Diagnosis, surveillance, and epidemiologic evaluation of viral infections in pediatric cardiac transplant recipients with the use of the polymerase chain reaction.
BACKGROUND
Viral infections, particularly those caused by cytomegalovirus, are a major cause of postoperative morbidity and mortality in heart transplant recipients. These infections have classically been diagnosed by history, physical examination, peripheral viral cultures, and serologic studies. These methods are often time-consuming and lack sensitivity. Positive viral cultures from the heart are rarely obtained, and viral myocarditis and acute cellular rejection are unable to be differentiated histologically. We have therefore used the polymerse chain reaction to diagnose possible viral infection in pediatric heart transplant recipients with findings consistent with acute unexplained rejection.


METHODS
Polymerase chain reaction was used as an aid to diagnose cytomegalovirus infection of cardiac tissue obtained by right ventricular endomyocardial biopsy and follow its long-term course. In addition, polymerase chain reaction was used to diagnose infection of the heart by other viruses in patients with clinical and histologic evidence of rejection, especially those with unexplained late rejection or chronic rejection. Polymerase chain reaction primers were designed to amplify nucleic acid sequences from cytomegalovirus, parvovirus, adenovirus, herpes simplex virus, Epstein-Barr virus, and the RNA viruses of the Enterovirus family.


RESULTS
Forty patients underwent serial right ventricular endomyocardial biopsy (129 samples) for rejection surveillance with positive results obtained in 41 samples (32%) from 21 patients. Viral genome amplified included cytomegalovirus in 16 samples, adenovirus in 14, enterovirus in 6, parvovirus in 3, and herpes simplex virus in 2. In 13 of the 21 patients positive for viral genome (62%), endomyocardial biopsy histologic scores were consistent with multifocal moderate to severe rejection (Internal Society for Heart and Lung Transplantation scores of 3A or greater).


CONCLUSIONS
Polymerase chain reactions may be used as a rapid and sensitive method to evaluate postoperative viral infections in heart transplant recipients, especially in those with late-onset rejection or chronic rejection. Polymerase chain reaction may also be useful in the serial analysis of cytomegalovirus status in transplant recipients. The use of multiple viral primers improves the diagnostic evaluation of these patients and may lead to a better understanding of the epidemiologic characteristics of posttransplantation viral infections and the cause of late or chronic rejection.
Schowengerdt
K O
KO
Department of Pediatrics (Cardiology and Infectious Diseases), Texas Children's Hospital, Houston, USA.
Ni
J
J
Denfield
S W
SW
Gajarski
R J
RJ
Radovancevic
B
B
Frazier
H O
HO
Demmler
G J
GJ
Kearney
D
D
Bricker
J T
JT
Towbin
J A
JA
D000260:Adenoviruses, Human / Q000235:genetics; D000293:Adolescent; D000328:Adult; D001483:Base Sequence / Q000235:genetics; D001706:Biopsy; D002648:Child; D002675:Child, Preschool; D003587:Cytomegalovirus / Q000235:genetics; D003586:Cytomegalovirus Infections / Q000175:diagnosis* / Q000276:immunology / Q000473:pathology / Q000635:transmission; D004279:DNA, Viral / Q000235:genetics; D003937:Diagnosis, Differential; D004359:Drug Therapy, Combination; D004699:Endocardium / Q000276:immunology / Q000473:pathology; D004770:Enterovirus / Q000235:genetics; D005260:Female; D006084:Graft Rejection / Q000175:diagnosis / Q000276:immunology / Q000473:pathology; D016027:Heart Transplantation / Q000276:immunology* / Q000473:pathology; D006352:Heart Ventricles / Q000276:immunology / Q000473:pathology; D004854:Herpesvirus 4, Human / Q000235:genetics; D006801:Humans; D007166:Immunosuppressive Agents / Q000009:adverse effects / Q000627:therapeutic use; D007223:Infant; D008297:Male; D008969:Molecular Sequence Data; D009206:Myocardium / Q000276:immunology / Q000473:pathology; D009894:Opportunistic Infections / Q000175:diagnosis* / Q000276:immunology / Q000473:pathology / Q000635:transmission; D017992:Parvovirus / Q000235:genetics; D016133:Polymerase Chain Reaction; D012307:Risk Factors; D018139:Simplexvirus / Q000235:genetics; D014019:Tissue Donors; D014777:Virus Diseases / Q000175:diagnosis* / Q000276:immunology / Q000473:pathology / Q000635:transmission
D004279:DNA, Viral; D007166:Immunosuppressive Agents