title: Viral epidemiologic shift in inflammatory heart disease: the increasing involvement of parvovirus B19 in the myocardium of pediatric cardiac transplant patients.
abstract: BACKGROUND
  Detection of viral genome in rejecting cardiac transplant patients has been reported, with coxsackievirus and adenovirus causing premature graft failure. Recently, parvovirus B19 (PVB19) genome in myocardial samples has been increasingly reported, but its role in cardiac pathology and effect on transplant graft survival are unknown. The objectives of this study were to determine if changes in the viruses identified in the myocardium represent an epidemiologic shift in viral myocardial disease and whether PVB19 adversely affects transplant graft survival.
  
  
  METHODS
  From September 2002 to December 2005, nested polymerase chain reaction was used to evaluate endomyocardial biopsy specimens for 99 children (aged 3 weeks-18 years) with heart transplants for the presence of viral genome. Cellular rejection was assessed by histology of specimens. Transplant coronary artery disease (TCAD) was diagnosed by coronary angiography or histopathology.
  
  
  RESULTS
  Specimens from 700 biopsies were evaluated from 99 patients; 121 specimens had viral genome, with 100 (82.6%) positive for PVB19, 24 for Epstein-Barr virus (EBV; 7 positive for PVB19 and EBV), 3 for CMV, and 1 for adenovirus. Presence of PVB19 genome did not correlate with rejection score, nor did a higher viral copy number. Early development of advanced TCAD (p < 0.001) occurred in 20 children with persistent PVB19 infection (> 6 months).
  
  
  CONCLUSIONS
  PVB19 is currently the predominant virus detected in heart transplant surveillance biopsy specimens, possibly representing an epidemiologic shift. Cellular rejection does not correlate with the presence or quantity of PVB19 genome in the myocardium, but children with chronic PVB19 infection have increased risk for earlier TCAD, supporting the hypothesis that PVB19 negatively affects graft survival.
authors.affiliation: Division of Pediatric Cardiology, Indiana University School of Medicine, Indianapolis, IN, USA. jpbreinh@iupui.edu
authors.forename: John P
authors.initials: JP
authors.lastname: Breinholt
authors.forename: Mousumi
authors.initials: M
authors.lastname: Moulik
authors.forename: William J
authors.initials: WJ
authors.lastname: Dreyer
authors.forename: Susan W
authors.initials: SW
authors.lastname: Denfield
authors.forename: Jeffrey J
authors.initials: JJ
authors.lastname: Kim
authors.forename: John L
authors.initials: JL
authors.lastname: Jefferies
authors.forename: Joseph W
authors.initials: JW
authors.lastname: Rossano
authors.forename: Corey M
authors.initials: CM
authors.lastname: Gates
authors.forename: Sarah K
authors.initials: SK
authors.lastname: Clunie
authors.forename: Karla R
authors.initials: KR
authors.lastname: Bowles
authors.forename: Debra L
authors.initials: DL
authors.lastname: Kearney
authors.forename: Neil E
authors.initials: NE
authors.lastname: Bowles
authors.forename: Jeffrey A
authors.initials: JA
authors.lastname: Towbin
mesh_terms: D000256:Adenoviridae; D000257:Adenoviridae Infections / Q000150:complications / Q000453:epidemiology; D000293:Adolescent; D001706:Biopsy; D002648:Child; D002675:Child, Preschool; D003324:Coronary Artery Disease / Q000453:epidemiology; D003384:Coxsackievirus Infections / Q000150:complications / Q000453:epidemiology; D004279:DNA, Viral / Q000097:blood; D004770:Enterovirus; D006321:Heart / Q000821:virology*; D006331:Heart Diseases / Q000097:blood / Q000821:virology*; D016027:Heart Transplantation / Q000639:trends*; D006801:Humans; D015994:Incidence; D007223:Infant; D007231:Infant, Newborn; D053208:Kaplan-Meier Estimate; D009206:Myocardium / Q000473:pathology; D010322:Parvoviridae Infections / Q000150:complications* / Q000453:epidemiology*; D016732:Parvovirus B19, Human / Q000302:isolation & purification*; D012189:Retrospective Studies; D012307:Risk Factors
chemical_list: D004279:DNA, Viral
references.citation: Eur Heart J. 1995 Dec;16 Suppl O:36-41
references.pmid: 8682098
references.citation: Hum Pathol. 2003 May;34(5):497-503
references.pmid: 12792925
references.citation: Blood Coagul Fibrinolysis. 1995 Oct;6(7):687
references.pmid: 8562844
references.citation: J Med Microbiol. 1988 Feb;25(2):151-3
references.pmid: 3339634
references.citation: J Heart Lung Transplant. 2006 Mar;25(3):261-70
references.pmid: 16507417
references.citation: Circulation. 1997 Nov 18;96(10):3549-54
references.pmid: 9396454
references.citation: J Gen Virol. 1996 Nov;77 ( Pt 11):2767-74
references.pmid: 8922470
references.citation: Circulation. 2005 Feb 22;111(7):879-86
references.pmid: 15710767
references.citation: J Med Virol. 2008 Jul;80(7):1243-51
references.pmid: 18461615
references.citation: Hum Pathol. 2003 Jan;34(1):92-5
references.pmid: 12605372
references.citation: J Heart Lung Transplant. 1998 Aug;17(8):744-53
references.pmid: 9730422
references.citation: J Heart Lung Transplant. 2006 Aug;25(8):893-903
references.pmid: 16890109
references.citation: N Engl J Med. 2004 Feb 5;350(6):586-97
references.pmid: 14762186
references.citation: J Hyg (Lond). 1974 Oct;73(2):165-72
references.pmid: 4529604
references.citation: Int J Cardiol. 1983 May;3(2):240-3
references.pmid: 6862710
references.citation: Cor Vasa. 1989;31(3):225-30
references.pmid: 2788555
references.citation: J Am Coll Cardiol. 2003 Aug 6;42(3):466-72
references.pmid: 12906974
references.citation: Diagn Mol Pathol. 1999 Mar;8(1):39-46
references.pmid: 10408792
references.citation: Hum Pathol. 2001 Mar;32(3):342-5
references.pmid: 11274646
references.citation: Ter Arkh. 1989;61(11):97-102
references.pmid: 2561232
references.citation: N Engl J Med. 2001 May 17;344(20):1498-503
references.pmid: 11357152
references.citation: Lancet. 1975 Jan 11;1(7898):72-3
references.pmid: 46024
references.citation: Clin Transplant. 2005 Dec;19(6):751-5
references.pmid: 16313320
references.citation: Pediatr Infect Dis J. 1994 Feb;13(2):144-50
references.pmid: 8190541
references.citation: J Heart Lung Transplant. 2004 Sep;23(9):1046-52
references.pmid: 15454170
references.citation: Southeast Asian J Trop Med Public Health. 2003 Sep;34(3):585-8
references.pmid: 15115134
references.citation: J Thorac Cardiovasc Surg. 1998 Oct;116(4):617-23
references.pmid: 9766590
references.citation: Circulation. 2005 Feb 22;111(7):887-93
references.pmid: 15699250
references.citation: Circulation. 2004 Apr 13;109(14):e179
references.pmid: 15078808
references.citation: Arthritis Rheum. 2003 Jun;48(6):1631-8
references.pmid: 12794831
references.citation: Transplantation. 2004 Jan 15;77(1):131-3
references.pmid: 14724448
references.citation: J Heart Transplant. 1990 Nov-Dec;9(6):587-93
references.pmid: 2277293
references.citation: Adv Pediatr Infect Dis. 1997;13:101-26
references.pmid: 9544309
references.citation: Mol Genet Metab. 1998 Feb;63(2):85-95
references.pmid: 9562961
references.citation: Herz. 1993 Aug;18(4):238-44
references.pmid: 8397158
references.citation: J Am Coll Cardiol. 1990 Jun;15(7):1688-94
references.pmid: 2161026
references.citation: Circulation. 1994 Jul;90(1):330-9
references.pmid: 8026015
references.citation: Clin Infect Dis. 2009 Dec 1;49(11):1660-6
references.pmid: 19863443
references.citation: Circulation. 1999 Mar 16;99(10):1348-54
references.pmid: 10077520
references.citation: J Clin Virol. 2004 Sep;31(1):32-9
references.pmid: 15288611
references.citation: J Clin Microbiol. 2002 Mar;40(3):933-6
references.pmid: 11880419