Purpose of Review This review highlights the epidemiology, diagnosis, and clinical manifestations of histoplasmosis. Recent Findings There is an increasing awareness of histoplasmosis in Central and South America in patients with human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS), and deaths from histoplasmosis in this region may outnumber deaths from tuberculosis. Diagnosis in this region is hampered by lack of rapid diagnostic tests. Growth of H. capsulatum in culture is definitive, but takes weeks. In areas in which antigen testing is available, this has become an important rapid diagnostic tool, and methods combining antigen and antibody testing appear to improve diagnostic accuracy for acute pulmonary and central nervous system histoplasmosis. Pulmonary histoplasmosis, although usually self-limited, rarely can lead to life-threatening complications. Uncommon, but serious and sometimes fatal complications of disseminated histoplasmosis include Addison's disease, meningitis, culture-negative endocarditis, and hemophagocytic lymphohistiocytosis. Summary The use of antigen testing has improved our ability to diagnose histoplasmosis, but these tests are not universally available. Complications of both pulmonary and disseminated histoplasmosis remain challenging.

Background: Few options are available for cytomegalovirus (CMV) treatment in transplant recipients resistant, refractory, or intolerant to approved agents. Letermovir (LET) is approved for prophylaxis in hematopoietic cell transplant (HCT) recipients, but little is known about efficacy in CMV infection. We conducted an observational study to determine the patterns of use and outcome of LET treatment of CMV infection in transplant recipients.Methods: Patients who received LET for treatment of CMV infection were identified at 13 transplant centers. Demographic and outcome data were collected.Results: Twenty-seven solid organ and 21 HCT recipients (one dual) from 13 medical centers were included. Forty-five of 47 (94%) were treated with other agents prior to LET, and 57% had a history of prior CMV disease. Seventy-seven percent were intolerant to other antivirals; 32% were started on LET because of resistance concerns. Among 37 patients with viral load < 1000 international units (IU)/ml at LET initiation, two experienced >1 log rise in viral load by week 12, and no deaths were attributed to

The diagnosis of blastomycosis and histoplasmosis can be difficult for clinicians who rarely see infections caused by these environmentally restricted dimorphic fungi. Historically, the diagnosis of blastomycosis has been established by culture and sometimes by histopathologic identification. Currently, antigen detection in urine and serum has been shown to aid in the rapid diagnosis of blastomycosis, and newer antibody assays are likely to contribute to our diagnostic capability in the near future. The gold standard for the diagnosis of histoplasmosis has been culture of the organism from involved tissues, aided in some patients by histopathological verification of the typical yeast forms in tissues. Antigen detection has contributed greatly to the ability of clinicians to rapidly establish the diagnosis of histoplasmosis, especially in severely ill and immunocompromised patients, and antibody testing for Histoplasma capsulatum provides important adjunctive diagnostic capability for several forms of both acute and chronic histoplasmosis. For both of these endemic mycoses, novel molecular tests are under active investigation, but remain available in only a few reference laboratories. In this review, we provide a synopsis of diagnostic test options that aid in establishing whether a patient has blastomycosis or histoplasmosis.

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Background Umbilical cord blood transplant (UCBT) is used for patients who do not have a matched donor, but engraftment often takes longer than with a standard allogeneic transplant, likely increasing the risk for infection. We characterized specific infections and outcomes in adults undergoing UCBT at our 2 centers. Methods All adults who underwent UCBT between January 1, 2006 and December 31, 2015 were included. Infectious episodes from 6 months before to 2 years after UCBT were reviewed. Results Fifty-seven patients underwent UCBT; 47 had neutrophil engraftment. A total of 179 infectious episodes occurred in 55 patients, 73 (41%) within 30 days post-UCBT. Viruses caused 85 (47%) infections. Cytomegalovirus caused 32 infectious episodes and was most common from day 30 to 100. Human herpesvirus 6 occurred in 28 episodes, was most common within 30 days, and caused 1 death. Bacteria were responsible for 82 (46%) infections, most commonly bacteremias due to Staphylococcus spp, Enterococcus spp, and Enterobacteriaceae. Of 11 invasive fungal infections, 9 were aspergillosis, 4 of which were fatal. Overall mortality was 56% in the first year. Thirteen deaths were from infection; 11 occurred in the first 100 days and 7 in the first 30 days post-UCBT. Of 10 patients who never engrafted, 9 died, 6 from infection, within 100 days post-UCBT. Conclusions Infectious complications were common after UCBT, especially in the first 30 days. Deaths from viral infections were fewer than expected. Delayed engraftment and nonengraftment continue to convey increased risk for fatal bacterial and fungal infections post-UCBT.

Background: Several newly developed biomarker tests for invasive pulmonary aspergillosis (IPA) have been developed, including the IMMY Aspergillus galactomannan lateral flow assay (Aspergillus GM-LFA) evaluated in this study. Methods: Twenty patients with proven/probable IPA (EORTC/MSGERC criteria) were matched by age and underlying disease with 20 patients without IPA. Bronchoalveolar lavage fluid (BALF) was analyzed in duplicate using the Aspergillus GM-LFA. Results were read visually by two blinded observers, and the optical density index (ODI) was obtained digitally with a cube reader. Results: Using a cutoff of ≥0.5 ODI, the Aspergillus GM-LFA had a sensitivity of 40%, specificity of 80%, positive predictive value (PPV) of 67% and negative predictive value (NPV) of 57%. When the cutoff was increased to ≥1.0 ODI, sensitivity remained at 40%, specificity rose to 95%, PPV was 89%, and NPV was 61%. Excellent agreement was found when duplicate samples were read either visually (κ = 1) or with the cube reader (κ = 0.89). Correlation of results obtained by visual inspection and those obtained using the cube reader was excellent (κ = 0.82). Conclusion: The Aspergillus GM-LFA had poor sensitivity but excellent specificity for proven/probable IPA in BALF. The assay was easy to interpret, and there was high concordance between results obtained visually and with a cube reader.