Respiratory tract outbreak modeling with case definition criteria: A proposal for a standardized clinical approach in nursing homes.

OBJECTIVES: This study aimed to monitor respiratory tract outbreaks in nursing homes (NH) by applying standardized case definition criteria, pathogen identification and estimated mortality impact. PATIENTS AND METHODS: This longitudinal, observational study described NH outbreaks with temperature (T°), upper respiratory sign, lower respiratory sign (LRS), general status deterioration, general signs, and mortality. Viral examinations allowed for analysis of developing outbreaks based on positive, negative, or no tests (Flu+/Flu-/NT-Flu). RESULTS: Forty-six influenza identification episodes (Flu+, 1067 patients), 14 Flu- (409 patients), and 18 NT-Flu (381 patients) were analyzed. Viral examinations were conducted mainly among residents with T° (84.8% [302/356]). A specific temperature pattern was observed in Flu+ outbreaks: 35.1% of infected residents with T° without LRS, 15.6% in Flu- episodes, and 17.1% vs. 29.1% in LRS without T°. A median temperature (MT) of ≥38.3 °C was observed in Flu+ outbreaks. MT analysis of the 18 NT-Flu episodes identified five outbreaks with high temperatures (MT ≥38.2 °C) and high mortality. Conversely, the 13 NT-Flu outbreaks with lower MT (<38.0 °C) were associated with lower total mortality. Similar clinical pictures led to closely comparable all-cause mortality impacts, particularly in Flu+, Flu-, and NT-Flu with MT of ≥38.2 °C. CONCLUSIONS: Validated sign/symptom monitoring highlighted some specificities of respiratory NH outbreaks and could be a complementary approach, taking into account common and atypical clinical pictures, assessing mortality and initiating virological investigations and infection control measures.

Influenza increases invasive meningococcal disease risk in temperate countries.

OBJECTIVES: Invasive meningococcal disease (IMD) is a severe bacterial infection that displays wintertime seasonality in temperate countries. Mechanisms driving seasonality are poorly understood and may include environmental conditions and/or respiratory virus infections. We evaluated the contribution of influenza and environmental conditions to IMD risk, using standardized methodology, across multiple geographical regions. METHODS: We evaluated 3276 IMD cases occurring between January 1999 and December 2011 in 11 jurisdictions in Australia, Canada, France and the United States. Effects of environmental exposures and normalized weekly influenza activity on IMD risk were evaluated using a case-crossover design. Meta-analytic methods were used to evaluate homogeneity of effects and to identify sources of between-region heterogeneity. RESULTS: After adjustment for environmental factors, elevated influenza activity at a 2-week lag was associated with increased IMD risk (adjusted odds ratio (OR) per standard deviation increase 1.29; 95% confidence interval, 1.04-1.59). This increase was homogeneous across the jurisdictions studied. By contrast, although associations between environmental exposures and IMD were identified in individual jurisdictions, none was generalizable. CONCLUSIONS: Using a self-matched design that adjusts for both coseasonality and case characteristics, we found that surges in influenza activity result in an acute increase in population-level IMD risk. This effect is seen across diverse geographic regions in North America, France and Australia. The impact of influenza infection on downstream meningococcal risk should be considered a potential benefit of influenza immunization programmes.

Influenza B burden during seasonal influenza epidemics in France.

CONTEXT: Seasonal flu outbreaks are linked to the circulation of influenza virus type A or B. Special attention has always been paid to influenza A epidemics; but recently, several studies have investigated the impact of influenza B virus epidemics, particularly as, since the 1980s, two antigenically different influenza B lineages co-circulate, raising the issue of vaccine matching. OBJECTIVES: We present the results of influenza B burden during nine influenza seasons (2003-2013) and vaccine matching of the circulating lineages. PATIENTS AND METHODS: Clinical and virological influenza surveillance data, collected by the Regional Groups for Influenza Surveillance Network in France, allows for studying the burden of influenza in the practice of the population of ambulatory care physicians. RESULTS AND CONCLUSION: Our analysis is based on 37,801 samples, of which 12,036 were virologically confirmed influenza cases (31.8%), including 3576 cases of influenza B (29.7% of influenza cases). Influenza B viruses significantly circulated during six seasons. For each season, the influenza B epidemic peaked later than the influenza A epidemic. Influenza B is very common in children of school age but also affects other age groups. Finally, more than one-third of the analyzed influenza B viruses belonged to a different lineage than the one used in the composition of the trivalent vaccine. Our results are comparable to those described in other countries.

Burden of gastroenteritis outbreaks: specific epidemiology in a cohort of institutions caring for dependent people.

BACKGROUND: In institutions caring for dependent people, viral gastroenteritis occurs frequently and is highly contagious. In elderly persons, these episodes can lead to hospitalization and occasionally death. AIM: To study the impact of gastroenteritis outbreaks (GOs) in institutions caring for dependent people. METHODS: This study was conducted on 18 sites consisting of 35 units from four different disciplines (geriatric medicine and rehabilitation, psychogeriatrics, geriatric nursing homes, and specialized care homes for adults with physical and mental disabilities). Spatio-temporal analysis of GOs was performed during six winter seasons, and clinical and viral data were analysed with regard to structural parameters (size of the sites and dining-room organization), virus epidemiology and chronology of the outbreaks and type of activities. RESULTS: A total of 98 outbreaks were recorded in the 35 units. The risk of GO was high even outside national epidemic periods. Viruses were searched for in 86 outbreaks and were identified in 96.5% (83/86) of these outbreaks: norovirus genotype GII.4 (59.0%, 49/83), other viruses (41.0%, 34/83). There were variations between surveillance periods in terms of GO frequencies and attack rates and types of viruses. Dining-room organization could be a factor in cross-infection at a site. CONCLUSION: Specific surveillance that takes into account the precise epidemiology needs to be developed in institutions caring for dependent people in order to improve infectious disease control and information for healthcare workers.

International Fusion Materials Irradiation Facility injector acceptance tests at CEA/Saclay: 140 mA/100 keV deuteron beam characterization.

In the framework of the ITER broader approach, the International Fusion Materials Irradiation Facility (IFMIF) deuteron accelerator (2 × 125 mA at 40 MeV) is an irradiation tool dedicated to high neutron flux production for future nuclear plant material studies. During the validation phase, the Linear IFMIF Prototype Accelerator (LIPAc) machine will be tested on the Rokkasho site in Japan. This demonstrator aims to produce 125 mA/9 MeV deuteron beam. Involved in the LIPAc project for several years, specialists from CEA/Saclay designed the injector based on a SILHI type ECR source operating at 2.45 GHz and a 2 solenoid low energy beam line to produce such high intensity beam. The whole injector, equipped with its dedicated diagnostics, has been then installed and tested on the Saclay site. Before shipment from Europe to Japan, acceptance tests have been performed in November 2012 with 100 keV deuteron beam and intensity as high as 140 mA in continuous and pulsed mode. In this paper, the emittance measurements done for different duty cycles and different beam intensities will be presented as well as beam species fraction analysis. Then the reinstallation in Japan and commissioning plan on site will be reported.

Factors associated with clinical and virological response in patients treated with oseltamivir or zanamivir for influenza A during the 2008-2009 winter.

Oseltamivir or zanamivir are effective in outpatients with seasonal influenza; however, factors associated with response have been incompletely described. During the 2008/2009 epidemic, in a randomized trial for influenza A-infected outpatients, clinical (time to alleviation of flu-related symptoms) and virological (rate of patients with day 2 nasal viral load <200 cgeq/µL) responses to oseltamivir or zanamivir were assessed and associated factors were determined using multivariate analysis. For oseltamivir (141 patients) and zanamivir (149 patients) median times to alleviation of symptoms were 3 and 4 days, respectively; 59% and 34% had virological response. For oseltamivir, a lower clinical response was associated with female gender (HR, 0.53; 95% CI, 0.36-0.79), baseline symptoms score >14 (HR, 0.47; 0.32-0.70), viral load ≥5 log cgeq/µL (HR, 0.63; 0.43-0.93), and initiation of antibiotics (HR, 0.30; 0.12-0.76); a lower virological response was associated with female gender (OR, 0.45; 0.21-0.96), baseline viral load ≥5 log cgeq/µL (OR, 0.40; 0.20-0.84) and days 0-2 incomplete compliance (OR, 0.31; 0.10-0.98). For zanamivir, virological response was associated with age ≥50 years (OR, 0.29; 0.10-0.85) and initiation of antibiotics at baseline (OR, 4.24; 1.07-17.50). Factors associated with lower response to neuraminidase inhibitors in outpatients appeared to be easily identifiable during routine clinical examination and, when appropriate, by nasal sampling at baseline. The unknown association between gender and response to oseltamivir was not explained by compliance.

[Clusters of respiratory tract infections and alert strategy in nursing homes]. / Cas groupés d'infections respiratoires aiguës et stratégie d'alerte en institutions de personnes âgées.

OBJECTIVE: Outbreaks of acute respiratory infections (ARI) are common in institutions for elderly people. We had for objective to investigate clusters of cases (lower respiratory tract infection and influenza-like illness [LRTI/ILI]) in order to improve and validate alert strategies in these institutions. METHODOLOGY: Prospective surveillance for LRTI/ILI was implemented in 11 institutions in Alsace, over five years. Clinical criteria were used to identify infected residents and clusters. Nasopharyngeal swabs were collected and rapid tests (Immunoassay) were performed to identify the influenza virus. RESULTS: The three week periods were analyzed if three cases or more were recorded during the first week. This analysis demonstrated an important risk of epidemic when this number of cases was reached in healthcare units. The influenza virus (10 clusters) and respiratory syncytial virus ([RSV], two clusters) were identified. CONCLUSION: The authors confirmed and emphasized the importance of adequate surveillance for clusters of respiratory tract infection cases. Early identification of an outbreak (three cases) is an important point to prevent transmission, especially during epidemic periods and if a virus is identified in the unit or institution.

Progress in the surveillance of respiratory syncytial virus (RSV) in Europe: 2001-2008.

Respiratory syncytial virus (RSV) surveillance is important to get insight into the burden of disease and epidemic pattern of RSV infection. This information is useful for healthcare resource allocation as well as the timing of preventive messages and palivizumab prophylaxis. For influenza surveillance the European Influenza Surveillance Scheme (EISS) was established in 1996, but no surveillance platform is available for RSV. To improve surveillance an RSV Task Group was established in 2003 and recommendations for RSV surveillance were developed. By 2008, progress was made for four out of six recommendations: the number of European countries testing specimens for RSV increased from six to fourteen; nose and/or throat swabs were generally used for detection of influenza and RSV; a total of 25 laboratories performed molecular testing for diagnosis and participated in a quality control assessment for RSV with an overall good performance; four of the ten countries that joined EISS in 2004 started reporting RSV detections in addition to influenza in the period 2004-8. Limited progress was achieved for standardising methods and the development of a sentinel surveillance system of representative hospitals. Improving RSV surveillance is possible by further harmonising the data collection and increased reporting of RSV.

[Immunoassay rapid test for influenza diagnosis in institutions for elderly people: a four-year surveillance with the GROG Géronto-Alsace]. / Tests rapides de surveillance (TRS) de la grippe en établissements accueillant des personnes âgées: évaluation de quatre années d'utilisation dans le cadre du réseau GROG Géronto-Alsace.

OBJECTIVE: Outbreaks of acute respiratory infections (ARI) are common in institutions for elderly people. The objective of our study was the assessment of immunoassay rapid test used for influenza diagnosis in institutions for elderly people. METHODOLOGY: Prospective surveillance for ARI was conducted in 11 institutions in Alsace over a four-year period. Clinical case definitions are used to identify the infected residents. For the identification of influenza virus, nasopharyngeal swabs are obtained and rapid tests (immunoassay) are performed. RESULTS: Influenza virus was identified with immunoassay rapid test. Then, prophylaxis according to the Conseil supérieur d'hygiène publique de France guidelines was implemented. Nevertheless, the use of the rapid test was not frequent in the individual institution and the information recorded at the GROG Géronto-Alsace level could be use to inform the institutions when it is important to perform these rapid tests. CONCLUSION: Ours findings show the value of the rapid test used in the influenza surveillance and how the networks could help to improve their uses.

[Respiratory tract infections in institutions for elderly people: the GROG Géronto-Alsace, strategy of surveillance and alert]. / Infections respiratoires aiguës dans les collectivités de personnes âgées: le GROG Géronto-Alsace, une démarche expérimentale de surveillance et d'alerte.

OBJECTIVE: Outbreaks of respiratory tract infections are common in institutions for elderly people. The objective of our study was the implementation of a network including 11 institutions to determine the frequency of such outbreaks. Using the collected data, criteria and alert levels are defined to assess the level of respiratory tract infections and develop appropriate interventions. METHODOLOGY: Prospective surveillance for respiratory tract infection was conducted in 11 institutions in Alsace for 2 years. Clinical definitions were used to identify the infected residents. For the identification of influenza virus, nasopharyngeal samples using swabs were obtained and rapid tests (immunoassay) were performed. RESULTS: During the surveillance, outbreaks were identified in institutions. The same observations occurred in all institutions at the same time. Alert levels were defined in order to characterize the outbreak period and to improve detection and control of outbreaks of respiratory tract infections. CONCLUSION: Ours findings show the importance of an adequate surveillance and networks improve the impact of such measures.

[General practice and surveillance: the example of influenza in France]. / Médecin généraliste et veille sanitaire: l'exemple de la grippe en France.

UNLABELLED: Data registration by the GROG national network (Regional Group for the Surveillance of Influenza) since 1984 has helped to identify methodological problems. The choice of sentinels and the selection of indicators depend on the analysis of actual influenza consequences. Various sentinels may be concerned: health insurance companies, private companies, schools, physicians, pharmacists. Health care organization modifies the validity of indicators. In France, for instance, home visits were an excellent indicator for early warning before 1995 but this indicator is no longer as efficient as before. The virological detection of Influenza depends on the organization of transportation (samples, results). The predictive value of cases definitions depends on the incidence of infection. The level of choice between specificity and sensibility modifies the perception of outbreaks. Sentinel participation rate influences the sample representativity. The farther this rate is from 100%, the more result validity decreases (in the same way that patients lost to follow-up compromise the validity of results in clinical trials). The publication of results can modify health expenses and behaviors. CONCLUSION: The GROG network stresses the important role that general practitioners play in health surveillance; it also raises questions in the field of mathematics, statistics, professional organization, training, education, and politics.

[Epidemiology and diagnosis of respiratory syncitial virus in adults]. / Epidémiologie et diagnostic des infections à virus respiratoire syncytial de l'adulte.

INTRODUCTION: Respiratory syncytial virus (RSV) is rarely searched for in respiratory infections in adults. This study assessed its frequency and diagnosis. METHODS: Three separate studies were conducted in adults presenting with (1) a flu-like illness, (2) a lower respiratory tract infection in the community, and (3) a severe pneumonia requiring hospitalisation. The diagnosis of RSV infection was sought by PCR in all cases, and compared to antigen detection and culture in two studies. RESULTS: RSV was identified in 20 (11.7%) of 170 influenza-vaccinated adults suffering from flu-like symptoms. In the 270 cases of non-severe lower respiratory tract illnesses in the community, viruses were identified in 86 (31.8%) cases, with RSV accounting for 13 (4.8%). In the 164 cases of acute bronchitis, a virus was detected in 64 (36.7%) of which 11 (6.3%) were RSV, 37 (21.3%) rhinovirus, 5 influenza viruses A and B, and 12 other viruses. In the 60 cases of infective exacerbations of chronic bronchitis, rhinovirus was detected in 9 (15%) and para-influenza 3 virus in 2 cases. In the 21 acute pneumonia's, 1 RSV, 1 influenza virus A and 2 rhinovirus cases were detected as well as 1 RSV, 1 parainfluenza 3 viruses and 4 rhinovirus cases in the 11 lower respiratory tract illnesses in patients with pre-existing lung disease. There were overall 19 viral and bacterial associated infections. Finally, in the 51 acute pneumonias hospitalised with respiratory distress syndrome, a virus was identified in 17 (33.3%) cases, including 3 (5.5%) RSV, 6 influenza A, 3 rhinovirus, 2 adenovirus, 2 herpes simplex virus and 1 cytomegalovirus. There were 6 bacterial-associated infections, and 4 were hospital-acquired. All RSV-infected patients were old people and had chronic pulmonary or cardiac disease. CONCLUSIONS: In adults, RSV is a frequent cause of flu-like symptoms. It can sometimes cause lower respiratory tract illness, which can be severe, and should be considered in the differential diagnosis in such cases. The PCR method is a particularly effective diagnostic test, but as yet is not routinely available.

Heterogeneous case definitions used for the surveillance of influenza in Europe.

We reviewed the case definitions used by 21 influenza sentinel-based surveillance networks in Western Europe. Two clinical syndromes were used with a wide range of case definitions that nevertheless shared common criteria. Although there is currently no international consensus, efforts are being undertaken to standardise influenza case definitions in Europe.

Monitoring of influenza in the EISS European network member countries from October 2000 to April 2001.

In countries covered by the European Influenza Surveillance Scheme (EISS), the 2000-2001 winter was marked mainly by the spread of influenza A(H1N1) viruses. Influenza B, which globally represented a minority of cases, was common later in the season and predominant in Great Britain, Ireland, and Portugal. Influenza activity was at its maximum during the period of January and February/March 2001 with little time lag between countries (maximum four weeks). Overall, the morbidity rates reported were much lower than for the previous season, illustrating a moderate level of influenza activity.

Effectiveness of rf phase modulation for increasing bunch length in electron storage rings

Aiming at increasing the apparent bunch length and hence the beam lifetime in electron storage rings, rf phase modulation near one parametric resonance has been experimentally investigated. Since the possible benefit of this technique depends greatly on the ring parameters, we studied the effect of such a modulation for different rf parameters on the longitudinal emittance. Theoretical predictions and results of simulations are compared and discussed. It is shown that synchrotron radiation tends to spoil the parametric resonance. In particular, a criterion for island survival has been found.

Comparison of three non-nested RT-PCR for the detection of influenza A viruses.

BACKGROUND: The viral isolation technique (VIT) is largely used as a gold standard for the detection of influenza A and B viruses in respiratory samples. Some recent studies have pointed out that the polymerase chain reaction (PCR) assays allow sensitive and rapid detection of influenza viruses, also providing excellent correlation with traditional methods. OBJECTIVES AND DESIGN STUDY: The aim of this study was to evaluate the efficiency of three non-nested PCR, two PCR-hybridization assays using primers defined in M and NS genes, and one PCR which uses primers defined in NP, NS and HA genes and combines the detection of H3N2 and H1N1 hemagglutinin genes using defined primers in NP, NS and HA genes (PCR3), in comparison with an IF assay (IFA) and viral isolation technique (VIT). The study was carried out on 244 nasal samples collected mainly by practitioners of the GROG surveillance network during winter 1998-1999 for the detection of influenza A virus. RESULTS: Overall influenza viruses were detected more frequently by PCR techniques in 157 (64.3%), 147 (60.2%), 110 (45%) cases for PCR1, PCR2, PCR3, respectively, than by VIT or IFA, in 100 (40.9%) and 74 (30.3%) cases, respectively. Taking the positive culture samples as a reference, 100 (41.8%) samples were found to be positive for influenza A, and the sensitivity of IFA, PCR 1, PCR 2 and PCR3 techniques were 70, 100, 99, and 90%, respectively as compared with viral isolation cultures. On the other hand, as 86.5% of positive samples were positive with at least two different techniques, the sensitivity, specificity, VPP and VPN of each technique were recalculated taking into account a further criterion defining a positive sample: positivity with two techniques. We observe that techniques PCR 2 and particularly PCR 1 have very good sensitivity, respectively 98.6 and 100%, far better than the traditional techniques, IFA and culture, whilst maintaining acceptable specificity: 94.1 and 86.1%, respectively. In both cases they enable 141 (57.7%) A-positive influenza samples to be detected instead of the 100 (40.9%) obtained when culture is the reference test. IFA, culture and PCR 3 are highly specific (VPP=100%), but in comparison with PCR 1 and 2 their sensitivity, respectively 51.7, 69. 9, 77.6%, and negative predictive value are unsatisfactory. PCR 1 and 2 are superior to the other techniques to a statistically highly significant degree in terms of sensitivity, but the difference between the two is not significant.