High prevalence of developmental concern amongst infants at 12 months following hospitalised parechovirus infection

Britton, Philip N; Khandaker, Gulam; Khatami, Ameneh; Teutsch, Suzy; Francis, Stephanie; McMullan, Brendan; Jones, Cheryl

doi:10.1111/jpc.13728

Cited by 35 publications

(30 citation statements)

References 23 publications

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“…This 2‐yearly pattern is similar to that observed in the United Kingdom 13 . However, in contrast to other countries, epidemics in Australia have been larger and associated with more severe disease (and poorer clinical outcomes) 14 , 15 . Recently, whole genome sequencing has shown that the first Australian epidemic was likely caused by a novel recombinant HPeV3 16 …”

Section: Virology and Epidemiologysupporting

confidence: 70%

“…Follow‐up studies have shown adverse neurological outcomes in patients with meningoencephalitis, and developmental concern among patients with sepsis‐like illness from the 2013–2014 epidemic 14 , 15 , 23 . A study of Australian infants hospitalised with HPeV3 in 2013 found that 19% showed significant concern in developmental attainment 12–16 months after infection and an additional 50% had some concern based on standardised tools 15 . An earlier study documented severe neurodevelopmental sequelae, including cerebral palsy, central visual impairment and gross motor impairment 14 .…”

Section: Managing Parechovirus Infectionmentioning

confidence: 99%

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Parechovirus: an important emerging infection in young infants

Britton

Jones

Macartney

et al. 2018

Medical Journal of Australia

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Epidemics of human parechovirus (HPeV) causing disease in young children have occurred every 2 years in Australia since 2013. HPeV genotype 3 caused the epidemic from late 2017 to early 2018. Most HPeV infections cause no or mild symptoms including gastroenteritis or influenza-like illness. Characteristically, young infants present with fever, irritability and on occasions a diffuse rash ("red, hot and angry" babies). Severe disease can manifest as meningoencephalitis, seizures or sepsis-like presentations (including septic shock), or less common presentations including signs of surgical abdomen. Testing for HPeV by specific molecular tests is indicated in children younger than 6 months of age with characteristic presentations without another confirmed diagnosis including febrile illnesses with other suggestive features (eg, rash, seizures), sepsis syndromes (including shock), and suspected meningoencephalitis (which may be detected by magnetic resonance imaging only). There are no effective antiviral therapies. Treatment is primarily supportive, including management of complications. Some infants with severe HPeV infection may have adverse neurodevelopment. Follow-up by a paediatrician is recommended.

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Section: Virology and Epidemiologysupporting

confidence: 70%

Section: Managing Parechovirus Infectionmentioning

confidence: 99%

Parechovirus: an important emerging infection in young infants

Britton

Jones

Macartney

et al. 2018

Medical Journal of Australia

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“…The largest of the four studies to investigate outcomes following HPeV meningitis showed neurodevelopmental sequelae in 14% of infants . Interestingly, findings from the Queensland study are consistent with other long‐term studies of infants with HPeV encephalitis in New South Wales, which show poor long‐term outcomes following hospital discharge . It is not clear whether more pathogenic strains of HPeV circulated during the outbreak in New South Wales compared with circulating strains in Western Europe or whether variation in maternal immunity, age of developing infection or differences in host response to the virus could account for worse outcomes in Australian cases compared with those described in the United Kingdom and Holland.…”

Section: Discussionmentioning

confidence: 52%

“…18 Interestingly, findings from the Queensland study are consistent with other long-term studies of infants with HPeV encephalitis in New South Wales, which show poor long-term outcomes following hospital discharge. 29 Conclusions from this systematic review should be taken with caution due to several limitations. The review only identified 14 studies over the last three decades, which reported outcomes following viral meningitis.…”

Section: Discussionmentioning

confidence: 98%

Outcomes beyond hospital discharge in infants and children with viral meningitis: A systematic review

Hudson

Broad

Martin

et al. 2019

Reviews in Medical Virology

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Summary Viruses are the commonest cause of childhood meningitis, but outcomes beyond hospital discharge are poorly described. We undertook a systematic literature review of long‐term outcomes following paediatric viral meningitis. A search was carried out using MEDLINE, Embase, and Cochrane Review for studies from 1 January 1990 to 31 December 2018. Studies were included where specific outcome measures were available beyond hospital discharge for children <16 years old with viral meningitis. In total, 3588 papers were identified of which 14 were eligible for inclusion. Four studies reported outcomes in children with nonenterovirus 71 meningitis. A US study of 16 cases demonstrated subtle language difficulties at 3‐year follow‐up in infants in contrast to an Australian study, which revealed no impairment in language. A Fijian study showed that two out of eight cases had sensorineural hearing loss compared with none in a UK cohort of 668 infants. Three studies evaluated outcomes of enterovirus 71 meningitis in China and Taiwan, two showed cases recovered without sequelae, while one demonstrated an increased risk of attention deficit hyperactivity disorder. Two studies including 141 cases of human parechovirus revealed no evidence of neurodevelopmental sequelae. Conversely, an Australian study demonstrated neurodevelopmental sequelae in 11 out of 77 infants with parechovirus meningitis. Most studies identified in this review demonstrated a high proportion of good clinical outcomes following viral meningitis. However, the data are limited, so robustly conducted neurodevelopmental studies are warranted to inform the evidence‐based management of viral meningitis beyond hospital discharge.

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“…7 Central nervous system conditions such as acute flaccid paralysis, meningitis and encephalitis are more often associated with PeV-3. [10][11][12][13] Inference about differential clinical manifestations is limited for most of the other PeV-A genotypes as they have only been isolated from a few cases.…”

Section: Introductionmentioning

confidence: 99%

Genotypic diversity and dynamic nomenclature ofParechovirus A

Parker

Han

Brouwer

et al. 2020

Preprint

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Human parechoviruses (PeV-A) can cause severe sepsis and neurological syndromes in neonates and children and are currently classified into 19 genotypes based on genetic divergence in the VP1 gene. However, the genotyping system has notable limitations including an arbitrary distance threshold and reliance on insufficiently robust phylogenetic reconstruction approaches leading to inconsistent genotype definitions. In order to improve the genotyping system, we investigated the molecular epidemiology of human parechoviruses, including the evolutionary history of the different PeV-A lineages as far as is possible. We found that PeV-A lineages suffer from severe substitution saturation in the VP1 gene which limit the inference of deep evolutionary timescales among the extant PeV-A and suggest that the degree of evolutionary divergence among current PeV-A lineages has been substantially underestimated, further confounding the current genotyping system. We propose an alternative nomenclature system based on robust, amino-acid level phylogenetic reconstruction and clustering with the PhyCLIP algorithm which delineates highly divergent currently designated genotypes more informatively. We also describe a dynamic nomenclature framework that combines PhyCLIPs progressive clustering with phylogenetic placement for genotype assignment.

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High prevalence of developmental concern amongst infants at 12 months following hospitalised parechovirus infection

Cited by 35 publications

References 23 publications

Parechovirus: an important emerging infection in young infants

Parechovirus: an important emerging infection in young infants

Outcomes beyond hospital discharge in infants and children with viral meningitis: A systematic review

Genotypic diversity and dynamic nomenclature ofParechovirus A

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