Classification of measles breakthrough cases in an elimination setting using a comprehensive algorithm of laboratory results: why sensitive and specific IgM assays are important.

OBJECTIVE: In 2006, a measles outbreak occurred in Catalonia (Spain), six years after endemic measles was declared eliminated. This study aimed to classify 19 confirmed measles breakthrough cases (BC) using a high-performance avidity assay developed in 2010. METHODS: Serum specimens were tested by indirect IgG, indirect IgM, capture IgM enzyme immunoassay, an endpoint-titer IgG avidity assay, and a plaque reduction neutralization assay. Serology and RNA detection results were combined in an algorithm for measles confirmation and classification of breakthrough cases and analyzed with clinical and epidemiological data. RESULTS: Of 19 samples, thirteen (68%) were conclusive with the classification of BCs, and six (32%) had false-positive IgM results on an indirect-format assay; they were classified as rash and fever illness of undetermined etiology. BCs were primary vaccine failures (seven or 54%), secondary vaccine failures (four or 31%), and two (15%) could not be classified. CONCLUSIONS: In measles elimination settings, high-performing assays and a comprehensive algorithm of laboratory results (IgG, IgM, and RNA detection), including IgG avidity and PRN results when necessary, can assist in accurate laboratory confirmation and classification of suspected measles cases for surveillance. Highly specific IgM assays are required to minimize the number of false-positive results.

Hospital-acquired influenza infections detected by a surveillance system over six seasons, from 2010/2011 to 2015/2016.

BACKGROUND: In addition to outbreaks of nosocomial influenza, sporadic nosocomial influenza infections also occur but are generally not reported in the literature. This study aimed to determine the epidemiologic characteristics of cases of nosocomial influenza compared with the remaining severe cases of severe influenza in acute hospitals in Catalonia (Spain) which were identified by surveillance. METHODS: An observational case-case epidemiological study was carried out in patients aged ≥18 years from Catalan 12 hospitals between 2010 and 2016. For each laboratory-confirmed influenza case (nosocomial or not) we collected demographic, virological and clinical characteristics. We defined patients with nosocomial influenza as those admitted to a hospital for a reason other than acute respiratory infection in whom ILI symptoms developed ≥48 h after admission and influenza virus infection was confirmed using RT-PCR. Mixed-effects regression was used to estimate the crude and adjusted OR. RESULTS: One thousand seven hundred twenty-two hospitalized patients with severe laboratory-confirmed influenza virus infection were included: 96 (5.6%) were classified as nosocomial influenza and more frequently had > 14 days of hospital stay (42.7% vs. 27.7%, P < .001) and higher mortality (18.8% vs. 12.6%, P < .02). The variables associated with nosocomial influenza cases in acute-care hospital settings were chronic renal disease (aOR 2.44 95% CI 1.44-4.15) and immunodeficiency (aOR 1.79 95% CI 1.04-3.06). CONCLUSIONS: Nosocomial infections are a recurring problem associated with high rates of chronic diseases and death. These findings underline the need for adherence to infection control guidelines.

Seasonal influenza surveillance: Observational study on the 2017-2018 season with predominant B influenza virus circulation.

INTRODUCTION: Influenza is a common respiratory infectious disease affecting population worldwide yearly. The aim of this work is to describe the 2017-2018 influenza season and how it affected elderly population in Catalonia despite moderate vaccine coverage among this age group. METHODS: Influenza surveillance based on a primary care sentinel surveillance, virological indicators systematic sampling of ILI attended and severe influenza confirmed cases (SHLCI) admitted to hospital.Analysis of data by Chi-squared, ANOVA, multiple regression and negative control test or case to case for vaccine effectiveness assessment in primary care and SHLCI respectively. RESULTS: Moderate-high intensity and early onset season with predominance of influenza B virus (IVB) (63%) followed by an increase of circulation of influenza A virus (IVA). A total of 419 IV from primary care samples. Vaccine effectiveness (VE) in primary care setting was 14% (95%CI: 0-47%). 1306 severe cases (adjusted cumulative incidence 18.54/100,000 inhabitants (95%CI: 17.54-19.55)). The highest proportion of severe cases were in the >64 (65.1%) (aOR 15.70; 95%CI: 12.06-20.46; p < 0.001) followed by 45-64 yo (25.4%) (aOR 6.03; 95%CI: 4.57-7.97). VE in preventing intensive care unit (ICU) admission was 35% (95%CI: 10-54%). Final outcome death while hospitalized occurred in 175 SHLCI cases with a case fatality rate of 13.4%. CONCLUSIONS: 2017-2018 influenza season was an unusual epidemic season with an early onset, great predominance of influenza B (Yamagata strain) virus with a high hospitalization rate of severe cases among elderly stressing the need to upgrade vaccine uptake in this age group.

INTRODUCCIÓN: La gripe es una enfermedad infecciosa respiratoria común que afecta cada año a una proporción importante de la población mundial. El objetivo de este trabajo es describir la temporada de influenza 2017-2018 y cómo afectó a la población anciana en Cataluña a pesar de la cobertura moderada de vacunas en este grupo de edad. MÉTODOS: Vigilancia de la gripe basada en la vigilancia centinela de atención primaria (AP), indicadores virológicos por muestreo sistemático semanal de pacientes con síndrome gripal (SG) atendidos en AP y casos graves de gripe confirmada grave ingresados ??en el hospital.Las estadísticas utilizadas para el análisis fueron el test ANOVA, la prueba de Chi-cuadrado, el análisis de regresión múltiple y la prueba de control negativo y caso a caso para la evaluación de la efectividad de la vacuna (EV, por sus siglas en inglés) en AP y casos graves hospitalizados, respectivamente. RESULTADOS: La temporada 2017-2018 se caracterizó por presentar una intensidad moderadamente alta, con inicio temprano y de larga duración. El predominio del virus de la gripe B (VGB) (63%) seguido por un aumento de la circulación del virus de la gripe A (VGA). Un total de 419 IV de muestras de AP. La VE para prevención de la infección en casos con SG en AP fue del 14% (IC 95%: 0-47%). Se registraron 1.306 casos graves (incidencia acumulada ajustada 18,54/100.000 habitantes (IC 95%: 17,54-19,55)). La proporción más alta de casos graves fue en > 64 años (65,1%) (OR: 15,70: IC 95%: 12,06-20,46; p < 0,001) seguido del grupo de 45-64 años (25,4%) (OR: 6,03; IC 95%: 4,57-7,97). La VE en la prevención de ingreso en la UCI fue del 35% (IC 95%: 10-54%). Se registraron 175 defunciones con una tasa de letalidad del 13,4%. CONCLUSIONES: La temporada de gripe 2017-2018 fue una temporada epidémica inusual con un inicio temprano, gran predominio del VGB (cepa Yamagata) con una elevada tasa de hospitalización de casos graves en ancianos, lo que subraya la necesidad de mejorar la aceptación de la vacuna en este grupo de edad.

Effectiveness of antiviral treatment in preventing death in severe hospitalised influenza cases over six seasons.

We investigated the predictors of neuraminidase inhibitor (NAI) treatment in severe hospitalised influenza cases and the association between antiviral treatment and mortality. An observational epidemiological study was carried out in Catalonia (Spain) during 2010-2016 in patients aged ⩾18 years. Severe hospitalised cases of laboratory-confirmed influenza requiring hospitalisation were included. We collected demographic, virological and clinical characteristics. Mixed-effects logistic regression was used to estimate crude and adjusted odds ratio (aOR). We included 1727 hospitalised patients, of whom 1577 (91.3%) received NAI. Receiving NAI ⩽48 h after onset of clinical symptoms (aOR 0.37, 95% confidence interval (CI) 0.22-0.63), ⩽3 days (aOR 0.49, 95% CI 0.30-0.79) and ⩽5 days (aOR 0.50, 95% CI 0.32-0.79) was associated with a reduction in deaths. In patients admitted to the intensive care unit (ICU) (595; 34.5%), treatment ⩽48 h (aOR 0.32, 95% CI 0.14-0.74), ⩽3 days (aOR 0.44, 95% CI 0.20-0.97) and ⩽5 days (aOR 0.45, 95% CI 0.22-0.96) was associated with a reduction in deaths. Receiving treatment >5 days after onset of clinical symptoms was not associated with the reduction in deaths in hospitalised patients or those admitted to the ICU. NAI treatment of hospitalised patients with severe confirmed influenza was effective in avoiding death, mainly when administered ⩽48 h after symptom onset, but also when no more than 5 days had elapsed.

Virological surveillance of influenza and other respiratory viruses during six consecutive seasons from 2006 to 2012 in Catalonia, Spain.

Most attention is given to seasonal influenza and respiratory syncytial virus outbreaks, but the cumulative burden caused by other respiratory viruses (RV) is not widely considered. The aim of the present study is to describe the circulation of RV in the general population during six consecutive seasons from 2006 to 2012 in Catalonia, Spain. Cell culture, immunofluorescence and PCR-based assays were used for the RV laboratory-confirmation and influenza subtyping. Phylogenetic and molecular characterizations of viral haemagglutinin, partial neuraminidase and matrix 2 proteins were performed from a representative sampling of influenza viruses. A total of 6315 nasopharyngeal samples were collected, of which 64% were laboratory-confirmed, mainly as influenza A viruses and rhinoviruses. Results show the significant burden of viral aetiological agents in acute respiratory infection, particularly in the youngest cases. The study of influenza strains reveals their continuous evolution through either progressive mutations or by segment reassortments. Moreover, the predominant influenza B lineage was different from that included in the recommended vaccine in half of the studied seasons, supporting the formulation and use of a quadrivalent influenza vaccine. Regarding neuraminidase inhibitors resistance, with the exception of the 2007/08 H275Y seasonal A(H1N1) strains, no other circulating influenza strains carrying known resistance genetic markers were found. Moreover, all circulating A(H1N1)pdm09 and A(H3N2) strains finally became genetically resistant to adamantanes. A wide knowledge of the seasonality patterns of the RV in the general population is well-appreciated, but it is a challenge due to the unpredictable circulation of RV, highlighting the value of local and global RV surveillance.

Estimating influenza vaccine effectiveness in Spain using sentinel surveillance data.

We aimed to estimate influenza vaccine effectiveness (VE) against laboratory-confirmed influenza during three influenza seasons (2010/11 to 2012/2013) in Spain using surveillance data and to compare the results with data obtained by the cycEVA study, the Spanish component of the Influenza Monitoring Vaccine Effectiveness (I-MOVE) network. We used the test-negative case­control design, with data from the Spanish Influenza Sentinel Surveillance System (SISS) or from the cycEVA study. Cases were laboratory-confirmed influenza patients with the predominant influenza virus of each season, and controls were those testing negative for any influenza virus. We calculated the overall and age-specific adjusted VE. Although the number of patients recorded in the SISS was three times higher than that in the cycEVA study, the quality of information for important variables, i.e. vaccination status and laboratory results, was high in both studies. Overall, the SISS and cycEVA influenza VE estimates were largely similar during the study period. For elderly patients (> 59 years), the SISS estimates were slightly lower than those of cycEVA, and estimates for children (0­14 years) were higher using SISS in two of the three seasons studied. Enhancing the SISS by collecting the date of influenza vaccination and reducing the percentage of patients with incomplete information would optimise the system to provide reliable annual influenza VE estimates to guide influenza vaccination policies.

High incidence of norovirus GII.4 outbreaks in hospitals and nursing homes in Catalonia (Spain), 2010-2011.

A descriptive study was performed between 1 January 2010 and 31 December 2011 to estimate the incidence of norovirus outbreaks in hospitals and nursing homes in Catalonia (Spain). Epidemiological surveys were done for each outbreak. Norovirus was confirmed using RT-PCR. The incidence of outbreaks/106 person-years by centre, and the attack rate, were calculated. Statistically significant differences were calculated using odds ratio (ORs) and 95% confidence intervals (CIs). Person-to-person transmission was responsible for 81·5% (22/27) of outbreaks. The incidence in the population was 156·7 outbreaks/106 person-years. The incidence by centre was 1·3% per year and was greater in hospitals (2·6%) than in nursing homes (0·9%) (OR 3·2, 95% CI 1·5-6·9). The global attack rate in residents and staff was 34·7% (816/2348). The mortality rate was 0·25% (2/816). Genogroup GII.4 caused 66·7% of outbreaks. Norovirus GII.4 outbreaks cause significant morbidity affecting both patients and staff.

Lack of detection of Middle East respiratory syndrome coronavirus in mild and severe respiratory infections in Catalonia, northeastern Spain.

Surveillance of Middle East respiratory syndrome coronavirus (MERS-CoV) was conducted to explore the possible introduction and circulation of this novel virus in Catalonia, northeastern Spain. Five hundred and sixty-three samples from mild and severe respiratory infections collected between January 2012 and April 2013 were screened using real-time RT-PCR. All samples were negative, suggesting that MERS-CoV is not circulating silently in Catalonia.

Cases of acute gastroenteritis due to calicivirus in outbreaks: clinical differences by age and aetiological agent.

The Caliciviridae family includes norovirus and sapovirus, which both cause acute gastroenteritis (AGE). Currently, norovirus is the most common cause of AGE in all age groups in many countries. We analysed clinical differences in reported cases of acute gastroenteritis caused by caliciviruses (AGC) by age group and agent involved. We conducted a descriptive study of AGE outbreaks reported to the Public Health Agency of Catalonia (Spain) in 2010 and 2011. The odds ratios (ORs) and corresponding 95% confidence intervals (CIs) were calculated to estimate the association between clinical symptoms and age. Clinical differences between the <15 years and ≥15 years age groups were statistically significant: children more frequently presented with vomiting (OR, 3.25; 95% CI, 2.56-4.13), abdominal pain (OR, 3.27; 95% CI, 2.60-4.12), fever (OR, 1.51; 95% CI, 1.17-1.96) and nausea (OR, 1.49; 95% CI, 1.19-1.85). Comparing clinical manifestations of sapovirus and norovirus infection in children aged <15 years, cases caused by norovirus more frequently presented with vomiting and fever (p <0.001), and cases caused by sapovirus more frequently presented with diarrhoea (p 0.013). Determination of the clinical differences associated with cases in outbreaks according to the age of the majority of cases and the symptoms most frequently detected may aid decision making and guide aetiological investigations and the adoption of prevention and control measures.

Norovirus: a growing cause of gastroenteritis in catalonia (Spain)?

Infectious acute gastroenteritis (AGE) is a major health problem worldwide. Salmonella is a leading cause of AGE outbreaks, but viruses may be responsible for up to 80% of cases. We compared the frequency and characteristics of AGE out breaks in Catalonia due to norovirus and Salmonella and the changes in these outbreaks from 2000 through 2010. In 2006 through 2010, we also investigated the distribution by season, setting, and implicated food, the incidence rates of cases associated, and the hospitalization rates. Differences in proportions were estimated by Pearson's chi-square test, and the odds ratio (OR) and 95% confidence interval (CI) were calculated. In 2000 through 2010, the number of AGE outbreaks caused by Salmonella decreased and those caused by norovirus significantly increased. From 2006 onward, norovirus was the most common etiology in AGE outbreaks, but in foodborne outbreaks, Salmonella was the more common cause until 2010. The incidence rate per 10(5) inhabitants was greater for norovirus (20.81 versus 3.97, P < 0.001), and the hospitalization rate was lower for norovirus (0.84 versus 4.69, P < 0.001). Salmonella infections occurred more frequently in the warmer months, and norovirus infections were more common in the colder months, both in terms of total outbreaks (OR = 4.50; 95% CI, 2.85 to 7.11; P < 0.001) and foodborne outbreaks (OR = 4.38; 95% CI, 2.42 to 7.95; P < 0.001). Norovirus infections were less common in private homes (OR = 0.08; 95% CI, 0.04 to 0.14; P < 0.001) and more common in nursing homes (P < 0.001) and hospitals or long-term care facilities (OR = 14.09; 95% CI, 3.35 to 59.33; P < 0.001). Foods most frequently implicated in norovirus infection outbreaks were seafood (22% ; OR = 7.89; 95% CI, 2.59 to 24.3; P < 0.001), and those most common in Salmonella infection outbreaks were mayonnaise and similar items (30.2%; OR = 0.05; 95% CI, 0.01 to 0.22; P < 0.001). Foodborne outbreaks in which the vehicle was not identified were more frequent in cases of norovirus infection (OR = 4.59; 95% CI, 2.54 to 8.30; P < 0.001). Our results indicate that norovirus rather than Salmonella is the most common cause of AGE outbreaks in Catalonia. Foodborne AGE outbreaks were more commonly caused by norovirus than by Salmonella only in 2010, the last year of the study.

Clinical features of influenza disease in admitted children during the first postpandemic season and risk factors for hospitalization: a multicentre Spanish experience.

The main objectives of this study were to describe the characteristics of children with influenza infection during the postpandemic outbreak, and to compare sociodemographic and clinical data between patients who required hospitalization and those managed on an outpatient basis with a matched case-control study design. This is a multicentre paediatric study in Spain that included patients aged 6 month to 18 years in whom influenza infection was confirmed by real-time reverse transcription-polymerase chain reaction between December 2010 and March 2011. Among the 143 admitted patients, the main reason for admission was respiratory failure (123/143). In 55 there was some previously known disease. The median age was lower in patients without comorbidity (1.8 years: interquartile range 1.0-3.0 versus 5.3 years: interquartile range 1.3-10.7); p <0.01). The lag time from onset of symptoms to starting antiviral treatment was correlated with the length of hospital stay (Rho Spearman = + 0.32; p 0.01). Twenty patients required admission to the paediatric intensive care units, all due to respiratory failure. Children with chest X-ray opacities in more than one quadrant more frequently required admission to intensive care. Having a neurological disease conferred the highest risk of requiring hospitalization (OR 17.18) in a multivariate analysis. This study concludes that influenza in the paediatric population requiring hospitalization during the postpandemic season affected mainly children with neurological or pulmonary comorbidities and children of parents with a lower educational level. Most of the influenza infections caused respiratory symptoms, although neurological manifestations were also observed. Early initiation of oseltamivir was associated with a shorter length of hospital stay.

Measles antibodies and response to vaccination in children aged less than 14 months: implications for age of vaccination.

Passive immunity against measles decreases during the first months of life. The objective of this study was to determine titres of measles antibodies in children aged 9-14 months and their mothers before vaccination, and the children's response to vaccination. Blood samples were collected by capillary puncture before and 28 days after vaccination. Samples were obtained between February and June 2007 during an ongoing measles outbreak. Titres of specific measles IgG antibodies were determined by enzyme-linked immunosorbent assay. Seroconversion was defined as the presence of antibodies after vaccination in subjects without antibodies before vaccination. Maternal antibodies were present in 37·7% of all 69 children included and in 45·1% of children aged 9 months. Of the 51 children in whom a second sample was obtained, 31 (60·8%) were seronegative before vaccination and 61·3% seroconverted. Interference of maternal antibodies was 30%. Advancing the first dose of measles vaccination from 15 to 12 months is a correct strategy, given the increase in the time of susceptibility of infants to measles.

Contacts with children and young people and adult risk of suffering herpes zoster.

We carried out a matched case-control study to analyze the possible association between exposure to the children and the risk of suffering herpes-zoster in adulthood. Cases of herpes zoster in immunocompetent healthy patients aged ≥ 25 years seen in the dermatology department of the Sagrado Corazón Hospital in 2007-2008 were matched with four controls. Data were analyzed using conditional logistic regression. 153 cases and 604 matched controls were included. Contacts with children were significantly associated with a reduction in the risk of suffering herpes zoster in adulthood (adjusted OR 0.56 [0.37-0.85]). Herpes-zoster vaccination in immunocompetent people aged ≥ 50 years could counteract the possible negative effects of mass varicella vaccination in childhood on the epidemiology of herpes zoster in adults.

Hepatitis A outbreaks: the effect of a mass vaccination programme.

A Hepatitis A vaccination programme of people belonging to risk groups begun in Catalonia in 1995 and a universal vaccination programme of pre-adolescents 12 years of age with the hepatitis A + B vaccine was added in 1998. The aim of the study was to investigate the characteristics of hepatitis A outbreaks occurring in Catalonia between 1991 and 2007 to determine the associated risk factors and optimize the use of vaccination. Incidence rates of outbreaks, cases and hospitalizations associated with outbreaks and the rate ratios (RR) of person-to-person transmission outbreaks between the periods before and after mass vaccination and their 95% confidence intervals (CI) were calculated. A rate of 2.45 outbreaks per million persons per year was found. The rate of cases affected in these outbreaks was 1.28 per 10(5) persons per year and the rate of hospitalizations was 0.45 per million persons per year. In person-to-person outbreaks, the highest incidence rate (5.26 and 6.33 per million persons per year) of outbreaks according to the age of the index case was in the 5 to 14 year age group in both periods (RR:0.83; 95% CI:0.48-1.43). A significant increase was observed in the 25 to 44 year age group (RR: 0.35; 95% CI 0.14-0.77). Hepatitis A vaccination has made an important impact on burden and characteristics of outbreaks and could provide greater benefits to the community if the vaccine was administrated to children during their first years of life.

Utility of clinical-epidemiological profiles in outbreaks of foodborne disease, Catalonia, 2002 through 2006.

The objective of this study was to evaluate the use of clinical-epidemiological profiles for classifying non-laboratory-confirmed outbreaks of foodborne disease (FBD) in Catalonia between 2002 and 2006 and for elucidating associations among factors contributing to these outbreaks. A total of 275 nonfamily outbreaks were studied, of which 190 (69.1%) were laboratory confirmed and 85 (30.9%) were not. In 176 (92.6%) of laboratory-confirmed outbreaks and 69 (81.2%) of non-laboratory-confirmed outbreaks, information was obtained on contributing factors (P = 0.009). In 72% of non-laboratory-confirmed outbreaks, the etiology was assigned by using clinical-epidemiological profiles; thus, 93% of outbreaks eventually were associated with an etiology. In laboratory-confirmed outbreaks, poor personal hygiene was positively associated with norovirus (odds ratio [OR], 2.69; 95% confidence interval [CI], 1.47 to 4.89; P = 0.0007) and negatively associated with Salmonella and Campylobacter (OR, 0.54; 95% CI, 0.33 to 0.89; P = 0.01), and an unsafe source was positively associated with Salmonella and Campylobacter (OR, 4.07; 95% CI, 1.72 to 10.09; P = 0.001) and negatively associated with norovirus (OR, 0.14; 95% CI, 0.04 to 0.58; P = 0.001). No differences were found among contributing factors associated with outbreaks with a laboratory-confirmed etiology and those associated with outbreaks with an etiology assigned according to the clinical-epidemiological profiles. Clinical-epidemiological profiles are useful for determining what prevention and control strategies are appropriate to the agents involved in each community and for designing outbreak investigations.

Epidemiological and clinical features of norovirus gastroenteritis in outbreaks: a population-based study.

Noroviruses are the most frequent cause of acute gastroenteritis in the community. In Catalonia, it is not clear how this type of viral gastroenteritis is evolving, and the objective of this prospective population-based study was to describe the incidence and epidemiological and clinical features of outbreaks of acute gastroenteritis due to norovirus in Catalonia between October 2004 and October 2005. Incidence rates were calculated using the estimated population of Catalonia in 2005. For each outbreak, the mode of transmission, the number of persons affected, demographic variables, clinical presentation, the date and time of onset of symptoms and the duration of symptoms, physician visits and hospitalizations were collected. Sixty viral outbreaks affecting 1791 people were identified, with no distinct seasonality. The mean number of outbreaks per month was 4.6. The global incidence was 24.6 per 100 000 person-years. The incidence was higher in women (25.7 per 100 000 person-years) and in the 5-11 years (52.4 per 100 000 person-years) and > or =65 years (42.4 per 100 000 person-years) age groups. The prevalence of vomiting, abdominal pain and general malaise was higher in children and adolescents, whereas the prevalence of diarrhoea and myalgia was higher in adults. These results suggest that norovirus infection has an important public health impact in Catalonia and that prevention strategies should be designed and implemented.