Mirian Fernández-Alonso

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 Jeryl Lynn-containing vaccine in Spanish children

We evaluated the effectiveness of the Jeryl Lynn strain vaccine in a large outbreak of mumps in Navarre, Spain, 2006-2008. Each of the 241 cases of mumps occurring in children over 15 months of age born between 1998 and 2005 was compared with 5 controls individually matched by sex, birth date, district of residence and paediatrician. Vaccination history was obtained blindly from clinical records. Conditional logistic regression was used to obtain the matched odds ratios (ORs), and effectiveness was calculated as 1-OR. Some 70% of cases had received one dose of measles-mumps-rubella vaccine, and 24% had received two doses. Overall vaccine effectiveness was 72% (95% CI, 39-87%). Two doses were more effective (83%; 54-94%) than a single dose (66%; 25-85%). Among vaccinated children, risk was higher in those who had received the first dose after 36 months of age (OR=3.1; 1.2-8.4) and those who had received the second dose 3 or more years before study enrolment (OR=10.2; 1.5-70.7). Early waning of immunity in children after the second dose may contribute to reduced vaccine effectiveness for mumps prevention.

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).

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.

Parvovirus B19 acute infection and a reactivation of cytomegalovirus and herpesvirus 6 in a chronic myeloid leukemia patient during treatment with dasatinib (BMS-354825).

T lymphocyte activation is controlled by the T cell antigen receptor (TCR) in combination with additional signals triggered by accessory molecules present on the surface of the antigen-presenting cells (APC). Several studies have reported that treatment with imatinib can induce inhibition of the T-cell mediated immune response [1,2]. Imatinib inhibits T cell receptor-mediated T cell proliferation and activation in a dose-dependent manner and reduces tyrosine phosphorylation of ZAP-70 and LAT in response to activation through TCR [1]. Studies conducted in a mouse model indicate that imatinib treatment also leads to a selective inhibition of memory CTLs without affecting primary T or B cells responses [2]. Recent reports describing the development of severe viral infections such as varicella-zoster [3] and fatal hepatitis B virus reactivation in patients with CML treated with imatinib along with in vitro data suggest that the potential for immune suppression and viral reactivation in patients treated with abl and src kinase inhibitors should be considered [4]. We describe the development of a cytomegalovirus and herpes 6 virus associated with treatment with dasatinib (BMS354825) in a patient with diagnosis of CML. A 53-year-old woman was diagnosed with CML in November 2003. Treatment with imatinib was initiated at doses of 400 mg/day and further increased to 800 mg/day due to the persistence of BCR-ABL chromosome after 1 year. Treatment with imatinib was discontinued 2 years after diagnosis (September 2005) due to the development of grade III/IV cutaneous and gastrointestinal complications. In March 2006 treatment with dasatinib (BMS354825) was started at doses of 140 mg/day. One month after initiation of treatment with dasatinib, the patient was admitted to the hospital with atypical pneumonia (bilateral infiltrates in chest radiography, fever, dry cough, dyspnea and pleuritic pain). Despite extensive work-up, only three positive citomegalovirus cells were identified by the rapid viral culture (shell vial method) from peripheral blood. The patient was treated with antiviral (Ganciclovir) and antibiotic therapy (TeicoplaninMeropenem) with good response and was discharged after 15 days. In May 2006, the patient presented with a generalized cutaneous rash with positive serological test for parvovirus B19 (IgG titer 512 and IgM titer 40) and herpesvirus 6 (IgG titer 80). This pattern is compatible with an acute infection from parvovirus B19 because detectable low levels of B19 specific IgM can be found within 7 – 10 days of the exposure. We excluded the possibility to herpesvirus 6 infection because the patient had low levels of specific herpesvirus 6 IgG and a percentage of healthy adults are IgM positive at any time, making

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.

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.