Bench-to-bedside review: Clostridium difficile colitis

In recent years, the incidence and severity of Clostridium difficile-associated disease (CDAD) have increased dramatically. Beginning in 2000, widespread regional outbreaks associated with a previously uncommon hypervirulent strain of C. difficile have occurred in North America and Europe. Most likely because of increased toxin production as well as other virulence factors, this epidemic strain has caused more severe and refractory disease leading to complications, including intensive care unit admission, colectomies, and death. Worldwide increasing use of fluoroquinolones and cephalosporins has likely contributed to the proliferation of this epidemic strain, which is highly resistant to both. The elderly have been disproportionately affected by CDAD, but C. difficile has also recently emerged in populations previously considered to be at low risk, including healthy outpatients and peripartum women, although it is unknown if these cases are related to the epidemic strain. Nevertheless, transmission within hospitals is the major source of C. difficile acquisition, and previous or concurrent antimicrobial use is almost universal among cases. Applying current evidence-based strategies for management and prevention is critically important, and clinicians should maintain an awareness of the changing epidemiology of CDAD and take measures to reduce the risk of disease in patients

Sialic Acid Glycobiology Unveils Trypanosoma cruzi Trypomastigote Membrane Physiology.

Trypanosoma cruzi, the flagellate protozoan agent of Chagas disease or American trypanosomiasis, is unable to synthesize sialic acids de novo. Mucins and trans-sialidase (TS) are substrate and enzyme, respectively, of the glycobiological system that scavenges sialic acid from the host in a crucial interplay for T. cruzi life cycle. The acquisition of the sialyl residue allows the parasite to avoid lysis by serum factors and to interact with the host cell. A major drawback to studying the sialylation kinetics and turnover of the trypomastigote glycoconjugates is the difficulty to identify and follow the recently acquired sialyl residues. To tackle this issue, we followed an unnatural sugar approach as bioorthogonal chemical reporters, where the use of azidosialyl residues allowed identifying the acquired sugar. Advanced microscopy techniques, together with biochemical methods, were used to study the trypomastigote membrane from its glycobiological perspective. Main sialyl acceptors were identified as mucins by biochemical procedures and protein markers. Together with determining their shedding and turnover rates, we also report that several membrane proteins, including TS and its substrates, both glycosylphosphatidylinositol-anchored proteins, are separately distributed on parasite surface and contained in different and highly stable membrane microdomains. Notably, labeling for α(1,3)Galactosyl residues only partially colocalize with sialylated mucins, indicating that two species of glycosylated mucins do exist, which are segregated at the parasite surface. Moreover, sialylated mucins were included in lipid-raft-domains, whereas TS molecules are not. The location of the surface-anchored TS resulted too far off as to be capable to sialylate mucins, a role played by the shed TS instead. Phosphatidylinositol-phospholipase-C activity is actually not present in trypomastigotes. Therefore, shedding of TS occurs via microvesicles instead of as a fully soluble form

Transmission of Yellow Fever Vaccine Virus Through Blood Transfusion and Organ Transplantation in the USA in 2021: Report of an Investigation

BACKGROUND: In 2021, four patients who had received solid organ transplants in the USA developed encephalitis beginning 2-6 weeks after transplantation from a common organ donor. We describe an investigation into the cause of encephalitis in these patients. METHODS: From Nov 7, 2021, to Feb 24, 2022, we conducted a public health investigation involving 15 agencies and medical centres in the USA. We tested various specimens (blood, cerebrospinal fluid, intraocular fluid, serum, and tissues) from the organ donor and recipients by serology, RT-PCR, immunohistochemistry, metagenomic next-generation sequencing, and host gene expression, and conducted a traceback of blood transfusions received by the organ donor. FINDINGS: We identified one read from yellow fever virus in cerebrospinal fluid from the recipient of a kidney using metagenomic next-generation sequencing. Recent infection with yellow fever virus was confirmed in all four organ recipients by identification of yellow fever virus RNA consistent with the 17D vaccine strain in brain tissue from one recipient and seroconversion after transplantation in three recipients. Two patients recovered and two patients had no neurological recovery and died. 3 days before organ procurement, the organ donor received a blood transfusion from a donor who had received a yellow fever vaccine 6 days before blood donation. INTERPRETATION: This investigation substantiates the use of metagenomic next-generation sequencing for the broad-based detection of rare or unexpected pathogens. Health-care workers providing vaccinations should inform patients of the need to defer blood donation for at least 2 weeks after receiving a yellow fever vaccine. Despite mitigation strategies and safety interventions, a low risk of transfusion-transmitted infections remains. FUNDING: US Centers for Disease Control and Prevention (CDC), the Biomedical Advanced Research and Development Authority, and the CDC Epidemiology and Laboratory Capacity Cooperative Agreement for Infectious Diseases

Rates of discharges from US short-stay hospitals of patients with -associated disease listed as any diagnosis by age 22

<p><b>Copyright information:</b></p><p>Taken from "Bench-to-bedside review:colitis"</p><p>http://ccforum.com/content/12/1/203</p><p>Critical Care 2008;12(1):203-203.</p><p>Published online 18 Jan 2008</p><p>PMCID:PMC2374604.</p><p></p