[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.

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.

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.

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.

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.

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.

Factors associated with hospital mortality in community-acquired legionellosis in France.

The aims of this study were to describe the clinical, biological and radiological features of community-acquired (CA) Legionnaires' disease (LD) and identify the predictors of mortality in hospitalised patients. Demographic data, risk factors, clinical and biological features, medical management, complications, and outcome from 540 hospitalised patients with confirmed CA LD were prospectively recorded. 8.1% of patients (44 out of 540) died. The predictors of survival after Kaplan-Meier analysis were male sex (p = 0.01), age <60 yrs (p = 0.02), general symptoms (p = 0.006), intensive care unit (ICU) stay (p<0.001), and class II-III Pneumonia Severity Index score (p = 0.004). Six predictors of death were identified by multivariate analysis: age (per 10-yr increment) (relative hazard (RH) 1.50, 95% CI 1.21-1.87), female sex (RH 2.00, 95% CI 1.08-3.69), ICU admission (RH 3.31, 95% CI 1.67-6.56), renal failure (RH 2.73, 95% CI 1.42-5.27), corticosteroid therapy (RH 2.54, 95% CI 1.04-6.20) and C-reactive protein (CRP) >500 mg · L(-1) (RH 2.14, 95% CI 1.02-4.48). Appropriate antibiotic therapy was prescribed for 70.8% (292 out of 412) of patients after admission and for 99.8% (537 out of 538) of patients after diagnosis confirmation. In conclusion, female sex, age, ICU stay, renal failure, corticosteroid treatment and increased level of CRP are significant risk factors for mortality in CA LD.

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.

[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.

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.

Assessing BCG vaccination coverage and incidence of paediatric tuberculosis following two major changes in BCG vaccination policy in France.

We report data on BCG vaccination coverage and paediatric tuberculosis (TB) incidence collected after the disappearance of the multipuncture device for BCG vaccination in January 2006 and the shift from universal to targeted vaccination in July 2007 in France.Vaccination coverage estimates in children for whom BCG is recommended allow assessing whether the recommendations are followed by doctors and/or accepted by the target population. In January and February 2006, BCG sales to the private sector in Îlede-France region were 74.2% and 41.3% of the ones for the same months the previous year. Total sales in 2006 amounted to 57.3% of those in 2005. Coverage decreased immediately after withdrawal of the multipuncture device, and remained generally insufficient in high risk children in the following years. However,the impact on paediatric TB incidence in 2008 seems very limited, although the duration of follow-up is still short. Training of doctors in intra-dermal vaccination and communication on the new vaccination policy should be strengthened

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.

Burden of infant bronchiolitis: data from a hospital network.

In France, surveillance of bronchiolitis is based on a pilot network of hospital emergency departments. The study was a 1-year observational study (2007-2008) carried out in a central region of metropolitan France. The hospitalization rate for bronchiolitis was 17.7/1000 children aged <1 year and the estimated prevalence of bronchiolitis ranged from 17.7% to 34.4% in children aged <1 year. Such a network constitutes a valuable tool to estimate the dynamic and the burden of infant bronchiolitis.

Cluster of Legionnaires' disease associated with a public whirlpool spa, France, April-May 2010.

In May 2010, a cluster of three cases of Legionnaires' disease was identified in France. The results of the epidemiological, environmental and microbiological investigations allowed the rapid identification of a public whirlpool spa as the most probable source of contamination and the implementation of appropriate control measures. This investigation has stressed the need for good cooperation between partners and the importance of the molecular analysis of Legionella strains.

Management and treatment outcomes of tuberculous patients, eastern Paris, France, 2004.

BACKGROUND: France was one of the few European countries without a national tuberculosis (TB) treatment outcome monitoring system until 2007. OBJECTIVE: To examine TB management and treatment outcomes in the eastern Paris region, and to identify patient- and management-dependent factors affecting treatment outcome. METHODS: This retrospective study focused on all cases of microbiologically confirmed Mycobacterium tuberculosis cases diagnosed in 2004 in the eastern Paris region, one of the areas of France with the highest frequency of TB. RESULTS: Treatment outcomes of 629 identified cases (males 69.6%, median age 37 years, socio-economically disadvantaged 44%, foreign-born 78%) were as follows: treatment success 70.1% (95%CI 66.5-73.7), treatment interruption 4.9% (95%CI 3.2-6.6), loss to follow-up 15.0% (95%CI 12.2-17.8), death 5.7% (95%CI 3.9-7.9), transfers 4.3% (95%CI 3.5-5.1). Non-completion of treatment was associated with sputum smear positivity, injection drug use, non-adherence and irregular follow-up in univariate analysis, and with irregular follow-up and non-adherence in multivariate analysis. Duration of TB treatment and follow-up medical visits were not applied as recommended in more than a third of cases. CONCLUSION: The treatment success rate observed in this study (70.1%) is below the World Health Organization target of 85%, and requires the implementation and evaluation of interventions to increase treatment success rates.

[Tuberculosis in France: new challenges for practitioners]. / Tuberculose en France : nouveaux enjeux pour le praticien en 2008.

The need for a national tuberculosis control program was based on disparities of incidence by geographical area or by population group, and differences in tuberculosis control practice. This program was developed within the context of the 2004 public health act that prioritised tuberculosis control with the objective "to stabilise the tuberculosis incidence by reinforcing control strategies in groups and zones at risk". The tuberculosis control programme, launched in July 2007, aims to consolidate the decrease of the tuberculosis incidence and to reduce the inequalities. This implies, in particular, reaching the most exposed populations, to ensure an adequate management of cases with a good treatment observance. This also implies preventing transmission in health care settings, and maintaining the low level of multiresistance and must be done despite the loss of expertise due to a decrease in incidence. The six major objectives of the tuberculosis control program are to ensure an early diagnosis and an adequate treatment for all tuberculosis cases, to improve screening, to optimise the BCG policy, to maintain antituberculosis resistance at a low level, to improve the epidemiological surveillance and the knowledge of the determinants of tuberculosis and to improve the management of tuberculosis control activities.

[Follow-up with the assistance of TB-info software of 208 tuberculosis patients who were treated in 2004]. / Intérêt de l'utilisation du logiciel TB-info pour le suivi des patients mis sous traitement antituberculeux: analyse des 208 patients de la cohorte 2004.

INTRODUCTION: The impact of the TB-info software was assessed on the care of patients treated with antituberculosis regimen (ATT). METHODS: Cohort study of patients with tuberculosis who received an ATT in 2004 in two hospitals and five medical centres in Paris. Follow-up was implemented with the TB-info software. Data were compared to those of the 1999-2003 cohort. RESULTS: Two hundred and nine ATT were initiated in 2004, with a mean duration of 7.2 months. Demographic and clinical data reflected this population precariousness: 79% were foreign-born, 25% lived in institutions and half of them had no or unusual health insurance. Compared to the previous cohort, viral co-infections were tested in more than 80% cases and showed association with HIV, HBV or HCV in 11, 10 and 5% of the patients, respectively. Twenty-one patients were lost for follow-up (11%) and 76% of the smear-positive pulmonary tuberculosis therapies were declared successful but only 34% were declared cured with the WHO criteria. CONCLUSION: Analysis of the data obtained with TB-info software showed an improvement of tuberculosis patients care with more co-infection tested and less lost for follow-up. These results confirm the usefulness of this software for patients care and assessment of physicians practice in France.

[Immigrants and tuberculosis: recent epidemiological data]. / Immigrants et tuberculose: données épidémiologiques récentes.

Immigrants, and especially those recently arrived in host countries, are a high-risk group for tuberculosis. In 2006 in France, nearly half of the new cases of tuberculosis were reported in this group. The incidence rate among people born abroad was about seven times higher than that observed in people born in France (38.9/10(5) vs 5.2/10(5)). The incidence was also the highest in districts with a high proportion of socioeconomically vulnerable population, such as Paris and greater Paris area. The characteristics of French born and non-French born cases differed. Patients born abroad were less likely to have pulmonary tuberculosis (68.2% vs 78.2; p<0.001) and were more likely to live in institutions (such as migrant shelters) and to harbor multiresistant tuberculosis strains. A national tuberculosis control program was launched in France in 2007, to decrease the prevalence of tuberculosis in targeted populations.

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.