Retrospective study of the use of an influenza disease two-tiered classification system to characterize clinical severity in US children.

In children <5 years, influenza is associated with higher risk of serious disease and hospitalization when compared with other age groups. Influenza vaccination reduces the risk of influenza and vaccination may attenuate the severity of disease. Recent studies in Europe suggest that classifying influenza disease as mild versus moderate-to-severe (M-S) using a novel definition may be clinically significant. We retrospectively evaluated whether this M-S definition also characterized influenza severity in a cohort of US children. We included children <18 years at Kaiser Permanente Northern California with PCR-confirmed influenza during the 2013-2014 influenza season. We classified children as M-S if they had ≥1 symptom: fever >39°C, acute otitis media, lower respiratory tract infection (LRTI), or extra-pulmonary complications; otherwise, they were classified as mild. We used multivariable log-binomial models to assess whether M-S influenza disease was associated with increased healthcare utilization. Nearly half of the 1,105 influenza positive children were classified as M-S. Children 6-35 months had the highest proportion of M-S disease (35.1%), mostly due to LRTI (63.2%) and fever (44.6%). Children ≥6 months who had M-S disease were associated with a 1.6 to 2.8 times increased likelihood of having had an emergency department or any follow-up outpatient visits. Those who had M-S disease were associated with an increased likelihood of receiving antibiotics, with the highest likelihood in children 6-35 months (RR 9.0, 95% CI 4.1, 19.8). While more studies are needed, an influenza classification system may distinguish children with more clinically significant disease.

Causality assessment of serious neurologic adverse events following 2009 H1N1 vaccination.

BACKGROUND: Adverse events occurring after vaccination are routinely reported to the Vaccine Adverse Event Reporting System (VAERS). We studied serious adverse events (SAEs) of a neurologic nature reported after receipt of influenza A (H1N1) 2009 monovalent vaccine during the 2009-2010 influenza season. Investigators in the Clinical Immunization Safety Assessment (CISA) network sought to characterize these SAEs and to assess their possible causal relationship to vaccination. METHODS: Centers for Disease Control and Prevention (CDC) and Food and Drug Administration (FDA) physicians reviewed all SAE reports (as defined by the Code of Federal Regulations, 21CFR§314.80) after receipt of H1N1 vaccine reported to VAERS between October 1, 2009 and March 31, 2010. Non-fatal SAE reports with neurologic presentation were referred to CISA investigators, who requested and reviewed additional medical records and clinical information as available. CISA investigators assessed the causal relationship between vaccination and the event using modified WHO criteria as defined. RESULTS: 212 VAERS reports of non-fatal serious neurological events were referred for CISA review. Case reports were equally distributed by gender (50.9% female) with an age range of 6 months to 83 years (median 38 years). The most frequent diagnoses reviewed were: Guillain-Barré Syndrome (37.3%), seizures (10.8%), cranial neuropathy (5.7%), and acute disseminated encephalomyelitis (3.8%). Causality assessment resulted in classification of 72 events as "possibly" related (33%), 108 as "unlikely" related (51%), and 20 as "unrelated" (9%) to H1N1 vaccination; none were classified as "probable" or "definite" and 12 were unclassifiable (6%). CONCLUSION: The absence of a specific test to indicate whether a vaccine component contributes to the pathogenesis of an event occurring within a biologically plausible time period makes assessing causality difficult. The development of standardized protocols for providers to use in evaluation of adverse events following immunization, and rapid identification and follow-up of VAERS reports could improve causality assessment.