Articles Severe respiratory illness associated with a nationwide outbreak of enterovirus D68 in the USA (2014): a descriptive epidemiological investigation (original) (raw)

Severe respiratory illness associated with a nationwide outbreak of enterovirus D68 in the USA (2014): a descriptive epidemiological investigation

The Lancet Respiratory Medicine, 2015

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Clinical Characterization of Children Presenting to the Hospital with Enterovirus D68 Infection During the 2014 Outbreak in St. Louis

Pediatric Infectious Disease Journal, 2016

Background-The largest known outbreak of enterovirus D68 (EV-D68) infections occurred during 2014. The goal of our study is to characterize the illness severity and clinical presentation of children infected with enterovirus-D68 (EV-D68) in comparison to non-EV-D68-Human Rhino/ Enteroviruses (HR/EV). Method-Our study is a retrospective analysis of severity level, charges and length of stay of children who presented to St. Louis Children's Hospital from 8/31/2014-10/31/2014 and tested positive for EV-D68 in comparison to non-EV-D68-HR/EV infected patients. Chart review was performed for all EV-D68 infected patients and age and severity matched non-EV-D68-HR/EV infected patients. Result-There was a striking increase in hospital census in August of 2014 in our hospital with simultaneous increase in the number of patients with EV-D68 infection. There was no significant difference in severity of illness, length of stay or total charges between EV-D68 and non-EV-D68-HR/EV infected children. EV-D68 infection was characterized by presenting complaints of difficulty breathing (80%) and wheezing (67%), and by findings of tachypnea (65%), wheezing (71%) and retractions (65%) on examination. The most common interventions were albuterol (79%) and corticosteroid (68%) treatments and the most common discharge diagnosis was asthma exacerbation (55%). Conclusion-EV-D68 caused a significant outbreak in 2014 with increased hospital admissions and associated increased charges. There was no significant difference in severity of illness caused by EV-D68 and non-EV-D68-HR/EV infections suggesting that the impact from EV-D68 was due to increased number of infected children presenting to the hospital and not necessarily due to increased severity of illness.

Enterovirus D68 and Human Respiratory Infections

Seminars in respiratory and critical care medicine, 2016

Enterovirus D68 (EV-D68) is a member of the species Enterovirus D in the genus Enterovirus of the Picornaviridae family. EV-D68 was first isolated in the United States in 1962 and is primarily an agent of respiratory disease. Infections with EV-D68 have been rarely reported until recently, when reports of EV-D68 associated with respiratory disease increased notably worldwide. An outbreak in 2014 in the United States, for example, involved more than 1,000 cases of severe respiratory disease that occurred across almost all states. Phylogenetic analysis of all EV-D68 sequences indicates that the circulating strains of EV-D68 can be classified into two lineages, lineage 1 and lineage 2. In contrast to the prototype Fermon strain, all circulating strains have deletions in their genomes. Respiratory illness associated with EV-D68 infection ranges from mild illness that just needs outpatient service to severe illness requiring intensive care and mechanical ventilation. To date, there are n...

Surveillance for the identification of cases of acute respiratory infection by enterovirus D68 in children in a tertiary level care hospital during 2014-2016

Boletín Médico del Hospital Infantil de México (English Edition)

Background: The reemergence of enterovirus (EV) D68 infections in the United States was reported from August-October 2014 (691 cases). In Mexico, an outbreak at the National Institute of Respiratory Diseases was reported (24 cases). The results of epidemiological surveillance (ES) of enterovirus and other respiratory viruses in a national pediatric tertiary care level hospital are presented. Methods: Following the alert issued by the reemergence of EV-D68 in 2014, ES-which only detected respiratory viruses by PCR in patients with influenza-like illness using nasopharyngeal swabs-expanded to include children with asthma exacerbation or acute respiratory distress. Positive samples for Enterovirus sp. (EV) were confirmed and typed by sequencing. Subsequent sequencing was used to obtain the complete viral genome. Results: Of 1705 samples, 13 were positive to EV. Patients with EV presented the following comorbidities: chronic lung disease (7.7%), neoplastic disease (15.4%), allergic asthma/rhinitis (23%), recurrent pneumonia (23%), and other (23%). Of the 13 samples positive for EV, three were positive for EV-D68. These cases required invasive mechanical ventilation, presented no neurological involvement and survived. Conclusions: The impact of the population studied by EV-D68 was lower than that reported in the country during the same period. Cases of EV-D68 infection had multiple comorbidities, but few pulmonary comorbidities, which could explain the low attack rate. The ES and infection prevention system may have contained the outbreak.

Enterovirus D68 in a community hospital: A test-negative case-control study

Official Journal of the Association of Medical Microbiology and Infectious Disease Canada, 2018

Background: In August 2014, a large North American outbreak of enterovirus D68 (EV-D68) was observed in association with severe respiratory illnesses in children as well as a possible association with acute flaccid paralysis. The full spectrum of clinical illness associated with EV-D68 is not well known. Objective: To compare children positive and negative for EV-D68 presenting to a community hospital during the North American outbreak in the fall of 2014. Methods: Consecutive nasopharyngeal swabs obtained from children (<18 years old) presenting to a large community hospital with respiratory symptoms in the fall of 2014 were tested for EV-D68. We conducted a test-negative case-control study between EV-D68 positive and EV-D68 negative children to describe the clinical and outcome characteristics. Controls were limited to children who had a nasopharyngeal swab obtained. EV-D68 indeterminate cases were excluded from the primary analysis. All nasopharyngeal swabs were referred to a ...

Epidemiological and clinical characteristics of patients infected with enterovirus D68, France, July to December 2014

Eurosurveillance, 2016

In 2014, the United States (US) experienced a nationwide outbreak of enterovirus D68 (EV-D68) infection with 1,152 cases reported mainly in hospitalised children with severe asthma or bronchiolitis. Following the US alert, 11 laboratories of the French enterovirus (EV) surveillance network participated in an EV-D68 survey. A total of 6,229 respiratory samples, collected from 1 July to 31 December 2014, were screened for EV-D68 resulting in 212 EV-D68-positive samples. These 212 samples corresponded to 200 EV-D68 cases. The overall EV-D68 positivity rates among respiratory samples were of 5% (184/3,645) and 1.1% (28/2,584) in hospitalised children and adults respectively. The maximum weekly EV-D68 positivity rates were of 16.1% for children (n = 24/149; week 43) and 2.6% for adults (n = 3/115; week 42). Of 173 children with EV-D68 infection alone, the main symptoms were asthma (n = 83; 48.0%) and bronchiolitis (n = 37; 21.4%). One child developed acute flaccid paralysis (AFP) following EV-D68-associated pneumonia. Although there was no significant increase in severe respiratory tract infections reported to the French public health authorities, 10.7% (19/177) of the EV-D68 infected children and 14.3% (3/21) of the EV-D68 infected adults were hospitalised in intensive care units. Phylogenetic analysis of the viral protein 1 (VP1) sequences of 179 EV-D68 cases, revealed that 117 sequences (65.4%), including that of the case of AFP, belonged to the B2 variant of clade B viruses. Continuous surveillance of EV-D68 infections is warranted and could benefit from existing influenza-like illness and EV surveillance networks.

Epidemiology of Enterovirus D68 in Ontario

PLOS ONE, 2015

In August 2014, children's hospitals in Kansas City, Missouri and Chicago, Illinois notified the Centers for Disease Control and Prevention (CDC) about increased numbers of pediatric patients hospitalized with severe respiratory illness (SRI). In response to CDC reports, Public Health Ontario Laboratories (PHOL) launched an investigation of patients being tested for enterovirus D-68 (EV-D68) in Ontario, Canada. The purpose of this investigation was to enhance our understanding of EV-D68 epidemiology and clinical features. Data for this study included specimens submitted for EV-D68 testing at PHOL from September 1, 2014 to October 31, 2014. Comparisons were made between patients who tested positive for the virus (cases) and those testing negative (controls). EV-D68 was identified in 153/907 (16.8%) of patients tested. In the logistic regression model adjusting for age, sex, setting and time to specimen collection, individuals younger than 20 years of age were more likely to be diagnosed with EV-D68 compared to those 20 and over, with peak positivity at ages 5-9 years. Cases were not more likely to be hospitalized than controls. Cases were more likely to be identified in September than October (OR 8.07; 95% CI 5.15 to 12.64). Routine viral culture and multiplex PCR were inadequate methods to identify EV-D68 due to poor sensitivity and inability to differentiate EV-D68 from other enterovirus serotypes or rhinovirus. Testing for EV-D68 in Ontario from July to December, 2014 detected the presence of EV-D68 virus among young children during September-October, 2014, with most cases detected in September. There was no difference in hospitalization status between cases and controls. In order to better understand the epidemiology of this virus, surveillance for EV-D68 should include testing of symptomatic individuals from all treatment settings and patient age groups, with collection and analysis of comprehensive clinical and epidemiological data.

First Enterovirus D68 (EV-D68) cases detected in hospitalised patients in a tertiary care university hospital in Spain, October 2014

Enfermedades infecciosas y microbiologia clinica, 2015

Several outbreaks of Enterovirus 68 (EV-D68) have recently been reported in the USA and Canada, causing substantial hospitalisation of children with severe respiratory disease. The acute flaccid paralysis detected in the USA and Canada among children with EV-D68 infection has raised concerns about the aetiological role of this EV serotype in severe neurological disease. The circulation of EV-D68 in the general European population seems to be low, but European Centre for Disease Prevention and Control (ECDC) recommends being vigilant to new cases, particularly in severely ill hospitalised patients. In October 2014, enteroviruses were detected in respiratory samples collected from five hospitalised patients, children and adults. Phylogenetic analysis of partial VP1 sequences confirmed that the detected enteroviruses belonged to the D68 serotype, which were also similar to strains reported in USA (2014). However, all five patients developed respiratory symptoms, but only one required I...

Respiratory Infections by Enterovirus D68 in Outpatients and Inpatients Spanish Children

Pediatric Infectious Disease Journal, 2016

Background: The incidence of enterovirus D68 (EV-D68) and the spectrum of clinical disease in children are not well known in European countries. We have designed a study with the objective of describing the clinical impact of EV-D68 detected in children with respiratory tract infections. Methods: As a part of a prospective study to identify the etiology and clinical characteristics of viral respiratory infections in children in Spain, we performed the analysis of the cases of EV infections in all children hospitalized in a secondary hospital in Madrid, during the epidemic respiratory season 2012-2013. A second group of samples was corresponded to infants of the same area, with ambulatory respiratory infection or asymptomatic. Phylogenetic EV-D68 analysis was made using the viral protein 1 gene (VP1). Clinical data of EV-D68 patients were compared with those infected by rhinovirus in the same period and population. Results: The study population consisted of 720 patients corresponding to 399 episodes of hospitalization for respiratory causes, 44 episodes of ambulatory respiratory infections and 277 children determined as a healthy control group. A total of 22 patients were positive for EVs (3.05%), and 12 of them were specifically typed as EV-D68 (11/443 respiratory infections, 2.5%). The most frequent diagnosis in the 10 hospitalized children with EV-D68 detection was recurrent wheezing. Hypoxia was present in 70% of cases, but admission in the intensive care unit was not required. No neurological signs or symptoms were observed. One patient had an ambulatory mild bronchiolitis and another was asymptomatic. No differences were found with rhinovirus infections except less duration of hypoxia and fever in EV-D68 group. Conclusions: EV-D68 infections were detected in 3.05% of respiratory studied samples (2.5% of admissions). The infection was associated with wheezing episodes with hypoxia. No admissions to intensive care unit or neurological symptoms were found.

Enterovirus D68 in Hospitalized Children, Barcelona, Spain, 2014–2021

Emerging Infectious Diseases

I n 1962, enterovirus D68 (EV-D68) was first isolated from the oropharynx of children in California, USA, who were hospitalized for lower respiratory tract infection (LRTI) (1). Although infections can occur at any age, children are the most susceptible to enterovirus infections (2). In temperate countries, enterovirus circulation usually follows a seasonal pattern, peaking in late summer and early autumn, but a second peak can also be detected during spring (3). Until 2007, EV-D68 was rarely implicated in severe diseases and was poorly detected, associated only with small outbreaks in the United States and the Netherlands (4,5). However, in 2014, EV-D68 gained attention because of a large outbreak in the United States that was associated with severe respiratory illness and, in some cases, with neurologic complications, such as acute flaccid paralysis (AFP) (6). In Europe, circulation of EV-D68 was low and mild, but circulation increased in the following years, especially in 2021, after preventive measures for SARS-CoV-2 were eased (7). We reviewed EV-D68-associated respiratory cases, particularly in children, diagnosed at a tertiary-care university hospital in Barcelona (Catalonia, Spain) during 2014-2021. Institutional review board approval (PR(AG)173/2017) was obtained from the HUVH Clinical Research Ethics Committee.