Severe parechovirus infection in infants: adding to the case for a role in later neurodevelopmental issues…

HPeV-1 predicted capsid structure.The figures/data were obtained from VIPERdb [11]

Human parechovirus (HPeV) infections favour the warmer weather and while we can all be infected, we usually note more severe disease in children.[2] Most infections are mild or probably not even noticed but on occasion, especially in the very young, HPeV infection can be life threatening.

Since 2013, HPeV infections have become a bigger deal in the news Down Under.[3,4,5] They are being tested for more often and as a result they are being found! That’s a good thing.

HPeV cases can include some very sick infants (1-12 month olds). At the severe end of disease, infants can develop a sepsis-like syndrome and meningoencephalitis. Sepsis is a system-wide immune response to a rampaging infection-usually, but not always, associated with bacterial bloodstream infections whereas meningoencephalitis is a tricky to diagnose inflammation of the linings of the brain and the brain tissue itself.[6,7]

A new study…

This brings us to a new Australian questionnaire-based follow-up study of 42 of 79 previous HPeV cases; all 42 had sepsis-like illness.[1]

While severe HPeV disease can be terrible enough for all involved at the time, this new study shows that problems may continue after infection among a proportion of severe cases. The problems may be related indirectly to the severity of the immune response to the infection or directly to the way in which, and where, HPeV causes its cellula

Genomes drawn to scale using Genbank sequences. These are viruses which might be important in presentations or outbreaks of paediatric fever of unknown origin.

r damage.

The latest study followed-up some HPeV cases identified in 2013-2014 by a collaborative team from the Australian southeastern state of New South Wales.[8] The new study found that a high proportion of hospitalised infants who had a confirmed HPeV genotype 3 (HPeV-3)-infection, were left with developmental issues 12-months later.[1] Other previous work from some of this team and others around Australia flagged poor outcomes after HPeV infection noting the development of cerebral palsy and visual impairment among some severe HPeV cases following on from neonatal encephalopathy.[9]

In this new preliminary study, the first to report long-term outcomes from HPeV cases, half of the infants followed up showed some level of neurodevelopmental “concern” with 19% described as having “significant” development concerns including gross motor and problem-solving issues. The study could not identify any clinical features that could be used to predict these developmental outcomes in future cases; an area for future work.

Also of concern to the authors was their finding that a high proportion of the infants with significant developmental concerns identified in this study, had initially been assessed as being without neurological sequelae (a condition following on from a previous disease or injury)- they were ‘recovered fully’ at discharge or at short-term follow-up. Following on from hard recent lessons taught to us by Ebola virus disease and Zika virus disease – we have another virus that doesn’t just come and go – it leaves a lasting reminder that messing with us early in life can have lasting consequences.

Hospitalisation for severe HPeV infection, perhaps more so among those needing a longer admission period, is currently the best indication of possible future neurodevelopmental impact. Infants and babies under 12 months of age are the group most likely to develop severe HPeV disease and should be referred for more detailed and careful follow-up if such disease develops.

Suspect HPeV infections in neonates (newborn) or young infants can present with a fever (>38.0°C) and:
(the following is skimmed from the excellent info provided at [10]; visit to read more detail )

  • Irritability and appearing to be in pain
  • Abnormal movements / jerking movements
  • Widespread rash
  • Rapid breathing
  • Excessive tiredness, drowsiness
  • Extended abdomen or diarrhoea

How is it diagnosed?

Stool samples, nose and throat swabs, cerebrospinal fluid (CSF), or blood can be tested for HPeV at a specialist laboratory using RT-PCR methods with nucleotide sequence to confirm the genotype. Other genotypes do circulate in Australia but their impact in infants is not as clear as that from HPeV-3.

Initial Management and Treatment

There is no specific treatment for HPeV, treatment is supportive only.

How can HPeV disease be prevented?

  • There is no vaccine to protect you from HPeV infection
  • Good hygiene is the best protection: wash hands with soap and water after going to the toilet, before eating, after wiping noses, and after changing nappies or soiled clothing
  • Avoid sharing cups, cutlery, towels, toothbrushes and clothing
  • Cover coughs and sneezes with a tissue; cough into an elbow, not your hand
  • Wipe nose and mouth with tissues, dispose of used tissues and then wash your hands.
  • People who are unwell with colds, flu-like illness or gastro illness should stay away from small babies.
  • If you are caring for a small baby and are unwell, wash your hands or use an alcohol-based hand rub before touching or feeding the baby.

References…

  1. High prevalence of developmental concern amongst infants at 12 months following hospitalised parechovirus infection
    https://www.ncbi.nlm.nih.gov/pubmed/28960646
  2. What to watch for with human parechovirus (HPeV) infections
    https://virologydownunder.blogspot.com.au/2013/12/what-to-watch-for-with-human.html
  3. Eleven cases of new baby virus – parechovirus – found in Queensland
    http://www.couriermail.com.au/news/queensland/eleven-cases-of-new-baby-virus-parechovirus-found-in-queensland/news-story/0ae9890af43c635c7c0958e43c49acd9
  4. Potentially fatal parechovirus afflicting babies prompts urgent Queensland probe
    http://www.abc.net.au/news/2014-06-04/urgent-study-into-parechovirus-fatal-to-babies-queensland-nsw/5499066
  5. ‘Mini-epidemic’ of virus infecting newborns, doctor warns
    http://www.smh.com.au/national/health/miniepidemic-of-virus-infecting-newborns-doctor-warns-20140625-zsl9d.html
  6. What is sepsis?
    https://www.cdc.gov/sepsis/basic/index.html
  7. Infectious Causes of Encephalitis and Meningoencephalitis in Thailand, 2003–2005
    https://wwwnc.cdc.gov/eid/article/21/2/14-0291_article
  8. Sepsis-like Disease in Infants Due to Human Parechovirus Type 3 During an Outbreak in Australia
    https://academic.oup.com/cid/article-lookup/doi/10.1093/cid/ciu784
  9. Parechovirus Encephalitis and Neurodevelopmental Outcomes
    http://pediatrics.aappublications.org/content/early/2016/01/19/peds.2015-2848
  10. A NSW Health factsheet on HPeV.
    http://www.health.nsw.gov.au/Infectious/factsheets/Pages/parechovirus.aspx
  11. VIPERdb2: an enhanced and web API enabled relational database for structural virology.
    Mauricio Carrillo-Tripp, Craig M. Shepherd, Ian A. Borelli, Sangita Venkataraman, Gabriel Lander, Padmaja Natarajan, John E. Johnson, Charles L. Brooks, III and Vijay S. Reddy. Nucleic Acid Research 37, D436-D442 (2009); doi: 10.1093/nar/gkn840
    https://www.ncbi.nlm.nih.gov/pubmed/18981051
    http://viperdb.scripps.edu

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