Abstract
BACKGROUND--New rapid diagnostic techniques offer the opportunity of early diagnosis of human cytomegalovirus (CMV) infection in immunocompromised patients at risk of developing CMV disease. The use of human CMV antigenaemia as a predictor of clinical CMV infection and disease in lung and heart transplant recipients was studied prospectively. METHODS--Twenty three heart and nine lung transplant recipients who survived 40 days were observed by standard CMV surveillance with serological testing, culture, and by sequential testing for CMV antigenaemia. CMV antigenaemia testing is a rapid and quantifiable technique in which a viral lower matrix protein is detected in cytospin preparations of peripheral blood polymorphonuclear leucocytes (PMNLs) by immunofluorescent staining. RESULTS--Eleven patients developed CMV infection and five developed CMV disease (four pneumonitis, one duodenitis). These clinical events occurred at a median of 65 days following transplantation. CMV antigenaemia occurred in 17 patients at a median of 35 days following transplantation. Detection of CMV antigenaemia had a sensitivity of 100%, a specificity of 93.7%, and a positive predictive value of 94.1% for CMV related illness. CMV antigenaemia was positive at a significant interval before the clinical event. High levels of CMV antigenaemia (> 50 CMV antigen positive cells/2 x 10(5) PMNLs) occurred in 11 patients and five of these developed disease. CMV antigenaemia of > 50 CMV antigen positive cells/2 x 10(5) PMNLs had a positive predictive value of 45.5% for disease but a negative predictive value of 100%. Patients with disease had higher levels of antigenaemia than those without disease. CONCLUSIONS--CMV antigenaemia is a rapid diagnostic technique which can identify patients likely to develop CMV disease, potentially allowing early treatment.
Full text
PDF




Images in this article
Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- Bailey T. C., Trulock E. P., Ettinger N. A., Storch G. A., Cooper J. D., Powderly W. G. Failure of prophylactic ganciclovir to prevent cytomegalovirus disease in recipients of lung transplants. J Infect Dis. 1992 Mar;165(3):548–552. doi: 10.1093/infdis/165.3.548. [DOI] [PubMed] [Google Scholar]
- Billingham M. E., Cary N. R., Hammond M. E., Kemnitz J., Marboe C., McCallister H. A., Snovar D. C., Winters G. L., Zerbe A. A working formulation for the standardization of nomenclature in the diagnosis of heart and lung rejection: Heart Rejection Study Group. The International Society for Heart Transplantation. J Heart Transplant. 1990 Nov-Dec;9(6):587–593. [PubMed] [Google Scholar]
- Drew W. L., Miner R. C., Busch D. F., Follansbee S. E., Gullett J., Mehalko S. G., Gordon S. M., Owen W. F., Jr, Matthews T. R., Buhles W. C. Prevalence of resistance in patients receiving ganciclovir for serious cytomegalovirus infection. J Infect Dis. 1991 Apr;163(4):716–719. doi: 10.1093/infdis/163.4.716. [DOI] [PubMed] [Google Scholar]
- Duncan S. R., Paradis I. L., Dauber J. H., Yousem S. A., Hardesty R. L., Griffith B. P. Ganciclovir prophylaxis for cytomegalovirus infections in pulmonary allograft recipients. Am Rev Respir Dis. 1992 Nov;146(5 Pt 1):1213–1215. doi: 10.1164/ajrccm/146.5_Pt_1.1213. [DOI] [PubMed] [Google Scholar]
- Duncan S. R., Paradis I. L., Yousem S. A., Similo S. L., Grgurich W. F., Williams P. A., Dauber J. H., Griffith B. P. Sequelae of cytomegalovirus pulmonary infections in lung allograft recipients. Am Rev Respir Dis. 1992 Dec;146(6):1419–1425. doi: 10.1164/ajrccm/146.6.1419. [DOI] [PubMed] [Google Scholar]
- Erice A., Chou S., Biron K. K., Stanat S. C., Balfour H. H., Jr, Jordan M. C. Progressive disease due to ganciclovir-resistant cytomegalovirus in immunocompromised patients. N Engl J Med. 1989 Feb 2;320(5):289–293. doi: 10.1056/NEJM198902023200505. [DOI] [PubMed] [Google Scholar]
- Ettinger N. A., Bailey T. C., Trulock E. P., Storch G. A., Anderson D., Raab S., Spitznagel E. L., Dresler C., Cooper J. D. Cytomegalovirus infection and pneumonitis. Impact after isolated lung transplantation. Washington University Lung Transplant Group. Am Rev Respir Dis. 1993 Apr;147(4):1017–1023. doi: 10.1164/ajrccm/147.4.1017. [DOI] [PubMed] [Google Scholar]
- Freeman R., Gould F. K., McMaster A. Management of cytomegalovirus antibody negative patients undergoing heart transplantation. J Clin Pathol. 1990 May;43(5):373–376. doi: 10.1136/jcp.43.5.373. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Gerna G., Revello M. G., Percivalle E., Morini F. Comparison of different immunostaining techniques and monoclonal antibodies to the lower matrix phosphoprotein (pp65) for optimal quantitation of human cytomegalovirus antigenemia. J Clin Microbiol. 1992 May;30(5):1232–1237. doi: 10.1128/jcm.30.5.1232-1237.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Grattan M. T., Moreno-Cabral C. E., Starnes V. A., Oyer P. E., Stinson E. B., Shumway N. E. Cytomegalovirus infection is associated with cardiac allograft rejection and atherosclerosis. JAMA. 1989 Jun 23;261(24):3561–3566. [PubMed] [Google Scholar]
- Grundy J. E., Lui S. F., Super M., Berry N. J., Sweny P., Fernando O. N., Moorhead J., Griffiths P. D. Symptomatic cytomegalovirus infection in seropositive kidney recipients: reinfection with donor virus rather than reactivation of recipient virus. Lancet. 1988 Jul 16;2(8603):132–135. doi: 10.1016/s0140-6736(88)90685-x. [DOI] [PubMed] [Google Scholar]
- Klauser R., Kotzmann H., Wamser P., Braza P., Popov-Kraupp T., Franz M., Traindl O., Watschinger B., Pohanka E., Mühlbacher F. Is determination of PP 65 useful for early diagnosis of cytomegalovirus infection in renal transplantation? Transplant Proc. 1992 Dec;24(6):2628–2630. [PubMed] [Google Scholar]
- McDonald K., Rector T. S., Braulin E. A., Kubo S. H., Olivari M. T. Association of coronary artery disease in cardiac transplant recipients with cytomegalovirus infection. Am J Cardiol. 1989 Aug 1;64(5):359–362. doi: 10.1016/0002-9149(89)90535-3. [DOI] [PubMed] [Google Scholar]
- Merigan T. C., Renlund D. G., Keay S., Bristow M. R., Starnes V., O'Connell J. B., Resta S., Dunn D., Gamberg P., Ratkovec R. M. A controlled trial of ganciclovir to prevent cytomegalovirus disease after heart transplantation. N Engl J Med. 1992 Apr 30;326(18):1182–1186. doi: 10.1056/NEJM199204303261803. [DOI] [PubMed] [Google Scholar]
- Schmidt G. M., Horak D. A., Niland J. C., Duncan S. R., Forman S. J., Zaia J. A. A randomized, controlled trial of prophylactic ganciclovir for cytomegalovirus pulmonary infection in recipients of allogeneic bone marrow transplants; The City of Hope-Stanford-Syntex CMV Study Group. N Engl J Med. 1991 Apr 11;324(15):1005–1011. doi: 10.1056/NEJM199104113241501. [DOI] [PubMed] [Google Scholar]
- Vecchio T. J. Predictive value of a single diagnostic test in unselected populations. N Engl J Med. 1966 May 26;274(21):1171–1173. doi: 10.1056/NEJM196605262742104. [DOI] [PubMed] [Google Scholar]