Infections in Patients With Aplastic Anemia Jessica M. Valdez, a,b Phillip Scheinberg, c Neal S. Young, c and Thomas J. Walsh b Infection is a major cause of death in patients with aplastic anemia (AA). There are differences between the immunocompromised state of a patient with AA and the patient who is neutropenic due to chemotherapy and this leads to a difference in the infections that they incur. Prolonged neutropenia is one of the largest risk factors for the development of infections with the invasive mycoses and bacteria. Recovery from neutropenia is directly related to survival, and supportive care plays a large role in protection while the patient is in a neutropenic state. The most common invasive mycoses include the Aspergillus species, Zygomycetes, Candida spp., and Fusarium spp. Bacterial infections that are seen in patients with AA include gram-positive coagulase-negative Staphylococcus species, Enterococcus, Staphylococus aureus, Clostridium spp., Micrococcus, alpha-hemolytic streptococci, Listeria monocytogenes, and Bacillus cereus. Gram-negative infec- tions including gram-negative bacilli, Escherichia coli, Salmonella, Bacteroides fragilis, Klebsiella oxytoca, Klebsiella pneumonia, Aeromonas hydrophilia, Pseudomonas aeruginosa, and Vibrio vulnificus. Viral infections are much less common but include those that belong to the Herpes- viridae family, community-acquired respiratory viral infection, and the viral hepatitides A, B, and C. Evidence of the parasite Strongyloides stercoralis has also been documented. This review discusses the major invasive fungal infections, bacterial pathogens, parasites, and viral infections that are found in patients with AA who are treated with immunosuppressive therapy. The specific immune impairment and current treatment parameters for each of these classes of infection will also be discussed. Semin Hematol 46:269 –276. © 2009 Published by Elsevier Inc. A plastic anemia (AA) is a bone marrow failure syndrome characterized by reduction of hema- topoietic stem and progenitor cells, empty bone marrow, and pancytopenia. Aplastic anemia, when severe, is life-threatening and if untreated is fa- tal. 1,2 Neutropenia associated with AA increases suscep- tibility to infections, particularly those caused by bac- teria and fungi. As neutropenia in patients with AA may be severe and prolonged, infection is the leading causes of death in these patients. 3 This monograph will review the major invasive fungal infections, bacterial pathogens, parasites, and viral infections that are found in patients with AA who are treated with immunosup- pressive therapy (IST). EPIDEMIOLOGY AND ETIOLOGY OF APLASTIC ANEMIA AA is rare, with an incidence of two cases per million in the West but a higher rate in East Asian countries. 1,4,5 Severe AA (SAA) is defined by at least two of the following peripheral blood count criteria: (1) absolute neutrophil count (ANC) 500/mL, (2) absolute reticulocyte count (ARC) 60,000/L, and (3) a platelet count 20,000/ L. 6 AA has been associated with exposures to drugs, chemicals, and toxins, as well as certain viral infections. However, despite the evidence of multiple epidemiologic associations, the cause of AA remains elusive in the ma- jority of cases 7 (Table 1). PATHOPHYSIOLOGY AND TREATMENT AA can be inherited or acquired. Inherited AA usu- ally presents in childhood and characteristic physical anomalies are frequently (but not always) present. Most AA is acquired and occurs in the first three decades of life. Clinical evidence and laboratory data suggest that the marrow failure in AA is due to an immune-mediated destruction of the hematopoietic compartment by au- toreactive cytotoxic lymphocytes. 2 A primary stem cell defect may contribute to the marrow failure as short- a Howard Hughes Medical Institute–National Institutes of Health Re- search Scholars Program, Bethesda, MD. b Pediatric Oncology Branch, National Cancer Institute, Bethesda, MD. c Hematology Branch, National Heart, Lung and Blood Institute, Be- thesda, MD. Address correspondence to Thomas J. Walsh, MD, Chief, Immunocom- promised Host Section, Pediatric Oncology Branch, National Cancer Institute, CRC 1-5750, 10 Center Dr, Bethesda, MD 20892. E-mail: walsht@mail.nih.gov 0037-1963/09/$ - see front matter © 2009 Published by Elsevier Inc. doi:10.1053/j.seminhematol.2009.03.008 Seminars in Hematology, Vol 46, No 3, July 2009, pp 269 –276 269