Successful organ transplantation requires a profound modification of the recipient's immune system to prevent graft rejection. Not surprisingly, graft recipients are susceptible to infection. As graft rejection is predominantly a cell-mediated process, immunosuppression is directed primarily at T cell responses, and the pattern of infection is again predictable. Agents commonly used are prednisolone, cyclosporin and azathioprine; antilymphocyte globulin is used occasionally. The duration of immunosuppression required is variable: marrow graft recipients typically require only a few months' immunosuppression to prevent graft-versus-host disease (GVHD), whilst renal graft recipients generally require life-long immunosuppression.
Bone marrow transplantation (BMT)
Although allogeneic BMT is occasionally performed for primary marrow failure (aplastic anemia), it is most widely used to allow very high doses of cytotoxic chemotherapy or radiation to be administered to patients with hematologic malignancy without fear of fatal marrow toxicity. Following such therapy, rejection of histocompatible grafts is rare, but immune competent cells derived from the graft may react against the host, producing damage to skin, gastrointestinal tract and liver. This GVHD can be prevented by selectively eliminating the cytotoxic T cell population from the donor marrow prior to transplantation, or modified by short-term immunosuppression with cyclosporine and/or other agents such as methotrexate, cyclophosphamide or prednisolone.
Following successful BMT, the recipient's immune system is replaced by cells of donor origin. Immune reconstitution takes about a year, but is delayed or prevented in patients with GVHD. Responses to infection are impaired until this process is complete, and may be severely compromised by GVHD.
The pattern of infection in BMT recipients changes with time after transplant. In the first 3-4 weeks patients experience severe mucosal ulceration, are profoundly neutropenic, and are prone to bacteremia and reactivation of herpes simplex infections. During the second and third months a major and often fatal problem is interstitial pneumonitis. Total body irradiation is an important factor in the development of pneumonitis, but about one-half are associated with CMV infection or reactivation. Pneumocystis pneumonia is uncommon. Primary CMV infection can be avoided in CMV-negative patients provided their donor is also CMV-negative and only CMV-negative blood products are used. Prevention of reactivation in CMV-positive recipients is difficult, but early detection and therapy with ganciclovir may be effective. Fatal CMV infections are less common following recovery of endogenous antibody production about 2 months after transplantation.
Life-threatening infections are uncommon after the first 3 months unless GVHD persists. Zoster reactivation occurs in about one-half of BMT recipients, but later than HSV and CMV infection. It may be typically segmented or more disseminated. Primary chickenpox is uncommon in adults, but less so in children. Presentation may be atypical with symptoms or signs of visceral rather than skin involvement.
Although long-term immunosuppression is usual in recipients of kidney, liver and heart transplants, the major risk of infection occurs in the first few months after transplantation. Immunosuppressive therapy is at its most intense as rejection is most likely to occur during this period. Patients are hospitalized for much of this time and therefore nosocomial infections are common. In addition, patients may develop bacterial infections associated with surgery or other invasive interventions, may experience exacerbations of preexisting infections, or may even acquire infection transmitted via the grafted organ itself.
In the first month after transplantation bacterial infections and HSV reactivation are common. CMV and Pneumocystis pneumonia are a hazard especially in the second and third months, though routine co-trimoxazole prophylaxis has reduced the latter. Herpes zoster occurs in around 25% but generally at a later time. Other opportunistic infections are seen occasionally.
Epstein-Barr virus (EBV) primary infection or reactivation is not uncommon following transplantation. It generally produces little or no distinctive clinical illness and may only be recognized retrospectively by serology. Its major importance is the increased incidence of EBV-associated B cell malignant lymphoma in transplant recipients.
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