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Preventing viral infections at an early stage is a key strategy for successfully improving transplant outcomes. Preemptive therapy and prophylaxis with antiviral agents have been ...successfully used to prevent clinically significant viral infections in hematopoietic cell transplant recipients. Major progress has been made over the past decades in preventing viral infections through a better understanding of the biology and risk factors, as well as the introduction of novel antiviral agents and advances in immunotherapy. High-quality evidence exists for the effective prevention of herpes simplex virus, varicella-zoster virus, and cytomegalovirus infection and disease. Few data are available on the effective prevention of human herpesvirus 6, Epstein-Barr virus, adenovirus, and BK virus infections. To highlight the spectrum of clinical practice, here we review high-risk situations that we handle with a high degree of uniformity and cases that feature differences in approaches, reflecting distinct hematopoietic cell transplant practices, such as ex vivo T-cell depletion.
Viral infection remains a serious cause of morbidity and mortality after hematopoietic stem cell transplantation (HSCT). Using a series of 5 illustrative cases, Dadwal and colleagues discuss preventative and preemptive therapy for the management of viral infections in patients undergoing HSCT.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Introduction: Fungal infection burden related to Mucorales has been on the rise with significant associated morbidity and mortality. The major obstacle in the management has been lack of a ...non-invasive rapid and a reliable diagnostic test. Developing a culture-independent biomarker for the early diagnosis of mucormycosis is a major unmet need in modern mycology. Several approaches have been developed, such as immunohistochemistry (IHC) that can confirm the histopathologic diagnosis of the invasive mold infection, polymerase chain reaction (PCR) on formalin-fixed paraffin-embedded (FFPE) or fresh tissue, body fluids such as bronchoalveolar fluid (BAL), and detection directly from serum/blood. Serologic tests, matrix assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF/MS), metabolomics and metagenomic shotgun sequencing are other evolving technologies.
Area covered: In this review paper, we report the current status of the molecular diagnostics in the diagnosis of mucormycosis: serologic tests, IHC, PCR, protein-based with MALDI-TOF, metabolomics and metagenomic sequencing.
Expert commentary: This review will conclude with an expert commentary on the potential uses/challenges of the currently available tests and the future of molecular diagnostics for mucormycosis.
PURPOSE OF REVIEWCytomegalovirus infection (CMVi) has been the troll of allogeneic hematopoietic cell transplantation (allo-HCT). Over the last 4 decades various approaches have been adopted to ...minimize the burden from CMVi. There has been major advancement in the management of CMVi in HCT within the last few years that is poised to change the approaches employed in preventing and managing CMVi. This review will summarize recent advances and potential future development in the management of CMV in HCT.
RECENT FINDINGThe major development has been the approval of letermovir for the prevention of CMVi in allo-HCT recipients. Also, with the potential availability of tests that can determine host CMV immunity a risk adapted approach to CMV prevention may become a possibility.
SUMMARYThe landscape of CMV prevention is about to change with the approval of a new anti-CMV antiviral that is safe and effective. However, the prophylaxis may lead to late onset CMVi in the context of ongoing risk factors after stopping prophylaxis and measures to counter this shifting epidemiology will need further research; such as extending the prophylaxis in high-risk patients vs. immunotherapy with vaccination and T-cell therapy.
Recombinant herpes zoster (HZ) vaccines may be an alternative to the live-attenuated HZ vaccine for immunocompromised individuals. This was a phase 1/2, randomized, observer-blind, placebo-controlled ...study in adults with multiple myeloma, non-Hodgkin lymphoma (B- or T-cell), Hodgkin lymphoma, or acute myeloid leukemia who had undergone autologous hematopoietic stem-cell transplant 50 to 70 days earlier. Subjects (N = 121) were randomized 1:1:1:1 to receive (at months 0, 1, 3) three doses of 50 μg varicella-zoster virus glycoprotein E (gE) adjuvanted with AS01B, 3 doses of gE adjuvanted with AS01E, 1 dose of saline followed by 2 doses of gE/AS01B, or 3 doses of saline. One month after the last dose (6 months after transplant), frequencies of CD4+ T cells expressing ≥2 activation markers after induction with gE and anti-gE antibody concentrations were higher with all gE/AS01 regimens than with saline. Both responses persisted up to 1 year in subjects vaccinated with gE/AS01. Immune responses were higher in the gE/AS01B 3-dose group than in the gE/AS01B 2-dose group but not higher than in the gE/AS01E 3-dose group. One serious adverse event (pneumonia) was considered vaccine related. Both formulations and both schedules were immunogenic and well tolerated in this population. This study was registered at www.clinicaltrials.gov as #NCT00920218.
•HCT recipients have increased susceptibility to herpes zoster, but live-attenuated vaccines are not appropriate for highly immunocompromised people.•An adjuvanted subunit vaccine against herpes zoster elicits strong immune responses with an acceptable safety profile in adult autologous HCT recipients.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
The stethoscope has long been at the center of patient care, as well as a symbol of the physician–patient relationship. While advancements in other diagnostic modalities have allowed for more ...efficient and accurate diagnosis, the stethoscope has evolved in parallel to address the needs of the modern era of medicine. These advancements include sound visualization, ambient noise reduction/cancellation, Bluetooth (Bluetooth SIG Inc, Kirkland, Wash) transmission, and computer algorithm diagnostic support. However, despite these advancements, the ever-changing climate of infection prevention, especially in the wake of the COVID-19 pandemic, has led many to question the stethoscope as a vector for infectious diseases. Stethoscopes have been reported to harbor bacteria with contamination levels comparable with a physician's hand. Although disinfection is recommended, stethoscope hygiene compliance remains low. In addition, disinfectants may not be completely effective in eliminating microorganisms. Despite these risks, the growing technological integration with the stethoscope continues to make it a highly valuable tool. Rather than casting our valuable tool and symbol of medicine aside, we must create and implement an effective method of stethoscope hygiene to keep patients safe.
Critically ill patients with cancer are vulnerable to infections because of the underlying malignancy, tumor-directed therapy, immunosuppression, breaches in mucosa or skin, malnutrition, and other ...factors. Neutropenia remains the most important risk factor for infection. Infectious complications occurring in critically ill patients with cancer can affect the bloodstream, lungs, gastrointestinal tract, central nervous system, urinary tract, and the skin. Pneumonias are the leading cause of infection in patients with cancer admitted to the intensive care unit. Consideration of opportunistic pathogens in the differential diagnosis is important in patients with impaired cellular and/or humoral immunity or compromised splenic function.
Cytomegalovirus (CMV) infection remains an important cause of morbidity and mortality in allogeneic hematopoietic cell transplant (allo-HCT) recipients. CMV cell-mediated immunity (CMV-CMI) as ...determined by a peptide-based enzyme-linked immunospot (ELISPOT) CMV assay may identify patients at risk for clinically significant CMV infection (CS-CMVi).
The CS-CMVi was defined as CMV viremia and/or disease necessitating antiviral therapy. CMV-CMI was characterized as high when the intermediate-early 1 (IE-1) antigen spot counts (SPCs) were >100 (cutoff 1) or when the IE-1 and phosphoprotein 65 antigen SPCs were both >100 SPCs per 250 000 cells (cutoff 2), and a low CMV-CMI when SPCs were below these thresholds. In this prospective multicenter study, we evaluated CMV-CMI every 2 weeks from the pretransplant period until 6 months posttransplantation in 241 allo-HCT recipients with positive CMV serostatus. The primary endpoint was CS-CMVi occurring within 2 weeks of the last measurement of CMV-CMI.
CS-CMVi occurred in 70 allo-HCT recipients (29%). CMV-CMI was low in patients who experienced CS-CMVi (94%), whereas those who had a high CMV-CMI were less likely to have CS-CMVi (P < .0001). Patients with CS-CMVi had higher all-cause mortality (P = .007), especially those with low CMV-CMI (P = .035). On multivariable analysis, CMV-CMI, sex, race, antithymocyte globulin, and steroid use were independent predictors of CS-CMVi, and the time from transplant to engraftment was the only predictor of mortality.
Measurement of CMV-CMI using a novel ELISPOT assay would be useful clinically to monitor allo-HCT recipients and distinguish between those at risk of developing CS-CMVi and requiring antiviral prophylaxis or therapy and those who are protected.
Osteoarticular Mycoses Gamaletsou, Maria N; Rammaert, Blandine; Brause, Barry ...
Clinical microbiology reviews,
12/2022, Volume:
35, Issue:
4
Journal Article
Peer reviewed
Open access
Osteoarticular mycoses are chronic debilitating infections that require extended courses of antifungal therapy and may warrant expert surgical intervention. As there has been no comprehensive review ...of these diseases, the International Consortium for Osteoarticular Mycoses prepared a definitive treatise for this important class of infections. Among the etiologies of osteoarticular mycoses are
spp., Aspergillus spp., Mucorales, dematiaceous fungi, non-Aspergillus hyaline molds, and endemic mycoses, including those caused by Histoplasma capsulatum, Blastomyces dermatitidis, and
species. This review analyzes the history, epidemiology, pathogenesis, clinical manifestations, diagnostic approaches, inflammatory biomarkers, diagnostic imaging modalities, treatments, and outcomes of osteomyelitis and septic arthritis caused by these organisms.
osteomyelitis and
arthritis are associated with greater events of hematogenous dissemination than those of most other osteoarticular mycoses. Traumatic inoculation is more commonly associated with osteoarticular mycoses caused by Aspergillus and non-Aspergillus molds. Synovial fluid cultures are highly sensitive in the detection of
and Aspergillus arthritis. Relapsed infection, particularly in
arthritis, may develop in relation to an inadequate duration of therapy. Overall mortality reflects survival from disseminated infection and underlying host factors.
First Case of Invasive Stachybotrys Sinusitis Semis, Margarita; Dadwal, Sanjeet S; Tegtmeier, Bernard R ...
Clinical infectious diseases,
04/2021, Volume:
72, Issue:
8
Journal Article
Peer reviewed
The toxigenic mold Stachybotrys has controversially been linked to idiopathic pulmonary hemorrhage and "sick building syndrome." However, there are no previous clinical records of invasive ...stachybotryosis.
Sinus biopsy specimens from a 23-year-old male with refractory acute lymphocytic leukemia were obtained at 3 different time points during the patient's hospitalization (139 days) and examined by histopathology and immunohistochemistry (IHC). Antifungal susceptibility testing and fungal speciation using multilocus sequence typing were performed.
Hemorrhage, fungal germination, and hyphal growth were observed in the first sinus biopsy tissues. Areas with fungal growth tested positive for Stachybotrys by IHC. Fungal isolates were genotyped and identified as Stachybotrys chlorohalonata. The patient was cured from Stachybotrys sinusitis following sinus surgery and antifungal treatment. While a subsequent second sinus biopsy and a bronchoscopy showed no signs of fungal infection, a later, third sinus biopsy tested positive for Aspergillus calidoustus, a rare human pathogen.
Here, we report the first case of invasive S. chlorohalonata sinusitis that was surgically and medically cured but followed by invasive A. calidoustus sinusitis in the setting of refractory leukemia. Our findings emphasize the risk for unusual fungal infections in severely immunocompromised patients.
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