Enterovirus infections in neonates
Introduction
The human enteroviruses belong to the family of picornaviridae and have historically been classified into echoviruses, coxsackie A and B viruses, and polioviruses. This traditional taxonomy is based on replication properties in culture, as well as the range of clinical symptoms caused by infection with these viruses in humans. Since the 1960s, rather than being assigned to one of the four major groups, newly identified enteroviruses have been given a numeric designation (‘numbered enteroviruses’, e.g. enterovirus 68 to 71). Further numbered enterovirus serotypes have been identified only in the last five years.1, 2
Relatively recent molecular data suggest that the traditional groups are genetically quite diverse, which has led to the adoption of a new taxonomy.3, 4 In this current taxonomy, enteroviruses are divided into five species: human enterovirus A, B, C and D, and polioviruses, with the traditional names retained for individual serotypes (Table 1).
This review focuses primarily on non-polio enterovirus infections. Poliovirus infections and poliomyelitis have become exceedingly rare in most developed countries as a result of routine immunisation programmes, and are discussed in detail elsewhere.8, 9 Also, parechoviruses, some of which were previously classified as echoviruses (echovirus 22 and 23), are not discussed in this review. Recent molecular sequencing data suggest that these are a separate group of viruses.10 However, the clinical manifestations associated with parechovirus infection show a considerable overlap with those produced by enteroviruses and disease can be virtually indistinguishable.11
Non-polio enteroviruses can produce a wide spectrum of acute illnesses with clinical manifestations ranging from non-specific febrile illness, mild upper respiratory tract infection or self-limiting gastroenteritis, to more severe entities such as myocarditis, hepatitis and encephalitis. Some diseases or manifestations are typically associated with a particular enterovirus group or even a particular serotype, such as herpangina (coxsackie A viruses),12 hand-foot-and-mouth disease [coxsackie A viruses (frequently A16), enterovirus 71],13, 14 pericarditis/myocarditis (coxsackie B viruses),15, 16 pleurodynia (Bornholm's disease; coxsackie B viruses)17 and haemorrhagic conjunctivitis (coxsackievirus A24, enterovirus 70).18, 19
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Epidemiology of enterovirus infections
Enteroviruses are among the most common viruses causing disease in humans. It has been estimated that in the USA alone 10–15 million symptomatic enterovirus infections occur each year.20 Enterovirus infections have a distinct seasonal pattern in temperate climates, with the majority of infections occurring during summer and fall,21, *22, *23, 24 although this seasonality appears to be less pronounced in the neonatal population.20
In Europe the most commonly isolated enterovirus serotypes are
Enterovirus transmission in neonates
There is evidence suggesting that enterovirus infections can be acquired antenatally, intrapartum and postnatally.
In-utero transmission in late gestation has been demonstrated in animal models,30 and a number of observations in humans also support the concept that enteroviruses can be transmitted antenatally – either transplacentally or potentially via ascending infection.
One prospective study during a community outbreak of echovirus 11 suggests that vertical transmission is relatively common
Clinical features of neonatal enterovirus infection
Enterovirus infections in the neonate are associated with a wide spectrum of signs and symptoms, which range from a non-specific febrile illness to potentially fatal multisystem disease, frequently referred to as ‘neonatal enterovirus sepsis’ or ‘enteroviral sepsis syndrome’.
The most common presenting features associated with neonatal enterovirus infection are fever, irritability, poor feeding and lethargy.*22, *38, 39, *40 A non-specific rash, which is frequently macular or maculo-papular in
Diagnosis of enterovirus infection
The detection of enteroviruses is traditionally based on viral isolation in cell culture, followed by immunofluorescence staining or typing with the use of antisera, which allows identification of the infecting serotype. Previous reports suggest that the highest isolation yields are achieved with samples from the upper respiratory tract (throat swabs/nasopharyngeal aspirates), gastrointestinal samples (rectal swabs/stool samples) and cerebrospinal fluid. Isolation from blood and urine is less
Prognosis of enterovirus infection in the neonatal period
The majority of infants who present with enterovirus infection in the neonatal period have a benign course and make a full recovery. Pyrexia generally resolves within three to five days, whereas resolution of symptoms occurs on average within four to seven days after onset.*22, *38, 39
Previous studies have reported overall mortality rates ranging between 0 and 42%.16, *22, *38, 39, 41 Risk factors for severe infection include prematurity,31, 39, 53 presence of maternal ‘viral symptoms’ at
Prophylaxis and treatment of enterovirus infection in neonates
As enteroviral infection is a self-limiting infection in immunocompetent individuals and most neonates have a benign course, the treatment of neonatal enterovirus infections predominately consists of supportive therapy.
Conflict of interest statement
None declared.
Funding sources
M.T. is supported by a Fellowship from the European Society of Paediatric Infectious Diseases and an International Research Scholarship from the University of Melbourne.
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Healthcare-Associated Infections
2023, Avery's Diseases of the NewbornCentral role of the placenta during viral infection: Immuno-competences and miRNA defensive responses
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2021, Anales de PediatriaNeonatal Fc receptor in human immunity: Function and role in therapeutic intervention
2020, Journal of Allergy and Clinical ImmunologyCitation Excerpt :Genome-wide association studies, which assessed common FCGRT polymorphisms (but would not capture the VNTRs), have not reported any disease associations. Echoviruses are common causes of aseptic meningitis worldwide, and also of severe hepatitis, neurological disease, and death in neonates and infants.70,71 Echovirus particles attach to the host cell surface by directly binding FcRn (Fig 4), a receptor both necessary and sufficient for echovirus infection.4,72
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