Spotlight – fatal neonatal parechovirus encephalitis

BMJ CASE REPORT Q&A: Fatal neonatal parechovirus encephalitis.
By Ahmad Mahmoud (BSc, MBBS) and Orane Delagneau (BSc [Hon], MBBS)

Now that you have read the case on Parechovirus and its potential fatal outcomes, test your knowledge with these questions.

1. CSF interpretation (predominant cell type | glucose CSF : peripheral blood | protein) in bacterial, viral, fungal and tuberculous meningitis compared to normal CSF

  • Normal: scant monocyte | normal 75% of serum glucose | normal
  • Bacterial: polymononuclear leukocytosis | markedly decreased | markedly increased
  • Viral: lymphocytosis | normal | normal to increased
  • Fungal: lymphocytosis | decreased | increased
  • Tuberculous: lymphocytosis | decreased | increased

Other factors that can affect interpretation of CSF results – traumatic tap, seizure activity, inflammatory conditions including autoimmune conditions (multiple sclerosis), inflammatory conditions including: vasculitis, sarcoidosis – atypical infections: ricketsial, parasitic.

2. What are the contraindications to lumbar puncture?

  • Proven or suspected ICP including altered level of consciousness, focal neurological
    signs, papilloedema, prolonged seizure activity
  • Cardiorespiratory or haemodynamic instability
  • Coagulation disorders including uncorrected coagulopathy or thrombocytopaenia
  • Localised skin infection at procedural site
  • Acute spinal trauma

3. As you have read in the case report, the clinical presentation can be difficult to associate with parechovirus infection as it can cause severe sepsis-like or meningitis-like illness in neonates. What signs and symptoms would you typically see with parechovirus infection?

Typically, human parechovirus (HPeV) infection is not associated with severe illness. In most
cases, it presents as a mild respiratory or gastrointestinal illness. However, in young infants less
than 3 months of age, and particularly HPeV type 3, it can cause serious illness.
Non-specific signs and symptoms include fevers, vomiting, diarrhoea, lethargy, feeding
difficulties, exanthema, coryza and lower respiratory symptoms within increase work of
breathing and oxygen requirements, irritability (due to cerebral irritation), and sepsis progressing
to septic shock.

4. How would you investigate and diagnose an infant with parechovirus?

  • Septic screen – respiratory PCR, CXR, urine MCS including PCR, blood culture, faecal
    microbial PCR
  • Lumbar puncture + CSF PCR, particularly in neonates (test to be specifically asked for
    as may not be included in usual panel of microbes for CSF testing)

5. As seen in this case report, parechovirus is a type of enterovirus that can have serious health implications for neonates. Can you discuss its prognosis, as well as the medium and long-term potential outcomes in neonates?

Overall prognosis is generally favourable with supportive treatment, with rare escalation to ICU
management. The prognosis has been found to be more serious in neonates compared
to older children, likely due to the immaturity of the neonatal immunological system.
Short-term outcomes can be serious, such as encephalitis and has been associated with death
as seen in this case. Early white matter changes have been seen to improve shortly after
resolution of the illness.

However, long-term outcomes can be a cause for concern, especially if the initial infection
presented with encephalitis. It may be associated with neurodevelopmental delay later in
childhood due to the initial cerebral insult. Different studies have reported:

  • Transient neurologic deficits
  • Delay in motor and cognitive skills
  • Receptive language difficulties at a few years of age have been reported
  • Cerebral palsy
  • Visual impairment

Ongoing prospective studies are required into further identifying poor neurological outcomes as
a result of parechovirus infections.

What medium to long term follow up is required for confirmed infected neonates?

Some recommendations have been made based on studies in different states in Australia.
There is no specific nationwide or statewide protocol followed and hospitals have different
policies. Some suggestions based on anecdotal studies are as follows:

  • Neurodevelopmental follow up with paediatrician into school years. Early detection of
    sequelae to facilitate early intervention.
  • Follow up neuroimaging with MRIs depending on the clinical course of the disease
    during admission. Persistent MRI changes have been reported in children with
    developmental concerns. However, early white-matter changes do not necessarily
    predict outcome and long term complications.
  • Early allied health input might be required in some cases.

References

Chamings, A. et al. Evolutionary analysis of human parechovirus type 3 and clinical outcomes of
infection during the 2017-18 Australian epidemic.Sci Rep. 2019 Jun 20;9(1):8906.
https://www.nature.com/articles/s41598-019-45445-z

Kielar, M. et al. Parechovirus and enterovirus infections in neonates. Folia Med Cracov.
2019;59(1):37-47. http://www.fmc.cm-uj.krakow.pl/pdf/59_1_37.pdf

Britton PN, Dale RC, Nissen MD, Crawford N, Elliott E, Macartney K, Khandaker G, Booy R,
Jones CA, PAEDS-ACE Investigators (2016) Parechovirus encephalitis and
neurodevelopmental outcomes. Pediatrics 137:e20152848. https://doi.org/10.1542/peds.2015-2848

Joseph, L. et al. Human Parechovirus 3 in Infants: Expanding Our Knowledge of Adverse
Outcomes. Pediatr Infect Dis J. 2019 Jan;38(1):1-5.
https://insights.ovid.com/pubmed?pmid=30204658

UpToDate
Local hospital policies NSW

Catherine L. Tacon and Oliver Flower, “Diagnosis and Management of Bacterial Meningitis in
the Paediatric Population: A Review,” Emergency Medicine International, vol. 2012, Article ID
320309, 8 pages, 2012. https://doi.org/10.1155/2012/320309.

A. R. Tunkel, B. J. Hartman, S. L. Kaplan et al., “Practice guidelines for the management of
bacterial meningitis,” Clinical Infectious Diseases, vol. 39, no. 9, pp. 1267–1284, 2004.