Chapter 126. Infections in Transplant Recipients (Part 7) docx

Chapter 126. Infections in Transplant Recipients (Part 7) Adenovirus can be isolated from HSCT recipients at rates varying from 5 to 18%. Although hemorrhagic cystitis, pneumonia, gastroenteritis, and fatal disseminated infection have been reported, adenovirus infection, which (like CMV infection) usually occurs in the first or second month after transplantation, is often asymptomatic. A role for cidofovir therapy has been suggested, but the efficacy of this agent is unproven. Infections with parvovirus B19 (presenting as anemia or occasionally as pancytopenia) and enteroviruses (sometimes fatal) can occur. Parvovirus infection may possibly respond to IVIg (Chap. 177). Intranasal pleconaril, a capsid-binding agent, is being studied for the treatment of enterovirus infection. Rhinoviruses and coronaviruses are frequent co-pathogens in HSCT recipients; however, whether they independently contribute to significant pulmonary infection is not known. Rotaviruses are a common cause of gastroenteritis in these patients. The polyomavirus BK virus is found at high titers in the urine of patients who are profoundly immunosuppressed. BK viruria may be associated with hemorrhagic cystitis in these patients. Compared with the incidence among patients with impaired T cell function due to HIV infection, progressive multifocal leukoencephalopathy caused by the related JC virus is rare among HSCT recipients (Chap. 376). When transmitted by mosquitoes or by blood transfusion, West Nile virus can cause encephalitis and death after hematopoietic stem cell transplantation. Infections in Solid Organ Transplant (SOT) Recipients Morbidity and mortality among SOT recipients are reduced by the use of effective antibiotics. The organisms that cause acute infections in recipients of SOT are different from those that infect HSCT recipients because SOT recipients do not go through a period of neutropenia. As the transplantation procedure involves major surgery, however, SOT recipients are subject to infections at anastomotic sites and to wound infections. Compared with HSCT recipients, SOT patients are immunosuppressed for longer periods (often permanently). Thus they are susceptible to many of the same organisms as patients with chronically impaired T cell immunity (Chap. 82, especially Table 82-1). During the early period (<1 month after transplantation), infections are most commonly caused by extracellular bacteria (staphylococci, streptococci, enterococci, E. coli, other gram-negative organisms), which often originate in surgical wound or anastomotic sites. The type of transplant largely determines the spectrum of infection. In subsequent weeks, the consequences of the administration of agents that suppress cell-mediated immunity become apparent, and acquisition or reactivation of viruses and parasites (from the recipient or from the transplanted organ) can occur. CMV infection is often a problem, particularly in the first 6 months after transplantation and may present as severe systemic disease or as infection of the transplanted organ. HHV-6 reactivation (assessed by plasma PCR) occurs within the first 2–4 weeks after transplantation and may be associated with fever, leukopenia, and possibly encephalitis. Data suggest that replication of HHV-6 and HHV-7 may exacerbate CMV-induced disease. CMV is associated not only with generalized immunosuppression but also with organ-specific, rejection-related syndromes: glomerulopathy in kidney transplant recipients, bronchiolitis obliterans in lung transplant recipients, vasculopathy in heart transplant recipients, and the vanishing bile duct syndrome in liver transplant recipients. A complex interplay between increased CMV replication and enhanced graft rejection is well established: increasing immunosuppression leads to increased CMV replication, which is associated with graft rejection. For this reason, considerable attention has been focused on the diagnosis, prophylaxis, and treatment of CMV infection in SOT recipients. Early transmission of West Nile virus to transplant recipients from an organ donor has been reported; however, the risk of West Nile acquisition has been reduced by implementation of screening procedures. Beyond 6 months after transplantation, infections characteristic of patients with defects in cell-mediated immunity—e.g., infections with Listeria, Nocardia, Rhodococcus, various fungi, and other intracellular pathogens—may be a problem. International patients and global travelers may experience reactivation of dormant infections with trypanosomes, Leishmania, Plasmodium, Strongyloides, and other parasites. Elimination of these late infections will not be possible until the patient develops specific tolerance to the transplanted organ in the absence of drugs that lead to generalized immunosuppression. Meanwhile, vigilance, prophylaxis/preemptive therapy (when indicated), and rapid diagnosis and treatment of infections can be lifesaving in SOT recipients, who, unlike most HSCT recipients, continue to be immunosuppressed. SOT recipients are susceptible to EBV-LPD from as early as 2 months to many years after transplantation. The prevalence of this complication is increased by potent and prolonged use of T cell–suppressive drugs. Decreasing the degree of immunosuppression may in some cases reverse the condition. Among SOT patients, those with heart and lung transplants—who receive the most intensive immunosuppressive regimens—are most likely to develop EBV-LPD, particularly in the lungs. Although the disease usually originates in recipient B cells, several cases of donor origin, particularly in the transplanted organ, have been noted. High organ-specific content of B lymphoid tissues (e.g., bronchial-associated lymphoid tissue in the lung), anatomic factors (e.g., lack of access of host T cells to the transplanted organ because of disturbed lymphatics), and differences in major histocompatibility loci between the host T cells and the organ (e.g., lack of cell migration or lack of effective T cell/macrophage cooperation) may result in defective elimination of EBV-infected B cells. SOT recipients are also highly susceptible to the development of Kaposi's sarcoma and less frequently to the B cell proliferative disorders associated with KSHV, such as primary effusion lymphoma and multicentric Castleman's disease. Kaposi's sarcoma is much more common (in fact, 550–1000 times more common than in the general population), can develop very rapidly after transplantation, and can also occur in the allograft. However, because the seroprevalence of KSHV is very low in Western countries, Kaposi's sarcoma is not often observed. . obliterans in lung transplant recipients, vasculopathy in heart transplant recipients, and the vanishing bile duct syndrome in liver transplant recipients. A complex interplay between increased. Chapter 126. Infections in Transplant Recipients (Part 7) Adenovirus can be isolated from HSCT recipients at rates varying from 5 to 18%. Although hemorrhagic. acute infections in recipients of SOT are different from those that infect HSCT recipients because SOT recipients do not go through a period of neutropenia. As the transplantation procedure involves