Cytomegalovirus and other herpesviruses infections in heart and bone marrow transplant recipients

Weinberg, Adriana; Vilas Boas, Lucy S.; Feher, Olavo; Strabelli, Tania M. V.; Fink, Maria Cristina D. S.; Dulley, Frederico L.; Uip, David E.; Bellotti, Giovani; Chamone, Dalton A. F.; Amato Neto, Vicente; Pannuti, Cláudio S.

doi:10.1590/S0036-46651990000500005

Abstracts

From January 1988 to January 1989 all the heart transplant and bone marrow recipients at the Instituto do Coração of the Hospital das Clínicas of the University of São Paulo Medical School were studied for the incidence and morbidity associated with herpesviruses infections after transplantation. Five bone marrow and 5 heart transplant recipients were followed for a mean of 4.2 months post-transplantation. All the patients were seropositive for cytomegalovirus (CMV) before admission and 80% experienced one or more recurrences during the observation period. Of the 12 episodes of CMV infection, that were identified in this study, 83% were accompanied by clinical or laboratory abnormalities. However, there was only one case of severe disease. The overall incidence of infection for herpes simplex (HSV) was 50%. Although most of HSV reactivations were oral or genital, one case of HSV hepatitis occurred. One of the 6 episodes of HSV infections that were treated with acyclovir showed an unsatisfactory response and was successfully managed with ganciclovir. All the individuals had anti-varicella zoster virus antibodies, but none of them developed infection. The study emphasizes the importance of active diagnostic surveillance of herpesvirus infections in transplant patients. Both CMV and HSV reactivations showed high incidence and important morbidity and thus, deserve prophylactic therapy.

Cytomegalovirus infection; Herpesviruses infection; Immunocompro-mised host; Transplantation

De janeiro de 1988 a janeiro de 1989 todos os pacientes submetidos a transplante de coração ou de medula óssea no Instituto do Coração do Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo foram estudados quanto à incidência e morbidade das infecções pós-transplante causadas por vírus do grupo herpes. Cinco recipientes de medula óssea e 5 transplantados cardíacos foram observados por um período médio de 4.2 meses após o transplante. Todos os pacientes tinham sorologia positiva para citomegalovírus (CMV) antes do transplante e 80% desenvolveram uma ou mais recorrências durante o período de observação. Dos 12 episódios de infecão por CMV detectados neste estudo, 83% foram acompanhados por alterações clínicas ou laboratoriais. Apenas um caso apresentou doença grave. A incidência de infecções causadas por vírus Herpes simplex (HSV), foi de 50%. Apesar da maioria das reativações do HSV fossem representadas por lesões orais ou genitais, houve também um caso de hepatite por HSV. Um dos 6 episódios de infecção, por HSV que foram tratados com aciclovir não respondeu ao tratamento. Posteriormente, o paciente se beneficiou com o uso de ganciclovir. Todos os indivíduos apresentavam antes do transplante anticorpos anti-vírus da varicela zoster. Porém, não houve nenhum caso de reativação. Este estudo realça a importância do controle diagnóstico ativo das infecções por herpes-vírus em pacientes transplantados. Tanto as infecções causadas por CMV como por HSV mostraram alta incidência e grande morbidade indicando a necessidade de quimioprofilaxia.

ORIGINAL ARTICLES

Cytomegalovirus and other herpesviruses infections in heart and bone marrow transplant recipients

Infecções causadas por citomegalovírus e outros vírus do grupo herpes em transplantados cardíacos e de medula óssea

Adriana Weinberg^I,II; Lucy S. Vilas Boas^I; Olavo Feher^III; Tania M. V. Strabelli^IV; Maria Cristina D. S. Fink^I; Frederico L. Dulley^III; David E. Uip^II,IV; Giovani Bellotti^V; Dalton A. F. Chamone^III; Vicente Amato Neto^II; Cláudio S. Pannuti^I

^IVirology laboratory of the Instituto de Medicina Tropical, São Paulo, HC-LIM-52

^IIDivision of Infectious Diseases of the Hospital das Clínicas of the University of São Paulo

^IIIDivision of Hematology, HC-FMUSP

^IVInfection Control Commitee of the Instituto do Coração of the HC-FMUSP (Incor)

^VClinical Division of the Incor

^{Address for correspondence} Address for correspondence: Dr. Claudio Sérgio Pannuti Instituto de Medicina Tropical de São Paulo, Laboratório de Virologia Av. Dr. Enéas de Carvalho Aguiar, 470 CEP 05403 São Paulo, SP, Brasil

SUMMARY

From January 1988 to January 1989 all the heart transplant and bone marrow recipients at the Instituto do Coração of the Hospital das Clínicas of the University of São Paulo Medical School were studied for the incidence and morbidity associated with herpesviruses infections after transplantation. Five bone marrow and 5 heart transplant recipients were followed for a mean of 4.2 months post-transplantation. All the patients were seropositive for cytomegalovirus (CMV) before admission and 80% experienced one or more recurrences during the observation period. Of the 12 episodes of CMV infection, that were identified in this study, 83% were accompanied by clinical or laboratory abnormalities. However, there was only one case of severe disease. The overall incidence of infection for herpes simplex (HSV) was 50%. Although most of HSV reactivations were oral or genital, one case of HSV hepatitis occurred. One of the 6 episodes of HSV infections that were treated with acyclovir showed an unsatisfactory response and was successfully managed with ganciclovir. All the individuals had anti-varicella zoster virus antibodies, but none of them developed infection. The study emphasizes the importance of active diagnostic surveillance of herpesvirus infections in transplant patients. Both CMV and HSV reactivations showed high incidence and important morbidity and thus, deserve prophylactic therapy.

Key words: Cytomegalovirus infection; Herpesviruses infection; Immunocompro-mised host; Transplantation.

RESUMO

De janeiro de 1988 a janeiro de 1989 todos os pacientes submetidos a transplante de coração ou de medula óssea no Instituto do Coração do Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo foram estudados quanto à incidência e morbidade das infecções pós-transplante causadas por vírus do grupo herpes. Cinco recipientes de medula óssea e 5 transplantados cardíacos foram observados por um período médio de 4.2 meses após o transplante. Todos os pacientes tinham sorologia positiva para citomegalovírus (CMV) antes do transplante e 80% desenvolveram uma ou mais recorrências durante o período de observação. Dos 12 episódios de infecão por CMV detectados neste estudo, 83% foram acompanhados por alterações clínicas ou laboratoriais. Apenas um caso apresentou doença grave. A incidência de infecções causadas por vírus Herpes simplex (HSV), foi de 50%. Apesar da maioria das reativações do HSV fossem representadas por lesões orais ou genitais, houve também um caso de hepatite por HSV. Um dos 6 episódios de infecção, por HSV que foram tratados com aciclovir não respondeu ao tratamento. Posteriormente, o paciente se beneficiou com o uso de ganciclovir. Todos os indivíduos apresentavam antes do transplante anticorpos anti-vírus da varicela zoster. Porém, não houve nenhum caso de reativação. Este estudo realça a importância do controle diagnóstico ativo das infecções por herpes-vírus em pacientes transplantados. Tanto as infecções causadas por CMV como por HSV mostraram alta incidência e grande morbidade indicando a necessidade de quimioprofilaxia.

Full text available only in PDF format.

Texto completo disponível apenas em PDF.

Recebido para publicação em 23/1/1990

This work was supported by the E. J. Zerbini Foundation and CNPq, grant no. 408741/88.

1. BALFOUR, H.H.; CHACE, B.A.; STAPLETON, J.T.; SIMMONS, R.J. & FRYD, D.S. A randomized, placebo controlled trial of oral acyclovir for the prevention of cytomegalovirus disease in recipients of renal allografts. New Engl. J. Med, 320: 1381-1387, 1989.
2. BOSTROM, L.; RINGDEN, O.; SUNDBERG, B.; LINDE, A.; TOLLEMAR, J. & NILSSON, B. Pretransplant herpesvirus serology and acute graft-versus-host disease. Transplantation, 46: 548-552, 1988.
3. BREINING, M.K.; ZITELLI, B.; STARZL, T.E. & HO, M. Epstein-Barr virus, cytomegalovirus, and other viral infections in children after liver transplantation. J. infect. Dis., 156: 273-279, 1987.
4. CONDIE. R. M. & O'REILLY, R.J. Prevention of cytomegalovirus infection by prophylaxis with an intravenous, hyperimmune, native, unmodified cytomegalovirus globulin. Randomized trial in bone marrow transplant recipients. Amer. J. Med., 76: 134-141, 1984.
5. DORSKY, D.Y. & CRUMPACKER, C.S. Drugs five years later: acyclovir. Ann. intern. Med., 107: 859-874, 1987.
6. DUMMER, J.S.; HARDY, A.; POORSATTAR, A. & HO, M. Early infections in kidney, heart and liver transplant recipients on cyclosporine. Transplantation, 36: 259-267, 1983.
7. EMMANUEL, D.; CUNNINGHAM, I.; JULES-ELYSEE, K.; BROCHSTEIN, J.A.; KERNAN, N.A.; LAVER, J.; STOVER, D.; WHITE, D.A.; FELS, A.; POLSKY, B.; CASTRO-MALASPINA, H.; PEPPARD, J.R.; BARTUS, P.; HAMMERLING, U. & O'REILLY, R.J. Cytomegalovirus pneumonia after bone marrow transplantation successfully treated with the combination of ganciclovir and high-dose intravenous immune globulin. Ann. intern. Med., 109: 777-782, 1988.
8. GORENSEK, M.J.; STEWART, R.W.; KEYS, T.F.; McHENRY, M.C. & GOORMASTIC, M. A multivariate analysis of the risk of cytomegalovirus infection in heart transplant recipients. J. infect. Dis., 157: 515-522, 1988.
9. GORENSEK, M.J.; STEWART, R.W.; KEYS, T.F.; McHENRY, M.C.; BABIAK, T. & GOORMASTIC, M. Symptomatic cytomegalovirus infection as a significant risk factor for major infections after cardiac transplantation. J. infect. Dis., 158: 884-887, 1987.
10. GRUNDY, J.E.; SUPER, M.; SWENY, P.; MOORHEAD, J.; LUI, S.F.; BERRY, N.J.; FERNANDO, O.N. & GRIFFITHS, P.D. Symptomatic cytomegalovirus infection in seropositive kidney recipients: reinfection with donor virus rather than reactivation of recipient virus. Lancet, 2: 132-135, 1988.
11. HAWKES, R.; NIDAY, E. & GORDON, J. A dot-immunobinding assay for monoclonal and other antibodies. Ann. Biochem., 119: 142-147, 1982.
12. KUSNE, S.; DUMMER, J.S.; SINGH, N.; IWATSUKI, S.; MAKOWKA, L.; ESQUIVEL, C.; TZIKIS, A.G.; STARZL, T.E. & HO, M. Infections after liver transplantation. An analysis of 101 consecutive cases. Medicine, 67: 132-143, 1988.
13. MARKER, S.C.; HOWARD, R.J.; SIMMONS, R.L.; KALIS, J.M.; CONNELLY, D.P.; NAJARIAN, J.S. & BALFOUR Jr., H.H. Cytomegalovirus infection: a quantitative prospective study of three hundred twenty consecutive renal transplants. Surgery, 89: 660-671, 1981.
14. MEYERS, J.D.; LESCZYNSKI, J.; ZAIA, J.A.; FLOURNOY, N.; NEWTON, B.; SNYDMAN, D.R.; WRIGHT, G.G.; LEVIN, M.J. & THOMAS, E.D. Prevention of cytomegalovirus infection by cytomegalovirus immune globulin after marrow transplantation. Ann. intern. Med., 98: 442-446, 1983.
15. MEYERS, J.D.; REED, E.C.; SHEPP, D.H.; THORNQUIST, M.; DANDLIKER, P.S.; VICARY, C.A.; FLOURNOY, N.; KIRK, L.E.; KERSEY, J.H.; THOMAS, E.D. & BALFOUR, H.H. Acyclovir for prevention of cytomegalovirus infection and disease after allogeneic marrow transplantation. New Engl. J. Med., 318: 70-75, 1988.
16. O'GRADY, J.G.; SUTHERLAND, S.; HARVEY, F.; CAYNE, R.Y.; ALEXANDER, G.J.; DONALDSON, P.T.; PORTMANN, B. & WILLIAMS, R. Cytomegalovirus infections and donor/recipient HLA antigens: interdependent co-factors in pathogenesis of vanishing bileduct syndrome after transplantation. Lancet, 2: 302-305, 1988.
17. PANNUTI, C.S.; GINGRICH, R.D.; PFALLER, M.A. & WENZEL, R.P. Nosocomial pneumonia in adult patients undergoing bone marrow transplantation: a nine year study (Submitted for publication, 1989).
18. PANNUTI, C.S.; VILAS BOAS, L.S.; AMATO NETO, V.; ANGELO, M.J.O., & SABBAGA, E. Detecçăo de anticorpos IgM nas infecçőes primárias e secundárias pelo citomegalovírus em pacientes submetidos a transplante renal. Rev. Inst. Med. trop. S. Paulo, 29: 317-322, 1987.
19. PETERSON, P.K.; BALFOUR, H.H.; MARKER, S.C.; FRYD, D.S.; HOWARD, R.J. & SIMMONS, R.L. Cytomegalovirus disease in renal allograft recipients: a prospective study of the clinical features, risk factors and impact on renal transplantation. Medicine, 59: 283-300, 1980.
20. PREIKSAITIS, J.K.; ROSNO, S.; GRUMET, C. & MERIGAN, T.C. Infection due to herpesviruses in cardiac transplant recipients: role of donor heart and immunosupressive therapy. J. infect. Dis., 147: 974-981, 1983.
21. RAND, K.H.; POLLARD, R.B. & MERIGAN, T.C. - Increased pulmonary superinfection in cardiac transplant patients undergoing primary cytomegalovirus infection. New Engl. J. Med., 288: 951-953, 1978.
22. REED, E.C.; BOWDEN, R.A.; DANDLIKER, P.S.; LILLEBY, K.E. & MEYERS, J.D. Treatment of cytomegalovirus pneumonia with ganciclovir and intravenous cytomegalovirus immunoglobulin in patients with bone marrow transplants. Ann. intern. Med., 109: 783-788, 1988.
23. RUBIN, R.H.; COSIMI, A.B.; TOLKOFF-RUBIN, N.E.; RUSSELL, R.S. & HIRSCH, M. Infectious disease syndromes attributable to cytomegalovirus and their significance among renal tansplant recipients. Transplantation, 24: 458-464, 1977.
24. SHEPP, D.H.; NEWTON, B.A.; DANDLIKER, P.S.; FLOURNOY, N. & MEYERS, J.D. Oral acyclovir therapy for mucocutaneous herpes simplex virus infections in immunocompromised marrow transplant recipients. Ann. intern. Med., 102: 783-785, 1985.
25. SINGH, N.; DUMMER, J.S.; KUSNE, S.; BREINIG, M.K.; ARMSTRONG, J.A.; MAKOWKA, L.; STARZL, T.E. & HO, M. Infections with cytomegalovirus and other herpesviruses in 121 liver transplant recipients: transmission by donated organ and the effect of OKT3 antibodies. J. intect. Dis., 158: 124-131, 1988.
26. SNYDMAN, R.D.; WERNER, B.G.; HEINZE-LACEY, B.; BERARDI, V.P.; TILNEY, N.L.; KIRKMAN, R.L.; MILFORD, E.L.; CHO, S.I.; BUSH, H.L.; LEVEY, A.S.; STROM, T.B.; CARPENTER, C.B.; LEVEY, R.H.; HARMON, W.E.; ZIMMERMAN, C.E.; SHAPIRO, M.E.; STEINMAN, T.; LOGERFO, F.; IDELSON, B.; SCHROTTER, G.P.J.; LEVIN, M.J.; MCIVER, J.; LESCZYNSKI, J. & GRADY, G.F. Use of cytomegalovirus immuneglobulin to prevent cytomegalovirus disease in renal transplant recipients. New Engl. J. Med., 317: 1049-1054, 1987.
27. STRAUS, S.E.; OSTROVE, J.M.; INCHAUSPE, G.; FELSER, J.M.; ALISON FREIFELD, A.; CROEN, K.D. & SAWYER, M.H. Varicella-zoster virus infections biology, natural history, treatment and prevention. Ann. intern. Med., 108: 221-237, 1988.
28. WADE, J.C.; NEWTON, B.; FLOURNOY, N. & MEYERS, J.D. Oral acyclovir for prevention of herpes simplex reactivation after marrow transplant. Ann. intern. Med., 100: 823-828, 1984.
29. WALMSLEY, S.L.; CHEW, E.; READ, S.E.; VELLEND, H.; SALIT, I.; RACHLIS, A. & FANNING, M.M. Treatment of cytomegalovirus retinitis with trisodium phosphonoformate hexahydrate (Foscarnet). J. infect. Dis., 157: 569-572, 1988.
30. WEINBERG, A.; BASHAM, T.Y. & MERINGAN, T.C. Regulation of the guinea pig immune functions by interleukin-2: critical role of natural killer activity in acute HSV-2 genital infection. J. Immunol., 137: 3310-3316, 1986.
31. WEINBERG, A.; RASMUSSEN, L. & MERIGAN, T.C. Acute genital infection in guinea pigs: effects of recombinant interleukin-2 on herpes simplex virus type 2. J. infect. Dis., 154: 134-138, 1986.
32. WHITLEY, R.J.; LEVIN, M.J.; BARTON, N.; HERSHEY, B.J.; DAVIS, G.; KEENEY, R.E.; WHELCHEL, J.; DIETHELM, A.G.; KARTUS, P. & SOONG, S. Infections caused by herpes simplex virus in the immunocompromised host: natural history and topical acyclovir therapy. J. infect. Dis., 150: 323-329, 1984.
33. WINSTON, D.J.; HO, G.H.; LIN, C.; BARTONI, K.; BUDINGER, M.D.; GALE, P.R. & CHAMPLIN, R.E. Intravenous immune globulin for prevention of cytomegalovirus infection and interstitial pneumonia after bone marrow transplantation. Ann. intern. Med., 106: 12-18, 1987.

Address for correspondence:

Dr. Claudio Sérgio Pannuti

Instituto de Medicina Tropical de São Paulo, Laboratório de Virologia

Av. Dr. Enéas de Carvalho Aguiar, 470

CEP 05403 São Paulo, SP, Brasil

Publication Dates

Publication in this collection
12 Sept 2006
Date of issue
Oct 1990

History

Received
23 Jan 1990

This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.

[1] 1. BALFOUR, H.H.; CHACE, B.A.; STAPLETON, J.T.; SIMMONS, R.J. & FRYD, D.S. A randomized, placebo controlled trial of oral acyclovir for the prevention of cytomegalovirus disease in recipients of renal allografts. New Engl. J. Med, 320: 1381-1387, 1989.

[2] 2. BOSTROM, L.; RINGDEN, O.; SUNDBERG, B.; LINDE, A.; TOLLEMAR, J. & NILSSON, B. Pretransplant herpesvirus serology and acute graft-versus-host disease. Transplantation, 46: 548-552, 1988.

[3] 3. BREINING, M.K.; ZITELLI, B.; STARZL, T.E. & HO, M. Epstein-Barr virus, cytomegalovirus, and other viral infections in children after liver transplantation. J. infect. Dis., 156: 273-279, 1987.

[4] 4. CONDIE. R. M. & O'REILLY, R.J. Prevention of cytomegalovirus infection by prophylaxis with an intravenous, hyperimmune, native, unmodified cytomegalovirus globulin. Randomized trial in bone marrow transplant recipients. Amer. J. Med., 76: 134-141, 1984.

[5] 5. DORSKY, D.Y. & CRUMPACKER, C.S. Drugs five years later: acyclovir. Ann. intern. Med., 107: 859-874, 1987.

[6] 6. DUMMER, J.S.; HARDY, A.; POORSATTAR, A. & HO, M. Early infections in kidney, heart and liver transplant recipients on cyclosporine. Transplantation, 36: 259-267, 1983.

[7] 7. EMMANUEL, D.; CUNNINGHAM, I.; JULES-ELYSEE, K.; BROCHSTEIN, J.A.; KERNAN, N.A.; LAVER, J.; STOVER, D.; WHITE, D.A.; FELS, A.; POLSKY, B.; CASTRO-MALASPINA, H.; PEPPARD, J.R.; BARTUS, P.; HAMMERLING, U. & O'REILLY, R.J. Cytomegalovirus pneumonia after bone marrow transplantation successfully treated with the combination of ganciclovir and high-dose intravenous immune globulin. Ann. intern. Med., 109: 777-782, 1988.

[8] 8. GORENSEK, M.J.; STEWART, R.W.; KEYS, T.F.; McHENRY, M.C. & GOORMASTIC, M. A multivariate analysis of the risk of cytomegalovirus infection in heart transplant recipients. J. infect. Dis., 157: 515-522, 1988.

[9] 9. GORENSEK, M.J.; STEWART, R.W.; KEYS, T.F.; McHENRY, M.C.; BABIAK, T. & GOORMASTIC, M. Symptomatic cytomegalovirus infection as a significant risk factor for major infections after cardiac transplantation. J. infect. Dis., 158: 884-887, 1987.

[10] 10. GRUNDY, J.E.; SUPER, M.; SWENY, P.; MOORHEAD, J.; LUI, S.F.; BERRY, N.J.; FERNANDO, O.N. & GRIFFITHS, P.D. Symptomatic cytomegalovirus infection in seropositive kidney recipients: reinfection with donor virus rather than reactivation of recipient virus. Lancet, 2: 132-135, 1988.

[11] 11. HAWKES, R.; NIDAY, E. & GORDON, J. A dot-immunobinding assay for monoclonal and other antibodies. Ann. Biochem., 119: 142-147, 1982.

[12] 12. KUSNE, S.; DUMMER, J.S.; SINGH, N.; IWATSUKI, S.; MAKOWKA, L.; ESQUIVEL, C.; TZIKIS, A.G.; STARZL, T.E. & HO, M. Infections after liver transplantation. An analysis of 101 consecutive cases. Medicine, 67: 132-143, 1988.

[13] 13. MARKER, S.C.; HOWARD, R.J.; SIMMONS, R.L.; KALIS, J.M.; CONNELLY, D.P.; NAJARIAN, J.S. & BALFOUR Jr., H.H. Cytomegalovirus infection: a quantitative prospective study of three hundred twenty consecutive renal transplants. Surgery, 89: 660-671, 1981.

[14] 14. MEYERS, J.D.; LESCZYNSKI, J.; ZAIA, J.A.; FLOURNOY, N.; NEWTON, B.; SNYDMAN, D.R.; WRIGHT, G.G.; LEVIN, M.J. & THOMAS, E.D. Prevention of cytomegalovirus infection by cytomegalovirus immune globulin after marrow transplantation. Ann. intern. Med., 98: 442-446, 1983.

[15] 15. MEYERS, J.D.; REED, E.C.; SHEPP, D.H.; THORNQUIST, M.; DANDLIKER, P.S.; VICARY, C.A.; FLOURNOY, N.; KIRK, L.E.; KERSEY, J.H.; THOMAS, E.D. & BALFOUR, H.H. Acyclovir for prevention of cytomegalovirus infection and disease after allogeneic marrow transplantation. New Engl. J. Med., 318: 70-75, 1988.

[16] 16. O'GRADY, J.G.; SUTHERLAND, S.; HARVEY, F.; CAYNE, R.Y.; ALEXANDER, G.J.; DONALDSON, P.T.; PORTMANN, B. & WILLIAMS, R. Cytomegalovirus infections and donor/recipient HLA antigens: interdependent co-factors in pathogenesis of vanishing bileduct syndrome after transplantation. Lancet, 2: 302-305, 1988.

[17] 17. PANNUTI, C.S.; GINGRICH, R.D.; PFALLER, M.A. & WENZEL, R.P. Nosocomial pneumonia in adult patients undergoing bone marrow transplantation: a nine year study (Submitted for publication, 1989).

[18] 18. PANNUTI, C.S.; VILAS BOAS, L.S.; AMATO NETO, V.; ANGELO, M.J.O., & SABBAGA, E. Detecçăo de anticorpos IgM nas infecçőes primárias e secundárias pelo citomegalovírus em pacientes submetidos a transplante renal. Rev. Inst. Med. trop. S. Paulo, 29: 317-322, 1987.

[19] 19. PETERSON, P.K.; BALFOUR, H.H.; MARKER, S.C.; FRYD, D.S.; HOWARD, R.J. & SIMMONS, R.L. Cytomegalovirus disease in renal allograft recipients: a prospective study of the clinical features, risk factors and impact on renal transplantation. Medicine, 59: 283-300, 1980.

[20] 20. PREIKSAITIS, J.K.; ROSNO, S.; GRUMET, C. & MERIGAN, T.C. Infection due to herpesviruses in cardiac transplant recipients: role of donor heart and immunosupressive therapy. J. infect. Dis., 147: 974-981, 1983.

[21] 21. RAND, K.H.; POLLARD, R.B. & MERIGAN, T.C. - Increased pulmonary superinfection in cardiac transplant patients undergoing primary cytomegalovirus infection. New Engl. J. Med., 288: 951-953, 1978.

[22] 22. REED, E.C.; BOWDEN, R.A.; DANDLIKER, P.S.; LILLEBY, K.E. & MEYERS, J.D. Treatment of cytomegalovirus pneumonia with ganciclovir and intravenous cytomegalovirus immunoglobulin in patients with bone marrow transplants. Ann. intern. Med., 109: 783-788, 1988.

[23] 23. RUBIN, R.H.; COSIMI, A.B.; TOLKOFF-RUBIN, N.E.; RUSSELL, R.S. & HIRSCH, M. Infectious disease syndromes attributable to cytomegalovirus and their significance among renal tansplant recipients. Transplantation, 24: 458-464, 1977.

[24] 24. SHEPP, D.H.; NEWTON, B.A.; DANDLIKER, P.S.; FLOURNOY, N. & MEYERS, J.D. Oral acyclovir therapy for mucocutaneous herpes simplex virus infections in immunocompromised marrow transplant recipients. Ann. intern. Med., 102: 783-785, 1985.

[25] 25. SINGH, N.; DUMMER, J.S.; KUSNE, S.; BREINIG, M.K.; ARMSTRONG, J.A.; MAKOWKA, L.; STARZL, T.E. & HO, M. Infections with cytomegalovirus and other herpesviruses in 121 liver transplant recipients: transmission by donated organ and the effect of OKT3 antibodies. J. intect. Dis., 158: 124-131, 1988.

[26] 26. SNYDMAN, R.D.; WERNER, B.G.; HEINZE-LACEY, B.; BERARDI, V.P.; TILNEY, N.L.; KIRKMAN, R.L.; MILFORD, E.L.; CHO, S.I.; BUSH, H.L.; LEVEY, A.S.; STROM, T.B.; CARPENTER, C.B.; LEVEY, R.H.; HARMON, W.E.; ZIMMERMAN, C.E.; SHAPIRO, M.E.; STEINMAN, T.; LOGERFO, F.; IDELSON, B.; SCHROTTER, G.P.J.; LEVIN, M.J.; MCIVER, J.; LESCZYNSKI, J. & GRADY, G.F. Use of cytomegalovirus immuneglobulin to prevent cytomegalovirus disease in renal transplant recipients. New Engl. J. Med., 317: 1049-1054, 1987.

[27] 27. STRAUS, S.E.; OSTROVE, J.M.; INCHAUSPE, G.; FELSER, J.M.; ALISON FREIFELD, A.; CROEN, K.D. & SAWYER, M.H. Varicella-zoster virus infections biology, natural history, treatment and prevention. Ann. intern. Med., 108: 221-237, 1988.

[28] 28. WADE, J.C.; NEWTON, B.; FLOURNOY, N. & MEYERS, J.D. Oral acyclovir for prevention of herpes simplex reactivation after marrow transplant. Ann. intern. Med., 100: 823-828, 1984.

[29] 29. WALMSLEY, S.L.; CHEW, E.; READ, S.E.; VELLEND, H.; SALIT, I.; RACHLIS, A. & FANNING, M.M. Treatment of cytomegalovirus retinitis with trisodium phosphonoformate hexahydrate (Foscarnet). J. infect. Dis., 157: 569-572, 1988.

[30] 30. WEINBERG, A.; BASHAM, T.Y. & MERINGAN, T.C. Regulation of the guinea pig immune functions by interleukin-2: critical role of natural killer activity in acute HSV-2 genital infection. J. Immunol., 137: 3310-3316, 1986.

[31] 31. WEINBERG, A.; RASMUSSEN, L. & MERIGAN, T.C. Acute genital infection in guinea pigs: effects of recombinant interleukin-2 on herpes simplex virus type 2. J. infect. Dis., 154: 134-138, 1986.

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