Gabriel Reina

Effectiveness of the monovalent influenza A(H1N1)2009 vaccine in Navarre, Spain, 2009-2010: Cohort and case-control study

We defined a population-based cohort (596,755 subjects) in Navarre, Spain, using electronic records from physicians, to evaluate the effectiveness of the monovalent A(H1N1)2009 vaccine in preventing influenza in the 2009-2010 pandemic season. During the 9-week period of vaccine availability and circulation of the A(H1N1)2009 virus, 4608 cases of medically attended influenza-like illness (MA-ILI) were registered (46 per 1000 person-years). After adjustment for sociodemographic covariables, outpatient visits and major chronic conditions, vaccination was associated with a 32% (95% CI: 8-50%) reduction in the overall incidence of MA-ILI. In a test negative case-control analysis nested in the cohort, swabs from 633 patients were included, and 123 were confirmed for A(H1N1)2009 influenza. No confirmed case had received A(H1N1)2009 vaccine versus 9.6% of controls (p<0.001). The vaccine effectiveness in preventing laboratory-confirmed influenza was 89% (95% CI: 36-100%) after adjusting for age, health care setting, major chronic conditions and period. Pandemic vaccine was effective in preventing MA-ILI and confirmed cases of influenza A(H1N1)2009 in the 2009-2010 season.

Effectiveness of the trivalent influenza vaccine in Navarre, Spain, 2010-2011: a population-based test-negative case-control study.

BackgroundSome studies have evaluated vaccine effectiveness in preventing outpatient influenza while others have analysed its effectiveness in preventing hospitalizations. This study evaluates the effectiveness of the trivalent influenza vaccine in preventing outpatient illness and hospitalizations from laboratory-confirmed influenza in the 2010–2011 season.MethodsWe conducted a nested case–control study in the population covered by the general practitioner sentinel network for influenza surveillance in Navarre, Spain. Patients with influenza-like illness in hospitals and primary health care were swabbed for influenza testing. Influenza vaccination status and other covariates were obtained from health care databases. Using logistic regression, the vaccination status of laboratory-confirmed influenza cases was compared with that of test-negative controls, adjusting for age, sex, comorbidity, outpatient visits in the previous 12 months, health care setting, time between symptom onset and swabbing, period and A(H1N1)pdm09 vaccination. Effectiveness was calculated as (1-odds ratio)x100.ResultsThe 303 confirmed influenza cases (88% for A(H1N1)pdm09 influenza) were compared with the 286 influenza test-negative controls. The percentage of persons vaccinated against influenza was 4.3% and 15.7%, respectively (p<0.001). The adjusted estimate of effectiveness was 67% (95% CI: 24%, 86%) for all patients and 64% (95% CI: 8%, 86%) in those with an indication for vaccination (persons age 60 or older or with major chronic conditions). Having received both the 2010–2011 seasonal influenza vaccine and the 2009–2010 pandemic influenza vaccine provided 87% protection (95% CI: 30%, 98%) as compared to those not vaccinated.ConclusionThe 2010–2011 seasonal influenza vaccine had a moderate protective effect in preventing laboratory-confirmed influenza.

Vaccine effectiveness in preventing laboratory-confirmed influenza in Navarre, Spain: 2013/14 mid-season analysis.

We estimate mid-2013/14 season vaccine effectiveness (VE) of the influenza trivalent vaccine in Navarre, Spain. Influenza-like illness cases attended in hospital (n=431) and primary healthcare (n=344) were included. The overall adjusted VE in preventing laboratory-confirmed influenza was 24% (95% CI: -14 to 50). The VE was 40% (95% CI: -12 to 68) against influenza A(H1)pdm09 and 13% (95% CI: -36 to 45) against influenza A(H3). These results suggest a moderate preventive effect against influenza A(H1)pdm09 and low protection against influenza A(H3).

Using NS5B Sequencing for Hepatitis C Virus Genotyping Reveals Discordances with Commercial Platforms

We aimed to evaluate the correct assignment of HCV genotypes by three commercial methods—Trugene HCV genotyping kit (Siemens), VERSANT HCV Genotype 2.0 assay (Siemens), and Real-Time HCV genotype II (Abbott)—compared to NS5B sequencing. We studied 327 clinical samples that carried representative HCV genotypes of the most frequent geno/subtypes in Spain. After commercial genotyping, the sequencing of a 367 bp fragment in the NS5B gene was used to assign genotypes. Major discrepancies were defined, e.g. differences in the assigned genotype by one of the three methods and NS5B sequencing, including misclassification of subtypes 1a and 1b. Minor discrepancies were considered when differences at subtype levels, other than 1a and 1b, were observed. The overall discordance with the reference method was 34% for Trugene and 15% for VERSANT HCV2.0. The Abbott assay correctly identified all 1a and 1b subtypes, but did not subtype all the 2, 3, 4 and 5 (34%) genotypes. Major discordances were found in 16% of cases for Trugene HCV, and the majority were 1b- to 1a-related discordances; major discordances were found for VERSANT HCV 2.0 in 6% of cases, which were all but one 1b to 1a cases. These results indicated that the Trugene assay especially, and to a lesser extent, Versant HCV 2.0, can fail to differentiate HCV subtypes 1a and 1b, and lead to critical errors in clinical practice for correctly using directly acting antiviral agents.

Genetic diversity of influenza A(H1N1)2009 virus circulating during the season 2010–2011 in Spain

BACKGROUND Genetic diversity of influenza A(H1N1)2009 viruses has been reported since the pandemic virus emerged in April 2009. Different genetic clades have been identified and defined based on amino acid substitutions found in the haemagglutinin (HA) protein sequences. In Spain, circulating influenza viruses are monitored each season by the regional laboratories enrolled in the Spanish Influenza Surveillance System (SISS). The analysis of the HA gene sequence helps to detect the genetic diversity and viral evolution. OBJECTIVES To perform an analysis of the genetic diversity of influenza A(H1N1)2009 viruses circulating in Spain during the season 2010-2011 based on analysis of the HA sequence gene. STUDY DESIGN Phylogenetic analysis based on the HA1 subunit of the haemagglutinin gene was carried out on 220 influenza A(H1N1)2009 viruses circulating during the season 2010-2011. RESULTS Six different genetic groups were identified among circulating A(H1N1)2009 viruses, five of them were previously reported during season 2010-2011. A new group, characterized by E172K and K308E changes and a proline at position 83, was observed in 12.27% of the Spanish viruses. CONCLUSION Co-circulation of six different genetic groups of influenza A(H1N1)2009 viruses was identified in Spain during the season 2010-2011. Nevertheless, at this stage, none of the groups identified to date have resulted in significant antigenic changes according to data collected by World Health Organization Collaborating Centres for influenza surveillance.

Effectiveness of subunit influenza vaccination in the 2014-2015 season and residual effect of split vaccination in previous seasons.

BACKGROUND In Navarra, Spain, subunit vaccine was first used in the 2014-2015 season, whereas trivalent split-virion influenza vaccines had been used in previous seasons. We estimate the effectiveness of the subunit vaccine in the current season and split vaccine in the two previous seasons against laboratory-confirmed influenza in the 2014-2015 season. METHODS Patients with influenza-like illness hospitalized or attended by sentinel general practitioners were swabbed for influenza testing. The previous and current vaccine status of laboratory-confirmed cases was compared to test-negative controls. RESULTS Among 1213 patients tested, 619 (51%) were confirmed for influenza virus: 52% influenza A(H3N2), 46% influenza B, and 2% A(H1N1)pdm09. The overall effectiveness for subunit vaccination in the current season was 19% (95% confidence interval [CI]: -13 to 42), 2% (95%CI: -47 to 35) against influenza A(H3N2) and 32% (95%CI: -4 to 56) against influenza B. The effectiveness against any influenza was 67% (95%CI: 17-87) for 2012-2013 and 2013-2014 vaccination only, 42% (95%CI: -31 to 74) for 2014-2015 vaccination only, and 38% (95%CI: 8-58) for vaccination in the 2012-2013, 2013-2014 and 2014-2015 seasons. The same estimates against influenza A(H3N2) were 47% (95%CI: -60 to 82), -54% (95%CI: -274 to 37) and 28% (95%CI: -17 to 56), and against influenza B were 82% (95%CI: 19-96), 93% (95%CI: 45-99) and 43% (95%CI: 5-66), respectively. CONCLUSION These results suggest a considerable residual protection of split vaccination in previous seasons, low overall effectiveness of current season subunit vaccination, and possible interference between current subunit and previous split vaccines.

Effects of previous episodes of influenza and vaccination in preventing laboratory-confirmed influenza in Navarre, Spain, 2013/14 season

We estimated whether previous episodes of influenza and trivalent influenza vaccination prevented laboratory-confirmed influenza in Navarre, Spain, in season 2013/14. Patients with medically-attended influenza-like illness (MA-ILI) in hospitals (n = 645) and primary healthcare (n = 525) were included. We compared 589 influenza cases and 581 negative controls. MA-ILI related to a specific virus subtype in the previous five seasons was defined as a laboratory-confirmed influenza infection with the same virus subtype or MA-ILI during weeks when more than 25% of swabs were positive for this subtype. Persons with previous MA-ILI had 30% (95% confidence interval (CI): -7 to 54) lower risk of MA-ILI, and those with previous MA-ILI related to A(H1N1)pdm09 or A(H3N2) virus, had a, respectively, 63% (95% CI: 16-84) and 65% (95% CI: 13-86) lower risk of new laboratory-confirmed influenza by the same subtype. Overall adjusted vaccine effectiveness in preventing laboratory-confirmed influenza was 31% (95% CI: 5-50): 45% (95% CI: 12-65) for A(H1N1)pdm09 and 20% (95% CI: -16 to 44) for A(H3N2). While a previous influenza episode induced high protection only against the same virus subtype, influenza vaccination provided low to moderate protection against all circulating subtypes. Influenza vaccine remains the main preventive option for high-risk populations.

Influenza vaccine effectiveness in preventing inpatient and outpatient cases in a season dominated by vaccine-matched influenza B virus

Studies that have evaluated the influenza vaccine effectiveness (VE) to prevent laboratory-confirmed influenza B cases are uncommon, and few have analyzed the effect in preventing hospitalized cases. We have evaluated the influenza VE in preventing outpatient and hospitalized cases with laboratory-confirmed influenza in the 2012–2013 season, which was dominated by a vaccine-matched influenza B virus. In the population covered by the Navarra Health Service, all hospitalized patients with influenza-like illness (ILI) and all ILI patients attended by a sentinel network of general practitioners were swabbed for influenza testing, and all were included in a test-negative case-control analysis. VE was calculated as (1-odds ratio)×100. Among 744 patients tested, 382 (51%) were positive for influenza virus: 70% for influenza B, 24% for A(H1N1)pdm09, and 5% for A(H3N2). The overall estimate of VE in preventing laboratory-confirmed influenza was 63% (95% confidence interval (CI): 34 to 79), 55% (1 to 80) in outpatients and 74% (33 to 90) in hospitalized patients. The VE was 70% (41 to 85) against influenza B and 43% (−45 to 78) against influenza A. The VE against virus B was 87% (52 to 96) in hospitalized patients and 56% in outpatients (−5 to 81). Adjusted comparison of vaccination status between inpatient and outpatient cases with influenza B did not show statistically significant differences (odds ratio: 1.13; p = 0.878). These results suggest a high protective effect of the vaccine in the 2012–2013 season, with no differences found for the effect between outpatient and hospitalized cases.

Diferencias entre las ondas gripales de verano y de otoño durante la pandemia de gripe (H1N1) 2009 en Navarra

BACKGROUND Two waves of influenza (H1N1) 2009 were produced in Navarre in 2009, one in the summer and the other in the fall. We aim to compare the characteristics of the two epidemic waves. METHODS We analysed individual influenza reports, virological confirmations in the primary care sentinel network, and hospitalised cases with confirmed influenza in Navarre. We compared the summer period (week 21 to 39 in 2009) with the fall-winter period (week 40 in 2009 to 20 in 2010). RESULTS Two waves of influenza A(H1N1)2009 occurred during 2009, with peaks in July and November. In the summer (week 21 to 39) 4389 cases of influenza syndrome were reported, with young adults the most affected group (58% aged 15-44 years). The highest incidence was registered after the San Fermin fiesta (92 cases per 100,000 population in week 29), with immediate return to baseline levels. A second wave occurred in the fall, with rates up to 7 times higher (667 cases per 100,000 in week 45); they remained above the epidemic threshold for 9 weeks, with children aged 5-14 years (111 per 1000) the most affected group. In the peak of both waves the percentage of smears confirmed for influenza reached 60%. During the summer there were 66 admissions with confirmed influenza (H1N1) 2009, and 158 than in the fall. The proportion of cases requiring admission to hospital was higher in the summer (1.5%) than in fall (0.8%: p<0,0001). CONCLUSION Influenza circulation was much lower in the summer. Serious cases occurred in periods of both high and low incidence of influenza syndromes.Fundamento: La gripe (H1N1) 2009 produjo en Navarra una onda en verano y otra en otono de 2009. El objetivo de este trabajo es comparar las caracteristicas de ambas ondas epidemicas. Metodos: Analizamos la notificacion individualizada de gripe, las confirmaciones virologicas en la red centinela de atencion primaria, y los casos hospitalizados con confirmacion de gripe en Navarra y comparamos los periodos de verano (semanas 21 a 39 de 2009) y otono-invierno (semanas 40 de 2009 a 20 de 2010). Resultados: Durante 2009 hubo dos ondas de gripe A(H1N1)2009, con picos en julio y noviembre. En verano (semana 21 a 39) se notificaron 4.389 casos de sindrome gripal, siendo los mas afectados los adultos jovenes (58! entre 15 y 44 anos). La mayor incidencia se registro tras las fiestas de San Fermin (92 casos por 100.000 en la semana 29) con retorno inmediato a niveles basales. En otono se produjo una segunda onda que alcanzo tasas 7 veces mayores (667 casos por 100.000 en la semana 45) y se mantuvieron 9 semanas por encima del umbral epidemico, siendo el grupo de edad mas afectado el de ninos de 5 a 14 anos (111 por 1000). En el pico de las dos ondas el porcentaje de frotis confirmados para gripe supero el 60!. Durante el verano se produjeron 66 ingresos con confirmacion de gripe (H1N1)2009, y en otono 158. La proporcion de casos que requirieron ingresos en hospital fue mayor en verano (1,5!) que en otono (0,8!; p<0,0001).

Caracterización de la pandemia de gripe A H1N1 2009 en Navarra

Background. To describe flu activity during the 2009-2010 pandemic in Navarre and compare it to previous seasons. Methods. An analysis was made of all flu cases reported in primary care and all the virological confirmations made in patients in primary care and in hospitals of Navarre between week 21 of 2009 and week 20 of 2010. Results. Influenza A (H1N1) Virus 2009 was detected in Navarre between week 23 of 2009 and week 2 of 2010, a period when 39 medically diagnosed cases of flu syndrome per 1,000 inhabitants were registered. The epidemic threshold was surpassed in two periods, with a peak in July and a greater one in November. The greatest incidence was reached in children aged between 5 and 14 years (121 per thousand), followed by the group of under fives. There were 224 hospitalisations (36 per 100,000 inhabitants) with confirmation of Influenza A (H1N1) Virus 2009, 8% of whom required admission to intensive care units and there were four deaths (0.6 per 100,000 inhabitants). The rate of hospitalisation was greater amongst children under five (163 per 100,000 inhabitants), while the probability of referral to intensive care increased with age. Conclusion. In spite of not having a specific vaccine available until the season was very well advanced, Influenza A (H1N1)Virus 2009 produced a flu wave with similar levels to those of other seasons and its repercussion in hospitalisations and serious cases was moderate.