Surveillance of enteroviruses from paediatric patients attended at a tertiary hospital in Catalonia from 2014 to 2017

Abstract

A B S T R A C TBackground: Enterovirus (EV) infections are usually asymptomatic or mild, but symptomatic infections can evolve to severe complications. Outbreaks of EV-A71 and EV-D68 have been recently reported worldwide, sometimes related to severe clinical outcomes. Objective: To describe EV genetic diversity and the clinical outcomes from paediatric patients attended at a tertiary university hospital in Barcelona (Catalonia, Spain) from 2014 to 2017. Study design: Specimens were collected from paediatric (< 17 years old) cases with suspicion of respiratory tract infection or EV infection. EV laboratory-confirmation was performed by specific real-time multiplex RT-PCR assay. Partial viral VP1 protein was sequenced for genetic characterisation by phylogenetic analyses. Results: A total of 376 (7%) from 5703 cases were EV laboratory-confirmed. Phylogenetic analyses of VP1 (210; 81%) sequences distinguished up to 27 different EV types distributed within EV-A (82; 40%), EV-B (90; 42%), EV-C (5; 2%), and EV-D (33; 15%), in addition to 50 (19%) rhinoviruses. The most predominant were EV-A71 (37; 45%) and EV-D68 (32; 99%). EV-A71 was highly related to neurological complications (25/39, 63%), of which 20/39 were rhombencephalitis, and most EV-D68 (28/32, 88%) were associated with lower respiratory tract infections (LRTI), and exceptionally one (3%) with acute flaccid paralysis. Conclusions: EV-A71 and EV-D68 were the most detected EV in respiratory specimens. EV-A71 was highly related to neurological disease and EV-D68 was often associated with LRTI. However, both potential relatedness to neurological diseases makes the monitoring of EV circulation obligatory.

Outbreak of Enterovirus Infection with Neurological Presentations in a Pediatric Population in Northern Spain: A Clinical Observational Study

“…Outcome of EV-A71 infection was very good (84.6% of patients asymptomatic 60 days following the onset), which is in accordance with reports from other Spanish series. [7][8][9][10][11][12][13] Nevertheless, this contrasts with reports of previous outbreaks in Asia in which grade III rhombencephalitis was more frequent and several deaths were reported. 6 Further investigations are needed to clarify if these differences are due to different strains of EV-A71 in each outbreak or to genetic individual susceptibility of the host-low expression of CD40 and IL-4, HLA genotype, CTLA-4 expression 1 -among other factors.…”

“…Brainstem encephalitis caused by EV-A71, which was rarely observed in these regions previously, manifested mainly with ataxia, lethargy, tremor, myoclonus, and dysmetria (grade I rhombencephalitis 6 in 30 cases) in accordance with what has been described in previous reports. [7][8][9][10][11][12][13] Additionally, seven patients presented with cranial nerve involvement (grade II rhombencephalitis 6 ). Only one patient had mild dysautonomic signs but could not be classified as grade III rhombencephalitis (no coma, apnea or shock reported).…”

“…More than 100 children were affected, according to data from the Spanish National Microbiology Centre, 7 presenting aseptic meningitis, encephalitis, brainstem encephalitis, and myelitis. The geographical distribution of cases was variable according to the different reports: Catalonia had the first and most numerous reports with 65 confirmed cases of EV-A71 with neurological involvement 8,9 followed by other crowded regions as Madrid (26 cases). 10,11 In other regions, sporadic cases were reported: only one case of aseptic meningitis by EV-A71 was reported in the Balearic Islands 12 and four not-typed EV related with brainstem encephalitis in Andalusia.…”

Human Coronaviruses and Other Respiratory Viruses: Underestimated Opportunistic Pathogens of the Central Nervous System?

“…Another source of concern when considering human respiratory pathogens associated with potential neuroinvasion and neurovirulence is the Enterovirus genus, which comprises hundreds of different serotypes, including polioviruses (PV), coxsackieviruses (CV), echoviruses, human rhinoviruses (HRV) and enteroviruses (EV). This genus constitutes one of the most common cause of respiratory infections (going from common cold to more severe illnesses) and some members (PV, EV-A71 and -D68, and to a lesser extent HRV) can invade and infect the CNS, with detrimental consequences [166][167][168][169]. Even though extremely rare, HRV-induced meningitis and cerebellitis have been described [170].…”

“…EV-D68 causes different types of upper and lower respiratory tract infections, including severe respiratory syndromes [171]. Both serotypes have been associated with neurological disorders like acute flaccid paralysis (AFP), myelitis (AFM), meningitis and encephalitis [166,[172][173][174][175].…”