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Ehrlichiosis has been infrequently described as transmissible through organ transplantation. Two donor-derived clusters of ehrlichiosis are described here. During the summer of 2020, 2 cases of ehrlichiosis were reported to the Organ Procurement and Transplantation Network (OPTN) and the Centers for Disease Control and Prevention (CDC) for investigation. Additional transplant centers were contacted to investigate similar illness in other recipients and samples were sent to the CDC. Two kidney recipients from a common donor developed fatal ehrlichiosis-induced hemophagocytic lymphocytic histiocytosis. Two kidney recipients and a liver recipient from another common donor developed ehrlichiosis. All 3 were successfully treated. Clinicians should consider donor-derived ehrlichiosis when evaluating recipients with fever early after transplantation after more common causes are ruled out, especially if the donor has epidemiological risk factors for infection. Suspected cases should be reported to the organ procurement organization and the OPTN for further investigation by public health authorities.

Background Invasive mold infections (IMIs) remain a significant cause of morbidity and mortality in patients with acute leukemia (AL) and those undergoing hematopoietic stem cell transplantation (HSCT). We describe the epidemiology of IMIs, the incidence of IMI in patients with acute myelogenous Leukemia (AML) post HSCT, and risk factors for mortality. Methods Patients were identified using ICD9 and ICD10 codes using a University of Kansas internal database from 2009-2019, microbiology records, and an AML HSCT database and were followed through May 1st, 2020. Patients’ electronic medical records were reviewed for inclusion. IMI was defined as proven or probable using the 2009 National Institute of Allergy and Infectious Diseases Mycoses Study Group (MSG) guidelines. Incidence was calculated as IMI cases/100-person-years. Risk factors for overall mortality were evaluated using a Cox regression model. Results We included 138 patients: 79 developed IMI after HSCT (8 autologous, 71 allogeneic) and 59 developed IMI after AL diagnosis. Seventeen of the AL patients underwent HSCT after IMI diagnosis (12 within 100 days of IMI). Proven IMI occurred in 45 (32.6%) and probable IMI occurred in 93 (67.4%) patients. The most common prophylactic agent prior to IMI diagnosis was fluconazole (31.2%), with 21.0% receiving none. Aspergillus was the most commonly identified mold with 91 (65.9%) cases. The average treatment duration was 101 (range 0 - 799) days. The incidence of IMI in patients with AML who underwent HSCT was 2.35 cases/100 person-years. All-cause mortality among patients with AL or HSCT who developed IMI was 23.1% at 6 weeks, 34.1% at 12 weeks, and 61.2% at 1 year. On univariate Cox model, Karnofsky performance status > 70 was associated with lower mortality (hazard ratio (HR) 0.317, 95% confidence interval (CI) [0.110, 0.914]) among HSCT recipients. ICU admission within 7 days prior to IMI diagnosis (HR 6.469, 95% CI [1.779, 23.530]) and each one point increase in BMI (HR 1.051, CI [1.001, 1.103]) were associated with increased mortality in the AL group. Figure 1 - Invasive mold infections by pathogen in HSCT-recipients and acute leukemia patients from 2009-2019. Figure 2 - Antifungal prophylactic agents prescribed for at least one week at time of IMI diagnosis Table 1 - Univariate survival analysis calculated using a Cox proportional-hazards regression model among patients who developed IMI after HSCT and patients who developed IMI after acute leukemia diagnosis Conclusion IMIs are associated with significant mortality in HSCT recipients and AL patients; patients at higher risk for mortality include those with lower baseline Karnofsky scores, recent ICU admissions, and higher BMI at time of IMI diagnosis. Disclosures Wissam El Atrouni, MD, ViiV (Advisor or Review Panel member)

Clinical manifestations of human parvovirus B19 infection can vary widely and may be atypical in solid organ transplant (SOT) recipients. However, disease is apparent when there is destruction of erythrocyte progenitor cells leading to severe acute or chronic anemia with lack of an appropriate reticulocyte response in the setting of active parvovirus B19 infection. Serology may not reliably establish the diagnosis. High-level viremia is more likely to be associated with symptomatic disease. Conversely, ongoing DNAemia after infection may not be clinically significant, if detected at low levels. Despite lack of robust data, intravenous immunoglobulin (IVIG) is frequently used for the treatment of SOT recipients with symptomatic parvovirus B19 infection. Although the optimal dosage and duration of IVIG is not known, most patients receive a total of 2 g/kg over a period of 2-5 days. A daily dose of 1 g/kg or more seems to be associated with higher incidence of toxicity. Application of standard and droplet isolation precautions remains the cornerstone for preventing human parvovirus B19 transmission. Additional research is needed to assess the efficacy of current and novel therapies and to develop a safe and effective parvovirus B19 vaccine.

The outcomes and optimal management of cirrhotic patients who develop cryptococcosis before transplantation are not fully known.We conducted a multicenter study involving consecutive patients with cirrhosis and cryptococcosis between January 2000 and March 2014. Data collected were generated as standard of care.In all, 112 patients were followed until death or up to 9 years. Disseminated disease and fungemia were present in 76.8% (86/112) and 90-day mortality was 57.1% (64/112). Of the 39 patients listed for transplant, 20.5% (8) underwent liver transplantation, including 2 with active but unrecognized disease before transplantation. Median duration of pretransplant antifungal therapy and posttransplant therapy was 43 days (interquartile range, 8-130 days) and 272 days (interquartile range, 180-630 days), respectively. Transplantation was associated with lower mortality (P = 0.002). None of the transplant recipients developed disease progression during the median follow-up of 3.5 years with a survival rate of 87.5%.Cryptococcosis in patients with cirrhosis has grave prognosis. Our findings suggest that transplantation after recent cryptococcal disease may not be a categorical exclusion and may be cautiously undertaken in liver transplant candidates who are otherwise deemed clinically stable.

Characteristics of cirrhosis-associated cryptococcosis first diagnosed after death are not fully known. In a multicenter study, data generated as standard of care was systematically collected in 113 consecutive patients with cirrhosis and cryptococcosis followed for 80 patient-years. The diagnosis of cryptococcosis was first established after death in 15.9% (18/113) of the patients. Compared to cases diagnosed while alive, these patients had higher MELD score (33 vs. 22, P = .029) and higher rate of cryptococcemia (75.0% vs. 41.9%, P = .027). Cases diagnosed after death, in comparison to those diagnosed during life were more likely to present with shock (OR 3.42, 95% CI 1.18-9.90, P = .023), require mechanical ventilation at admission (OR 8.5, 95% CI 2.74-26.38, P = .001), less likely to undergo testing for serum cryptococcal antigen (OR 0.07, 95% CI 0.02-0.21, P < .001) and have positive antigen when the test was performed (OR 0.07, 95% CI 0.01-0.60, P = .016). In a subset of cirrhotic patients with advanced liver disease cryptococcosis was first recognized after death. These patients had the characteristics of presenting with fulminant fungemia, were less likely to have positive serum cryptococcal antigen and posed a diagnostic challenge for care providers.

Solid organ and hematopoietic stem cell transplant recipients are uniquely predisposed to develop clinical illness, often with increased severity, due to a variety of common and opportunistic viruses. Patients may acquire viral infections from the donor (donor-derived infections), from reactivation of endogenous latent virus, or from the community. Herpes viruses, most notably cytomegalovirus and Epstein Barr virus, are the most common among opportunistic viral pathogens that cause infection after solid organ and hematopoietic stem cell transplantation. The polyoma BK virus causes opportunistic clinical syndromes predominantly in kidney and allogeneic hematopoietic stem cell transplant recipients. The agents of viral hepatitis B and C present unique challenges particularly among liver transplant recipients. Respiratory viral illnesses due to influenza, respiratory syncytial virus, and parainfluenza virus may affect all types of transplant recipients, although severe clinical disease is observed more commonly among lung and allogeneic hematopoietic stem cell transplant recipients. Less common viral infections affecting transplant recipients include those caused by adenoviruses, parvovirus B19, and West Nile virus. Treatment for viruses with proven effective antiviral drug therapies should be complemented by reduction in the degree of immunosuppression. For others with no proven antiviral drugs for therapy, reduction in the degree of immunosuppression remains as the sole effective strategy for management. Prevention of viral infections is therefore of utmost importance, and this may be accomplished through vaccination, antiviral strategies, and aggressive infection control measures.

Background Liver transplantation is increasingly performed in patients aged ≥65 years. Per the United Network for Organ Sharing data, infections are the leading primary and contributory cause of death in older liver transplant (LT) recipients. This study aims to describe the epidemiology and outcomes of infections within the first 200 days of LT in older adults. Methods We performed a retrospective, observational multi-center study of patients aged ≥65 years who underwent primary LT from January 1, 2010 to June 30, 2015. Data collection included patient demographics, co-morbidities, transplant data, infection event in 200 days of LT and death. Severe infection was defined as the presence of sepsis, septic shock, or sepsis with multi-organ failure. Results A total of 255 patients met inclusion criteria with median follow-up of 690 days (range 1– 2095). The mean age was 67.6 years (SD 2.4). Majority were male (67%) and white (85%). Frequent indications of LT were hepatocellular carcinoma (46%) and hepatitis C (32%). The median MELD score at the time of LT was 22 (range 6–47). Only 3% of recipients received thymoglobulin for induction. Acute rejection within 200 days of LT occurred in 31 (12%); graft failure in 8 (3%); and re-transplantation in 5 (2%). One hundred twenty-seven patients (50%) developed 274 infections; 63 (25%) had 1 infection and 64 (25%) had ≥ 2 infections. Median time to first infection after LT was 26 days [IQR 9–72]. Out of 274 infections, 182 (66%) occurred in Conclusion Infections are common in this older LT cohort and occurred mainly in the early post-LT period. OIs were infrequent except for CMV. Despite concerns for immunosuppression and immunosenescence, the outcome of infection within the 200 days of LT was overall favorable. Disclosures All authors: No reported disclosures.

Background. Histoplasmosis is a common fungal infection in the southeastern, mid-Atlantic, and central states; however, its presentation can be atypical.Case Presentation. We report a case ofHistoplasma capsulatuminfection presenting as slowly progressive weakness in the lower extremities, followed by the development of numbness below the midthoracic area, urinary incontinence, and slurred speech. Brain MRI showed leptomeningeal enhancement, predominantly linear, involving the basal cisterns, the brainstem, and spinal cord. Cerebrospinal fluid analysis showed lymphocytic pleocytosis.Discussion. CNS histoplasmosis is usually seen in patients with disseminated histoplasmosis. Isolated CNS histoplasmosis is rarely seen, especially in immunocompetent patients.Conclusions. Histoplasmosis should be considered in the differential diagnosis of patients experiencing slowly progressive neurological deficit.