Epidemiology and outcomes of Clostridium difficile infection in allogeneic hematopoietic cell and lung transplant recipients

BackgroundClostridium difficile infection (CDI) is a common complication of lung and allogeneic hematopoietic cell (HCT) transplant, but the epidemiology and outcomes of CDI after transplant are poorly described.MethodsWe performed a prospective, multicenter study of CDI within 365 days post‐allogeneic HCT or lung transplantation. Data were collected via patient interviews and medical chart review. Participants were followed weekly in the 12 weeks post‐transplant and while hospitalized and contacted monthly up to 18 months post‐transplantation.ResultsSix sites participated in the study with 614 total participants; 4 enrolled allogeneic HCT (385 participants) and 5 enrolled lung transplant recipients (229 participants). One hundred and fifty CDI cases occurred within 1 year of transplantation; the incidence among lung transplant recipients was 13.1% and among allogeneic HCTs was 31.2%. Median time to CDI was significantly shorter among allogeneic HCT than lung transplant recipients (27 days vs 90 days; P = .037). CDI was associated with significantly higher mortality from 31 to 180 days post‐index date among the allogeneic HCT recipients (Hazard ratio [HR] = 1.80; P = .007). There was a trend towards increased mortality among lung transplant recipients from 120 to 180 days post‐index date (HR = 4.7, P = .09).ConclusionsThe epidemiology and outcomes of CDI vary by transplant population; surveillance for CDI should continue beyond the immediate post‐transplant period.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/143790/1/tid12855_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/143790/2/tid12855.pd

Endemic fungal infections in solid organ and hematopoietic cell transplant recipients enrolled in the Transplant‐Associated Infection Surveillance Network ( TRANSNET )

Background Invasive fungal infections are a major cause of morbidity and mortality among solid organ transplant ( SOT ) and hematopoietic cell transplant ( HCT ) recipients, but few data have been reported on the epidemiology of endemic fungal infections in these populations. Methods Fifteen institutions belonging to the Transplant‐Associated Infection Surveillance Network prospectively enrolled SOT and HCT recipients with histoplasmosis, blastomycosis, or coccidioidomycosis occurring between March 2001 and March 2006. Results A total of 70 patients (64 SOT recipients and 6 HCT recipients) had infection with an endemic mycosis, including 52 with histoplasmosis, 9 with blastomycosis, and 9 with coccidioidomycosis. The 12‐month cumulative incidence rate among SOT recipients for histoplasmosis was 0.102%. Occurrence of infection was bimodal; 28 (40%) infections occurred in the first 6 months post transplantation, and 24 (34%) occurred between 2 and 11 years post transplantation. Three patients were documented to have acquired infection from the donor organ. Seven SOT recipients with histoplasmosis and 3 with coccidioidomycosis died (16%); no HCT recipient died. Conclusions This 5‐year multicenter prospective surveillance study found that endemic mycoses occur uncommonly in SOT and HCT recipients, and that the period at risk extends for years after transplantation.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/106980/1/tid12186.pd

Cardiovascular screening of potential renal transplant recipients provides no survival benefit

Having defined CTL-associated transcripts (CATs) in CTL in vitro, we used microarrays to quantify the burden of CAT sets compared with individual transcripts in human renal transplant biopsies with T-cell mediated rejection (TCMR). CAT sets in TCMR resembled diluted CTL RNA, maintaining overall hierarchy of expression relative to CTL in vitro. NK selective sets were not detected in TCMR, indicating the CATs mainly reflect T cells. We selected 25 highly expressed CATs that diluted quantitatively in kidney RNA (QCATs) and remained detectable after 32-fold dilution. QCAT burden in 14 kidneys with TCMR was 3 to 15% of CTL RNA, correlating with infiltration. One biopsy diagnosed as TCMR only by endothelialitis had little interstitial infiltrate and lowest CAT burden. CAT sets were more consistent than individual CATs such as perforin or granzyme B, which showed heterogeneity. In luster and principal component analysis, QCATs grouped biopsies with TCMR together, in close relationship to in vitro CTL. Thus QCAT sets robustly measure the burden of CTL and effector memory T cells in biopsies as %CTL RNA, in a manner not achieved by measurement of individual transcripts

Aplicación de ensayos de PCR en tiempo real para el diagnóstico de histoplasmosis utilizando tres dianas moleculares en tejidos FFPE humanos y sangre completa

Objective: Histoplasmosis is a fungal infection that causes significant morbidity and mortality in persons living with HIV/AIDS, especially in countries with limited resources. Currently used diagnostic tests rely on culture and serology, lack sensitivity and often require weeks to obtain results causing significant diagnosis delays; molecular assays are not commercially available. Methods: we aimed to apply quantitative real-time PCR (qPCR) targeting three protein-coding genes of Histoplasma capsulatum (100-kDa, H and M antigens) for detection of H. capsulatum infection in formalin-fixed paraffin-embedded (FFPE) and whole blood (WB) samples from patients with proven histoplasmosis. Results: For FFPE samples, the sensitivity of 100-kDa, H and M qPCR assays were 93.9%, 91% and 57%, respectively; however, the same qPCR assays showed only 23%, 19% and 11.5% of sensitivity for 100-kDa, H y M qPCR assays when used with the WB samples. The specificity of qPCR was determined by testing samples from patients with other clinical infections and healthy controls and was 93%-100% depending upon the assay and the specimen type. Conclusion: we applied three qPCR assays for detecting H. capsulatum DNA in human samples, and demonstrated that the molecular protocols based on amplification of 100-kDa and H antigen can be successfully used for diagnosing this mycosis when using FFPE samples; however, we do not recommend WB for routine diagnosis of histoplasmosis by qPCR in patients with progressive disseminated histoplasmosis

Coronavirus Disease 2019 (COVID-19) in a Patient with Disseminated Histoplasmosis and HIV-A Case Report from Argentina and Literature Review

The disease caused by the new SARS-CoV-2, known as Coronavirus disease 2019 (COVID-19), was first identified in China in December 2019 and rapidly spread around the world. Coinfections with fungal pathogens in patients with COVID-19 add challenges to patient care. We conducted a literature review on fungal coinfections in patients with COVID-19. We describe a report of a patient with disseminated histoplasmosis who was likely infected with SARS-CoV-2 and experienced COVID-19 during hospital care in Buenos Aires, Argentina. This patient presented with advanced HIV disease, a well-known factor for disseminated histoplasmosis; on the other hand, we suspected that COVID-19 was acquired during hospitalization but there is not enough evidence to support this hypothesis. Clinical correlation and the use of specific Histoplasma and COVID-19 rapid diagnostics assays were key to the timely diagnosis of both infections, permitting appropriate treatment and patient care

Cross-reactivity of antibodies in human infections by the kinetoplastid protozoa Trypanosoma cruzi, Leishmania chagasi and Leishmania (Viannia) braziliensis Reatividade cruzada de anticorpos em pacientes com infecções pelos protozoários Trypanosoma cruzi, Leishmania chagasi e Leishmania (Viannia) braziliensis

We have detected antibodies, in the sera of Chagas disease, Kala-azar and Mucocutaneous leishmaniasis patients, that bind multiple antigens shared between the three causative agents. The Chagas disease sera showed 98 to 100% positive results by ELISA when the Leishmania braziliensis and Leishmania chagasi antigens were used, respectively. The Kala-azar sera showed 100% positive results with Trypanosoma cruzi or L. braziliensis antigens by immunofluorescence assays. The antibodies in the sera of Mucocutaneous leishmaniasis patients showed 100% positive results by ELISA assays with T. cruzi or L. chagasi antigens. Furthermore, the direct agglutination of L. chagasi promastigotes showed that 95% of Kala-azar and 35% of Mucocutaneous leishmaniasis sera agglutinated the parasite in dilutions above 1:512. In contrast, 15% of Chagas sera agglutinated the parasite in dilutions 1:16 and below. Western blot analysis showed that the Chagas sera that formed at least 24 bands with the T. cruzi also formed 13 bands with the L. chagasi and 17 bands with the L. braziliensis. The Kala-azar sera that recognized at least 29 bands with the homologous antigen also formed 14 bands with the T. cruzi and 10 bands with the L. braziliensis antigens. Finally, the Mucocutaneous leishmaniasis sera that formed at least 17 bands with the homologous antigen also formed 10 bands with the T. cruzi and four bands with the L. chagasi antigens. These results indicate the presence of common antigenic determinants in several protozoal proteins and, therefore, explain the serologic cross-reactions reported here.<br>Foram detectados anticorpos, nos soros de pacientes com doença de Chagas, Calazar e Leishnnaniose cutâneo-mucosa, que se ligam a antígenos compartilhados pelos três agentes causais. Os pacientes chagásicos mostraram 98 a 100% de soropositividade pelo ELISA quando antígenos de Leishmania braziliensis e de Leishmania chagasi foram usados, respectivamente. Os soros de Calazar mostraram resultados positivos com antígenos de Trypanosoma cruzi ou com L. braziliensis pela imunofluorescência. Ademais, os anticorpos nos soros de pacientes com Leishmaniose cutâneo-mucosa tinham 100% de resultados positivos pelo ELISA com antígenos de T. cruzi ou de L. chagasi. Ademais, a aglutinação direta de promastigotas de L. chagasi mostrou que 95% dos soros de Calazar e 35% de Leishmaniose cutâneo-mucosa algutinaram o parasito em diluições acima de 1:512. Em contraste, 15% dos soros chagásicos aglutinaram o parasito na diluição de 1:16 ou abaixo. Análises pelo Western blot mostraram que os soros chagásicos que formaram pelo menos 24 bandas com antígeno de T. cruzi também foramaram 13 bandas com antígeno de L. chagasi e 17 bandas com L. braziliensis. Os soros de Calazar que reconheceram pelo menos 29 bandas com o antígeno homólogo também formaram 14 bandas com o T. cruzi e 10 bandas com L. braziliensis. Finalmente, os soros de Leishmaniose cutâneo-mucosa que formaram pelo menos 17 bandas com o antígeno homólogo também formaram 10 bandas com os antígenos de T. cruzi e quatro com L. braziliensis. Esses resultados indicam a presença de determinantes antigênicos comuns em várias proteínas desses protozoários e, portanto, explicam as reações sorológicas cruzadas descritas aqui