Human Parechoviruses: Biology and Infection

Abstract

Infections with human parechoviruses (HPeVs) are highly prevalent, particularly in neonates, where they may cause substantial morbidity and mortality. The clinical presentation of HPeV infection in neonates is indistinguishable from that of enterovirus (EV) infection and may vary from mild disease involving gastrointestinal and/or respiratory symptoms to more severe illness with sepsis‐like symptoms such as fever, seizures, irritability, rash and/or feeding problems. HPeV is among the most common single causes of aseptic meningitis/meningoencephalitis in infants <90 days old worldwide. The mainstay of diagnosis for HPeV infections involves the use of molecular diagnostic techniques for detection of virus RNA (ribonucleic acid) in various materials (e.g. faeces, cerebrospinal fluid (CSF), nasopharyngeal, bronchial and autopsy materials). Despite the relatedness of HPeV and EV both at the genomic and clinical presentation levels, routine nucleic acid detection methods for EV will not detect HPeV. Laboratory diagnosis of these viral infections is important not only for differential diagnostic purposes and determining a patient's prognosis but also for guidance of clinical management. Clinical disease varies somewhat among genotypes; while HPeV1 mostly causes gastrointestinal illness, HPeV3 prominence is due to sepsis syndromes and central nervous system (CNS) infections in preterm and term infants. Of diagnostic importance, HPeV3 CNS infections usually lack CSF pleocytosis, and despite ‘unremarkable’ CSF, HPeV3 RNA can be amplified from CSF, nasopharyngeal and rectal swabs in an infected individual. Taking the global incidence of reported laboratory‐confirmed HPeV cases into consideration, mortality and sequelae are overall uncommon and usually accompanying initially severe or neurologically complicated acute illnesses. However, underreporting due to lack of testing and/or appropriate diagnostic methodology likely means gross underestimation of the true incidence of HPeV disease. Currently, neither effective treatment nor vaccines are available in the control of these common viruses with the potential to cause severe harm in neonates and young children worldwide.

Key Concepts

  • HPeV infections are common among infants and children worldwide.
  • HPeV infections are underdiagnosed, and HPeV disease burden underestimated.
  • Nineteen HPeV types identified so far – their role/significance in human infections unclear except for HPeV3.
  • HPeV3 is a major cause of neonatal infections including severe meningoencephalitis.
  • Genomic differences between EV and HPeV.
  • Diagnostics: HPeV required specific PCR for detection, not that easy to culture.
  • Majority of children with HPeV3 infection lack pleocytosis in CSF/have normal CSF.
  • Having older siblings are associated with higher risk for an infant to be hospitalised with severe HPeV infection.
  • HPeV infection should always be ruled out when caring for infants with sepsis‐like illness and/or CNS infection.

Keywords: parechovirus; epidemiology; infection; diagnostic; subtyping; diagnostic guidelines; clinical presentation

Figure 1. Phylogeny of available VP1 sequences of HPeV types. HPeV sequences that were >90% complete in the VP1 genome region were aligned using the program MUSCLE (ref.) within the SSE editor v, 1.2 (ref.). An optimal substitution model (general time reversible + gamma + invariant sites) was estimated using the program MEGA6 (ref.) and used in a maximum likelihood evolutionary reconstruction. Data was bootstrap resampled 50 times; % bootstrap support values are shown on branches. The labels are annotated with the type designations reported by the Picornavirus Study Group (http://www.picornaviridae.com/parechovirus/parechovirus_a/parechovirus_a.htm).
Figure 2. Schematic diagram of the HPeV genome showing the structural and nonstructural genes. Adapted from Stanway and Hyypia 1999.
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Further Reading

Bennett S, Harvala H, Witteveldt J, et al. (2011) Rapid simultaneous detection of enterovirus and parechovirus RNAs in clinical samples by one‐step real‐time reverse transcription‐PCR assay. Journal of Clinical Microbiology 49 (7): 2620–2624.

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Nielsen AC, Bottiger B, Midgley SE and Nielsen LP (2013) A novel enterovirus and parechovirus multiplex one‐step real‐time PCR‐validation and clinical experience. Journal of Virological Methods 193 (2): 359–363.

Selvaraju SB, Nix WA, Oberste MS and Selvarangan R (2013) Optimization of a combined human parechovirus‐enterovirus real‐time reverse transcription‐PCR assay and evaluation of a new parechovirus 3‐specific assay for cerebrospinal fluid specimen testing. Journal of Clinical Microbiology 51 (2): 452–458.

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Fischer, Thea K, Harvala, Heli, and Midgley, Sofie(Jul 2017) Human Parechoviruses: Biology and Infection. In: eLS. John Wiley & Sons Ltd, Chichester. http://www.els.net [doi: 10.1002/9780470015902.a0022506]