Non-polio enteroviral neonatal infection remain common, especially in the warmer months, and most (up to 80%) remain asymptomatic. Only in a minority of cases do neonates develop hepatic or cardiac involvement; in which case infection may be sever or fatal.¹
The acid-stable, gut-tropic, Coxsackie and Echo virus, together with Poliovirus, make up an Enterovirus genus, part of a larger Picornavirus (small RNA viruses) family of virions that include the ubiquitous rhinovirus (figure 1).
According to community-based data, published in 2006, infants have between two and five acute respiratory infections in that first year of life, one-third of which are lower respiratory tract infections. One-half of all these respiratory infections of infancy—whether infections of the upper or of the lower respiratory tract—are caused by rhinoviruses.¹ In fact, rhinovirus remains a significant cause of wheezing illness in the first year of life—a significant cause of bronchiolitis.
But although less commonly implicated, the related Enteroviruses have similar potential to cause significant infant morbidity. Quite unlike rhinovirus, however, enteroviruses have been implicated with a lethal sepsis-like syndrome in neonates.
Original enterovirus classification, based on animal studies and cytopathologic effect in tissue culture, divided the genus into four species: poliovirus, coxsackie A, coxsackie B, and echovirus. Newly identified strains of enterovirus did not, however, fit nicely into this schema and, since 1974, were designated separate Human Enterovirus (HEV A, B, C, and D) type numbers.²
Figure 1: Taxonomy of Enteroviruses (Goodman et al, 2009)³
Non-enveloped, single-stranded RNA viruses, the acid-stable enteroviruses show a predilection (tropism) for the gastrointestinal tract; main site of otherwise self-limiting infections of childhood if not for the occasional serious respiratory disease and propensity for spread thereafter to the central nervous system, especially neonates infected through vertical transmission (in-utero or postnatally).
However, ex-utero faecal-oral transmission is the rule and younger children, who frequently remain asymptomatic, act as reservoir of infection, which peaks in the spring/summer months. It is the neonate with siblings attending Day Care, for instance, who remains particularly at risk to enterovirus exposure. Asking in the history after their older sibling’s recent flu-like illness—inclusive of rash, sore throat (mouth sores), conjunctivitis, and vomiting often without diarrhoea—may tip the clinician to the neonate’s infection. Hand hygiene remains an important part of infection control.
Because of this, enteroviruses have a wide-spectrum of clinical presentation in the newborn infant, from non-specific febrile illness to fatal multisystem disease:
- non-specific: fever, irritability, poor feeding, lethargy (20%)
- maculopapular rash (50%)
- respiratory symptoms (50%)
- gastrointestinal symptoms (20%)
- hepatitis (50%)
- myocarditis
- meningoencephalitis – prognosis remains good except where part of disseminated organ system involvement³
Note the common genus and family predilection for gastrointestinal, respiratory, and nervous systems. Serious manifestations of enteroviral disease in neonates, however, suggest widespread viraemia and include myocarditis and hepatitis, often accompanied by encephalitis.³
The younger neonate who develops infection from vertical transmission remains particularly at risk for hepatic necrosis and coagulopathy (HNC) or myocarditis (coxsackie virus group B often implicated), associated with a mortality of 24% and 71%, respectively.
Comparator Vital Signs for a Full-term Neonate (< 28 days old)
- PR 120-160 bpm
- SBP > 60 mmHg
- Respirations 40-60 breaths per minute
Nasopharyngeal (or blood, CSF, tissue specimens) PCR confirms the diagnosis an index of suspicion for enteroviral infection exists. Perform PCR testing also for parechovirus at the same time. “Compared with PCR, the sensitivity of viral culture is approximately 75%”.¹
Treatment is supportive. However, intravenous immune globulin (IVIG) hastens resolution of viraemia and has also been used prophylactically in exposed neonates.²
Note: RNA viruses use host RNA-Replicase to transcribe copies of their genome (and then to translate protein). Some RNA viruses lyse their host, others escaping without lysing.
Originally described in 1956 and known as echoviruses, considered a type of enterovirus, in the 1990s, advanced molecular virology and genotyping techniques demonstrated heretofore unknown differences between these viruses affording the subsequent distinction to “parechovirus”. Human parechovirus (HPeV) causes a spectrum of disease not unlike enteroviruses.
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Clinical Pathway For Treatment Of Enterovirus In The Neonate
Human parechovirus (NSW Health)
References
- Hawkes, M. T., and Vaudry, W. “Nonpolio enterovirus infection in the neonate and young infant.” Paediatr Child Health 10(7); Sep 2005.
- Kusel, Merci M. H.; de Klerk, Nicholas H.; Holt, Patrick G.; Kebadze, Tatiana; Johnston, Sebastian L.; Sly, Peter D. Role of Respiratory Viruses in Acute Upper and Lower Respiratory Tract Illness in the First Year of Life: A Birth Cohort Study. The Pediatric Infectious Disease Journal. 25(8):680-686, August 2006.
- Palasanthrian, Pamela, Starr, Mike, Jones Cheryl, Giles, Michelle. “Enterovirus”. In Management of Perinatal Infections. Sydney: Australasian Society for Infectious Diseases, 2014: 11-14.
- Goodman, Karen, Garcia, Sylvia, and Paul, Audrey. Enterovirus And The Neonate: Controversies In The Diagnosis And Management Of Potentially Lethal Infections. Pediatric Emergency Medicine Practice 6(3), March 2009: 1-22.
Other articles of interest
Hawkes, Michael T; and Vaudry, Wendy. “Nonpolio enterovirus infection in the neonate and young infant.” Paediatr Child Health 10(7) Sep 2005: 383-388.
