Infections in temporal proximity to HPV vaccination and adverse effects following vaccination in Denmark: A nationwide register-based cohort study and case-crossover analysis. — CFSMEATLAS
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Infections in temporal proximity to HPV vaccination and adverse effects following vaccination in Denmark: A nationwide register-based cohort study and case-crossover analysis.
Krogsgaard, Lene Wulff, Petersen, Irene, Plana-Ripoll, Oleguer et al. · PLoS medicine · 2021 · DOI
Quick Summary
This study examined whether having an infection around the time of HPV vaccination increases the risk of developing illness symptoms afterward in Danish women. Researchers found that women who had a treated infection within one month before or after their first HPV vaccine dose were more likely to later seek care at specialized centers for suspected vaccine side effects. The symptoms reported were similar to those seen in chronic fatigue syndrome.
Why It Matters
This is the first study to systematically investigate whether infection timing relative to HPV vaccination triggers CFS-like symptoms in a subset of vaccine recipients. Understanding this potential mechanism is crucial for ME/CFS research, as infection is a well-established trigger for post-infectious CFS, and clarifying vaccine-infection interactions may help identify vulnerable subgroups and prevent illness onset.
Observed Findings
Hospital-treated infection in the ±1 month window around HPV vaccination was associated with 2.75-fold increased odds of later HPV centre referral (95% CI 1.72–4.40, P<0.001).
Anti-infective medication redemption during the same period was associated with 1.56-fold increased odds of referral (95% CI 1.33–1.83, P<0.001).
Rapid streptococcal testing ±1 month around vaccination was associated with 1.45-fold increased odds of referral (95% CI 1.10–1.93, P=0.010).
Of 600,400 vaccinated females, 48,361 (9.7%) had evidence of infection around vaccination time; 1,755 (0.3%) were referred to an HPV centre.
Case-crossover analysis confirmed the associations, supporting a temporal relationship.
Inferred Conclusions
Treated infection in temporal proximity to HPV vaccination is associated with increased risk for later specialist referral with suspected adverse vaccine effects.
Infection may act as a trigger for CFS-like symptoms in a subset of referred females, analogous to post-infectious mechanisms in CFS.
The findings suggest potential vulnerability windows around vaccination when concurrent infection may increase adverse outcome risk.
Remaining Questions
Does the association reflect true causation or confounding by healthcare-seeking behavior and symptom reporting bias in those with recent infections?
What This Study Does Not Prove
This study does not prove that HPV vaccination causes CFS or that infection during vaccination directly causes adverse effects—it shows an association only. The study cannot establish causation, and heightened symptom reporting or healthcare-seeking behavior among those with recent infections may partially explain the findings. Additionally, the study endpoint was specialist referral for suspected effects, not confirmed diagnoses of CFS or verified adverse outcomes.
Tags
Symptom:Fatigue
Phenotype:Infection-TriggeredPediatric
Method Flag:PEM Not DefinedWeak Case DefinitionMixed Cohort
About the PEM badge: “PEM required” means post-exertional malaise was an explicit required diagnostic criterion for participant inclusion in this study — not that PEM was studied, observed, or discussed. Studies using criteria that do not require PEM (e.g. Fukuda, Oxford) are tagged “PEM not required”. How the atlas works →
What specific pathogens or infection types confer the highest risk, and are certain vaccine recipients more vulnerable based on immune status or genetic factors?
Why did specialist centres only open in June 2015, and how many cases of suspected adverse effects went unrecognized before this date?
Can mechanistic studies identify immune or physiological pathways linking concurrent infection and vaccination to CFS-like symptom development?