other infections in children that resulted in hospitalizations for at least a day. The final sample population consisted of 1,096,594 children.

The researchers found that 26% of the final study population was hospitalized for at least a day and 74% was hospitalized for less than a day. As age increased from 12 to 24 months, the number of admissions decreased. Among children who received the MMR+MenC vaccine as their most recent vaccine, admission rates also declined, whereas, with children who received the DTaP-IPV-Hib+PCV vaccine as the most recent vaccine, admission rates declined until receipt of the MMR+MenC vaccine, where admission rates then increased until 17 months of age. A similar pattern was seen comparing hospital admissions for those who received the fourth DTaP-IPV-Hib+PCV to those who received the third DTaP-IPV-Hib+PCV vaccine as the most recent vaccination. The rate decreased in those with a fourth DTaP-IPV-Hib+PCV vaccination, and remained stable in children with the third DTaP-IPV-Hib+PCV vaccination until receipt of the fourth vaccination at 11 months, after which it increased until 14 months. The results were recently published in the British Medical Journal.

Lower Hospital Admissions

This study revealed that receipt of a MMR+MenC vaccine versus a DTaP-IPV-Hib+PCV vaccine as the most recent vaccination in youth resulted in lower hospital admissions, but as similar results were seen with a fourth DTaP-IPV-Hib+PCV vaccine compared to a third DTaP-IPV-Hib+PCV vaccine as the most recent vaccination, the non-specific effects are not specific to MMR+MenC but the general result of additional vaccinations.

This study had a large population which allowed the results to be stratified in various ways but was limited in regards to hospital admissions data. The national register received admissions data from hospitals on a voluntary basis, and as such there was a decrease in the amount of data coverage from 97% in 2005 to 25% in 2012. Future studies would benefit from examining acute infections that resulted in general practitioner visits and their relation to the most recent vaccinations.

Healthy Vaccine Bias

The results suggest that healthy vaccine bias may partly explain the decrease in hospital admissions from any cause immediately following a vaccine. Healthy vaccine bias occurs when children who are more susceptible to illness are vaccinated later, or not at all. Because vaccines are not administered to babies who are ill, chronic or frequent illness can delay the vaccine schedule. When the children are no longer ill, they receive their vaccines, and this may result in an overestimation of the beneficial effects of the next vaccine. This study demonstrates that caution must be taken when interpreting the results of observational studies on the non-specific effects of vaccines in high-income populations.

Written by Monica Naatey-Ahumah, BSc


Tielemans, S., de Melker,H, E., Hahné, S.J.M., Boef, A.G.C., van der Klis, F.R.M., Sanders,
E.A.M, van der Sande, M.A.B., Knol, M.J. (2017). Non-specific effects of measles,
mumps, and rubella (MMR) vaccination in high income setting: population based cohort
study in the Netherlands. BMJ, 358 (j3862), doi:

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