Reassessment of the risk of narcolepsy in children in England 8 years after receipt of the AS03-adjuvanted H1N1 pandemic vaccine: A case-coverage study

Abstract

Background Early studies of narcolepsy after AS03-adjuvanted pandemic A/H1N12009 vaccine (Pandemrix) could not define the duration of elevated risk post-vaccination nor the risk in children aged under 5 years who may not present until much older. Methods/Findings Clinical information and sleep test results, extracted from hospital notes at 3 large pediatric sleep centers in England between September 2017 and June 2018 for narcolepsy cases aged 4–19 years with symptom onset since January 2009, were reviewed by an expert panel to confirm the diagnosis. Vaccination histories were independently obtained from general practitioners (GPs). The odds of vaccination in narcolepsy cases compared with the age-matched English population was calculated after adjustment for clinical conditions that were indications for vaccination. GP questionnaires were returned for 242 of the 244 children with confirmed narcolepsy. Of these 5 were under 5 years, 118 were 5–11 years, and 119 were 12–19 years old at diagnosis; 39 were vaccinated with Pandemrix before onset. The odds ratio (OR) for onset at any time after vaccination was 1.94 (95% confidence interval [CI] 1.30–2.89), The elevated risk period was restricted to onsets within 12 months of vaccination (OR 6.65 [3.44–12.85]) and was highest within the first 6 months. After one year, ORs were not significantly different from 1 up to 8 years after vaccination. The ORs were similar in under five-year-olds and older ages. The estimated attributable risk was 1 in 34,500 doses. Our study is limited by including cases from only 3 sleep centers, who may differ from cases diagnosed in nonparticipating centers, and by imprecision in defining the centers’ catchment population. The potential for biased recall of onset shortly after vaccination in cases aware of the association cannot be excluded. Conclusions In this study, we found that vaccine-attributable cases have onset of narcolepsy within 12 months of Pandemrix vaccination. The attributable risk is higher than previously estimated in England because of identification of vaccine-attributable cases with late diagnoses. Absence of a compensatory drop in risk 1–8 years after vaccination suggests that Pandemrix does not trigger onsets in those in whom narcolepsy would have occurred later.

Fluorescence‐Quenching Lateral Flow Immunoassay for “Turn‐On” and Sensitive Detection of Anti‐SARS‐Cov‐2 Neutralizing Antibodies in Human Serum

“…Booster vaccination is an effective way to attenuate NAbs and reorganize immune resistance. [ 32 ] However, owing to differences in individual immunity, some vaccinated individuals lose the protection of NAbs before booster vaccination, and this window period may be long. Hence, an accurate, rapid, and easy‐to‐operate method for detecting anti‐SARS‐CoV‐2 NAbs is the key to guiding individuals to schedule booster doses and maintain effective resistance against SARS‐CoV‐2.…”

Narcolepsy and H1N1 influenza immunology a decade later: What have we learned?

“…More recently, a modelling study of de novo European cases concluded that the NT1 peak in children detected in 2013 (thus in the absence of recent Pandemrix vaccination), was most likely triggered by other risk factors, such as viral infections caused by H1N1 recirculation, or circulation of other/new influenza strains, e.g., influenza B (55). A recent study by Stowe et al shows that an increased risk of NT1 associated with Pandemrix vaccination was "confined to those with onset within the first 12 months with a return to baseline thereafter" (56). This limited (~1 year) timeframe in which the vaccine could be linked to NT1 onsets thus suggests that thereafter other risk factors would have become more likely causes.…”

“…A recent study by Stowe et al. shows that an increased risk of NT1 associated with Pandemrix vaccination was “confined to those with onset within the first 12 months with a return to baseline thereafter” ( 56 ). This limited (~1 year) timeframe in which the vaccine could be linked to NT1 onsets thus suggests that thereafter other risk factors would have become more likely causes.…”

On the concept and ethics of vaccination for the sake of others

“…Vaccines have been recalled in the past after adverse effects in children were identified when the vaccine was already in routine use (Collignon, Doshi, and Jefferson 2010). In some cases, the adverse effects occurred many months after vaccine administration (Jamrozik et al 2021;Stowe et al 2020). The lack of long-term safety data therefore warrants caution about vaccinating children against COVID-19.…”