Determinants of Non-Vaccination against Pandemic 2009 H1N1 Influenza in Pregnant Women: A Prospective Cohort Study

International audienceBACKGROUND: In October 2009, the French government organized a national-wide, free of charge vaccination campaign against pandemic H1N1 influenza virus, especially targeting pregnant women, a high risk group for severe illness. The study objective was to evaluate pandemic flu vaccine uptake and factors associated with non-vaccination in a population of pregnant women. METHODOLOGY/PRINCIPAL FINDINGS: In a prospective cohort conducted in 3 maternity hospitals in Paris, 882 pregnant women were randomly included between October 12, 2009 and February 3, 2010, with the aim to study characteristics of pandemic influenza during pregnancy. At inclusion, socio-demographic, medical, obstetrical factors and those associated with a higher risk of flu exposition and disease-spreading were systematically collected. Pandemic flu vaccine uptake was checked until delivery. 555 (62.9%) women did not get vaccinated. Determinants associated with non-vaccination in a multivariate logistic regression were: geographic origin (Sub-Saharan African origin, adjusted Odd Ratio aOR = 5.4[2.3-12.7], North African origin, aOR = 2.5[1.3-4.7] and Asian origin, aOR = 2.1[1.7-2.6] compared to French and European origin) and socio-professional categories (farmers, craftsmen and tradesmen, aOR = 2.3[2.0-2.6], intermediate professionals, aOR = 1.3[1.0-1.6], employees and manual workers, aOR = 2.5[1.4-4.4] compared to managers and intellectual professionals). The probability of not receiving pandemic flu vaccine was lower among women vaccinated against seasonal flu in the previous 5 years (aOR = 0.6[0.4-0.8]) and among those who stopped smoking before or early during pregnancy (aOR = 0.6[0.4-0.8]). Number of children less than 18 years old living at home, work in contact with children or in healthcare area, or professional contact with the public, were not associated with a higher vaccine uptake. CONCLUSIONS/SIGNIFICANCE: In this cohort of pregnant women, vaccine coverage against pandemic 2009 A/H1N1 flu was low, particularly in immigrant women and those having a low socio-economic status. To improve its effectiveness, future vaccination campaign for pregnant women should be more specifically tailored for these populations

Cryptococcal Cell Morphology Affects Host Cell Interactions and Pathogenicity

Cryptococcus neoformans is a common life-threatening human fungal pathogen. The size of cryptococcal cells is typically 5 to 10 µm. Cell enlargement was observed in vivo, producing cells up to 100 µm. These morphological changes in cell size affected pathogenicity via reducing phagocytosis by host mononuclear cells, increasing resistance to oxidative and nitrosative stress, and correlated with reduced penetration of the central nervous system. Cell enlargement was stimulated by coinfection with strains of opposite mating type, and ste3aΔ pheromone receptor mutant strains had reduced cell enlargement. Finally, analysis of DNA content in this novel cell type revealed that these enlarged cells were polyploid, uninucleate, and produced daughter cells in vivo. These results describe a novel mechanism by which C. neoformans evades host phagocytosis to allow survival of a subset of the population at early stages of infection. Thus, morphological changes play unique and specialized roles during infection

Psychosocial Characteristics Associated with Breast Cancer Survivors’ Intimate Partners’ Needs for Information and Support After Primary Breast Cancer Treatment

This study examines which psychosocial characteristics are associated with breast cancer survivors' partners' posttreatment needs for information and support. Eighty-four partners completed measures of coping, social support, illness representations, perceived stress, self-efficacy, anxiety, depression, and marital malfunctioning. Partners in need reported higher anxiety and depression, emotional illness representations, and emotion-oriented coping than partners without needs. Moreover, partners needing information and support took a more negative view on the timeline and consequences of their spouse's posttreatment condition. Interventions aimed at enhancing partners' posttreatment adjustment should focus on partners responding emotionally as well as perceiving their spouse's condition as a chronic condition

Antimicrobial stewardship in high-risk febrile neutropenia patients

International audienceBackground: The 2011 4th European Conference on Infections in Leukemia (ECIL4) guidelines recommend antibiotics de-escalation/discontinuation in selected febrile neutropenia (FN) patients. We aimed to assess the impact of an antimicrobial stewardship (AMS) program based on these guidelines on antibiotics use and clinical outcomes in high-risk FN patients. Methods: We conducted an observational study in the hematology department of Cochin University Hospital in Paris, France. An ECIL4-based antibiotics de-escalation and discontinuation strategy was implemented jointly by the hematologists and the AMS team. The pre-intervention (January–October 2018) and post-intervention (January-October 2019) periods were compared. We retrospectively collected clinical and microbiological data. We compiled antibiotics consumptions via hospital pharmacy data and standardized them by calculating defined daily doses per 1000 patient-days. We analyzed the two-monthly antibiotic consumption using an interrupted time series method and built a composite endpoint for clinical outcomes based on transfer to the intensive care unit (ICU) and/or hospital death. Results: Overall, 273 hospital stays (164 patients) in the pre-intervention and 217 (148 patients) in the post-intervention periods were analyzed. Patients were mainly hospitalized for intensive chemotherapy for acute leukemia or autologous stem-cell transplant for myeloma. Patients were slightly younger in the pre-intervention compared to the post-intervention period (median age 60.4 vs 65.2 years, p = 0.049), but otherwise comparable. After implementation of the AMS program, glycopeptide and carbapenem use decreased by 85% (p = 0.03) and 72% (p = 0.04), respectively. After adjustment on confounders, the risk of transfer to the ICU/death decreased significantly after implementation of the AMS program (post-intervention period: odds-ratio = 0.29, 95% Confidence Interval: 0.15–0.53, p < 0.001). Conclusion: Implementation of a multidisciplinary AMS program for high-risk neutropenic patients was associated with lower carbapenem and glycopeptide use and improved clinical outcomes

CCDC 273358: Experimental Crystal Structure Determination

An entry from the Cambridge Structural Database, the world’s repository for small molecule crystal structures. The entry contains experimental data from a crystal diffraction study. The deposited dataset for this entry is freely available from the CCDC and typically includes 3D coordinates, cell parameters, space group, experimental conditions and quality measures.An entry from the Cambridge Structural Database, the world’s repository for small molecule crystal structures. The entry contains experimental data from a crystal diffraction study. The deposited dataset for this entry is freely available from the CCDC and typically includes 3D coordinates, cell parameters, space group, experimental conditions and quality measures

Hippocampal expression of a virus-derived protein impairs memory in mice

International audienceThe analysis of the biology of neurotropic viruses, notably of their interference with cellular signaling, provides a useful tool to get further insight into the role of specific pathways in the control of behavioral functions. Here, we exploited the natural property of a viral protein identified as a major effector of behavioral disorders during infection. We used the phosphoprotein (P) of Borna disease virus, which acts as a decoy substrate for protein kinase C (PKC) when expressed in neurons and disrupts synaptic plasticity. By a lentiviral-based strategy, we directed the singled-out expression of P in the dentate gyrus of the hippocampus and we examined its impact on mouse behavior. Mice expressing the P protein displayed increased anxiety and impaired long-term memory in contextual and spatial memory tasks. Interestingly, these effects were dependent on P protein phosphorylation by PKC, as expression of a mutant form of P devoid of its PKC phosphorylation sites had no effect on these behaviors. We also revealed features of behavioral impairment induced by P protein expression but that were independent of its phosphorylation by PKC. Altogether, our findings provide insight into the behavioral correlates of viral infection , as well as into the impact of virus-mediated alterations of the PKC pathway on behavioral functions. dentate gyrus | hippocampus | virus | memory | protein kinase

Clinical features and prognostic factors of listeriosis: the MONALISA national prospective cohort study

Listeriosis is a severe foodborne infection and a notifiable disease in France. We did a nationwide prospective study to characterise its clinical features and prognostic factors

Diagnosis and Treatment of Listeria monocytogenes Endophthalmitis: A Systematic Review

Purpose: Describe patient characteristics, treatment, and vision outcomes of Listeria monocytogenes endophthalmitis, an exceedingly rare form of listeriosis. Methods: L. monocytogenes endophthalmitis cases in human adults, located through Medline (32) and from disease surveillance centers (11). L. monocytogenes conjunctivitis and keratitis were excluded. Results: Most cases occurred in 2000-2015 (22/43), and almost all in Europe or North America (40/43). Patients were a median 61 years, 57% male (24/42) and half were immunosuppressed. Median days from entering care to diagnosis was 8 (IQR = 5-17). Only four were exogenous infections. L. monocytogenes was identified in 31/35 of anterior eye fluid samples (89%). Antibiotic regimens varied markedly (mostly ≥3 drugs). At diagnosis, most were blind in the affected eye (85%, 28/33), only a third regained normal vision (12/36). Older patients had poorer outcomes. Conclusions: Cases increased over time. Diagnostic delays were common and visual impairment often refractory to treatment, especially in older adults. The condition\u27s rarity and variation in treatment makes it difficult to identify optimum therapy

Diagnosis and Treatment of <i>Listeria monocytogenes</i> Endophthalmitis: A Systematic Review

<p><i>Purpose</i>: Describe patient characteristics, treatment, and vision outcomes of <i>Listeria monocytogenes</i> endophthalmitis, an exceedingly rare form of listeriosis.</p> <p><i>Methods: L. monocytogenes</i> endophthalmitis cases in human adults, located through Medline (32) and from disease surveillance centers (11). <i>L. monocytogenes</i> conjunctivitis and keratitis were excluded.</p> <p><i>Results</i>: Most cases occurred in 2000–2015 (22/43), and almost all in Europe or North America (40/43). Patients were a median 61 years, 57% male (24/42) and half were immunosuppressed. Median days from entering care to diagnosis was 8 (IQR = 5–17). Only four were exogenous infections. <i>L. monocytogenes</i> was identified in 31/35 of anterior eye fluid samples (89%). Antibiotic regimens varied markedly (mostly ≥3 drugs). At diagnosis, most were blind in the affected eye (85%, 28/33), only a third regained normal vision (12/36). Older patients had poorer outcomes.</p> <p><i>Conclusions</i>: Cases increased over time. Diagnostic delays were common and visual impairment often refractory to treatment, especially in older adults. The condition’s rarity and variation in treatment makes it difficult to identify optimum therapy.</p

Uncovering Listeria monocytogenes hypervirulence by harnessing its biodiversity

Corrigendum: Uncovering Listeria monocytogenes hypervirulence by harnessing its biodiversity. [Nat Genet. 2017]Erratum: Uncovering Listeria monocytogenes hypervirulence by harnessing its biodiversity. [Nat Genet. 2017]Comment in Biodiversity and hypervirulence of Listeria monocytogenes. [Nat Genet. 2016] Bacterial GWAS: not just gilding the lily. [Nat Rev Microbiol. 2016]International audienceMicrobial pathogenesis studies are typically performed with reference strains, thereby overlooking within-species heterogeneity in microbial virulence. Here we integrated human epidemiological and clinical data with bacterial population genomics to harness the biodiversity of the model foodborne pathogen Listeria monocytogenes and decipher the basis of its neural and placental tropisms. Taking advantage of the clonal structure of this bacterial species, we identify clones epidemiologically associated either with food or with human central nervous system (CNS) or maternal-neonatal (MN) listeriosis. The latter clones are also most prevalent in patients without immunosuppressive comorbidities. Strikingly, CNS- and MN-associated clones are hypervirulent in a humanized mouse model of listeriosis. By integrating epidemiological data and comparative genomics, we have uncovered multiple new putative virulence factors and demonstrate experimentally the contribution of the first gene cluster mediating L. monocytogenes neural and placental tropisms. This study illustrates the exceptional power in harnessing microbial biodiversity to identify clinically relevant microbial virulence attribute