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Summary Background In May, 2018, Children's Hospital Colorado noted an outbreak of enterovirus A71 (EV-A71) neurological disease. We aimed to characterise the clinical features of EV-A71 neurological disease during this outbreak. Methods In this retrospective observational cohort study, children (younger than 18 years) who presented to Children's Hospital Colorado (Aurora, CO, USA) between March 1 and November 30, 2018, with neurological disease (defined by non-mutually exclusive criteria, including meningitis, encephalitis, acute flaccid myelitis, and seizures) and enterovirus detected from any biological specimen were eligible for study inclusion. The clinical characteristics of children with neurological disease associated with EV-A71 were compared with those of children with neurological disease associated with other enteroviruses during the same period. To explore the differences in clinical presentation of acute flaccid myelitis, we also used a subgroup analysis to compare clinical findings in children with EV-A71-associated acute flaccid myelitis during the study period with these findings in those with enterovirus D68 (EV-D68)-associated acute flaccid myelitis at the same hospital between 2013 and 2018. Findings Between March 10 and Nov 10, 2018, 74 children presenting to Children's Hospital Colorado were found to have enterovirus neurological disease; EV-A71 was identified in 43 (58%) of these children. The median age of the children with EV-A71 neurological disease was 22·7 months (IQR 4·0–31·9), and most of these children were male (34 [79%] children). 40 (93%) children with EV-A71 neurological disease had findings suggestive of meningitis, 31 (72%) children showed evidence of encephalitis, and ten (23%) children met our case definition of acute flaccid myelitis. All children with EV-A71 disease had fever and 18 (42%) children had hand, foot, or mouth lesions at or before neurological onset. Children with EV-A71 disease were best differentiated from those with other enteroviruses (n=31) by the neurological findings of myoclonus, ataxia, weakness, and autonomic instability. Of the specimens collected from children with EV-A71, this enterovirus was detected in 94% of rectal, 79% of oropharyngeal, 56% of nasopharyngeal, and 20% of cerebrospinal fluid specimens. 39 (93%) of 42 children with EV-A71 neurological disease who could be followed up showed complete recovery by 1–2 months. Compared with children with EV-D68-associated acute flaccid myelitis, children with EV-A71-associated acute flaccid myelitis were younger, showed neurological onset earlier after prodromal symptom onset, had milder weakness, showed more rapid improvement, and were more likely to completely recover. Interpretation This outbreak of EV-A71 neurological disease, the largest reported in the Americas, was characterised by fever, myoclonus, ataxia, weakness, autonomic instability, and full recovery in most patients. Because EV-A71 epidemiology outside of Asia remains difficult to predict, identification of future outbreaks will be aided by prompt recognition of these distinct clinical findings, testing of non-sterile and sterile site specimens, and enhanced enterovirus surveillance. Funding None.

Objective Despite relatively high national vaccination coverage for measles, geographic vaccination variation exists resulting in clusters of susceptibility. A portion of this geographic variation can be explained by differences in state policies related to nonmedical vaccine exemptions. The objective of this analysis was to determine the magnitude, likelihood, and cost of a measles outbreak under different nonmedical vaccine exemption policies. Methods An agent-based transmission model simulated the likelihood and magnitude of a measles outbreak under different nonmedical vaccine exemption policies, previously categorized as easy, medium, or difficult. The model accounted for measles herd immunity, infectiousness of the pathogen, vaccine efficacy, duration of incubation and communicable periods, acquired natural immunity, and the rate of recovery. Public health contact tracing was also modeled. Model outcomes, including the number of secondary cases, hospitalizations, and deaths, were monetized to determine the economic burden of the simulated outbreaks. Results A state with easy nonmedical vaccine exemption policies is 140% and 190% more likely to experience a measles outbreak compared with states with medium or difficult policies, respectively. The magnitude of these outbreaks can be reduced by half by strengthening exemption policies. These declines are associated with significant cost reductions to public health, the health care system, and the individual. Conclusions Strengthening nonmedical vaccine exemption policies is 1 mechanism to increase vaccination coverage to reduce the health and economic effect of a measles outbreak. States exploring options for decreasing their vulnerability to outbreaks of vaccine-preventable diseases should consider more stringent requirements for nonmedical vaccine exemptions.

Background: In May 2018, Children's Hospital Colorado (CHCO) noted an outbreak of enterovirus (EV) A71-associated neurologic disease. Methods: A case of EV-associated neurologic disease was defined as any child presenting to CHCO with meningitis, encephalitis, acute flaccid myelitis (AFM), and/or seizures between March 1 and November 30, 2018 with an EV detected from a biologic specimen. EV-A71 cases were compared to other EV cases during the same period. EV-A71-associated AFM cases were also compared to EV-D68-associated AFM cases from 2013-2018. Findings: Of seventy-four children with EV-associated neurologic disease, forty-three (58%) were EV-A71-associated. Median age of EV-A71 cases was 22.7 months (IQR: 4-31.9 months); 34 (79%) were male. Neurologic involvement in EV-A71 cases included meningitis (93%), encephalitis (72%), and AFM (23%). All EV-A71 cases had fever; eighteen (42%) had hand, foot, or mouth (HFM) lesions. Neurologic findings distinguishing EV-A71-associated cases from other EV-associated cases (n=31) included myoclonus (60% vs. 16%, p