Where are we in our understanding of the association between narcolepsy and one of the 2009 adjuvanted influenza A (H1N1) vaccines?

Johansen, Kari; Brasseur, Daniel; MacDonald, Noni; Nohynek, Hanna; Vandeputte, J.; Wood, David D.; Neels, Pieter

doi:10.1016/j.biologicals.2016.04.007

Cited by 12 publications

(9 citation statements)

References 15 publications

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“…40 Moreover, the added value of such studies was clearly shown when an unexpected increase in narcolepsy cases was reported in Finland and Sweden in 2010, after vaccination with Pandemrix Ò . 41 There are a lot of expectations coming from the recent scientific progresses in the development of new universal influenza vaccine that is long-lasting and not subject to antigenic modifications, 42 however, the introduction and use must be supported by strong evidence, in terms of higher immunogenicity and greater effectiveness, in order to combat the growing phenomenon of vaccine hesitancy. Indeed, public debate over vaccine effectiveness, which largely depends on matching between circulating influenza strains and vaccine strains, can negatively impact on vaccination coverage.…”

Section: Discussionmentioning

confidence: 99%

Strategies in recommending influenza vaccination in Europe and US

Rizzo

Rezza

Ricciardi

2018

Human Vaccines & Immunotherapeutics

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There is potential for influenza vaccine programmes to make a substantial impact on the disease burden. The World Health Organization (WHO) has identified young children, pregnant women, persons with chronic medical conditions, and the elderly as being at risk for severe influenza disease and therefore important groups to be considered for influenza vaccination. Applying the methodology of scoping review of grey and scientific literature we described the European and the US approach to influenza vaccine prevention. Although vaccination remains the most effective means of reducing the incidence and severity of influenza, vaccine uptake in many European countries remains suboptimal (i.e. 45.5% in the elderly, 24% in health care workers, from 49.8% in patients with chronic medical conditions, median 23.6% in pregnant women) and vaccine strategies are not harmonized in particular with regard to vaccinating healthy children. Whereas in the US the vaccine strategies are more standardized across states and vaccine coverage are higher than those reported in EU on average. The integration of different strategies is crucial in order to increase influenza vaccine coverage: public health authorities should encourage healthcare workers to vaccinate themselves, as target category, and to recommend seasonal influenza vaccination to people in the target groups; there should also be structured communication campaigns on influenza and influenza vaccines, directed specifically at these target groups, and an adequate and sustainable funding is also an important factor to achieve higher vaccination coverage rates.

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Section: Discussionmentioning

confidence: 99%

Strategies in recommending influenza vaccination in Europe and US

Rizzo

Rezza

Ricciardi

2018

Human Vaccines & Immunotherapeutics

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“…Other sleep disorders such as insomnia have a high co-occurrence with psychiatric disorders (6). Recently the possible relationship between vaccinations and narcolepsy has been explored, with a recent reported increase in narcolepsy cases in Europe associated with large-scale population immunization campaigns such as the adjuvanted 2009 influenza A (H1N1) pandemic vaccines (7). In Alberta, Canada, the prevalence of sleep disorders, in particular OSA, is increasing mainly due to the aging population and rising rates of chronic obstructive pulmonary disease and obesity (8).…”

Section: Introductionmentioning

confidence: 99%

Identifying Cases of Sleep Disorders through International Classification of Diseases (ICD) Codes in Administrative Data

Jolley

Liang

Peng

et al. 2018

IJPDS

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ObjectivesPrevalence, and associated morbidity and mortality of chronic sleep disorders have been limited to small cohort studies, however, administrative data may be used to provide representation of larger population estimates of disease. With no guidelines to inform the identification of cases of sleep disorders in administrative data, the objective of this study was to develop and validate a set of ICD-codes used to define sleep disorders including narcolepsy, insomnia, and obstructive sleep apnea (OSA) in administrative data. MethodsA cohort of adult patients, with medical records reviewed by two independent board-certified sleep physicians from a sleep clinic in Calgary, Alberta between January 1, 2009 and December 31, 2011, was used as the reference standard. We developed a general ICD-coded case definition for sleep disorders which included conditions of narcolepsy, insomnia, and OSA using: 1) physician claims data, 2) inpatient visit data, 3) emergency department (ED) and ambulatory care data. We linked the reference standard data and administrative data to examine the validity of different case definitions, calculating estimates of sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV). ResultsFrom a total of 1186 patients from the sleep clinic, 1045 (88.1%) were classified as sleep disorder positive, with 606 (51.1%) diagnosed with OSA, 407 (34.4%) with insomnia, and 59 (5.0%) with narcolepsy. The most frequently used ICD-9 codes were general codes of 307.4 (Nonorganic sleep disorder, unspecified), 780.5 (unspecified sleep disturbance) and ICD-10 codes of G47.8 (other sleep disorders), G47.9 (sleep disorder, unspecified). The best definition for identifying a sleep disorder was an ICD code (from physician claims) 2 years prior and 1 year post sleep clinic visit: sensitivity 79.2%, specificity 28.4%, PPV 89.1%, and NPV 15.6%. ICD codes from ED/ambulatory care data provided similar diagnostic performance when at least 2 codes appeared in a time period of 2 years prior and 1 year post sleep clinic visit: sensitivity 71.9%, specificity 54.6%, PPV 92.1%, and NPV 20.8%. The inpatient data yielded poor results in all tested ICD code combinations. ConclusionSleep disorders in administrative data can be identified mainly through physician claims data and with some being determined through outpatient/ambulatory care data ICD codes, however these are poorly coded within inpatient data sources. This may be a function of how sleep disorders are diagnosed and/or reported by physicians in inpatient and outpatient settings within medical records. Future work to optimize administrative data case definitions through data linkage are needed.

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“…In Finnish children aged 4–19 years there was a rate ratio of 12.7 (95% CI, 6.1–30.8), with a vaccine-attributable risk of 1:16,000 (95% CI, 1:13,000–1:21,000) of developing narcolepsy following receipt of Pandemrix ® ( 176 ). The EMA Eudravigilance database had received almost 1,400 reports of narcolepsy in Pandemrix ® -recipients by 2015 ( 183 ).…”

Section: Safetymentioning

confidence: 99%

“…Arepanrix ® , the AS03-adjuvanted pandemic vaccine used in Canada, has not been associated with such a significant risk of narcolepsy, with only one extra case of narcolepsy per million doses received ( 183 , 188 ). This is despite both Pandemrix ® and Arepanrix ® vaccines containing similar amounts of HA and AS03.…”

Section: Safetymentioning

confidence: 99%

AS03- and MF59-Adjuvanted Influenza Vaccines in Children

et al. 2017

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Influenza is a major cause of respiratory disease leading to hospitalization in young children. However, seasonal trivalent influenza vaccines (TIVs) have been shown to be ineffective and poorly immunogenic in this population. The development of live-attenuated influenza vaccines and adjuvanted vaccines are important advances in the prevention of influenza in young children. The oil-in-water emulsions MF59 and adjuvant systems 03 (AS03) have been used as adjuvants in both seasonal adjuvanted trivalent influenza vaccines (ATIVs) and pandemic monovalent influenza vaccines. Compared with non-adjuvanted vaccine responses, these vaccines induce a more robust and persistent antibody response for both homologous and heterologous influenza strains in infants and young children. Evidence of a significant improvement in vaccine efficacy with these adjuvanted vaccines resulted in the use of the monovalent (A/H1N1) AS03-adjuvanted vaccine in children in the 2009 influenza pandemic and the licensure of the seasonal MF59 ATIV for children aged 6 months to 2 years in Canada. The mechanism of action of MF59 and AS03 remains unclear. Adjuvants such as MF59 induce proinflammatory cytokines and chemokines, including CXCL10, but independently of type-1 interferon. This proinflammatory response is associated with improved recruitment, activation and maturation of antigen presenting cells at the injection site. In young children MF59 ATIV produced more homogenous and robust transcriptional responses, more similar to adult-like patterns, than did TIV. Early gene signatures characteristic of the innate immune response, which correlated with antibody titers were also identified. Differences were detected when comparing child and adult responses including opposite trends in gene set enrichment at day 3 postvaccination and, unlike adult data, a lack of correlation between magnitude of plasmablast response at day 7 and antibody titers at day 28 in children. These insights show the utility of novel approaches in understanding new adjuvants and their importance for developing improved influenza vaccines for children.

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Where are we in our understanding of the association between narcolepsy and one of the 2009 adjuvanted influenza A (H1N1) vaccines?

Cited by 12 publications

References 15 publications

Strategies in recommending influenza vaccination in Europe and US

Strategies in recommending influenza vaccination in Europe and US

Identifying Cases of Sleep Disorders through International Classification of Diseases (ICD) Codes in Administrative Data

AS03- and MF59-Adjuvanted Influenza Vaccines in Children

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