Diarrhea is a frequent and potentially debilitating condition in immunocompromised pediatric patients. Gastrointestinal illnesses can present with prolonged symptoms and systemic and/or disseminated disease among children with immunocompromising conditions, such as solid organ transplantation, hematopoietic stem cell transplantation, or congenital immunodeficiencies. The increasing availability and use of molecular diagnostic testing has improved our understanding of the burden of specific pathogens causing gastrointestinal illness in immunocompromised children. Supportive care remains as the mainstay of therapy with immunosuppression reduction when feasible. Vaccine has been successful for prevention of rotavirus, and additional vaccines for other viral causes of gastroenteritis are needed.

Fever and neutropenia is common complication of chemotherapy for pediatric malignancy and conditioning for hematopoietic stem cell transplantation. The epidemiology of fever and neutropenia has evolved over decades and the majority of infections are related to gram-positive organisms. The pediatric evidence base for prevention as well as for empirical antibiotic and antifungal therapy has improved greatly since the turn of the century. Current practices allow for variation in supportive care measures depending on the underlying severity of neutropenia.

Pneumocystis jirovecii (PJP) is an uncommon but potentially severe cause of fungal pneumonia in pediatric transplant recipients and children with oncologic disease who have impaired cell-mediated immunity. As administration of PJP prophylaxis significantly reduces the risk of PJP, knowledge of the indications for PJP prophylaxis and appropriate prophylaxis regimens is of utmost importance. Recognition of risk factors for and clinical manifestations of PJP pneumonia in pediatric solid organ and bone marrow transplant recipients and in children with malignancy is critical to facilitate early diagnosis of this condition. A clear approach to diagnosis and treatment of PJP pneumonia is provided, taking into account the specific challenges often faced in this complex patient population.

Respiratory viruses are commonly detected in both healthy and immunocompromised children. In most healthy children, respiratory viruses are associated with self-limited upper respiratory tract infections and are not accompanied by significant morbidity. In immunocompromised hosts, including hematopoietic cell transplant recipients, solid organ transplant recipients, and oncology patients, respiratory viruses can be associated with significant clinical manifestations, including prolonged viral shedding, lower respiratory tract disease, the need for supplemental oxygen, late airflow obstruction, and even death. This chapter reviews the major respiratory viruses, including respiratory syncytial virus, human metapneumovirus, influenza, parainfluenza viruses, human rhinoviruses, and human coronaviruses. Other viruses can manifest as pulmonary infection; however, these viruses are discussed elsewhere (see Chapter 17 for discussion of cytomegalovirus and Chapter 22 for discussion of adenoviruses).

Adenoviruses can complicate the peritransplant course of pediatric solid organ and hematopoietic stem cell transplant recipients. Distinguishing adenovirus infection and disease is an important aspect of clinical management. This chapter outlines the epidemiology, risk factors, clinical manifestations, diagnosis and management of adenovirus disease in these populations.

Epstein-Barr virus (EBV) is an important cause of morbidity and mortality in children undergoing solid organ and hematopoetic stem cell transplantation but is an uncommon cause of important disease in children being treated for cancer. Although EBV can be associated with a range of clinical symptoms and a spectrum of histologic disease, the most important of these are lymphoproliferative disorders, including lymphoma. This chapter provides an overview of the epidemiology and guidance toward the diagnosis and management of EBV-related disease, including lymphoproliferative disorders, focusing on the specific at-risk population of children experiencing these complications.

Infections remain an important cause of morbidity and mortality in children after solid organ transplantation (SOT). Factors related to the host, transplantation with its associated immunosuppressive medications, and epidemiologic exposures determine the risk for infection. Understanding these risks and implementing preventive strategies allows for risk mitigation and contributes to successful outcomes in children after SOT.

BK polyomavirus (BKPyV) was isolated in 1971 from a kidney transplant patient shedding decoy cells in the urine. The isolation of JC polyomavirus (JCPyV) was also reported in 1971 from postmortem tissues of patients with progressive multifocal leukoencephalopathy. Clinical and histopathologic evidence of disease is available for six human polyomaviruses, which almost exclusively affect immunocompromised patients. Specifically, BKPyV is most commonly associated with an allogeneic transplant setting resulting in direct kidney injury (nephropathy) after kidney transplant or hemorrhagic cystitis after allogeneic hematopoietic cell transplantation. Less commonly, polyomavirus infections have been linked with gastrointestinal, pulmonary, ophthalmologic, hepatic, neurologic and skin disease, including cancer. JCPyV has been less frequently associated with clinical manifestations after transplantation, among which the diagnosis of progressive multifocal leukoencephalopathy is the most devastating one. This chapter reviews the recent literature on human polyomaviruses in immunocompromised children as the result of solid organ transplantation, hematopoietic cell transplantation or cancer/chemotherapy.

Human herpesviruses 6, 7, and 8 are ubiquitous viruses that are commonly detected in solid organ transplant and allogeneic hematopoietic transplant recipients. In this overview, we discuss epidemiology and risk factors for infection and reactivation in immunocompromised patients. Asymptomatic viremia is often described, but we also review clinical manifestations, including both direct and indirect sequelae, that have been associated with viral reactivation and primary infection. Diagnosis and treatment options are also reviewed.

Nocardia and Actinomyces species are gram-positive filamentous bacteria associated with a wide range of clinical infections in the immunocompromised host. Although relatively rare among pediatric solid organ transplant recipients, hematopoietic stem cell transplant recipients, and hematology/oncology patients overall, they present unique diagnostic and treatment challenges and can lead to significant morbidity and mortality. Nocardia are ubiquitous environmental pathogens most frequently associated with pulmonary disease with high rates of dissemination in the immunocompromised host. The central nervous system is particularly prone to secondary infection, with high mortality despite treatment. Although molecular testing is increasingly available, diagnosis is often delayed and is typically dependent on histopathology and culture. Trimethoprim-sulfamethoxazole remains the backbone of treatment for nocardiosis despite a wide range of antimicrobial resistance patterns. Combination therapy is recommended in severe infections and antimicrobial susceptibility testing is vital. Treatment is typically prolonged with limited data on the risk of recurrence or the role for secondary prophylaxis. Actinomyces are rare opportunistic gram-positive rods known for their tendency to cross tissue planes and cause soft tissue infections in both compromised and immunocompetent hosts. Infections typically present as cervicofacial, thoracic, or abdominal in nature and can manifest in various forms ranging from oropharyngeal ulcerations and abscesses to pulmonary consolidations and destructive soft tissue masses. Diagnosis is made by culture and histopathology, but may be delayed as Actinomyces can take up to 14 to 21 days to grow. Actinomyces are uniformly susceptible to penicillin as well as a number of other antimicrobial agents, and treatment is typically prolonged.