Childhood infections, vaccinations, and tonsillectomy and risk of first clinical diagnosis of CNS demyelination in the Ausimmune Study

Abstract

Background: The association between childhood vaccinations and infections and risk of multiple sclerosis is unclear; few studies have considered age at vaccination/infection. Objective: To explore age-related associations between childhood vaccinations, infection and tonsillectomy and risk of a first clinical diagnosis of CNS demyelination. Methods: Data on case (n = 275, 76.6% female; mean age 38.6 years) and age-and sex-matched control (n = 529) participants in an incident population-based case-control study included self-reported age at time of childhood vaccinations, infections, and tonsillectomy. Conditional logistic regression models were used to calculate adjusted odds ratios (AOR) and 95% confidence intervals (CI). Results: Poliomyelitis vaccination prior to school-age was associated with increased risk of a first clinical diagnosis of CNS demyelination (AOR = 2.60, 95%CI 1.02-6.68), based on a very small unvaccinated reference group. Late (11-15 years) rubella vaccination (compared to none) was associated with lower odds of being a case (AOR = 0.47, 95%CI 0.27-0.83). Past infectious mononucleosis at 11-15 years (AOR = 2.84, 95%CI 1.0-7.57) and 16-20 years (AOR = 1.92, 95%CI 1.12-3.27) or tonsillectomy in adolescence (11-15 years: AOR = 2.45, 95%CI 1.12-5.35), including after adjustment for IM, were associated with increased risk of a first clinical diagnosis of CNS demyelination. Conclusions: Age at vaccination, infection or tonsillectomy may alter the risk of subsequent CNS demyelination. Failing to account for age effects may explain inconsistencies in past findings.

Risk of a first clinical diagnosis of central nervous system demyelination in relation to human herpesviruses in the context of Epstein–Barr virus

“…A recent study reported that a greater proportion of people with MS, compared to the general population, reported a past history of chickenpox and/or herpes zoster [34]. Our previous analysis of self‐reported chickenpox in the Ausimmune Study found no association with FCD risk [11]. In a French study, clinically observed chickenpox was associated with lower risk of MS onset during childhood [10].…”

“…Primary infection with varicella zoster virus (VZV) causes chickenpox, and reactivation of the virus, herpes zoster (shingles). The evidence for an association between VZV infection and MS has been largely based on history of chickenpox and/or shingles, showing increased [9], reduced [10], or no association [11]. Cytomegalovirus (CMV) infection may be asymptomatic or mild, and can present as infectious mononucleosis.…”

Reducing infection risk in multiple sclerosis and neuromyelitis optica spectrum disorders: a Brazilian reference center's approach

“… 24 The link between exposure to infections and immune dysregulating triggering autoimmune disorders, including acquired demyelinating syndromes (ADS), is a special concern in the pediatric population. 25 26 No association between vaccination and acquired demyelinating syndromes (ADSs) has consistently been described, including pediatric-onset of MS. 27 28 Studies focusing on pediatric NMOSD are lacking. It is currently accepted that vaccines might act by accelerating the transition from subclinical to clinically relevant inflammatory events.…”