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Human parechovirus infection as an undiagnosed cause of adult pericarditis
Accepted Manuscript Title: Human parechovirus infection as an undiagnosed cause of adult pericarditis Author: Thomas McGregor, Frances A. Bu'Lock, Martin Wiselka, Julian W. Tang PII: DOI: Reference:
S0163-4453(17)30341-9 https://doi.org/doi:10.1016/j.jinf.2017.10.011 YJINF 4006
To appear in:
Journal of Infection
Accepted date:
23-10-2017
Please cite this article as: Thomas McGregor, Frances A. Bu'Lock, Martin Wiselka, Julian W. Tang, Human parechovirus infection as an undiagnosed cause of adult pericarditis, Journal of Infection (2017), https://doi.org/doi:10.1016/j.jinf.2017.10.011. This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
To the Editor, Journal of Infection (Letter)
Human parechovirus infection as an undiagnosed cause of adult pericarditis Thomas McGregor T1, Frances A Bu'Lock 2, Martin Wiselka3,4, Julian W Tang4,5
1
School of Veterinary Medicine, University of Nottingham, Sutton Bonington, UK
2
East Midlands Congenital Heart Centre and University of Leicester, Glenfield Hospital,
Leicester, UK 3
Infectious Diseases Unit, University Hospitals of Leicester NHS Trust, Leicester, UK
4
Infection, Immunity, Inflammation, University of Leicester, Leicester, UK
5
Clinical Microbiology and Virology, University Hospitals of Leicester NHS Trust, Leicester,
UK
Correspondence to: Dr Julian W Tang Clinical Microbiology, University Hospitals of Leicester NHS Trust Level 5 Sandringham Building, Leicester Royal Infirmary Infirmary Square, Leicester LE1 5WW, UK. Email: [email protected]; [email protected] Tel: 0116 258 6516. Fax: 0116 255 1949
Declarations: All authors have contributed to this case report and have seen and approved the final version. None have any conflicts of interest to declare. This manuscript has not been submitted elsewhere for consideration for publication.
1 Page 1 of 10
Graphical abstract
Highlights
Parechoviruses belong to the same virus family as rhinoviruses and enteroviruses Human parechoviruses are well-recognised to cause neonatal and infant sepsis Less is known about their contribution to older child and adult infection and disease Human parechovirus myocarditis and pericarditis have now been described in adults Commercial kits are now available to assist routine diagnostic testing for this virus
2 Page 2 of 10
Dear Editor,
Human parechoviruses (HPeV) are non-enveloped, single-stranded, positive-sense RNA viruses. They belong to the family Picornaviridae, which includes rhinoviruses and enteroviruses. They usually cause self-limiting, mild gastroenteritis and respiratory infections in young children. Previous reports in the Journal on HPeV infections have mostly focused on neonates and infants, 1,2 as reported elsewhere,3-5 which can occasionally lead to more severe neurological complications.6 Large clusters of HPeV infections have been recently reported in Australia and the UK.5,6 Other teams have reported epidemic myalgia and myocarditis in adults with HPeV infection.7,8 Here we broaden the spectrum of adult associations with HPeV infection and disease by reporting a case of human parechovirus pericarditis in an otherwise healthy 19-year old male. The patient presented with two episodes of sudden-onset, sharp, central chest pain, over a two-week period that was worse on lying down and during inspiration. The pain was relieved on sitting upright and leaning forward. He gave no history of recent contact with sick children. He did not present to healthcare services on the first episode, which resolved on oral analgesia and rest. However, after the second episode, he was seen in clinic. A clinical diagnosis of pericarditis was made. An electrocardiogram (ECG) was performed, which showed changes consistent with pericarditis (Fig. 1A). Both the chest Xray and echocardiogram were normal. Polymerase chain reaction (PCR) testing on sputum, blood and stool was performed for enteroviruses and adenoviruses (as described elsewhere),9 which are recognised viral causes of pericarditis. Testing for HPeV was also included due to the recent surge in HPeV genotype 3 infections reported in this population during this period.5
3 Page 3 of 10
The sputum sample was positive for HPeV RNA on PCR testing, but none was detected in the blood and stool. No enteroviruses or adenoviruses were detected in these samples, and no other infectious agents were found. The patient’s symptoms eventually resolved with bed-rest and oral analgesia. A repeat ECG nine days later showed complete resolution of his pericarditis (Fig. 1B). Human parechovirus infections are mostly diagnosed in neonates and infants where cardiac presentations are also well-described,1-6 but much more rarely in adults. This may be due to a lack of awareness as well as a possible lack of testing capability in some laboratories for this pathogen.5 On the basis of these case reports, we thus recommend that HPeV infections should be considered as part of the differential diagnosis for acute myocarditis and pericarditis in both children and adults. However, the diagnosis may often be missed because many commercial PCR kits do not include this virus as a target, which makes it difficult for many routine diagnostic laboratories to screen for this pathogen. Yet a heightened awareness of this virus, as highlighted in this case report, will prompt clinical teams to request such testing to be performed at a specialist reference laboratory, as required.
References 1. Harvala H, Griffiths M, Solomon T, Simmonds P. Distinct systemic and central nervous system disease patterns in enterovirus and parechovirus infected children. J Infect 2014;69(1):69-74. doi: 10.1016/j.jinf.2014.02.017. 2. Aizawa Y, Suzuki Y, Watanabe K, Oishi T, Saitoh A. Clinical utility of serum samples for human parechovirus type 3 infection in neonates and young infants: The 2014 epidemic in Japan. J Infect 2016;72(2):223-32. doi: 10.1016/j.jinf.2015.10.010.
4 Page 4 of 10
3. 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;50(3):357-61. doi: 10.1086/649863. 4. Janes VA, Minnaar R, Koen G, van Eijk H, Dijkman-de Haan K, Pajkrt D, et al. Presence of human non-polio enterovirus and parechovirus genotypes in an Amsterdam hospital in 2007 to 2011 compared to national and international published surveillance data: a comprehensive review. Euro Surveill 2014;19(46). pii: 20964. 5. Tang JW, Holmes CW, Elsanousi FA, Patel A, Adam F, Speight R, et al. Cluster of human parechovirus infections as the predominant cause of sepsis in neonates and infants, Leicester, United Kingdom, 8 May to 2 August 2016. Euro Surveill 2016;21(34). doi: 10.2807/1560-7917.ES.2016.21.34.30326. 6. Britton PN, Dale RC, Nissen MD, Crawford N, Elliott E, Macartney K, et al. Parechovirus Encephalitis and Neurodevelopmental Outcomes. Pediatrics 2016;137(2):e20152848. doi: 10.1542/peds.2015-2848. 7. Mizuta K, Kuroda M, Kurimura M, Yahata Y, Sekizuka T, Aoki Y, et al. Epidemic myalgia in adults associated with human parechovirus type 3 infection, Yamagata, Japan, 2008. Emerg Infect Dis 2012;18(11):1787-93. doi: 10.3201/eid1811.111570. 8. Kong KL, Lau JSY, Goh SM, Wilson HL, Catton M, Korman TM. Myocarditis Caused by Human Parechovirus in Adult. Emerg Infect Dis 2017;23(9):1571-73. doi: 10.3201/eid2309.161256. 9. Veater J, Wong N, Stephenson I, Kirk-Granger H, Baxter LF, Cannon R, et al. Resource impact of managing suspected Middle East respiratory syndrome patients in a UK teaching hospital. J Hosp Infect 2017;95(3):280-85. doi: 10.1016/j.jhin.2016.12.010.
5 Page 5 of 10
Figure legend
Figure 1 A On acute presentation with chest pain: saddle-shaped, acute ST elevation in inferior leads II, II, aVF, and reduced voltages in the QRS complexes of the limb leads, indicating pericarditis. B Normalisation of ST segment changes in inferior leads II, II, aVF, and the QRS voltages of the limb leads, during convalescence, 9 days later.
6 Page 6 of 10
7 Page 7 of 10
Fig 1A.png
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Fig 1B.png
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S0163-4453(17)30341-9 https://doi.org/doi:10.1016/j.jinf.2017.10.011 YJINF 4006
To appear in:
Journal of Infection
Accepted date:
23-10-2017
Please cite this article as: Thomas McGregor, Frances A. Bu'Lock, Martin Wiselka, Julian W. Tang, Human parechovirus infection as an undiagnosed cause of adult pericarditis, Journal of Infection (2017), https://doi.org/doi:10.1016/j.jinf.2017.10.011. This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
To the Editor, Journal of Infection (Letter)
Human parechovirus infection as an undiagnosed cause of adult pericarditis Thomas McGregor T1, Frances A Bu'Lock 2, Martin Wiselka3,4, Julian W Tang4,5
1
School of Veterinary Medicine, University of Nottingham, Sutton Bonington, UK
2
East Midlands Congenital Heart Centre and University of Leicester, Glenfield Hospital,
Leicester, UK 3
Infectious Diseases Unit, University Hospitals of Leicester NHS Trust, Leicester, UK
4
Infection, Immunity, Inflammation, University of Leicester, Leicester, UK
5
Clinical Microbiology and Virology, University Hospitals of Leicester NHS Trust, Leicester,
UK
Correspondence to: Dr Julian W Tang Clinical Microbiology, University Hospitals of Leicester NHS Trust Level 5 Sandringham Building, Leicester Royal Infirmary Infirmary Square, Leicester LE1 5WW, UK. Email: [email protected]; [email protected] Tel: 0116 258 6516. Fax: 0116 255 1949
Declarations: All authors have contributed to this case report and have seen and approved the final version. None have any conflicts of interest to declare. This manuscript has not been submitted elsewhere for consideration for publication.
1 Page 1 of 10
Graphical abstract
Highlights
Parechoviruses belong to the same virus family as rhinoviruses and enteroviruses Human parechoviruses are well-recognised to cause neonatal and infant sepsis Less is known about their contribution to older child and adult infection and disease Human parechovirus myocarditis and pericarditis have now been described in adults Commercial kits are now available to assist routine diagnostic testing for this virus
2 Page 2 of 10
Dear Editor,
Human parechoviruses (HPeV) are non-enveloped, single-stranded, positive-sense RNA viruses. They belong to the family Picornaviridae, which includes rhinoviruses and enteroviruses. They usually cause self-limiting, mild gastroenteritis and respiratory infections in young children. Previous reports in the Journal on HPeV infections have mostly focused on neonates and infants, 1,2 as reported elsewhere,3-5 which can occasionally lead to more severe neurological complications.6 Large clusters of HPeV infections have been recently reported in Australia and the UK.5,6 Other teams have reported epidemic myalgia and myocarditis in adults with HPeV infection.7,8 Here we broaden the spectrum of adult associations with HPeV infection and disease by reporting a case of human parechovirus pericarditis in an otherwise healthy 19-year old male. The patient presented with two episodes of sudden-onset, sharp, central chest pain, over a two-week period that was worse on lying down and during inspiration. The pain was relieved on sitting upright and leaning forward. He gave no history of recent contact with sick children. He did not present to healthcare services on the first episode, which resolved on oral analgesia and rest. However, after the second episode, he was seen in clinic. A clinical diagnosis of pericarditis was made. An electrocardiogram (ECG) was performed, which showed changes consistent with pericarditis (Fig. 1A). Both the chest Xray and echocardiogram were normal. Polymerase chain reaction (PCR) testing on sputum, blood and stool was performed for enteroviruses and adenoviruses (as described elsewhere),9 which are recognised viral causes of pericarditis. Testing for HPeV was also included due to the recent surge in HPeV genotype 3 infections reported in this population during this period.5
3 Page 3 of 10
The sputum sample was positive for HPeV RNA on PCR testing, but none was detected in the blood and stool. No enteroviruses or adenoviruses were detected in these samples, and no other infectious agents were found. The patient’s symptoms eventually resolved with bed-rest and oral analgesia. A repeat ECG nine days later showed complete resolution of his pericarditis (Fig. 1B). Human parechovirus infections are mostly diagnosed in neonates and infants where cardiac presentations are also well-described,1-6 but much more rarely in adults. This may be due to a lack of awareness as well as a possible lack of testing capability in some laboratories for this pathogen.5 On the basis of these case reports, we thus recommend that HPeV infections should be considered as part of the differential diagnosis for acute myocarditis and pericarditis in both children and adults. However, the diagnosis may often be missed because many commercial PCR kits do not include this virus as a target, which makes it difficult for many routine diagnostic laboratories to screen for this pathogen. Yet a heightened awareness of this virus, as highlighted in this case report, will prompt clinical teams to request such testing to be performed at a specialist reference laboratory, as required.
References 1. Harvala H, Griffiths M, Solomon T, Simmonds P. Distinct systemic and central nervous system disease patterns in enterovirus and parechovirus infected children. J Infect 2014;69(1):69-74. doi: 10.1016/j.jinf.2014.02.017. 2. Aizawa Y, Suzuki Y, Watanabe K, Oishi T, Saitoh A. Clinical utility of serum samples for human parechovirus type 3 infection in neonates and young infants: The 2014 epidemic in Japan. J Infect 2016;72(2):223-32. doi: 10.1016/j.jinf.2015.10.010.
4 Page 4 of 10
3. 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;50(3):357-61. doi: 10.1086/649863. 4. Janes VA, Minnaar R, Koen G, van Eijk H, Dijkman-de Haan K, Pajkrt D, et al. Presence of human non-polio enterovirus and parechovirus genotypes in an Amsterdam hospital in 2007 to 2011 compared to national and international published surveillance data: a comprehensive review. Euro Surveill 2014;19(46). pii: 20964. 5. Tang JW, Holmes CW, Elsanousi FA, Patel A, Adam F, Speight R, et al. Cluster of human parechovirus infections as the predominant cause of sepsis in neonates and infants, Leicester, United Kingdom, 8 May to 2 August 2016. Euro Surveill 2016;21(34). doi: 10.2807/1560-7917.ES.2016.21.34.30326. 6. Britton PN, Dale RC, Nissen MD, Crawford N, Elliott E, Macartney K, et al. Parechovirus Encephalitis and Neurodevelopmental Outcomes. Pediatrics 2016;137(2):e20152848. doi: 10.1542/peds.2015-2848. 7. Mizuta K, Kuroda M, Kurimura M, Yahata Y, Sekizuka T, Aoki Y, et al. Epidemic myalgia in adults associated with human parechovirus type 3 infection, Yamagata, Japan, 2008. Emerg Infect Dis 2012;18(11):1787-93. doi: 10.3201/eid1811.111570. 8. Kong KL, Lau JSY, Goh SM, Wilson HL, Catton M, Korman TM. Myocarditis Caused by Human Parechovirus in Adult. Emerg Infect Dis 2017;23(9):1571-73. doi: 10.3201/eid2309.161256. 9. Veater J, Wong N, Stephenson I, Kirk-Granger H, Baxter LF, Cannon R, et al. Resource impact of managing suspected Middle East respiratory syndrome patients in a UK teaching hospital. J Hosp Infect 2017;95(3):280-85. doi: 10.1016/j.jhin.2016.12.010.
5 Page 5 of 10
Figure legend
Figure 1 A On acute presentation with chest pain: saddle-shaped, acute ST elevation in inferior leads II, II, aVF, and reduced voltages in the QRS complexes of the limb leads, indicating pericarditis. B Normalisation of ST segment changes in inferior leads II, II, aVF, and the QRS voltages of the limb leads, during convalescence, 9 days later.
6 Page 6 of 10
7 Page 7 of 10
Fig 1A.png
8 Page 8 of 10
9 Page 9 of 10
Fig 1B.png
10 Page 10 of 10