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Opportunistic infections in children following renal transplantation

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Abstract

Opportunistic infections following renal transplantation in children are a major cause of severe morbidity and mortality. These infections account for the majority of early post renal-transplant deaths in children. General risk factors which affect the incidence and severity of these infections include: transmission of the infectious agent by the donor organ; history of immunity in the recipient prior to transplantation; type and amount of immunosuppression including treatment for rejection episodes; availability of specific treatment for the infection. Children are at particular risk because of the lack of exposure to certain pathogens prior to transplantation. There have been recent advances in the prevention and treatment of important infections which occur in children following transplantation, including varicella,Pneumocystis carinii pneumonia (PCP) and cytomegalovirus (CMV) disease. Varicella is treatable with acyclovir, often without decreasing immunosuppression and placing the graft at risk. Prophylaxis against PCP may be achieved by provision of alternate-day trimethoprim sulpha, but clear guidelines for determining who should be treated are lacking. Treatment of this disease with high-dose trimethoprim sulfa or pentamidine is usually successful. CMV disease is frequently severe, especially when the donor is seropositive and the recipient seronegative. In these situations, prophylactic CMV immunoglobulin reduces the morbidity and the mortality of the disease and prophylactic oral acyclovir may decrease its incidence. Treatment of severe CMV disease with gancyclovir is promising.

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References

  1. Fine RN (1985) Renal transplantation for children — the only realistic choice. Kidney Int Suppl 17:15–17

    Google Scholar 

  2. Ingelfinger JR, Grupe WE, Harmon WE, Fernback SK, Levey RH (1981) Growth acceleration following renal transplantation in children less than 7 years of age. Pediatrics 68:255–259

    Google Scholar 

  3. Avner ED, Harmon WE, Grupe WE, Ingelfinger JR, Eraklis AJ, Levey RH (1981) Mortality of chronic dialysis and renal transplantation in pediatric end-stage renal disease. Pediatrics 67:412–416

    Google Scholar 

  4. Kim MS, Jabs KJ, Harmon ME (1991) Long term patient survival in a pediatric renal transplantation program. Transplantation (in press)

  5. Rubin RH, Wolfson JS, Cosimi AB, Tolkoff-Rubin NE (1981) Infection in the renal transplant recipient. Am J Med 70:405–411

    Google Scholar 

  6. Rubin RH, Young LS (eds) (1988) Clinical approach to infection in the compromised host. Plenum, New York

    Google Scholar 

  7. Moore EH, Webb WR, Amend WJ (1988) Pulmonary infections in renal transplantation patients treated with cyclosporine. Radiology 167:97–103

    Google Scholar 

  8. Stratta RJ, D'Allesandr AM, Armbrust MJ, Pirsch JD, Sollinger HW, Kalayoglu M, Belzer FO (1989) Sequential antilymphocyte globulin/cyclosporine immunosuppression in cadaveric renal transplantation. Effect of duration of ALG therapy. Transplantation 47: 96–102

    Google Scholar 

  9. Ponticelli C, Minetti L, DiPalo FQ, Vegeto A, Belli L, Corbetta G, Tarantino A, Civati G (1988) The Milan clinic trial with cyclosporine in cadaveric renal transplantation. A three-year follow-up. Transplantation 45:908–913

    Google Scholar 

  10. Olivari MT, Antolick A, Kaye MP, Jamieson SW, Ring WS (1988) Heart transplantation in elderly patients. J Heart Transplant 7: 258–264

    Google Scholar 

  11. Gamberg P, Miller JL, Lough ME (1987) Impact of protection isolation on the incidence of infection after heart transplantation. J Heart Transplant 6:147–149

    Google Scholar 

  12. Andreone PA, Olivari MT, Elick B, Arentzen CE, Sibley RK, Bolman RM, Simmons RL, Ring WS (1986) Reduction of infectious complications following heart transplantation with triple-drug immunotherapy. J Heart Transplant 5:13–19

    Google Scholar 

  13. Spielberger M, Schmid T, Sandbichler P, Pernthaler H, Bosmuller C, Semenitz E, Margreiter R (1989) Infectious complications in the early phase following kidney transplantation. Wien Klin Wochenschr 101:238–241

    Google Scholar 

  14. Ettenger RB, Blifield C, Prince H, Gruskin DB, Cho S, Sehiya N, Salusky IB, Fine RN (1987) A pediatric nephrologist's dilemma: grwoth after renal transplantation and its interaction with age as a possible immunologic variable. J Pediatr 111:1022–1025

    Google Scholar 

  15. Ettenger RB, Rosenthal JT, Marks J, Forsythe S, Malekzadeh MH, Kamil E, Salusky IB, Fine RN (1989) Factors influencing the improvement in cadaveric renal transplant survival in pediatric recipients. Transplant Proc 21:1693–1695

    Google Scholar 

  16. Rizzoni B, Broyer M, Guest G, Fine R, Holliday MA (1986) Growth retardation with chronic renal disease. Scope of the problem. Am J Kidney Dis 7:256–261

    Google Scholar 

  17. Cutler SJ, Ederer F (1958) Maximum utilization of the life table method in analyzing survival. J Chronic Dis 8:699–705

    Google Scholar 

  18. Weller TH (1983) Varicella and herpes zoster. N Engl J Med 309: 1362–1368, 1434–1440

    Google Scholar 

  19. Feldhoff CM, Balfour HH, Simmons RL, Najarian JS, Mauer SM (1981) Varicella in children with renal transplants. J Pediatr 98: 25–31

    Google Scholar 

  20. Shulman ST (1985) Acyclovir treatment of disseminated varicella in childhood malignant neoplasms. Am J Dis Child 139:137–140

    Google Scholar 

  21. Balfour HH Jr (1988) Varicella zoster virus infections in immunocompromised hosts. A review of the natural history and management. Am J Med 85:68–73

    Google Scholar 

  22. McGregor RS, Zitelli BJ, Urbach AH, Malatack JJ, Gartner JC Jr (1989) Varicella in pediatric orthotopic liver transplant recipients. Pediatrics 83:256–261

    Google Scholar 

  23. Nyerges G, Meszner Z, Gyarmati E, Kerpel, Fronious S (1988) Acyclovir prevents dissemination of varicella in immunocompromised children. J Infect Dis 157:309–313

    Google Scholar 

  24. Bradley JR, Wreghitt TG, Evans DB (1987) Chickenpox in adult renal transplant recipients. Nephrol Dial Transplant 1:242–245

    Google Scholar 

  25. Van der Meer JW, Versteeg J (1982) Acyclovir in severe herpes virus infections. Am J Med 73:271–274

    Google Scholar 

  26. Alford CA (1982) Acyclovir treatment of herpes simplex virus infections in immunocompromised humans. An overview. Am J Med 73: 225–228

    Google Scholar 

  27. Shepp DH, Dandliker PS, Meyers JD (1988) Current therapy of varicella zoster virus infection in immunocompromised patients. A comparison of acyclovir and vidarabine. Am J Med 85:96–98

    Google Scholar 

  28. Balfour HH Jr, McMonigal KA, Bean B (1983) Acyclovir therapy of varicella-zoster virus infections in immunocompromised patients. J Antimicrob Chemother [Suppl B]: 169–179

  29. Balfour HH, Bean B, Laskin OL, Ambinder RF, Meyers JD, Wade JC, Zaia JA, Aeppli D, Kirk LE, Segreti AC, Keeney RE (1983) Acyclovir halts progression of herpes zoster in immunocompromised patients. N Engl J Med 308:1448–1453

    Google Scholar 

  30. Dorsky DI, Crumpacker CS (1987) Drugs five years later: acyclovir. Ann Intern Med 107:859–874

    Google Scholar 

  31. Nyerges G, Meszner Z (1988) Treatment of chickenpox in immunocompromised children. Am J Med 85:94–95

    Google Scholar 

  32. Pahwa S, Biron K, Lim W, Swenson P, Kaplan MH, Sadick N, Pahwa R (1988) Continuous varicella-zoster infection associated with acyclovir resistance in a child with AIDS. JAMA 260: 2879–2882

    Google Scholar 

  33. Gershon AA, Steinberg SP (1989) Persistence of immunity to varicella in children with leukemia immunized with live attenuated varicella vaccine. N Engl J Med 320:892–897

    Google Scholar 

  34. Kovacs JA, Hiemenz JW, Macher AM, Stover D, Murray HW, Shelhamer J, Lane HC, Urmacher C, Honig C, Longo DL, Parker MM, Natanson C, Parrillo JE, Fauci AS, Pizzo PA, Masur H (1984)Pheumocystis carinii pneumonia: a comparison between patients with the acquired immunodeficiency syndrome and patients with other immunodeficiencies. Ann Intern Med 100:663–671

    Google Scholar 

  35. Sterling RP, Bradley BB, Khalil KG, Kerman RH, Conklin RH (1984) Comparison of biopsy-provenPneumocystis carinii pneumonia in acquired immune deficiency syndrome patients and renal allograft recipients. Ann Thorac Surg 38:494–499

    Google Scholar 

  36. Ballardie FW, Winearls CG, Cohen J, Carr DH, Rees AJ, Williams G (1985)Pneumocystis carinii pneumonia in renal transplant recipients — clinical and radiographic features, diagnosis and complications of treatment. QJ Med 57:729–747

    Google Scholar 

  37. Talseth T, Holdaas H, Albrechtsen D, Berg KJ, Fauchald P, Naalsund A, Nordal KP, Skar AG, Sodal G, Flatmark A (1988) Increasing incidence ofPneumocystis carinii pneumonia in renal transplant patients. Transplant Proc 20:400–401

    Google Scholar 

  38. Franson TR, Kauffman HM Jr, Adams MB, Lemann J Jr, Cabrera E, Hanacik L (1987) Cyclosporine therapy and refractoryPneumocystis carinii pneumonia. A potential association. Arch Surg 122: 1034–1035

    Google Scholar 

  39. Fischl MA, Dickinson GM, LaVoie L (1988) Safety and effecacy of sulfamethoxazole and trimethoprim chemoprophylaxis forPneumocystis carinii pneumonia in AIDS. JAMA 259:1185–1189

    Google Scholar 

  40. Hughes WT (1984) Five-year absence ofPneumocystis carinii pneumonitis in a pediatric oncology center. J Infect Dis 150:305–306

    Google Scholar 

  41. Masur H, Kovacs JA (1988) Treatment and prophylaxis ofPneumocystis carinii pneumonia. Infect Dis Clin North Am 2: 419–428

    Google Scholar 

  42. Montgomery AB, Debs RJ, Luce JM, Corkery KJ, Turner J, Brunette EN, Lin ET, Hopewell PC (1988) Selective delivery of pentamidine to the lung by aerosol. Am Rev Respir Dis 137:477–478

    Google Scholar 

  43. Conte JE Jr, Hollander H, Golden JA (1987) Inhaled or reduced-dose intravenous pentamidine forPneumocystis carinii pneumonia. A pilot study. Ann Intern Med: 495–498

  44. Girard PM, Brun-Pascaud M, Farinotti R, Tamisier L, Kernbaum S (1987) Pentamidine aerosol in prophylaxis and treatment of murinePneumocystis carinii pneumonia. Antimicrob Agents Chemother 31: 978–981

    Google Scholar 

  45. Young FE, Nightingale SL, Cooper EC, Trapnell CB (1989) Aerosolized pentamidine. Approved for HIV-infected individuals at high risk forPneumocystis carinii pneumonia. Arch Intern Med 149: 2412–2413

    Google Scholar 

  46. Jarowenko M, Pifer L, Kerman R, Kahan BD (1986) Serologic methods for the early diagnosis ofPneumocystis carinii infection in renal allograft recipients. Transplantation 41:436–442

    Google Scholar 

  47. Girard PM, Landman R, Gaudebout C, Lepretre A, Lottin P, Michon C, DeTruchis P, Matheron S, Camus F, Farinotti R, Marche C, Coulaud JP, Salmot AG (1989) Prevention ofPneumocystis carinii pneumonia relapse by pentamidine aerosol in zidovudine-treated AIDS patients. Lancet I:1348–1353

    Google Scholar 

  48. Tuazon CU, Delaney MD, Simon GL, Witorsch P, Varma VM (1985) Utility of gallium67 scintigraphy and bronchial washings in the diagnosis and treatment ofPneumocystis carinii pneumonia in patients with the acquired immune deficiency syndrome. Am Rev Respir Dis 132:1087–1092

    Google Scholar 

  49. Zaman MK, Wooten OJ, Suprahmanya B, Ankobiah W, Finch PJ, Kamholz SL (1988) Rapid noninvasive diagnosis ofPneumocystis carinii from induced liquefied sputum. Ann Intern Med 109:7–10

    Google Scholar 

  50. Masur H, Gill VJ, Ognibene FP, Shelhamer J, Godwin C, Kovacs JA (1988) Diagnosis ofPneumocystis pneumonia by induced sputum technique in patients without the acquired immunodeficiency syndrome. Ann Intern Med 109:755–756

    Google Scholar 

  51. Siegel SE, Wolff LJ, Baehner RL, Hammond D (1984) Treatment ofPneumocystis carinii pneumonitis. A comparative trial of sulfamethoxazole-trimethoprim v pentamidine in pediatric patients with cancer report from the Children's Cancer Study Group. Am J Dis Child 138:1051–1054

    Google Scholar 

  52. Sattler FR, Cowan R, Nielsen DM, Ruskin J (1988) Trimethoprimsulfamethoxazole compared with pentamidine for treatment ofPneumocystis carinii pneumonia in the acquired immunodeficiency syndrome. A prospective, noncrossover study. Ann Intern Med 109: 280–287

    Google Scholar 

  53. Whyarton JM, Coleman DL, Wofsy CB, Luce JM, Blumenfeld W, Hadley WK, Ingram-Drake L Volberding PA, Hopewell PC (1986) Trimethoprim-sulfamethoxazole or pentamidine forPneumocystis carinii pneumonia in the acquired immunodeficiency syndrome. A prospective randomized trial. Ann Intern Med 105:37–44

    Google Scholar 

  54. Montgomery AB, Debs RJ, Luce JM, Corkery KJ, Turner J, Hopewell PC (1989) Aerosolized pentamidine as second line therapy in patients with AIDS andPneumocystis carinii pneumonia. Chest 95:747–750

    Google Scholar 

  55. Montgomery AB, Debs RJ, Luce JM, Corkery KJ, Turner J, Brunette EN, Lin ET, Hopewell PC (1987) Aerosolised pentamidine as sole therapy forPneumocystis carinii pneumonia in patients with acquired immunodeficiency syndrome. Lancet II:480–483

    Google Scholar 

  56. Cohen EB, Komorowski RA, Kauffman HM Jr, Adams M (1985) Unexpectedly high incidence of cytomegalovirus infection in apparent peptic ulcers in renal transplant recipients. Surgery 97: 606–612

    Google Scholar 

  57. Lewis RM, Johnson PC, Golden D, Van Buren CT, Kerman RH, Kahan BD (1988) The adverse impact of cytomegalovirus infection on clinical outcome in cyclosporine-prednisone treated renal allograft recipients. Transplantation 45:353–359

    Google Scholar 

  58. Pollak R, Barber PL, Prusak BF, Mozes MF (1987) Cytomegalovirus as a risk factor in living-related renal transplantation. A prospective study. Ann Surg 205:302–304

    Google Scholar 

  59. Luby JP, Ware AJ, Hull AR, Helderman JH, Gailiunas P, Butler S, Arkins C (1983) Disease due to cytomegalovirus and its long-term consequences in renal transplant recipients. Correlation of allograft survival with disease due to cytomegalovirus and rubella antibody level. Arch Intern Med 143:1126–1129

    Google Scholar 

  60. Pollard RB (1988) Cytomegalovirus infections in renal, heart, heartlung and liver tranplantation. Pediatr Infect Dis J 7 [Suppl 5]: S97-S102

    Google Scholar 

  61. Chou SW (1986) Acquisition of donor strains of cytomegalovirus by renal-transplant recipients. N Engl J Med 314:1418–1423

    Google Scholar 

  62. Chou SW, Norman DJ (1988) The influence of donor factors other than serologic status on transmission of cytomegalovirus to transplant recipients. Transplantation 46:89–93

    Google Scholar 

  63. Verdonck LF, deGraan-Hentzen YC, Dekker AW, Mudde GC, deGast GC (1987) Cytomegalovirus seronegative platelets and leukocyte-poor red blood cells from random donors can prevent primary cytomegalovirus infection after bone marrow transplantation. Bone Marrow Transplant 2:73–78

    Google Scholar 

  64. Rook AH, Quinnan GV Jr, Frederick WJ, Manischewitz JF, Kirmani N, Dantzler T, Lee BB, Currier CB Jr (1984) Importance of cytotoxic lymphocytes during cytomegalovirus infection in renal transplant recipients. Am J Med 76:385–392

    Google Scholar 

  65. Roenhorst HW, Tegzess AM, Beelen JM, Middeldorp JM (1985) The TH HLA-DRw6 as a risk factor for active cytomegalaovirus but not for herpes simplex virus infection after renal allograft transplantation. Br Med J [Clin Res] 291:619–622

    Google Scholar 

  66. Glazer JP, Friedman HM, Grossman RA, Starr SE, Barker CF, Perloff LJ, Huang ES, Plotkin SA (1979) Live cytomegalovirus vaccination of renal transplant candidates. A preliminary trial. Ann Intern Med 91:676–683

    Google Scholar 

  67. Snydman DR, Werner BG, Heinz-Lacey B, Berardi VP, Tilney NL, Kirkman RL, Milford EL, Cho SI, Bush HL Jr, Levey AS, Strom TB, Carpenter CB, Levey RH, Harmon WE, Zimmerman CE, Shapiro ME, Steinman T, Logerfo F, Idelson B, Schroter GPJ, Levin MJ, McIver J, Lesczynski J, Grady GF (1987) Use of cytomegalovirus immune globulin to prevent cytomegalovirus disease in renal transplant recipients. N Engl J Med 317: 1049–1054

    Google Scholar 

  68. Johnson PC, Lewis RM, Golden DL, Oefinger PE, Van Buren CT, Kerman RH, Kahan BD (1988) The impact of cytomegalovirus infection on seronegative recipients of seropositive donor kidneys versus seropositive recipients treated with cyclosporine-prednisone immunosuppression. Transplantation 45:116–121

    Google Scholar 

  69. Brayman KL, Dafoe DC, Smythe WR, Barker CF, Perloff LJ, Naji A, Fox IJ, Grossman RA, Jorkasky DK, Starr SE, Friedman HM, Plotkin SA (1988) Prophylaxis of serious cytomegalovirus infection in renal transplant candidates using live human cytomegalovirus vaccine. Interim results of a randomized controlled trial. Arch Surg 123:1502–1508

    Google Scholar 

  70. Chou SW (1989) Reactivation and recombination of multiple cytomegalovirus strains from individual organ donors. J Infect Dis 160: 11–15

    Google Scholar 

  71. Grundy JE, Lui SF, Super M, Berry NJ, Sweny P, Fernando ON, Moorehead J, Griffiths PD (1988) Symptomatic cytomegalovirus infection in seropositive kidney recipients: reinfection with donor virus rather than reactivation of recipient virus. Lancet II:132–135

    Google Scholar 

  72. Snydman DR, Werner BG, Tilney NL, Kirkman RL, Milford EL, Cho SI, Bush HL Jr, Levey AS, Strom TB, Carpenter CB, Berardi VP, Levey RH, Harmon WE, Zimmerman CE, Tenny A, Heinz-Lacey B, Shapiro ME, Steinman T, Logerfo F, Idelson B, McIver J, Leszcynski J, Grady GF (1988) A further analysis of primary cytomegalovirus disease prevention in renal transplant recipients with a cytomegalovirus immune globulin interim comparison of a randomized and an open-label trial. Transplant Proc 20 [6 Suppl 8]: 24–30

    Google Scholar 

  73. Balfour HH Jr, Chace BA, Stapleton JT, Simmons RL, Fryd DS, (1989) A randomized, placebo-controlled trial of oral acyclovir for the prevention of cytomegalovirus disease in recipients of renal allografts. N Engl J Med 320:1381–1387

    Google Scholar 

  74. Erice A, Jordan MC, Chace BA, Fletcher C, Chinnock BJ, Balfour HH Jr (1987) Ganciclovir treatment of cytomegalovirus disease in transplant recipients and other immunocompromised hosts. JAMA 257:3082–3087

    Google Scholar 

  75. Harbison MA, DeGirolami PC, Jenkins RL, Hammer SM (1988) Ganciclovir therapy of severe cytomegalovirus infections in solid organ transplant recipients. Transplantation 46:82–88

    Google Scholar 

  76. Fletcher CV, Chinnock BJ, Chace B, Balfour HH Jr (1988) Pharmacokinetics and safety of high-dose oral acyclovir for suppression of cytomegalovirus disease after renal transplantation. Clin Pharmacol Ther 44:158–163

    Google Scholar 

  77. Paya CV, Hermans PE, Smith TF, Rakela J, Wiesner RH, Krom RA, Torres VE, Sterioff S, Wilkowske CJ (1988) Efficacy of ganciclovir in liver and kidney transplant recipients with severe cytomegalovirus infection. Transplantation 46:229–234

    Google Scholar 

  78. Ringden O, Lonnqvist B, Paulin T, Ahlmen J, Klintmalm G, Wahren B, Lernestedt JO (1986) Pharmacokinetics, safety and preliminary clinical experiences using foscarnet in the treatment of cytomegalovirus infections in bone marrow and renal transplant recipients. J Antimicrob Chemother 17:373–387

    Google Scholar 

  79. Ahlmen J, Wijnween AC, Brynger H, Lycke E (1985) Clinical experiences with phosphonoformate (foscarnet) treatment of viral diseases following renal transplantation. Scand J Urol Nephrol Suppl 92:41–44

    Google Scholar 

  80. Nyberg G, Svalander C, Blohme I, Persson H (1989) Tubulointerstitial nephritis caused by the antiviral agent foscarnet. Transplant Int 2: 223–227

    Google Scholar 

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Harmon, W.E. Opportunistic infections in children following renal transplantation. Pediatr Nephrol 5, 118–125 (1991). https://doi.org/10.1007/BF00852868

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