[Preliminary studies on the role of mast cells in the phenotype and immune activation of type 2 inflammatory cytokine release of atopic dermatitis].

Objective: To investigate the role of mast cells in atopic dermatitis (AD) phenotype and the immune activation of type 2 inflammatory cytokine release. Methods: Nine AD skin samples were obtained from the Department of Dermatology, the Second Affiliated Hospital of Xi'an Jiaotong University, and nine healthy skin control samples were obtained from the surgical excision of excess normal skin by orthopedic surgery, the Second Affiliated Hospital of Xi'an Jiaotong University, which were subjected to toluidine blue staining and fluorescence staining to clarify the mast cell degranulation activation status of the AD skin lesions. We investigated whether MC903 could directly activate mast cells in vivo through the toe swelling and exudation assay in wild-type mice; we constructed the MC903-AD model using wild-type and KitW-sh/W-sh mast cell-deficient mice in order to investigate whether mast cells affected the phenotype, histopathology, and the level of type 2 inflammatory factors in AD mice; we extracted mouse peritoneal mast cells and the ability of MC903 to activate mast cells to release inflammatory mediators in vitro was explored by calcium imaging, tryptase and ß-aminohexokinase release assays, and MCP-1 and CXCL-2 release assays. Results: The number of degranulated mast cells in an activated state was increased in skin lesions of AD patients compared to healthy controls, with (5.40±1.14) and (2.20±0.84), respectively (P<0.001). KitW-sh/W-sh mast cell-deficient AD mice had an attenuated phenotype with ADI scores of (5.50±1.05), compared to wild-type AD mice with (10.00±0.89) (P<0.001). The release of type 2 inflammatory factors in wild-type AD mice was higher than those in KitW-sh/W-sh mast cell-deficient AD mice, with IL-4 levels of (29.50±1.87) and (15.33±1.86) pg/mg (P<0.001), IL-13 levels were (6.32±0.25) and (3.93±0.22) pg/mg (P<0.001), IL-31 levels were (9.73±0.38) and (6.89±0.27) pg/mg (P<0.001), and TSLP levels were (206.00±4.43) and (99.00±4.86) pg/mg (P<0.001), respectively. MC903 could cause mast cell activation in wild-type mice, leading to increased swelling and exudation in the toes of mice, and MC903 could activate mast cells in vitro, leading to increased degranulation and release of inflammatory factors such as MCP-1 and CXCL-2. Conclusions: The number of activated mast cells was increased in skin lesions of AD patients than in healthy controls. KitW-sh/W-sh mast cell-deficient AD mice showed significantly reduced phenotype, histopathology, and type 2 inflammatory factor levels compared with wild-type AD mice. MC903 activates mast cells in vivo and in vitro. Mast cells play a key role in AD phenotype and immune activation.

Association between transforming growth factors-ß and matrix metalloproteinases in the aqueous humor and plasma in myopic patients.

PURPOSE: To investigate the relationship between levels of transforming growth factor beta (TGF-beta), matrix metalloproteinase (MMP) and tissue inhibitors of MMP (TIMP) in the aqueous humor (AH) and plasma (PL) of myopic patients. METHODS: Aqueous humor and plasma were collected intraoperatively from 37 myopic patients with various axial lengths (AL) during ICL surgery. The concentrations of TGF-ß1, TGF-ß2, TGF-ß3, MMP-1, MMP-2, MMP-7, MMP-9, MMP-10, TIMP-1, TIMP-2, TIMP-3 and TIMP-4 were measured using Luminex xMAP Technology kits (Milliplex xMAP kits). The association between TGFß and MMP/TIMP levels were analyzed based on the Spearman's correlation test or Pearson's correlation test. RESULTS: There was a negative correlation between TGF-ß1 and MMP-1, TIMP-2, TIMP-3 and TIMP-4 in the AH, and a positive correlation between TGF-ß1 and MMP-1 in the PL. In the AH, levels of TGF-ß2 were positively correlated with levels of TIMP-3 (r=0.441; P < 0.001). In the PL, levels of TGF-ß2 also correlated positively with levels of TIMP-3 (r=0.427; P < 0.001)). CONCLUSION: The level of TGF-ß2 was the highest among TGF-ßs in the AH. A consistent positive correlation between TGF-ß2 and TIMP-3 was found both in the AH and PL, indicating that systemic levels of TGF-ß2 and MMPs/TIMPs may also play a role in myopic progression.

Evaluation of a web-based self-reporting method for monitoring international passengers returning from an area of emerging infection.

OBJECTIVES: Emerging infectious diseases are a public health issue of international concern. Identifying methods to limit their expansion is essential. We assessed the feasibility of a screening strategy in which each traveler would actively participate in the screening process after an intercontinental flight by reporting their own health status via a web-based self-administered questionnaire. PATIENTS AND METHODS: In 2015 and 2017, we invited passengers arriving at or departing from Pointe-à-Pitre international airport to answer an online health questionnaire during the four days following their arrival from or at Paris-Orly international airport. SPIRE 1 was intended for passengers arriving at Pointe-à-Pitre and was conceived as a pilot study. SPIRE 2 was an improved version of SPIRE 1 and consisted in three parts, which permitted to further assess the benefits of pre-flight request and email follow-up. Endpoints were the connection rates and response rates to online health questionnaire. RESULTS: For SPIRE 1, 4/1038 travelers (0.4%) completed the two steps of the online health questionnaire. In SPIRE 2, response rates ranged from 3/1059 (0.3%) to 19/819 (2.3%). Response rates were significantly better when passengers were approached before their flight. CONCLUSIONS: The yield of an online health questionnaire was unexpectedly low.

The French Infectious Diseases Society's readiness and response to epidemic or biological risk-the current situation following the Middle East respiratory syndrome coronavirus and Ebola virus disease alerts.

CONTEXT: In 2012, the French Infectious Diseases Society (French acronym SPILF) initiated the "Coordination of epidemic and biological risk" (SPILF-COREB - Emergences [SCE]) group to support the readiness and response of healthcare workers (HCWs) to new alerts. OBJECTIVE: To present the SCE group, its functioning, and the main support it provided for frontline HCWs. METHODS: A multidisciplinary group of heads of infectious disease departments from reference hospitals was created to build a network of clinical expertise for care, training, and research in the field of epidemic and biological risk (EBR). The network developed a set of standardized operational procedures (SOPs) to guide interventions to manage EBR-suspect patients. RESULTS: A working group created the SOP aimed at frontline HCWs taking care of patients. Priority was given to the development of a generic procedure, which was then adapted according to the current alert. Five key steps were identified and hierarchized: detecting, protecting, caring for, alerting, and referring the EBR patient. The interaction between clinicians and those responsible for the protection of the community was crucial. The SOPs validated by the SPILF and its affiliates were disseminated to a wide range of key stakeholders through various media including workshops and the SPILF's website. CONCLUSION: SPILF can easily adapt and timely mobilize the EBR expertise in case of an alert. The present work suggests that sharing and discussing this experience, initiated at the European level, can generate a new collective expertise and needs to be further developed and strengthened.

Epidemiologic characteristics associated with ST23 clones compared to ST1 and ST47 clones of Legionnaires disease cases in France.

In France, approximately 1200 cases of Legionnaires disease (LD) are reported annually, and isolates are available for approximately 20% of cases identified since 2000. All Legionella pneumophila serogroup 1 (sg1) isolates are characterized by sequence-based typing at the National Reference Centre. LD cases caused by L. pneumophila sg1 reported from 2008 through 2012 were considered for the study. Our study objective was to describe cases according to their sequence type (ST). We also constructed multivariable modified Poisson regression models to estimate the incidence rate ratio (IRR) and to identify characteristics potentially associated with ST23 clones compared to ST1 and ST47 clones. We studied 1192 patients infected by ST1 (n = 109), ST23 (n = 236), ST47 (n = 123) or other STs (n = 724). The geographic distribution of the ST23 cases across the country was significantly different compared to other ST groups. This genotype was significantly associated with the absence of corticosteroid therapy compared to ST1 (IRR = 0.56; p 0.016). Concerning exposure, the ST23 genotype was significantly less associated with hospital-acquired infections compared to ST1 (IRR = 0.32; p 0.001), but it was more associated with infections acquired in hospitals and elderly settings compared with ST47. Finally, the ST23 genotype was less frequently associated with travel than other STs. Despite the large number of cases of ST23 infection, we did not identify any characteristics specific to this ST. However, we identified independent associations between ST1 and nosocomial transmission and steroid therapy. These findings should encourage further exploration, especially in terms of environmental diffusion, strain virulence and host factors.

Impact of the BCG vaccination policy on tuberculous meningitis in children under 6 years in metropolitan France between 2000 and 2011.

In France, Bacillus Calmette­Guérin (BCG) vaccination by multipuncture device was withdrawn in 2006. In 2007, universal mandatory BCG vaccination was replaced by vaccination of high-risk children. To evaluate the impact of these changes on tuberculous meningitis (TBM) epidemiology, data on culture-positive and culture-negative (or unknown microbiological result) TBM in ≤5 years olds were collected from 2000­2011. Ten culture-positive and 17 culture-negative TBM cases were identified, with an annual incidence rate ranging from 0.16 to 0.66 cases per 10 million inhabitants. The average annual numbers of TBM cases were 2.7 and 1.8 from 2000­2005 and 2006­2011, respectively. In Ile-de-France where all children are considered at risk, the overall incidence rates were 1.14 and 0.29 per million for the two periods. In other regions where only at-risk children are vaccinated since 2007, rates were 0.30 and 0.47, respectively. None of these differences were significant. Annual incidence rates for each one year age group cohort were comparable before and after changes. Childhood TBM remains rare in France. No increase in incidence was observed after changes in BCG vaccination strategy. Ongoing surveillance should be maintained, as a slight increase in TBM in the coming years remains possible, in the context of suboptimal vaccination coverage of high-risk children.

Legionnaires' disease in France.

The aim of this review was to describe the current knowledge of Legionnaires' disease (LD) illustrated by the epidemiological situation in France in 2013. LD is a severe pneumonia commonly caused by Legionella pneumophila serogroup 1. The diagnosis is usually based on the urinary antigen test. This rapid method reduces the delay between clinical suspicion and initiation of an appropriate treatment. However, the availability of a clinical strain is important to improve knowledge of circulating bacteria, to document case clusters, and to identify the sources of contamination. The source of contamination is unknown in most cases. The main contamination sources generating aerosols are water network systems and cooling towers. Thanks to the strengthening of clinical and environmental monitoring and to several guidelines, no epidemic has been reported in France since 2006. Despite these efforts, the number of LD cases has not decreased in recent years. It is essential that applied research continue to better understand the spatial and temporal dynamics of the disease and its characteristics (impact of environmental factors, sources of exposure, strains, host, etc.). Fundamental knowledge has been greatly improved (pathogenesis, immune mechanisms, etc.). The results of this research should help define new strategies for the diagnosis, prevention, and control to decrease the number of LD cases diagnosed every year.

Epidemiology of pulmonary tuberculosis in France. Can the hospital discharge database be a reliable source of information?

OBJECTIVE: In France, tuberculosis surveillance is based on mandatory notification (MN) of cases. However, the MN does not allow the full description of cases, and underreporting limits data interpretation. Aiming at better describing the cases of tuberculosis, the hospital record database (PMSI) was analyzed. PATIENTS AND METHOD: Incident cases of active pulmonary tuberculosis identified in 2010 in France in the PMSI were included and their characteristics were compared with those of the cases identified through the MN. RESULTS: In 2010, 5158 incident cases of pulmonary tuberculosis were identified in the PMSI. The mean duration of hospitalization was higher for cases considered contagious ­ at least one positive test result on pulmonary sample ­ (22 vs 13 days, P < 0.001). Among all cases, 5% were infected by HIV. Death was reported for 4% of cases. The number of pulmonary TB cases reported in the MN was 3781 in 2010. PMSI data by sex, region of residence and month of diagnosis were similar with those of the MN but patients were older in the PMSI (52 vs 47 years, P < 0.001). Considering the PMSI as exhaustive, sensitivity of the MN was estimated at 73.3% in 2010. CONCLUSION: PMSI data were compatible with those of the MN and the estimation of the sensitivity was close to other French studies. PMSI can be considered as an interesting tool aiming at improving our knowledge about tuberculosis (TB) cases and strengthening awareness where the sensitivity of the MN is low.

Decrease in the incidence of culture-positive meningitis and cerebral tuberculomas in France from 1990 to 2007.

We evaluated the incidence rate of culture-positive central nervous system tuberculosis (CNS TB) in France in 2007 and its time trend between 1990 and 2007. We used a capture-recapture analysis by using data recorded in 2007 by the mandatory notification system and the national network of the National Reference Centre (NRC). The 2007 sensitivity of the NRC was 79·4%. The previous sensitivity for 2000 (75·6%) and that for 2007 yielded a pooled estimate of 77·4% (95% confidence interval 64·8-88·0), which was used to extrapolate the number of culture-positive CNS TB cases from those reported in four surveys (1990, 1995, 2000, 2007). The extrapolated number of culture-positive CNS TB cases fell from 90 to 35 between 1990 and 2007, and the extrapolated incidence rates fell from 1·6 to 0·55 cases/million (P < 0·001). This favourable trend should be closely monitored following the change of the BCG vaccination policy in 2007.

First cases of Middle East Respiratory Syndrome Coronavirus (MERS-CoV) infections in France, investigations and implications for the prevention of human-to-human transmission, France, May 2013.

In May 2013, Middle East Respiratory Syndrome Coronavirus (MERS-CoV) infection was diagnosed in an adult male in France with severe respiratory illness, who had travelled to the United Arab Emirates before symptom onset. Contact tracing identified a secondary case in a patient hospitalised in the same hospital room. No other cases of MERS-CoV infection were identified among the index case's 123 contacts, nor among 39 contacts of the secondary case, during the 10-day follow-up period.

Treatment outcome monitoring of pulmonary tuberculosis cases notified in France in 2009.

The proportion of patients considered to be cured is a key indicator to assess national tuberculosis (TB) control. In France, TB treatment outcome monitoring was implemented in 2007. This article presents national results on treatment outcome among patients with pulmonary TB reported in France in 2009 and explores determinants of potentially unfavourable outcome. Information on treatment outcome was reported for 63% of eligible pulmonary cases of whom 70% had a successful outcome. In a multivariate analysis, potentially unfavourable outcome (17%), compared to treatment success, was significantly associated with being male, born abroad and having lived in France for less than 10 years, being in congregate settings when treatment was initiated, or having a previous history of anti-TB treatment. Enhanced awareness of treatment outcome monitoring is essential to improve the coverage and the quality of information. Earlier diagnosis and improved management of the disease in the elderly may reduce death due to TB. The high proportion of potentially unfavourable outcomes should be further investigated as they may require additional vigilance and/or actions in term of efforts of TB control in some population groups.

Legionnaires' disease in France: sensitivity of the mandatory notification has improved over the last decade.

The notification rate of Legionnaires' disease (LD) in France was 2.4/100 000 population in 2010, varying across regions with an increasing rate from west to east. Two sources [mandatory notifications (MN) and a survey of hospital laboratories] were used in a capture-recapture study to estimate the number of LD cases and the sensitivity of the MN system at national and regional levels in 2010. The number of missed cases was estimated using Chapman's method. The estimated sensitivity of MN was 88.5% (95% CI 88.0-89.0) and ranged from 70% to 100% by region. The estimated incidence was 2.7/100 000 population. Sensitivity of the MN system improved since the previous capture-recapture estimates (10% in 1995, 33% in 1998). This study confirmed that the observed west-east gradient is not related to regional notification disparities. Ecological studies should be conducted to better understand the observed spatial variations in LD incidence.

The efficacy and safety of low-molecular-weight heparin use for cancer treatment: a meta-analysis.

BACKGROUND: Low-molecular-weight heparin (LMWH) has an anti-tumour effect in-vitro and in animal models of malignancy; however, the evidence from clinical trials is controversial. Thus, we performed a meta-analysis from the results of randomised controlled trials (RCTs) to assess LMWH efficacy and safety in cancer patients who had no venous thromboembolism (VTE). METHODS: We searched the MEDLINE, EMBASE and CENTRAL (The Cochrane Central Register of Controlled Trails) databases covering all papers published up until April 2012. Two reviewers (D. H. Che and J. Y. Cao) extracted the data independently. The inclusion criteria used were patients with cancer who had no VTE and were treated with LMWH. The outcomes of interest included the 1-year mortality rate, VTE, bleeding and major bleeding complications. The results were presented as a relative risk (RR), and the STATA 11.0 package was used for comprehensive quantitative analysis. RESULTS: A total of 11 studies with 3835 cases and 3449 controls were included. The meta-analysis showed significant differences in the rates of bleeding with an RR: 1.32 [95% confidence interval (95% CI, 1.08-1.62)] and VTE with an RR: 0.53 (95% CI, 0.42-0.67) in cancer patients when LMWH was compared with placebo or no anticoagulant. There were no significant differences in the 1-year mortality rate with an RR: 0.97 (95% CI, 0.92-1.02) and major bleeding with an RR: 1.22 (95% CI, 0.87-1.71). CONCLUSION: LMWH does not significantly reduce the 1-year mortality rate for cancer patients. Although LMWH can prevent VTE, we should consider the risk-effect ratio (in case of an increased bleeding event) when we use LMWH in the patients with cancer. Thus, further research is still needed to confirm these results.

[Increasing incidence of scabies in France, 1999-2010, and public health implications]. / La gale en France entre 1999 et 2010 : augmentation de l'incidence et implications en santé publique.

INTRODUCTION: Scabies is a contagious parasitic infestation that is benign in most cases; however, delay in diagnosis and treatment can cause numerous problems for patients and people in their vicinity, as well as a risk of secondary spread. Following numerous reports suggesting increased incidence of scabies in France, we analysed various available indicators. METHODS: We analysed spontaneous and mandatory reports submitted to public health bodies as well as sales figures for scabies treatments in France over the period between 1999 and 2010. RESULTS: Reports submitted to public health structures suggest an increase in the number of cases of scabies both within the community and in healthcare establishments. An increase was seen in regional and national sales of scabies treatments. At the national level, between 2005 and 2009, sales rose from 283 to 402 bottles per 100,000 persons per year (+10% per year) for benzyl benzoate and from 216 to 495 treatments per 100,000 persons per year (+22%) for ivermectin. Based on these data, the minimum estimated annual incidence of scabies in France is 328 cases per 100,000 persons. DISCUSSION: There is some discussion surrounding the interpretation of these data, particularly the bias associated with reporting practice and with the protocols used to treat affected subjects and those in their vicinity. However, all of the information gathered indicates a real increase in the incidence of scabies in France, as a result of which we recommend increased information for the general public, clinical practitioners and public health partners in order to ensure early diagnosis and treatment.

[Bronchiolitis among infants under 1 year of age in France: epidemiology and factors associated with mortality]. / Bronchiolite aiguë du nourrisson en France : bilan des cas hospitalisés en 2009 et facteurs de létalité

Little information is available on the characteristics of infants hospitalized for acute bronchiolitis in France. An analysis of hospital records (PMSI) was conducted at the national level to describe the cases of bronchiolitis that require hospitalization among infants under 1 year of age and the factors associated with death. The analysis of all admissions that occurred during 2009, for which the diagnosis of acute bronchiolitis was recorded in the PMSI database for infants aged less than 1 year, was performed. Cases were described according to age, sex, underlying conditions (including bronchopulmonary dysplasia, cystic fibrosis, and congenital heart disease), length of hospital stay, recurrent admissions, admission to an intensive care unit (ICU), and use of assisted ventilation. Factors associated with death during hospitalization were studied by logistic regression. The hospitalization rate was 35.8 per 1000 infants under 1 year in 2009 in France. Approximately 10% of hospitalized infants required ICU admission. Twenty-two infants died. The estimated case-fatality rate was 0.08% among hospitalized infants and 0.56% for those hospitalized in the ICU. Mortality among all infants under 1 year was 2.6/10(5) in France. Factors associated with death were bronchopulmonary dysplasia (OR=6.7, 95% CI [1.5-29.8]), hospitalization in an ICU (OR=6.46, 95% CI [2.4-17.4]), and the use of assisted ventilation (OR=6.2, 95% CI [2.2-17.1]). This study has enabled the quantification of the rate of hospitalization and mortality, and a better description of infants who need hospitalization. The results are consistent with international literature, but further prospective analysis will be needed to better describe the cases at higher risk, aiming to improve their management.

Factors associated with patient and health care system delay in the diagnosis of tuberculosis in France.

OBJECTIVE: To analyse diagnostic delay in tuberculosis (TB) patients. DESIGN: Cross-sectional study: all patients with TB notified to the French national surveillance system from April to June 2010 were interviewed face-to-face using a standardised questionnaire to assess symptom history and health-seeking trajectories. RESULTS: Of 225 patients enrolled, 172 (76.4%) had pulmonary TB, including 88 who were smear-positive. Mean delay between first symptoms and diagnosis (total delay) was 97 days (median 68, IQR 33-111), with a mean of 47 days (median 14, IQR 0-53) between first symptoms and health care contact (patient delay), and 48 days (median 25, IQR 6-67) between health care contact and diagnosis (health system delay). Factors independently associated with shortened total delay were medical insurance (OR 0.24, P = 0.014) and previous TB (OR 0.28, P = 0.049). Those associated with reduced patient delay were initial fever (OR 0.42, P = 0.03) and being followed by a general practitioner (OR 0.22, P = 0.004), while those associated with reduced health system delay were first health care contact within a hospital (OR 0.15, P < 0.001). Empirical antibiotic treatment was associated with increased health system delay (OR 4.4, P = 0.001). CONCLUSION: TB diagnostic delay needs to be reduced in France. This may be achieved through improved access to care, earlier hospital referral, and less use of empirical antibiotic treatment.

Contribution of amoebic coculture to recovery of Legionella isolates from respiratory samples: prospective analysis over a period of 32 months.

We evaluated the contribution of amoebic coculture to the recovery of Legionella spp. from 379 respiratory samples. The sensitivity of axenic culture was 42.1%. The combination of axenic culture with amoebic coculture increased the Legionella isolation rate to 47.1%. Amoebic coculture was particularly efficient in isolating Legionella spp. from respiratory samples contaminated with oropharyngeal flora.