Chapter 126. Infections in Transplant Recipients (Part 6) PCR can be used to monitor EBV production after hematopoietic stem cell transplantation. High or increasing viral loads predict an enhanced likelihood of developing EBV-LPD and should prompt rapid reduction of immunosuppression and search for a focus of disease. If reduction of immunosuppression does not have the desired effect, administration of a monoclonal antibody to CD20 (rituximab or others) for the treatment of B cell lymphomas that express this surface protein has elicited dramatic responses and currently constitutes first-line therapy for CD20-positive EBV-LPD. However, long-term suppression of new antibody responses accompanies therapy, and recurrences are not infrequent. Additional B cell–directed antibodies, including anti-CD22, are under study. The role of antivirals is uncertain because no available agents have been documented to have activity against the different forms of latent EBV infection. Preventing lytic replication in these patients would theoretically produce a statistical decrease in the frequency of latent disease by decreasing the number of virions available to cause additional infection. In case reports and small animal studies, ganciclovir and/or high-dose zidovudine together with other agents has been used to eradicate EBV-LPD and CNS lymphomas, another EBV-associated complication of transplantation. Both interferon and retinoic acid have been employed in the treatment of EBV-LPD, as has IVIg, but no large prospective studies have assessed the efficacy of any of these agents. Several additional drugs are undergoing preclinical evaluation. Standard chemotherapeutic regimens have been used as a last resort, even though patients' tolerance and long-term results have been disappointing. EBV-specific T cells generated from the donor have been used experimentally to prevent and to treat EBV-LPD in allogeneic recipients, and efforts are under way to increase the activity and specificity of ex vivo–generated T cells. For further discussion, see Chap. 174. Human Herpesvirus 8 The EBV-related gammaherpesvirus KSHV, which is causally associated with Kaposi's sarcoma, with primary effusion lymphoma, and with multicentric Castleman's disease, has rarely resulted in disease in HSCT recipients, although some cases of virus-associated marrow aplasia have been reported in the peritransplantation period. The relatively low seroprevalence of KSHV in the population and the limited duration of profound T cell suppression after hematopoietic stem cell transplantation provide a probable explanation for the currently low incidence of KSHV disease. For further discussion, see Chap. 175. Other (Nonherpes) Viruses The diagnosis of pneumonia in HSCT recipients poses some special problems. Because patients have undergone treatment with multiple chemotherapeutic agents and sometimes irradiation, their differential diagnosis should include—in addition to bacterial and fungal pneumonia—CMV pneumonitis, pneumonia of other viral etiologies, parasitic pneumonia, diffuse alveolar hemorrhage, and chemical- or radiation-associated pneumonitis. Since fungi and viruses [e.g., influenza A and B viruses, respiratory syncytial virus (RSV), parainfluenza virus (types 1, 2, and 3), metapneumoviruses, and adenoviruses] are also causes of pneumonia in this setting, it is important to diagnose CMV specifically (see "Cytomegalovirus," above). M. tuberculosis has been an uncommon cause of pneumonia among HSCT recipients in Western countries (accounting for <0.1–0.2% of cases) but is common in Hong Kong (5.5%) and in countries where the prevalence of tuberculosis is high. The recipient's exposure history is clearly critical in an assessment of posttransplantation infections. Both RSV and parainfluenza viruses, particularly type 3, can cause severe or even fatal pneumonia in HSCT recipients. Infections with both of these agents sometimes occur as disastrous nosocomial epidemics. Preemptive treatment of upper airway infection and therapy for established lower tract invasion with aerosolized ribavirin and/or the anti-RSV monoclonal antibody palivizumab have been reported to lessen the severity of RSV disease in some studies. (Respigam, a polyclonal anti-RSV preparation, is no longer available.) However, no large prospective studies establishing the efficacy of these agents in HSCT recipients have been performed. Aerosolized ribavirin is difficult to administer. Antibody in particular may prove more active in immunocompromised hosts, but relevant evaluation is lacking. Influenza also occurs in HSCT recipients and generally mirrors the presence of infection in the community. Progression to pneumonia is more common when infection occurs early after transplantation and when the recipient is lymphopenic. Several drugs are available for the treatment of influenza. Amantadine and rimantadine have limited effects, primarily reducing symptoms and shortening the duration of illness caused by sensitive strains of influenza A virus. The neuraminidase inhibitors oseltamivir (oral) and zanamivir (aerosolized) are active against both influenza A virus and influenza B virus and are a reasonable treatment option. Parenteral forms of neuraminidase inhibitors are undergoing clinical trials. An important preventive measure is immunization of household members, hospital staff members, and other frequent contacts. Human metapneumovirus, a paramyxovirus, can sometimes cause severe pneumonia and respiratory failure in HSCT recipients; however, mild or even asymptomatic infection may be more common. At present, the overall contribution of human metapneumovirus to the burden of lower respiratory tract disease in HSCT recipients is unknown. . Chapter 126. Infections in Transplant Recipients (Part 6) PCR can be used to monitor EBV production after hematopoietic stem cell transplantation. High or increasing viral loads. an assessment of posttransplantation infections. Both RSV and parainfluenza viruses, particularly type 3, can cause severe or even fatal pneumonia in HSCT recipients. Infections with both of. Aerosolized ribavirin is difficult to administer. Antibody in particular may prove more active in immunocompromised hosts, but relevant evaluation is lacking. Influenza also occurs in HSCT recipients