1887

Abstract

Serial surveillance samples of urine collected from 103 renal transplant recipients were analysed by polymerase chain reaction (PCR) for the presence of human cytomegalovirus (HCMV) DNA. The PCR results were consistently negative in 70 patients, none of whom developed HCMV disease, and PCR positive in 33 patients of whom 10 developed HCMV disease ( < 0.001). In 12 patients, PCR results were positive in three or more consecutive samples indicating extensive HCMV replication. HCMV load in 104 samples from these patients was analysed using a quantitative coamplification PCR system. The maximal viral burden in the symptomatic patients ranged from 10 to 10 genomes/ml urine (median 10) and in the asymptomatic patients from 10 to 10 genomes/ml urine (median 10). The 10 difference between these median values was significant ( < 0.01). Individual kinetic profiles of viral burden showed that high levels of HCMV correlated with clinically apparent disease. In the majority of the asymptomatic individuals HCMV load remained between 10 and 10 genomes/ml urine; however, in two patients fluctuations in viral load were observed involving higher viral levels (up to 10 genomes/ml urine) suggesting that immune responses able to modulate viral replication could be studied in individual patients. Analysis of the temporal appearance and quantity of HCMV in the urine with alterations in white cell numbers showed that leukopenia occurred following the appearance of HCMV in the urine of symptomatic patients but preceded HCMV in the urine of asymptomatic patients ( = 0.01). Overall, these results show that longitudinal analysis using fully quantitative PCR methods for HCMV can provide insight into the natural history of HCMV disease in renal transplant recipients.

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1995-02-01
2024-04-16
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References

  1. Balfour H. H., Chase B. A., Stapleton J. T., Simmons R. L., Fryd D. S. 1989; A randomised, placebo trial of oral acyclovir for the prevention of cytomegalovirus disease in recipients of renal allografts. New England Journal of Medicine 320:1381–1387
    [Google Scholar]
  2. Cagle P. T., Buffone G., Holland V. A., Samo T., Demmler G. J., Noon G. P., Lawrence E. C. 1992; Semiquantitative measurement of cytomegalovirus DNA in lung and heart-lung transplant patients by in vitro DNA amplification. Chest 101:93–96
    [Google Scholar]
  3. Chee M. S., Bankier A. T., Beck S., Bohni R., Brown C. M., Cerny R., Horsnell T., Hutchinson C. A. III, Kouzarides T., Martignetti J. A., Preddle E., Satchwell S. C., Tomlinson P., Weston K. M., Barrell B. G. 1990; Analysis of the protein coding content of human cytomegalovirus strain AD169. Current Topics in Microbiology and Immunology 154:125–169
    [Google Scholar]
  4. Connor R. I., Mohri H., Cao Y., Ho D. D. 1993; Increased viral burden and cytopathicity correlate temporally with CD4+ T-lymphocyte decline and clinical progression in human immunodeficiency virus type 1-infected individuals. Journal of Virology 67:1772–1777
    [Google Scholar]
  5. Darlington J., Super M., Patel K., Grundy J. E., Griffiths P. D., Emery V. C. 1991; Use of the polymerase chain reaction to analyse sequence variation within a major neutralizing epitope of glycoprotein B (gp58) in clinical isolates of human cytomegalovirus. Journal of General Virology 72:1985–1989
    [Google Scholar]
  6. Dummer J. S., White L. T., Ho M., Griffith B. P., Hardesty R. L., Bahnson H. T. 1985; Morbidity of cytomegalovirus infection in recipients of heart or heart-lung transplants who receive cyclosporin. Journal of Infectious Diseases 152:1182–1190
    [Google Scholar]
  7. Einsele H., Steidle M., Vallbracht A., Saal J. G., Ehninger G., Muller C. A. 1991; Early occurrence of human cytomegalovirus infection after bone marrow transplantation as demonstrated by the polymerase chain reaction technique. Blood 77:1104–1110
    [Google Scholar]
  8. Fox J. C., Emery V. C. 1992; Quantification of viruses in clinical material. Reviews in Medical Virology 2:195–204
    [Google Scholar]
  9. Fox J. C., Griffiths P. D., Emery V. C. 1992; Quantification of human cytomegalovirus DNA using the polymerase chain reaction. Journal of General Virology 73:2405–2408
    [Google Scholar]
  10. Fong T.-L., Di Bisceglie A. M., Biswas R., Waggoner J. G., Wilson L., Claggett J., Hoofnagle J. H. 1994; High levels of viral replication during acute hepatitis B infection predict progression to chronicity. Journal of Medical Virology 43:155–158
    [Google Scholar]
  11. Gerdes J. C., Spees E. K., Fitting K., Hiraki M., Sheenan M., Duda D., Jarvi T., Roehl C., Robertson A. D. 1993; Prospective study utilising a quantitative polymerase chain reaction for detection of cytomegalovirus DNA in the blood of renal transplant patients. Transplantation Proceedings 25:1411–1413
    [Google Scholar]
  12. Grundy J. E., Super M., Lui S., Sweny P., Griffiths P. D. 1987; The source of cytomegalovirus infection in seropositive renal allograft recipients is frequently the donor kidney. Transplantation Proceedings 19:2126–2128
    [Google Scholar]
  13. Grundy J. E., Lui S. F., Super M., Berry N. J., Sweny P., Fernando O.N., Moorhead J., Griffiths P. D. 1988; Symptomatic cytomegalovirus infection in seropositive kidney recipients: reinfection with donor virus rather than reactivation of recipient virus. Lancet ii:132–135
    [Google Scholar]
  14. Hagiwara H., Hayastic N., Mita E., Naito M., Kasahara A., Fusamoto H., Kamada T. 1993; Quantification of Hepatitis C virus RNA in Serum of asymptomatic blood donors and patients with type C chronic liver disease. Hepatology 17:545–550
    [Google Scholar]
  15. Iragorri S., Pillay D., Scrine M., Trompeter R. S., Rees L., Griffiths P. D. 1993; Prospective cytomegalovirus surveillance in paediatric renal transplant recipients. Paediatric Nephrology 7:55–60
    [Google Scholar]
  16. Kato N., Yokosuka O., Hosoda K., Ito Y., Ohto M., Omata M. 1993; Quantification of Hepatitis C virus by competitive reverse transcription-polymerase chain reaction: increase of the virus in advanced liver disease. Hepatology 18:16–20
    [Google Scholar]
  17. Kidd I. M., Fox J. C., Pillay D., Charman H., Griffiths P. D., Emery V. C. 1993; Routine application of the polymerase chain reaction for cytomegalovirus provides prognostic information in immunocompromised patients. Transplantation 56:867–871
    [Google Scholar]
  18. Kwok S., Higuchi R. 1989; Avoiding false positives with PCR. Nature 339:237–238
    [Google Scholar]
  19. Landry M. L., Ferguson D. 1993; Comparison of quantitative cytomegalovirus antigenemia assay with culture methods and correlation with clinical disease. Journal of Clinical Microbiology 31:2851–2856
    [Google Scholar]
  20. Lui S., Sweny P., Grundy J. E., Blaxill A., Griffiths P. D., Moorhead J. F., Fernando O. 1987; The clinical application of a rapid diagnostic test for the detection of CMV infection in renal transplant recipients. Transplantation Proceedings 19:2129–2130
    [Google Scholar]
  21. McCormick J. B., King I. J., Webb P. A., Scribner C. L., Craven R. B., Johnson K. M., Elliot L. H., Belmont-Williams R. 1986; Lassa fever. Effective therapy with ribavirin. New England Journal of Medicine 314:20–26
    [Google Scholar]
  22. Meyers J. D., Ljungman P., Fisher L. D. 1990; Cytomegalovirus excretion as a predictor of cytomegalovirus disease after marrow transplantation: importance of marrow viremia. Journal of Infectious Diseases 162:373–380
    [Google Scholar]
  23. Pass R. F., Whitley R. L., Dethelm A. G., Whelchel J. D., Reynolds D. W., Alford C. A. 1980; Cytomegalovirus infection in patients with renal transplants. Journal of Infectious Diseases 142:9–17
    [Google Scholar]
  24. Paya C. V., Hermans P. E., Wiesner R. H., Ludwig J., Smith T. F., Rakela J., Krom R. A. F. 1989; Cytomegalovirus hepatitis in liver transplantation: prospective analysis of 93 consecutive orthotopic liver transplantations. Journal of Infectious Diseases 160:752–758
    [Google Scholar]
  25. Peterson P. K., Balfour H. H., Marker S. C., Fryd D. S., Howard R. J., Simmons R. L. 1980; Cytomegalovirus disease in renal allograft recipients: a prospective study of the clinical features, risk factors and impact on renal transplantation. Medicine (. Baltimore) 59:283–300
    [Google Scholar]
  26. Piatak M. Jr, Saag M. S., Yang L. C., Clark S. J., Kappes J. C., Luk K. C., Hahn B. H., Shaw G. M., Lifson J. D. 1993; High levels of HIV-1 in plasma during all stages of infection determined by competitor PCR. Science 262:1585–1586
    [Google Scholar]
  27. Pillay D., Charman H., Burroughs A. K., Smith M., Rolles K., Griffiths P. D. 1992; Surveillance for CMV infection in orthotopic liver transplant recipients. Transplantation 53:1261–1265
    [Google Scholar]
  28. Pillay D., Ali A., Lui S. F., Kops E., Sweny P., Griffiths P. D. 1993; The prognostic significance of positive CMV cultures during surveillance of renal transplant recipients. Transplantation 56:103–108
    [Google Scholar]
  29. Plotkin S., Starr S. E., Friedman H. M., Brayman K., Harris S., Jackson S., Tustin N. B., Grossman R., Dafoe D., Barker C. 1991; Effect of Towne live virus vaccine on cytomegalovirus disease after renal transplant. Annals of International Medicine 114:525–531
    [Google Scholar]
  30. Rubin R. H., Cosimi A. B., Tolkoff-Rubin N. E., Russell P. S., Hirsch M. S. 1977; Infectious disease syndromes attributable to cytomegalovirus and their significance among renal transplant recipients. Transplantation 24:458–464
    [Google Scholar]
  31. Saltzman R. L., Quirk M. R., Jordan M. C. 1992; High levels of circulating cytomegalovirus DNA reflect visceral organ disease in viremic immunosuppressed patients other than marrow recipients. Journal of Clinical Investigation 90:1832–1838
    [Google Scholar]
  32. Sambrook J., Fritsch E. F., Maniatis T. 1989 Molecular Cloning: A Laboratory Manual 2nd edn New York: Cold Spring Harbor Laboratory;
    [Google Scholar]
  33. Schafer P., Braun R. W., Mohring K., Henco K., Kang J., Wendland T., Kuhn J. E. 1993; Quantitative determination of human cytomegalovirus target sequences in peripheral blood leukocytes by nested polymerase chain reaction and temperature gradient gel electrophoresis. Journal of General Virology 74:2699–2707
    [Google Scholar]
  34. Shanley J. D., Biczak L., Formon S. J. 1993; Acute murine cytomegalovirus infection induces lethal hepatitis. Journal of Infectious Diseases 167:264–269
    [Google Scholar]
  35. Stagno S., Reynolds D. W., Tsiantos A., Fuccillo D. A., Long W., Alford C. A. 1975; Comparative serial virologic and serologic studies of symptomatic and subclinical congenitally and natally acquired cytomegalovirus. Journal of Infectious Diseases 132:568–577
    [Google Scholar]
  36. Van-der-Bij W., Schirm J., Torensma R., Van-Son W. J., Tegzess A. M., The T. H. 1988; Comparison between viremia and antigenemia for detection of cytomegalovirus in blood. Journal of Clinical Microbiology 26:2531–2535
    [Google Scholar]
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