Saturday, 30 November 2013

Parechovirus infections in babies in New South Wales, Australia

UPDATE #1. 10AUG2016
The parechoviruses (HPeVs; par -echo-virus) don't make the headlines too often. 

I'm not sure why but I expect it is mostly because they are (a) not frequently sought and (b) not frequently found. That last point is a matter of perspective though as we see in a report on the ABC news site today. 

NSW health reports 20 babies (<16-weeks of age) as being positive for an HPeV (?typed). What this cluster's symptoms are is unclear but the HPeVs have often been found in people (often notably in young children) with fever, cough, acute gastroenteritis and rash as well as liver and central nervous system symptoms. They have been linked with nosocomial (within hospital) infection acquisitions.


Click on image to enlarge.
Genomes drawn to scale using Genbank sequences. 

These are viruses might be important in presentations
or outbreaks of paediatric fever of unknown origin.
Feel free to use the graphic, just cite this website
and Assoc.Prof Ian M. Mackay.
The human parechoviruses comprise 16 members of the family Picornaviridae, genus Parechovirus, species Human parechovirus. They are not a "new virus" as the ABC news report stated, but have been known of since the 1950s when they were thought of as enteroviruses called echovirus 22 and 23 (ECHO-enteric, cytopathogenic, orphan ; now HPeV-1 and HPeV-22). The first complete polyprotein sequence of HPeV-1 was lodged on GenBank in 1992 and from 1991 it was noted that a redefinition of these viruses into a separate genus may be more realistic3,9,11 because of a range of genetic and biological features that differentiated them from other enteroviruses.

A small research grant I had some years back funded a study which also detected and reported on parechoviruses (HPeVs) in a retrospective, hospital-based PCR screening study investigating mostly nasopharyngeal aspirate specimens collected in 2003 from around South East Queensland, Australia. We reported this in 2006. We found 2 instances among 315 patient specimens (prevalence of 0.6%). We didn't type the HPeVs at that stage. Our energies were directed toward some weird rhinoviruses we'd found (later to be known as RV-C); we were trying to work out just how weird they were. Both HPeVs were co-detected in samples from female children (an 8-month and a 1-year, 7-month old) along with a bocavirus; 1 also had another picornavirus, human rhinovirus (3 viruses in total) detected and both had cough on their admission slip.
The HPeVs are ubiquitous, more prevalent during the summer and they usually infect children under 3-years of age. All can be detected using real-time RT-PCR methods and can be grown in Vero cell culture (I haven't had much luck myself!). There is still a lot of room to define causal links between detection and disease, among other things.

As ever, hand-washing, especially by kids,  plays a major role in blocking the transmission chain.

Most cases of infection resolve within days - but if those days are spent with your feverish baby lying in hospital bed and a lab diagnosis not available to you or your Doctor....those can be the longest days of your life...and the nights are made much darker by the possibilities that churn through your mind.

So it's great to see these extended molecular (PCR-based) testing panels being used by labs to seek out the causes of disease.

h/t to FluTrackers for noting this story and the page they have on it at http://www.flutrackers.com/forum/showthread.php?p=515648&posted=1#post515648/ Also thanks to my excellent student, Donna McNeale, for pointing out an error (now corrected) about the date of early mentions of the need for a new genus.

Other reading on parechoviruses...
    1. Reference to the genus: http://vir.sgmjournals.org/content/79/4/649.long
    2. [First ICTV inclusion of genus] King, A. M. Q., F. Brown, P. Christian, T. Hovi, T. Hyypia¨, N. J. Knowles, S. M. Lemon, P. D. Minor, A. C. Palmenberg, T. Skern, and G. Stanway. 1999. Picornaviridae, p. 996. In M. H. V. Van Regenmortel, C. M. Fauquet, D. H. L. Bishop, C. H. Calisher, E. B. Carsten, M. K. Estes, S. M. Lemon, J. Maniloff, M. A. Mayo, D. J. McGeoch, C. R. Pringle, and R. B. Wickner (ed.), Virus taxonomy. Seventh Report of the International Committee for the Taxonomy of Viruses. Academic Press, New York, N.Y. 
    3. Harvala H, Simmonds P. Human parechoviruses: biology, epidemiology and clinical significance. J Clin Virol 2009 May;45(1):1-9. 
    4. Tapia G, Cinek O, Witso E, Kulich M, Rasmussen T, Grinde B et al. Longitudinal observation of parechovirus in stool samples from Norwegian infants. J Med Virol 2008 October;80(10):1835-42.
    5. Al-Sunaidi M, Williams CH, Hughes PJ, Schnurr DP, Stanway G. Analysis of a new human parechovirus allows the definition of parechovirus types and the identification of RNA structural domains. J Virol 2007;81(2):1013-21.
    6. Benschop KSM, Schinkel J, Luken ME, van der Broek PJM, Beersma MFC, Menelik N et al. Fourth human parechovirus serotype. Emerg Infect Dis 2006;12(10):1572-5.
    7. Nix WA, Maher K, Johansson ES, Niklasson B, Lindberg AM, Pallansch MA et al. Detection of all known parechoviruses by real-time PCR. J Clin Microbiol 2008 August;46(8):2519-24.
    8. Sedmak G, Nix WA, Jentzen J, Haupt TE, Davis JP, Bhattacharyya S et al. Infant deaths associated with human parechovirus infection in wisconsin. Clin Infect Dis 2010 February 1;50(3):357-61.
    9. M. Steven Oberste, Kaija Maher, Mark A. Pallansch. Complete sequence of echovirus 23 and its relationship to echovirus 22 and other human enteroviruses. Vir Res 1998 56(2): 217-23
    10. Arden KE, McErlean P, Nissen MD, Sloots TP, Mackay IM. Frequent detection of human rhinoviruses, paramyxoviruses, coronaviruses, and bocavirus during acute respiratory tract infections. J Med Virol. 2006 Sep;78(9):1232-40.
    11. B-A. G. Coller, S.M. Tracy, D. Etchison. Cap-Binding Complex Protein p220 Is Not Cleaved during Echovirus 22 Replication in HeLa Cells. J Virol 1991 65(7):3903-05
      http://jvi.asm.org/content/65/7/3903.long
    12. T Hyypia, C Horsnell, M Maaronen, M Khan, N Kaljkkinen, P Auvinen, L Kinnunen, G Stanway. A distinct picornavirus group identified by sequence analysis. PNAS. 1992 89:8847-51
      http://www.pnas.org/content/89/18/8847.long
    Updates...

    1. Amended to note that one Echovirus 23 (CT86-6760) is not HPeV-2, but a misclassified HPeV-5 - Al-Sunaidi et al. J Virol 81;2. 1013-1021

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