Changing profile of encephalitis: Results of a 4-year study in France.

CONTEXT: In 2007, we performed a nationwide prospective study to assess the epidemiology of encephalitis in France. We aimed to evaluate epidemiological changes 10years later. METHODS: We performed a 4-year prospective cohort study in France (ENCEIF) from 2016 to 2019. Medical history, comorbidities, as well as clinical, biological, imaging, and demographic data were collected. For the comparison analysis, we selected similar data from adult patients enrolled in the 2007 study. We used Stata statistical software, version 15 (Stata Corp). Indicative variable distributions were compared using Pearson's Chi2 test, and means were compared using Student's t-test for continuous variables. RESULTS: We analyzed 494 cases from 62 hospitals. A causative agent was identified in 65.7% of cases. Viruses represented 81.8% of causative agents, Herpesviridae being the most frequent (63.6%). Arboviruses accounted for 10.8%. Bacteria and parasites were responsible for respectively 14.8% and 1.2% of documented cases. Zoonotic infections represented 21% of cases. When comparing ENCEIF with the 2007 cohort (222 adults patients from 59 hospitals), a higher proportion of etiologies were obtained in 2016-2019 (66% vs. 53%). Between 2007 and 2016-2019, the proportions of Herpes simplex virus and Listeria encephalitis cases remained similar, but the proportion of tuberculosis cases decreased (P=0.0001), while tick-borne encephalitis virus (P=0.01) and VZV cases (P=0.03) increased. In the 2016-2019 study, 32 causative agents were identified, whereas only 17 were identified in the 2007 study. CONCLUSION: Our results emphasize the need to regularly perform such studies to monitor the evolution of infectious encephalitis and to adapt guidelines.

Community-acquired bacterial meningitis in adults: in-hospital prognosis, long-term disability and determinants of outcome in a multicentre prospective cohort.

OBJECTIVES: To identify factors associated with unfavourable in-hospital outcome (death or disability) in adults with community-acquired bacterial meningitis (CABM). METHODS: In a prospective multicentre cohort study (COMBAT; February 2013 to July 2015), all consecutive cases of CABM in the 69 participating centres in France were enrolled and followed up for 12 months. Factors associated with unfavourable outcome were identified by logistic regression and long-term disability was analysed. RESULTS: Among the 533 individuals enrolled, (Streptococcus pneumoniae 53.8% (280/520 isolates identified), Neisseria meningitidis 21.3% (111/520), others 24.9% (129/520)), case fatality rate was 16.9% (90/533) and unfavourable outcome occurred in 45.0% (225/500). Factors independently associated with unfavourable outcome were: age >70 years (adjusted odds ratio (aOR) 4.64; 95% CI 1.93-11.15), male gender (aOR 2.11; 95% CI 1.25-3.57), chronic renal failure (aOR 6.65; 95% CI 1.57-28.12), purpura fulminans (aOR 4.37; 95% CI 1.38-13.81), localized neurological signs (aOR 3.72; 95% CI 2.29-6.05), disseminated intravascular coagulation (aOR 3.19; 95% CI 1.16-8.79), cerebrospinal fluid (CSF) white-cell count <1500 cells/µL (aOR 2.40; 95% CI 1.42-4.03), CSF glucose concentration (0.1-2.5 g/L: aOR 1.92; 95% CI 1.01-3.67; <0.1 g/L: aOR 2.24; 95% CI 1.01-4.97), elevated CSF protein concentration (aOR 1.09; 95% CI 1.03-1.17), time interval between hospitalization and lumbar puncture >1 day (aOR 2.94; 95% CI 1.32-6.54), and S. pneumoniae meningitis (aOR 4.99; 95% CI 1.98-12.56), or meningitis other than N. meningitidis (aOR 4.54; 95% CI 1.68-12.27). At 12 months, 26.7% (74/277) had hearing loss, 32.8% (87/265) depressive symptoms, 31.0% (86/277) persistent headache, and 53.4% had a physical health-related quality of life (142/266) <25th centile of the distribution of the score in the general French population (p < 0.0001). CONCLUSIONS: The burden of CABM (death, disability, depression, impaired quality of life and hearing loss) is high. Identification of cases from the first symptoms may improve prognosis. CLINICALTRIAL: Gov identification number: NCT01730690.

Acceptance of pregnant women's vaccination against pertussis among French women and health professionals: PREVACOQ-1 and -2 studies.

OBJECTIVES: Protection of French young infants against pertussis only relies on their relatives' vaccination. The alternative is vaccination of pregnant women against pertussis (cocooning strategy), but this strategy is not yet recommended in France. We assessed the acceptance of this strategy among French postpartum women and health professionals. PATIENTS AND METHODS: We performed a multicenter survey in 2016 among postpartum women and health professionals (family physicians, obstetricians-gynecologists, midwives, and medical students) to determine the acceptance of anti-pertussis vaccination. We evaluated knowledge, perception, and attitude towards vaccination to identify factors associated with acceptance. RESULTS: Questionnaires were completed by 52% (1208/2337) of women and 40% (694/1754) of health professionals. Seventy-seven per cent of women (95% CI: 74-79) and 93% of health professionals (95% CI: 91-95) were favorable to anti-pertussis vaccination of pregnant women. Thirty-three per cent (227/687) of health professionals believed that pertussis induced life-long immunity and 20% (136/687) of them were not aware of the cocooning strategy. In multivariate analysis, factors associated with acceptance among women were younger age, higher knowledge, having received advice during pregnancy, being vaccinated against influenza, and having never refused any vaccine; among health professionals, factors associated with acceptance were belief that inactivated vaccines are obstetrically safe, regular practice of influenza vaccination in pregnant women, pertussis cocooning strategy, and never prescribing preventive homeopathy for influenza. CONCLUSION: Vaccination of pregnant women against pertussis should be well-accepted by informed mothers and health professionals. If this strategy were to be implemented in France, efforts should be made towards adequate information.

Infections Revealing Complement Deficiency in Adults: A French Nationwide Study Enrolling 41 Patients.

Complement system is a part of innate immunity, its main function is to protect human from bacterial infection. As genetic disorders, complement deficiencies are often diagnosed in pediatric population. However, complement deficiencies can also be revealed in adults but have been poorly investigated. Herein, we describe a case series of infections revealing complement deficiency in adults to study clinical spectrum and management of complement deficiencies.A nationwide retrospective study was conducted in French university and general hospitals in departments of internal medicine, infectious diseases enrolling patients older than 15 years old who had presented at least one infection leading to a complement deficiency diagnosis.Forty-one patients included between 2002 and 2015 in 19 different departments were enrolled in this study. The male-to-female ratio was 1.3 and the mean age at diagnosis was 28 ±â€Š14 (15-67) years. The main clinical feature was Neisseria meningitidis meningitis 75% (n = 31/41) often involving rare serotype: Y (n = 9) and W 135 (n = 7). The main complement deficiency observed was the common final pathway deficiency 83% (n = 34/41). Half of the cohort displayed severe sepsis or septic shock at diagnosis (n = 22/41) but no patient died. No patient had family history of complement deficiency. The mean follow-up was 1.15 ±â€Š1.95 (0.1-10) years. Half of the patients had already suffered from at least one infection before diagnosis of complement deficiency: meningitis (n = 13), pneumonia (n = 4), fulminans purpura (n = 1), or recurrent otitis (n = 1). Near one-third (n = 10/39) had received prophylactic antibiotics (cotrimoxazole or penicillin) after diagnosis of complement deficiency. The vaccination coverage rate, at the end of the follow-up, for N meningitidis, Streptococcus pneumonia, and Haemophilius influenzae were, respectively, 90% (n = 33/37), 47% (n = 17/36), and 35% (n = 14/34).This large study emphasizes that complement deficiencies can be revealed in adults by infectious episodes. Most of them were meningococcal infections revealing common final pathway deficiency. To avoid undiagnosis or late diagnosis, adult displaying first episode of N meningitidis infection should be tested for complement deficiency.

Francisella tularensis aortitis.

Francisella tularensis, the agent of tularemia, is a Gram-negative coccobacillus primarily pathogen for animals and occasionally for humans. The clinical manifestations of tularemia include pneumonia, ulceroglandular, oropharyngeal, or typhoidal disease. Rare manifestations are also described, but to our knowledge, we describe here the first case of F. tularensis aortitis in a human. Diagnosis was confirmed by the presence of F. tularensis in blood culture, by the presence of F. tularensis DNA in the aortic biopsy and by specific IgG and IgM responses against the bacteria. The outcome was favorable after surgery and specific antimicrobial therapy.

Renal dysfunction in adults during measles.

BACKGROUND: Many cases of measles in adults were notified during the epidemic in France in 2008. Studying these cases can lead to a better understanding of their potential complications, little data having been reported on renal dysfunction during measles. METHODS: A retrospective study of biologically confirmed measles cases in patients hospitalized for more than 24 hours was carried out in the Nantes Teaching Hospital, between January and December 2011. The renal function was assessed using the modification of diet in renal disease (MDRD) equation. RESULTS: Thirty-eight patients were included, 17 (45%) presented with a clearance below 90 mL/min. One patient presented with acute renal failure, with a clearance at 37 mL/min, and proteinuria at 2.8 g/L. His renal function was restored on day 2. CONCLUSION: Acute renal failure can occur during measles in adults. Serum creatinine should be systematically assessed during the initial medical evaluation.

[Syphilis in Nantes tertiary care hospital between 2000 and 2010: a case series of 36 hospitalized patients]. / La syphilis au CHU de Nantes entre 2000 et 2010 : à propos de 36 patients hospitalisés.

PURPOSE: Syphilis infection increase has been observed since the early 2000s. The medical records of patients hospitalized for syphilis at the tertiary care hospital of Nantes between 2000 and 2010 were retrospectively reviewed. METHODS: Cases were selected on the basis of serological database of the laboratory of bacteriology and extraction from the PMIS. Syphilis cases were defined by both positive TPHA and VDRL tests. RESULTS: The number of positive serology testing was increased eightfold within ten years. Among the 36 patients with syphilis hospitalized cases, 97% were male, aged 17 to 75 years. Eighteen were HIV-infected patients. Among them, 94% were homosexuals and 67% had a history of sexually transmitted infections. The mean time between symptoms and diagnosis was significantly higher in non HIV-infected patients. Clinical forms of syphilis were cutaneomucous secondary syphilis with frequent systemic symptoms for 33%, neurosyphilis, including frequent uveitis for 50%, and gummatous tertiary syphilis involving bones for one patient. Secondary syphilis cases were treated with one to three doses of benzathine penicillin G. Late syphilis and cases of neurosyphilis were treated with penicillin G or ceftriaxone. Neurosensory sequelae accounted for 39% neurosyphilis cases. CONCLUSION: This study highlights the incidence increase of syphilis cases in France, frequent poor prognosis of neurosyphilis cases, and diagnosis difficulties, particularly in non HIV-infected patients. This emphasizes the broader use of syphilis serology for compatible medical situations.

[DVT and combined oral contraceptives: update of the pluridisciplinary CNGOF-FNCGM-GEHT-SFMV group]. / Thrombose et contraception estroprogestative : mise au point du groupe de travail pluridisciplinaire CNGOF-FNCGM-GEHT-SFMV.

Thrombotic risk among combined oral contraceptives (COC) users has recently been debated following a court action initiated by a patient. Recent epidemiological data, as well as accumulating biological data underlying these data, have led French Health authorities to modify COC prescription and reimbursement modalities. A short synthesis is proposed by a multidisciplinary group of experts from four French societies (CGOF, FNCGM, GHT, and SFMV).

[Measles in the Nantes Teaching Hospital during the 2008-2009 epidemic]. / Rougeole au CHU de Nantes au cours de l'épidémie 2008-2009.

OBJECTIVE: A recent measles epidemic in France incited us to report and describe measles cases requiring hospitalization, to raise the awareness of health professionals on under-diagnosis and frequent complications of this viral disease. DESIGN: We carried out a retrospective and epidemiologic study of measles cases recorded in the Nantes Teaching Hospital between August 2008 and September 2009. All these cases where confirmed by biological diagnosis and recorded by the Teaching Hospital virological laboratory. RESULTS: Thirteen cases of measles (11 adults and two children) were recorded during the study period. Adults were young (mean age 21.4 years); the oldest was 35 years old. We noted two severe cases with viral pneumonia and hypoxemia and one case with bacterial pneumonia. Two female patients were pregnant; one delivered prematurely, in the acute phase of measles, with no complication for the newborn. Two cases occurred in the nursing staff by documented nosocomial transmission. Sixty-nine percent of the patients were not vaccinated whereas the vaccinal status was not documented for 31%. CONCLUSIONS: These cases underline the potential severity of this infection and the difficulty to diagnose measles at the early phase because of lack of awareness of medical staff. It will be necessary to reinforce prevention messages and promote measles vaccination in children as well as in young people and health workers.

[Progestogens, progesterone, coagulation and vascular tone]. / Progestatifs, progestérone, coagulation et tonus vasculaire.

Epidemiological studies suggest that estrogens may have opposite effects on vessels: estrogens used for contraception are known to increase both arterial and venous risk, while hormone replacement therapy could reduce the risk of cardiovascular disease. In both situations, estrogens are associated with progestogens. Progestogens are rarely used alone, thus the effect of progestogens on haemostasis or vessel wall is unclear. Data can be obtained from studies using progestogens alone or from studies comparing unopposed estrogens to combined estrogen-progestogen therapy. Progestogens alone have few effect on the haemostatic system. In combined therapy used for contraception, progestogens modify the effects of estrogens on haemostasis and endothelium: the overall effect, including modifications of coagulation factors and inhibitors could a prothrombogen trend, mainly for third generation progestogens. Unopposed estrogens are also rarely used for post menopausal hormone replacement therapy (HRT). Experimental studies have shown that progestogens are able to inhibit the beneficial effect of estrogens. Two mechanisms have been suggested: first, progestogens may reduce the endothelium-dependent vasodilatator action of estrogens. Another explanation concerns the neointimal proliferation leading to atherosclerosis: Estradiol are known to reduce this proliferation. Progestogens could reduce the protective effect of estrogens. These pharmacological effect of progestogens must be taken in account to interpret the negative results of HERS study that failed to demonstrate a cardiovascular benefit of estrogens plus progestin therapy in postmenopausal women.

Innate immune responses to LCMV infections: natural killer cells and cytokines.

Although much remains to be learned, the study of early responses to LCMV infections of mice has contributed to the basic understanding of the regulation of a variety of important innate immune responses. Major discoveries have included the appreciation of the levels of type 1 IFNs induced during endogenous responses to viral infections, the importance of IFN-alpha/beta for induction of NK cell cytotoxicity, and the roles for IFN-alpha/beta in regulating the expression of other innate cytokines, i.e., IL-12 and IFN-gamma produced by NK cells (Fig. 11). Taken together with the characterization of adaptive responses to LCMV, a paradigm is emerging for a possible initial to innate to adaptive response cascade during infections with viruses eliciting endogenous expression of high levels of IFN-alpha/beta. The results not only advance the understanding of endogenous responses to viral infections and how they are balanced to achieve the best possible outcome for the host, but also give insights into possible consequences of therapeutic intervention with type 1 IFNs.

Mouse type I IFN-producing cells are immature APCs with plasmacytoid morphology.

We show here that mouse interferon-alpha (IFN-alpha)-producing cells (mIPCs) are a unique subset of immature antigen-presenting cells (APCs) that secrete IFN-alpha upon stimulation with viruses. mIPCs have a plasmacytoid morphology, can be stained with an antibody to Ly6G and Ly6C (anti-Ly6G/C) and are Ly6C+B220+CD11cloCD4+; unlike other dendritic cell subsets, however, they do not express CD8alpha or CD11b. Although mIPCs undergo apoptosis in vitro, stimulation with viruses, IFN-alpha or CpG oligonucleotides enhanced their survival and T cell stimulatory activity. In vivo, mIPCs were the main producers of IFN-alpha in cytomegalovirus-infected mice, as depletion of Ly6G+/C+ cells abrogated IFN-alpha production. mIPCs produced interleukin 12 (IL-12) in response to viruses and CpG oligodeoxynucleotides, but not bacterial products. Although different pathogens can selectively engage various APC subsets for IL-12 production, IFN-alpha production is restricted to mIPCs' response to viral infection.

NK cell functions restrain T cell responses during viral infections.

NK cell functions for regulation of T cell responses were evaluated during acute viral infections. In vivo depletion studies established that the presence of NK cells in murine cytomegalovirus (MCMV)-infected immunocompetent mice negatively affected CD4 and CD8 T cell IFN-gamma expression, bromodeoxyuridine (BrdU) incorporation, and expansion. To evaluate NK cell effects, under conditions when NK cells do not control viral replication, experiments were performed using lymphocytic choriomeningitis virus (LCMV). Depletion of NK cells did not affect LCMV-elicited T cell responses in immunocompetent mice; however, the presence of NK cells did inhibit CD4 T cell IFN-gamma production, BrdU incorporation, and expansion in infected MHC class I- and CD8 T cell-deficient beta2M-/- mice. Together, the results reveal a previously unappreciated immunoregulatory role of NK cells for downstream T cell responses.

NK cells and NKT cells in innate defense against viral infections.

NK cells contribute to innate defense during certain viral infections, but the mechanisms for their regulation and delivery of antiviral effects are incompletely understood. A second NK cell population, from within T cell populations--NKT cells--has a unique potential to initiate cellular effector mechanisms, including those delivered by NK cells, provided that the antigen for their restricted TCR is induced during infection. If elicited, particular innate cytokine responses promote activation of NK cell cytotoxicity or IFN-gamma production. These responses can contribute to defense by mediating antiviral and/or immunoregulatory effects. Roles of positive or negative receptors for target cells in protection against viruses are less clear. Exciting new data indicate that, in at least one system, NK cell receptors that positively signal for activation participate in the recruitment of these cells into antiviral defense mechanisms. Other recent evidence suggests that NKT cells may be important for protection during one viral infection and may be artificially activated by delivery of antigen to promote antiviral defense. Taken together, these recent advances in the characterization of the NK and NKT cell responses are filling in the details of the complex and critical events taking place, at the earliest times after challenge, to promote resistance to viruses.