Skip to main content
  • ASM
    • Antimicrobial Agents and Chemotherapy
    • Applied and Environmental Microbiology
    • Clinical Microbiology Reviews
    • Clinical and Vaccine Immunology
    • EcoSal Plus
    • Eukaryotic Cell
    • Infection and Immunity
    • Journal of Bacteriology
    • Journal of Clinical Microbiology
    • Journal of Microbiology & Biology Education
    • Journal of Virology
    • mBio
    • Microbiology and Molecular Biology Reviews
    • Microbiology Resource Announcements
    • Microbiology Spectrum
    • Molecular and Cellular Biology
    • mSphere
    • mSystems
  • Log in
  • My alerts
  • My Cart

Main menu

  • Home
  • Articles
    • Current Issue
    • Accepted Manuscripts
    • COVID-19 Special Collection
    • Archive
    • Minireviews
  • For Authors
    • Submit a Manuscript
    • Scope
    • Editorial Policy
    • Submission, Review, & Publication Processes
    • Organization and Format
    • Errata, Author Corrections, Retractions
    • Illustrations and Tables
    • Nomenclature
    • Abbreviations and Conventions
    • Publication Fees
    • Ethics Resources and Policies
  • About the Journal
    • About JCM
    • Editor in Chief
    • Editorial Board
    • For Reviewers
    • For the Media
    • For Librarians
    • For Advertisers
    • Alerts
    • RSS
    • FAQ
  • Subscribe
    • Members
    • Institutions
  • ASM
    • Antimicrobial Agents and Chemotherapy
    • Applied and Environmental Microbiology
    • Clinical Microbiology Reviews
    • Clinical and Vaccine Immunology
    • EcoSal Plus
    • Eukaryotic Cell
    • Infection and Immunity
    • Journal of Bacteriology
    • Journal of Clinical Microbiology
    • Journal of Microbiology & Biology Education
    • Journal of Virology
    • mBio
    • Microbiology and Molecular Biology Reviews
    • Microbiology Resource Announcements
    • Microbiology Spectrum
    • Molecular and Cellular Biology
    • mSphere
    • mSystems

User menu

  • Log in
  • My alerts
  • My Cart

Search

  • Advanced search
Journal of Clinical Microbiology
publisher-logosite-logo

Advanced Search

  • Home
  • Articles
    • Current Issue
    • Accepted Manuscripts
    • COVID-19 Special Collection
    • Archive
    • Minireviews
  • For Authors
    • Submit a Manuscript
    • Scope
    • Editorial Policy
    • Submission, Review, & Publication Processes
    • Organization and Format
    • Errata, Author Corrections, Retractions
    • Illustrations and Tables
    • Nomenclature
    • Abbreviations and Conventions
    • Publication Fees
    • Ethics Resources and Policies
  • About the Journal
    • About JCM
    • Editor in Chief
    • Editorial Board
    • For Reviewers
    • For the Media
    • For Librarians
    • For Advertisers
    • Alerts
    • RSS
    • FAQ
  • Subscribe
    • Members
    • Institutions
CASE REPORTS

Fatal Myocarditis Associated with Acute Parvovirus B19 and Human Herpesvirus 6 Coinfection

Jacques Rohayem, Jürgen Dinger, Rainer Fischer, Karin Klingel, Reinhard Kandolf, Axel Rethwilm
Jacques Rohayem
Institut für Virologie,
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Jürgen Dinger
Klinik für Kinderheilkunde, and
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Rainer Fischer
Institut für Pathologie, Medizinische Fakultät “Carl Gustav Carus,” Technische Universität Dresden, 01307 Dresden, and
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Karin Klingel
Abteilung für Molekulare Pathologie, Institut für Pathologie, Universität Tübingen, 72076 Tübingen, Germany
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Reinhard Kandolf
Abteilung für Molekulare Pathologie, Institut für Pathologie, Universität Tübingen, 72076 Tübingen, Germany
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Axel Rethwilm
Institut für Virologie,
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
DOI: 10.1128/JCM.39.12.4585-4587.2001
  • Article
  • Figures & Data
  • Info & Metrics
  • PDF
Loading

ABSTRACT

We report on the case of a healthy young boy who developed a fulminant myocarditis due to acute coinfection with erythrovirus (parvovirus B19) and human herpesvirus 6 (HHV-6) in the absence of an antiviral immune response. We suggest that the HHV-6-induced immunosuppression enhanced dissemination of parvovirus B19, which led to fatal myocarditis.

CASE REPORT

An 11-year-old boy was admitted with a 3-day history of fever that progressed within a few hours to acute distress. He had no notable medical history; in particular, there were no signs of a preexisting immunodeficiency. On examination he was lethargic and cyanotic with tachypnea and had a fever (41.3°C). His blood pressure was 73/31 mm Hg, and his pulse was 201 beats/min. Erythema and exudates on the tonsils were noted, as were cervical lymphadenopathies and a rash involving both arms and the neck. Examination of the head, lungs, and abdomen was normal. There were no focal neurological signs. He was intubated. Intravenous dopamine and dobutamine were given. Arterial blood gas analysis showed a pH of 7.26 and partial O2 pressure of 3.48 kPa, with an O2 saturation level of 43.4%. Cardiac arrest occurred suddenly; resuscitation efforts were successful only for a short time, and the patient died of congestive heart failure 55 min later.

Biochemical laboratory findings were normal except for C-reactive protein (64.5 mg/liter; normal level, <10 mg/liter), creatinine kinase (6.60 μkat/liter; normal level, 0.10 to 3.17 μkat/liter), and troponin T (0.59 ng/ml; normal level, <0.1 ng/ml) levels. The white blood cell count was 5 × 109/liter, with lymphocytopenia (lymphocyte count, 0.35 × 109/liter) and thrombocytopenia (platelet count, 36 × 109/liter).

Postmortem examination of the heart revealed enlargement of both ventricles, with pericardial and subpleural petechial hemorrhage. Histopathological examination showed a diffuse myocarditis with interstitial infiltrates of mononuclear cells (predominantly CD8+ lymphocytes). Histological examination of the pharynx revealed diffuse interstitial infiltrates of mononuclear cells.

Serological results did not indicate acute infection with adenovirus, herpes simplex virus type 1 or 2, Epstein-Barr virus, cytomegalovirus, influenza type A or B virus, coxsackievirus type A or B, echovirus, or hantavirus. Testing for parvovirus B19-specific antibodies was performed by a commercially available enzyme immunoassay (Medac) with baculovirus-expressed VP1 and VP2 proteins as antigens. Testing for human herpesvirus 6 (HHV-6)-specific antibodies was performed by an indirect immunofluorescence technique with MT4 cells infected with HHV-6 variant B (HHV-6B), strain Z29, and HSB-2 cells infected with HHV-6 variant A (HHV-6A), strain GS. Testing for immunoglobulin G (IgG) and IgM antibodies to parvovirus B19 and HHV-6A and HHV-6B was negative. Bacteriological cultures of blood specimens and cerebrospinal fluid were negative. Attempts to isolate virus from the patient's blood, cerebrospinal fluid, lung, spleen, and brain tissue were unsuccessful.

Nucleic acid isolation was performed with the QiaAmp viral kit (Qiagen) for body fluids or by the method of Chomczynski and Sacchi (5) for samples recovered postmortem. All samples that tested positive were extracted a second time and reanalyzed. On the basis of the parvovirus B19 DNA sequence (GenBank accession numberAB030694 ), a nested PCR was performed to amplify a region of the gene for capsid proteins VP1 and VP2. Primers P1 (5′-GTA CAG GAG GTA CAG CAT C; base pairs 3728 to 3746) and P2 (5′-ACC CAC TCC TTG CTG ATA C; base pairs 4176 to 4158) were used for the first-round PCR, and primers P3 (5′-AGA GGG CTG CAG TCA ACA C; base pairs 3786 to 3804) and P4 (5′-GGT GGT ATG GCT GAG ACA C; base pairs 4075 to 4057) were used for the nested reaction. Parvovirus B19 DNA was detected in the patient's spleen tissue, lung tissue, brain tissue, and myocardium (Table1). For the detection of HHV-6 DNA by nested PCR, primers that amplify a region of the gene for the putative large tegument protein gene were used (2, 10). HHV-6 DNA was detected in the pharynx, spleen tissue, and lung tissue (Table 1). Amplimers were molecularly cloned with the TOPO-TA cloning kit (Invitrogen). DNA sequences were determined on an ABI PRISM 377 DNA sequencer with an ABI PRISM dye terminator cycle sequencing kit (Applied Biosystems). The parvovirus B19 DNA sequence detected in spleen tissue and the myocardium showed 99% similarity to that of parvovirus B19 isolate Rm (GenBank accession number AB030694 ). The HHV-6 DNA sequences detected in the pharynx, spleen tissue, and lung tissue showed 99 and 97% similarities to those of HHV-6B strains Z29 and HST, respectively (GenBank accession numbers AF157706 and AB021506 , respectively). Except for the detection of Epstein-Barr virus DNA in the spleen, no other viral DNA or RNA was detected (Table 1). In situ DNA and RNA hybridization analyses (9) of paraffin-embedded myocardial specimens showed that they were positive for parvovirus B19 DNA and negative for enterovirus RNA.

View this table:
  • View inline
  • View popup
Table 1.

Viral DNA and RNA detection by PCR and in situ hybridizationa

Discussion.Both parvovirus B19 and HHV-6 are ubiquitous viruses that usually cause mild diseases in childhood. Parvovirus B19 is the causative agent of erythema infectiosum, also called fifth disease. Parvovirus B19 infection has been reported to be a rare but severe cause of myocarditis in infants and children (7, 11, 13). HHV-6 is the causative agent of exanthema subitum, also called sixth disease. On the basis of its biological properties and genomic sequences, HHV-6 has been divided into two subgroups, defined as HHV-6A and HHV-6B (1). Primary HHV-6 infections are caused almost exclusively by HHV-6B (6).

To our knowledge, this is the first report of a patient with fatal myocarditis due to parvovirus B19 in the course of a concomitant HHV-6 infection. Our patient presented with clinical symptoms compatible with both primary parvovirus B19 and primary HHV-6 infections, i.e., a 4-day history of fever, cervical lymphadenopathy, erythema, and exudates of the tonsils, as well as a cutaneous rash involving both the arms and the legs. A diffuse pharyngitis is compatible with a viral infection transmitted by the respiratory route. The lymphocytopenia is compatible with an immunosuppression caused by an acute viral infection. Thrombocytopenia is compatible with a primary parvovirus B19 infection (3, 12). The postmortem examination of the heart showed a histology typical of that caused by viral myocarditis, and in situ hybridization analysis confirmed myocardial invasion with parvovirus B19. Amplified HHV-6 sequences showed the highest degrees of homology to HHV-6B.

All these findings and the patient's clinical history provide strong evidence for a primary coinfection with parvovirus B19 and HHV-6, although no serological response to either virus was detected. The absence of serological markers is not surprising. IgM responses to HHV-6 can be detected only 5 to 7 days following the onset of symptoms, and many infected children may not develop detectable IgM responses (4). IgM responses to parvovirus B19 can be detected only 3 to 4 days following the onset of symptoms. The clinical history of our patient was only 4 days.

We suggest that HHV-6 induced a severe immunosuppression that enhanced the dissemination of parvovirus B19, leading to fulminant myocarditis. HHV-6 is thought to exhibit a unique spectrum of biological properties that make it an immunosuppressive agent of its own (8). To date, two reports have described severe HHV-6-associated illness: one in an 11-month-old child (14) and another in a 37-year-old man (15), both of whom were immunocompetent. In both patients, an immunosuppression caused by HHV-6 was hypothesized. Our patient was rather old to have a primary HHV-6 infection, which may have resulted in more severe complications.

Although quite unusual, this case report underlines the importance of recognizing a primary coinfection with two viruses, each of which by itself usually causes a benign infection.

ACKNOWLEDGMENTS

We thank Tino Schwarz and Hans Nitschko for communicating the parvovirus B19-specific primer sequences and Claudia Seiler for technical assistance.

FOOTNOTES

    • Received 3 August 2001.
    • Returned for modification 4 September 2001.
    • Accepted 11 September 2001.
  • Copyright © 2001 American Society for Microbiology

REFERENCES

  1. 1.↵
    1. Ablashi D. V.,
    2. Balachandran N.,
    3. Josephs S. F.,
    4. Hung C. L.,
    5. Krueger G. R.,
    6. Kramarsky B.,
    7. Salahuddin S. Z.,
    8. Gallo R. C.
    Genomic polymorphism, growth properties, and immunologic variations in human herpesvirus-6 isolates.Virology1841991545552
    OpenUrlCrossRefPubMedWeb of Science
  2. 2.↵
    1. Aubin J. T.,
    2. Agut H.,
    3. Collandre H.,
    4. Yamanishi K.,
    5. Chandran B.,
    6. Montagnier L.,
    7. Huraux J. M.
    Antigenic and genetic differentiation of the two putative types of human herpes virus 6.J. Virol. Methods411993223234
    OpenUrlCrossRefPubMedWeb of Science
  3. 3.↵
    1. Barlow G. D.,
    2. McKendrick M. W.
    Parvovirus B19 causing leucopenia and neutropenia in a healthy adult.J. Infect.402000192195
    OpenUrlCrossRefPubMedWeb of Science
  4. 4.↵
    1. Braun D. K.,
    2. Dominguez G.,
    3. Pellett P. E.
    Human herpesvirus 6.Clin. Microbiol. Rev.101997521567
    OpenUrlAbstract/FREE Full Text
  5. 5.↵
    1. Chomczynski P.,
    2. Sacchi N.
    Single-step method of RNA isolation by acid guanidinium thiocyanate-phenol-chloroform extraction.Anal. Biochem.1621987156159
    OpenUrlCrossRefPubMedWeb of Science
  6. 6.↵
    1. Dewhurst S.,
    2. McIntyre K.,
    3. Schnabel K.,
    4. Hall C. B.
    Human herpesvirus 6 (HHV-6) variant B accounts for the majority of symptomatic primary HHV-6 infections in a population of U.S. infants.J. Clin. Microbiol.311993416418
    OpenUrlAbstract/FREE Full Text
  7. 7.↵
    1. Enders G.,
    2. Dotsch J.,
    3. Bauer J.,
    4. Nutzenadel W.,
    5. Hengel H.,
    6. Haffner D.,
    7. Schalasta G.,
    8. Searle K.,
    9. Brown K. E.
    Life-threatening parvovirus B19-associated myocarditis and cardiac transplantation as possible therapy: two case reports.Clin. Infect. Dis.261998355358
    OpenUrlCrossRefPubMedWeb of Science
  8. 8.↵
    1. Flamand L.,
    2. Gosselin J.,
    3. Stefanescu I.,
    4. Ablashi D.,
    5. Menezes J.
    Immunosuppressive effect of human herpesvirus 6 on T-cell functions: suppression of interleukin-2 synthesis and cell proliferation.Blood85199512631271
    OpenUrlAbstract/FREE Full Text
  9. 9.↵
    1. Klingel K.,
    2. Hohenadl C.,
    3. Canu A.,
    4. Albrecht M.,
    5. Seemann M.,
    6. Mall G.,
    7. Kandolf R.
    Ongoing enterovirus-induced myocarditis is associated with persistent heart muscle infection: quantitative analysis of virus replication, tissue damage, and inflammation.Proc. Natl. Acad. Sci. USA891992314318
    OpenUrlAbstract/FREE Full Text
  10. 10.↵
    1. Klotman M. E.,
    2. Lusso P.,
    3. Bacchus D.,
    4. Corbellino M.,
    5. Jarrett R. F.,
    6. Berneman Z. N.
    Detection of human herpesvirus 6 and human herpesvirus 7 by PCR amplification Diagnostic molecular microbiology: principles and applications. Persing D. H., Smith T. H., Tenover F. C., White T. J. 1993 501 510 American Society for Microbiology Washington, D.C.
  11. 11.↵
    1. Murry C. E.,
    2. Jerome K. R.,
    3. Reichenbach D. D.
    Fatal parvovirus myocarditis in a 5-year-old girl.Hum. Pathol.322001342345
    OpenUrlCrossRefPubMedWeb of Science
  12. 12.↵
    1. Oeda E.,
    2. Shinohara K.,
    3. Inoue H.,
    4. Nomiyama J.
    Parvovirus B19 infection causing severe peripheral blood thrombocytopenia and persistent viremia.Am. J. Hematol.451994274275
    OpenUrlPubMed
  13. 13.↵
    1. Porter H. J.,
    2. Quantrill A. M.,
    3. Fleming K. A.
    B19 parvovirus infection of myocardial cells.Lanceti1988535536
    OpenUrl
  14. 14.↵
    1. Prezioso P. J.,
    2. Cangiarella J.,
    3. Lee M.,
    4. Nuovo G. J.,
    5. Borkowsky W.,
    6. Orlow S. J.,
    7. Greco M. A.
    Fatal disseminated infection with human herpesvirus-6.J. Pediatr.1201992921923
    OpenUrlCrossRefPubMedWeb of Science
  15. 15.↵
    1. Russler S. K.,
    2. Tapper M. A.,
    3. Knox K. K.,
    4. Liepins A.,
    5. Carrigan D. R.
    Pneumonitis associated with coinfection by human herpesvirus 6 and Legionella in an immunocompetent adult.Am. J. Pathol.138199114051411
    OpenUrlPubMedWeb of Science
PreviousNext
Back to top
Download PDF
Citation Tools
Fatal Myocarditis Associated with Acute Parvovirus B19 and Human Herpesvirus 6 Coinfection
Jacques Rohayem, Jürgen Dinger, Rainer Fischer, Karin Klingel, Reinhard Kandolf, Axel Rethwilm
Journal of Clinical Microbiology Dec 2001, 39 (12) 4585-4587; DOI: 10.1128/JCM.39.12.4585-4587.2001

Citation Manager Formats

  • BibTeX
  • Bookends
  • EasyBib
  • EndNote (tagged)
  • EndNote 8 (xml)
  • Medlars
  • Mendeley
  • Papers
  • RefWorks Tagged
  • Ref Manager
  • RIS
  • Zotero
Print

Alerts
Sign In to Email Alerts with your Email Address
Email

Thank you for sharing this Journal of Clinical Microbiology article.

NOTE: We request your email address only to inform the recipient that it was you who recommended this article, and that it is not junk mail. We do not retain these email addresses.

Enter multiple addresses on separate lines or separate them with commas.
Fatal Myocarditis Associated with Acute Parvovirus B19 and Human Herpesvirus 6 Coinfection
(Your Name) has forwarded a page to you from Journal of Clinical Microbiology
(Your Name) thought you would be interested in this article in Journal of Clinical Microbiology.
CAPTCHA
This question is for testing whether or not you are a human visitor and to prevent automated spam submissions.
Share
Fatal Myocarditis Associated with Acute Parvovirus B19 and Human Herpesvirus 6 Coinfection
Jacques Rohayem, Jürgen Dinger, Rainer Fischer, Karin Klingel, Reinhard Kandolf, Axel Rethwilm
Journal of Clinical Microbiology Dec 2001, 39 (12) 4585-4587; DOI: 10.1128/JCM.39.12.4585-4587.2001
del.icio.us logo Digg logo Reddit logo Twitter logo CiteULike logo Facebook logo Google logo Mendeley logo
  • Top
  • Article
    • ABSTRACT
    • CASE REPORT
    • ACKNOWLEDGMENTS
    • FOOTNOTES
    • REFERENCES
  • Figures & Data
  • Info & Metrics
  • PDF

KEYWORDS

Erythema Infectiosum
Herpesviridae Infections
Herpesvirus 6, Human
Myocarditis
Parvovirus B19, Human

Related Articles

Cited By...

About

  • About JCM
  • Editor in Chief
  • Board of Editors
  • Editor Conflicts of Interest
  • For Reviewers
  • For the Media
  • For Librarians
  • For Advertisers
  • Alerts
  • RSS
  • FAQ
  • Permissions
  • Journal Announcements

Authors

  • ASM Author Center
  • Submit a Manuscript
  • Article Types
  • Resources for Clinical Microbiologists
  • Ethics
  • Contact Us

Follow #JClinMicro

@ASMicrobiology

       

ASM Journals

ASM journals are the most prominent publications in the field, delivering up-to-date and authoritative coverage of both basic and clinical microbiology.

About ASM | Contact Us | Press Room

 

ASM is a member of

Scientific Society Publisher Alliance

 

American Society for Microbiology
1752 N St. NW
Washington, DC 20036
Phone: (202) 737-3600

 

Copyright © 2021 American Society for Microbiology | Privacy Policy | Website feedback

Print ISSN: 0095-1137; Online ISSN: 1098-660X