Atypical strain of Toxoplasma gondii causing fatal reactivation after hematopoietic stem cell transplantion in a patient with an underlying immunological deficiency

International audienceIn immunocompromized patients, including hematopoietic stem cell transplant (HSCT) recipients, life-threatening toxoplasmosis may result from reactivation of previous infection. We report a case of severe disseminated toxoplasmosis that developed early after allogeneic HSCT for T-cell lymphoblastic leukemia/lymphoma in a 15-year-old Toxoplasma gondii-seropositive boy with Nijmegen breakage syndrome, a rare genetic DNA repair disorder associated with immunodeficiency. The donor was the patient's HLA-identical brother. Prophylaxis with cotrimoxazole was discontinued a day before the HSCT procedure. Signs of lung infection appeared as early as day 14 post-HSCT. The presence of tachyzoite-like structures on Giemsa-stained bronchoalveolar lavage (BAL) fluid smears suggested toxoplasmosis. Real-time PCR targeted at the T. gondii AF146527 gene revealed extremely high parasite burdens in both blood and BAL fluid. Although immediate introduction of specific treatment resulted in a marked reduction of the parasite load and transient clinical improvement, the patient deteriorated and died of multiple organ failure on day 39 post-HSCT. Direct genotyping of T. gondii DNA from blood and BAL fluid with the PCR-restriction fragment length polymorphism method revealed type II alleles with SAG1, SAG2, and GRA6 markers but alleles of both type I and type II with GRA7. Additional analysis with 15 microsatellite markers showed that the T. gondii DNA was atypical and genetically divergent from that of the clonal type I, II, and III strains. This is the first report of increased clinical severity of toxoplasmosis associated with an atypical strain in the setting of immunosuppression, which emphasizes the need to diagnose and monitor toxoplasmosis by quantitative molecular methods in cases of reactivation risk

Pathogenic Mouse Hepatitis Virus or Poly(I:C) Induce IL-33 in Hepatocytes in Murine Models of Hepatitis.

International audienceThe IL-33/ST2 axis is known to be involved in liver pathologies. Although, the IL-33 levels increased in sera of viral hepatitis patients in human, the cellular sources of IL-33 in viral hepatitis remained obscure. Therefore, we aimed to investigate the expression of IL-33 in murine fulminant hepatitis induced by a Toll like receptor (TLR3) viral mimetic, poly(I:C) or by pathogenic mouse hepatitis virus (L2-MHV3). The administration of poly(I:C) plus D-galactosamine (D-GalN) in mice led to acute liver injury associated with the induction of IL-33 expression in liver sinusoidal endothelial cells (LSEC) and vascular endothelial cells (VEC), while the administration of poly(I:C) alone led to hepatocyte specific IL-33 expression in addition to vascular IL-33 expression. The hepatocyte-specific IL-33 expression was down-regulated in NK-depleted poly(I:C) treated mice suggesting a partial regulation of IL-33 by NK cells. The CD1d KO (NKT deficient) mice showed hepatoprotection against poly(I:C)-induced hepatitis in association with increased number of IL-33 expressing hepatocytes in CD1d KO mice than WT controls. These results suggest that hepatocyte-specific IL-33 expression in poly(I:C) induced liver injury was partially dependent of NK cells and with limited role of NKT cells. In parallel, the L2-MHV3 infection in mice induced fulminant hepatitis associated with up-regulated IL-33 expression as well as pro-inflammatory cytokine microenvironment in liver. The LSEC and VEC expressed inducible expression of IL-33 following L2-MHV3 infection but the hepatocyte-specific IL-33 expression was only evident between 24 to 32h of post infection. In conclusion, the alarmin cytokine IL-33 was over-expressed during fulminant hepatitis in mice with LSEC, VEC and hepatocytes as potential sources of IL-33

Treatment of Community-Acquired Pneumonia in Immunocompromised Adults:A Consensus Statement Regarding Initial Strategies

Background Community-acquired pneumonia (CAP) guidelines have improved the treatment and outcomes of patients with CAP, primarily by standardization of initial empirical therapy. But current society-published guidelines exclude immunocompromised patients. Research Question There is no consensus regarding the initial treatment of immunocompromised patients with suspected CAP. Study Design and Methods This consensus document was created by a multidisciplinary panel of 45 physicians with experience in the treatment of CAP in immunocompromised patients. The Delphi survey methodology was used to reach consensus. Results The panel focused on 21 questions addressing initial management strategies. The panel achieved consensus in defining the population, site of care, likely pathogens, microbiologic workup, general principles of empirical therapy, and empirical therapy for specific pathogens. Interpretation This document offers general suggestions for the initial treatment of the immunocompromised patient who arrives at the hospital with pneumonia

Méningites bactériennes : facteurs associés au délai d’instauration d’une antibiothérapie adaptée aux urgences [Bacterial meningitis: factors related to the delay before appropriate antibiotic administration in the emergency department].

International audienceWe had for aim to check the appropriateness of our practices according to French guidelines (17th consensus conference, SPILF 2008) and to identify variables associated with the delay before appropriate measures were implemented. Our retrospective observational study (2009-2011) focused on acute bacterial meningitis (ABM) in adults. Data was collected on a standardized questionnaire from medical charts and nurse reports. We included 31 adults presenting with ABM; 29 (93.5%) received ceftriaxone or cefotaxime in the emergency department. Indications for corticosteroids and brain imaging complied with guidelines in respectively 71.0% and 83.9% of cases. The median delays (IQR) were: admission/lumbar puncture (LP), 2h43 [1h09-5h57]; admission/antimicrobials, 3h21 [1h34-5h11]. The indication of suspected ABM in the admission letter was associated with earlier LP (P=0.01), and was almost significantly associated also with faster initiation of adequate antibiotic therapy (P=0.05). Suspicion of ABM mentioned in the admission letter was associated to a better management in the emergency department

Current role of CT and whole body MRI in multiple myeloma

International audienceRadiology of bone lacunae can help differentiate between smouldering and symptomatic myeloma. CT seems to be more apt for this purpose than a standard X-ray but appropriate principles must be applied when performing and reading it. Lesions visible in an MRI above all allow myelomas to be monitored during treatment. Because of the radiation dose, whole body CT must be performed with a slice thickness of 2mm, increments of 1.5 and intensity of 40mAs. It should be read associating the reading of the axial slices with reading the mean coronal and sagittal projections of a thickness of 2cm. Whole body MRI must associate T1-weighted sagittal, STIR coronal and b-800 diffusion-weighted axial sequences. Changes in the disease correlate with changes in the diffusion, STIR and T1-weighted images interpreted together. While whole body CT has a place in clinical routine, the indication for whole body MRI still needs to be clarified and has yet to take its place in research protocols

A pilot project of expert nurses for the follow-up of complex intravenous antimicrobial treatment

International audienceOBJECTIVE: To report a pilot project of expert nurses for outpatient parenteral antimicrobial treatment (OPAT) follow-up. METHODS: Three nurses with specific training on antibiotics started a state-funded programme including: i) consultations for OPAT follow-up; ii) hotline for satellite hospitals; iii) peer training. Patients’ data were prospectively collected. A representative sample of patients and physicians was interviewed to learn about their opinion on the project. RESULTS: From December 2020 to December 2021, 118 patients (median age 66.5 years [52-75], male-to-female ratio 2.5) were enrolled, for a total of 621 consultations. Patients were mostly on OPAT for bone and joint infections (n = 76, 64 %) and cardiovascular infections (n = 16, 14 %), for a median duration of 29 days [22-57]. Eleven patients (9 %) required unplanned hospital admissions, and three experienced treatment failure. Most patients (21/22) and physicians in charge (10/10) reported a high level of satisfaction. CONCLUSIONS: Nurses may be important actors for OPAT follow-up