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.

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

BACKGROUND: Some 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. METHODS: We 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. RESULTS: The 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. CONCLUSION: The 2010-2011 seasonal influenza vaccine had a moderate protective effect in preventing laboratory-confirmed influenza.

Mortality by causes in HIV-infected adults: comparison with the general population.

BACKGROUND: We compared mortality by cause of death in HIV-infected adults in the era of combined antiretroviral therapy with mortality in the general population in the same age and sex groups. METHODS: Mortality by cause of death was analyzed for the period 1999-2006 in the cohort of persons aged 20-59 years diagnosed with HIV infection and residing in Navarre (Spain). This was compared with mortality from the same causes in the general population of the same age and sex using standardized mortality ratios (SMR). RESULTS: There were 210 deaths among 1145 persons diagnosed with HIV (29.5 per 1000 person-years). About 50% of these deaths were from AIDS. Persons diagnosed with HIV infection had exceeded all-cause mortality (SMR 14.0, 95% CI 12.2 to 16.1) and non-AIDS mortality (SMR 6.9, 5.7 to 8.5). The analysis showed excess mortality from hepatic disease (SMR 69.0, 48.1 to 78.6), drug overdose or addiction (SMR 46.0, 29.2 to 69.0), suicide (SMR 9.6, 3.8 to 19.7), cancer (SMR 3.2, 1.8 to 5.1) and cardiovascular disease (SMR 3.1, 1.3 to 6.1). Mortality in HIV-infected intravenous drug users did not change significantly between the periods 1999-2002 and 2003-2006, but it declined by 56% in non-injecting drug users (P = 0.007). CONCLUSIONS: Persons with HIV infection continue to have considerable excess mortality despite the availability of effective antiretroviral treatments. However, excess mortality in the HIV patients has declined since these treatments were introduced, especially in persons without a history of intravenous drug use.

Effectiveness of the 7-valent pneumococcal conjugate vaccine: a population-based case-control study.

BACKGROUND: The 7-valent pneumococcal conjugate vaccine (PCV7) has shown high efficacy in preventing invasive pneumococcal disease (IPD) caused by vaccine serotypes. We aimed to assess the overall effectiveness of PCV7 against IPD in Navarra, Spain. METHODS: All children aged <5 years who were diagnosed with IPD during the period 2001-2005 (n=85) and 5 control subjects per case patient (n=425), individually matched by birth date and birth hospital, were analyzed. Vaccination records were obtained from the regional immunization registry. Conditional logistic regression was used to estimate odds ratios. RESULTS: Eighteen case patients (21%) and 114 control subjects (27%) had received >or=1 dose of PCV7. PCV7 serotypes were responsible for 34 (51%) of the cases in unvaccinated children. The overall effectiveness for case prevention was 31% (odds ratio, 0.69; 95% confidence interval, 0.37-1.27). In a separate analysis, vaccination with PCV7 was 88% effective in preventing IPD due to vaccine serotypes (odds ratio, 0.12; 95% confidence interval, 0.02-0.91) and was associated with a higher risk of IPD due to nonvaccine serogroups (odds ratio, 6.16; 95% confidence interval, 1.63-23.3). CONCLUSIONS: These data reveal a higher risk of IPD caused by non-PCV7 serogroups among vaccinated children. Consequently, the overall effectiveness of PCV7 for IPD prevention may be greatly reduced.

[Invasive pneumococcal disease in children younger than 5 years in Navarra, Spain (2000-2005). Impact of the conjugate vaccine]. / Enfermedad neumocócica invasiva en la población menor de 5 años de edad de Navarra (2000-2005): impacto de la vacuna conjugada.

BACKGROUND AND OBJECTIVE: The 7-valent pneumococcal conjugate vaccine (PCV7) has been commercialized in Spain since June 2001. We aim to evaluate the impact of this vaccine in the incidence of invasive pneumococcal disease (IPD) in Navarre. POPULATION AND METHOD: The laboratories of microbiology of Navarre declare all the isolations of Streptococcus pneumoniae in samples of normally sterile corporal fluids. We analyzed the incidence of IPD in children younger than 5 years between weeks 41 of 2000 and 40 of 2005. RESULTS: The doses of PCV7 sold up to 2005 would provide a cover of 27% in children younger than 5 years, having assumed 4 dose schedules. In the 5 seasons, 103 cases of IPD were diagnosed. From the 2 first seasons (2000-2002) to the last one (2004-2005) a reduction of 69% in the incidence rate of IPD caused by vaccine serotypes was observed (from 33 to 10 cases by 100,000 children under 5 years; p = 0.003). Between those same periods the incidence of IPD caused by non-vaccine serotypes increased a 36% (from 42 to 57 by 100,000; p = 0.405). The global incidence of IPD diminished a 12% (from 77 to 67 by 100,000; p = 0.689). The percentage of cases that had received PCV7 increased until 45% in season 2004-2005 (p < 0.001). The meningitis and bacteraemic pneumonias supposed 42% of the IPD, without significant changes during the period (p = 0.442). CONCLUSIONS: Since the PCV7 was marketed the pattern of serotypes has changed, but the expected reduction in the total IPD incidence has not been achieved.

[Evaluation of the surveillance system for human immunodeficiency virus infections of Navarra, Spain, 1985-2003]. / Evaluación del sistema de información de Navarra sobre diagnósticos de infección por el VIH, 1985-2003.

BACKGROUND: Navarra has an information system of HIV diagnoses working since the beginning of the epidemic up to the present day. This study aims at describing and evaluating this system, focusing on its sensitivity. METHODS: The updated guidelines for evaluating public health surveillance systems from the CDC were used to describe the purpose and operation of the system and to analyse its attributes for the period 1985-2003. For the evaluation of the sensitivity the regional database of antiretrovirals distribution was used. RESULTS: The HIV surveillance system of Navarra is confidential and name-based, and includes all HIV-infection cases diagnosed each year. The information sources of the system are: (a) all the laboratories in the public health system that perform the western blot test, and (b) hospital discharge registries. The system covers the entire population of Navarre (584,734 inhabitants). It uses the HIV case definition proposed by the European Centre for the Epidemiological Monitoring of AIDS. The system is well-accepted by the community and by all the stakeholders, including those providing data. By the end of 2003 it included 2302 HIV cases, and 98.8% of all patients who had ever received antiretrovirals in Navarra. CONCLUSIONS: The HIV information system of Navarra is simple, useful, well-accepted and highly sensitive. The information about antiretroviral distribution was useful for this evaluation.

[Considerations on surveillance of HIV infections. The experience of Navarre (Spain)]. / Consideraciones sobre la cuantificación de las infecciones por el VIH. La experiencia de Navarra.

OBJECTIVE AND METHODS: The number and proportion of cases in the HIV registry of Navarre (Spain) that were residents of this region were quantified, according to the census and the healthcare card database. RESULTS: Of the 2,385 persons diagnosed with HIV infection to 2003, only 1,610 (67.5%) were residents of Navarre. The rate of HIV cases diagnosed among residents in Navarre was over 90 cases per million between 1994 and 1998, with values similar to those of Switzerland. In contrast with the time-trend in other European countries, the time-trend in Navarre decreased from 1994 to 2003. Since 2000 the rate of new HIV cases in Navarre has been lower than rates in Portugal, Switzerland, Luxembourg, Belgium, Ireland, and the United Kingdom. CONCLUSION: To prevent overestimation of the number of HIV infections, cases duplicated between regions should be excluded. This could be achieved by a national HIV surveillance system.

Enhanced Estimates of the Influenza Vaccination Effect in Preventing Mortality: A Prospective Cohort Study.

Mortality is a major end-point in the evaluation of influenza vaccine effectiveness. However, this effect is not well known, since most previous studies failed to show good control of biases. We aimed to estimate the effectiveness of influenza vaccination in preventing all-cause mortality in community-dwelling seniors.Since 2009, a population-based cohort study using healthcare databases has been conducted in Navarra, Spain. In 2 late influenza seasons, 2011/2012 and 2012/2013, all-cause mortality in the period January to May was compared between seniors (65 years or over) who received the trivalent influenza vaccine and those who were unvaccinated, adjusting for demographics, major chronic conditions, dependence, previous hospitalization, and pneumococcal vaccination.The cohort included 103,156 seniors in the 2011/2012 season and 105,140 in the 2012/2013 season (58% vaccinated). Seniors vaccinated in the previous season who discontinued vaccination (6% of the total) had excess mortality and were excluded to prevent frailty bias. The final analysis included 80,730 person-years and 2778 deaths. Vaccinated seniors had 16% less all-cause mortality than those unvaccinated (adjusted rate ratio [RR] = 0.84; 95% confidence interval 0.76-0.93). This association disappeared in the post-influenza period (adjusted RR = 0.96; 95% confidence interval 0.85-1.09). A similar comparison did not find an association in January to May of the 2009/2010 pandemic season (adjusted RR = 0.98; 95% confidence interval 0.84-1.14), when no effect of the seasonal vaccine was expected. On average, 1 death was prevented for every 328 seniors vaccinated: 1 for every 649 in the 65 to 74 year age group and 1 for every 251 among those aged 75 and over.These results suggest a moderate preventive effect and a high potential impact of the seasonal influenza vaccine against all-cause mortality. This reinforces the recommendation of annual influenza vaccination in seniors.

Household transmission of influenza A(H1N1)pdm09 in the pandemic and post-pandemic seasons.

BACKGROUND: The transmission of influenza viruses occurs person to person and is facilitated by contacts within enclosed environments such as households. The aim of this study was to evaluate secondary attack rates and factors associated with household transmission of laboratory-confirmed influenza A(H1N1)pdm09 in the pandemic and post-pandemic seasons. METHODS: During the 2009-2010 and 2010-2011 influenza seasons, 76 sentinel physicians in Navarra, Spain, took nasopharyngeal and pharyngeal swabs from patients diagnosed with influenza-like illness. A trained nurse telephoned households of those patients who were laboratory-confirmed for influenza A(H1N1)pdm09 to ask about the symptoms, risk factors and vaccination status of each household member. RESULTS: In the 405 households with a patient laboratory-confirmed for influenza A(H1N1)pdm09, 977 susceptible contacts were identified; 16% of them (95% CI 14-19%) presented influenza-like illness and were considered as secondary cases. The secondary attack rate was 14% in 2009-2010 and 19% in the 2010-2011 season (p=0.049), an increase that mainly affected persons with major chronic conditions. In the multivariate logistic regression analysis, the risk of being a secondary case was higher in the 2010-2011 season than in the 2009-2010 season (adjusted odds ratio: 1.72; 95% CI 1.17-2.54), and in children under 5 years, with a decreasing risk in older contacts. Influenza vaccination was associated with lesser incidence of influenza-like illness near to statistical significance (adjusted odds ratio: 0.29; 95% CI 0.08-1.03). CONCLUSION: The secondary attack rate in households was higher in the second season than in the first pandemic season. Children had a greater risk of infection. Preventive measures should be maintained in the second pandemic season, especially in high-risk persons.

Vaccine effectiveness in preventing influenza hospitalizations in Navarre, Spain, 2010-2011: cohort and case-control study.

We evaluated the 2010-2011 seasonal influenza vaccine effectiveness in preventing hospitalizations. Using healthcare databases we defined the target population for vaccination in Navarre, Spain, consisting of 217,320 people with major chronic conditions or aged 60 years and older. All hospitalized patients with influenza-like illness (ILI) were swabbed for influenza testing. A total of 269 patients with ILI were hospitalized and 61 of them were found positive for influenza virus: 58 for A(H1N1)2009 and 3 for B virus. The incidence rates of hospitalization with laboratory-confirmed influenza were compared by vaccination status. In the Cox regression model adjusted for sex, age, children in the household, urban/rural residence, comorbidity, pandemic vaccination, pneumococcal vaccination, outpatient visits and hospitalization in the previous year, the seasonal vaccine effectiveness was 58% (95% CI: 16-79%). The nested test-negative case-control analysis gave an adjusted estimate of 59% (95% CI: 4-83%). These results suggest a moderate effect of the 2010-2011 seasonal influenza vaccine in preventing hospitalization in a risk population. The close estimates obtained in the cohort and the test-negative case-control analyses suggest good control of biases.

[Impact of vaccination against influenza (H1N1) 2009 in Navarre: comparison of different scenarios]. / Impacto de la vacunación frente a la gripe (H1N1) 2009 en Navarra: comparación de diferentes escenarios.

BACKGROUND: A specific vaccination campaign against influenza A (H1N1) was conducted in 2009. We evaluated its impact in Navarre. METHODS: In the cohort of non-institutionalised population with chronic diseases covered by the Navarre Health Service (n=131,333), assuming 100% effectiveness from day 8 after administration of the pandemic vaccine, we estimated its impact on the prevention of influenza A (H1N1) 2009 cases and hospitalisations between weeks 47/2009 and 3/2010. RESULTS: In the nine weeks of the study, 973 cases of influenza syndrome were diagnosed (7 per 1000); but only 28% were due to influenza A (H1N1) 2009. In addition, there were 14 hospitalisations with virological confirmation (11 per 100,000). With 19% coverage with the pandemic vaccine (versus 40% with the seasonal vaccine), 7.7% of cases and 10.5% of hospitalisations were prevented during the study period. For each case prevented, 1092 doses of pandemic vaccine were administered, and for each hospitalisation avoided 15,021 doses were administered. If coverage had been the same as for the seasonal vaccine, it would have been possible to prevent 16.2% of cases and 22.2% of hospitalisations. If coverage had been double than for the seasonal vaccine and vaccination campaign had taken place two weeks earlier, it would have been possible to prevent 70.7% of cases and 68.0% of hospitalizations, with 261 doses needed to prevent one case and 6206 doses to avoid one hospitalisation. CONCLUSION: Despite the high effectiveness of the vaccine, its impact in Navarre has been minimal due to low coverage and late initiation of the vaccination campaign.

[Differences between summer and fall waves of influenza in the pandemic of influenza (H1N1) 2009 in Navarre, Spain]. / 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.

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.

[Trends in mortality and causes of death among persons with HIV infection, 1985-2004]. / Cambios en la mortalidad y en las causas de defunción en las personas con diagnóstico de infección por el VIH, 1985-2004.

OBJECTIVE: To describe the changes in causes of death among persons with HIV infection. METHODS: An analysis of mortality according to cause was performed in persons diagnosed with HIV infection and residing in the province of Navarre (Spain) from 1985 to 2004. RESULTS: Among 1,649 persons diagnosed with HIV infection up to 2004, 709 (43.0%) had died. Mortality reached the maximum in 1993-1996 with 83.1 deaths per 1,000 person-years (PY). Since that time and up to 2001-2004, mortality due to AIDS decreased from 68.3 to 14.1 per 1,000 PY (p = 0.0001). From 1989-1992 period to the 2001-2004 period, mortality due to drug overdose dropped from 9.2 to 3.6 per 1,000 PY (p = 0.0035) and mortality due to hepatic disease rose from 1.6 to 6.6 per 1000 PY (p = 0.0061), with no significant changes in all other causes. In 2001-2004, AIDS continued to be the first cause of death (44.4%) in this population, followed by hepatic disease (20.9%) and drug overdose (11.3%). In the era of potent antiretroviral therapy (1997-2004), death caused by AIDS (rate ratio = 0.63; p = 0.0344) and by all other causes (RR = 0.59; p = 0.0232) was lower among women. In addition, mortality due to causes other than AIDS was higher in persons 40 years of age and older (RR = 1.77; P = 0.0050) and mortality was lower in homosexual men (RR = 0.22; p = 0.0360). A simultaneous diagnosis of HIV infection and AIDS was associated with higher mortality by AIDS (RR, 3.39; p < 0.0001). CONCLUSIONS: AIDS continues to be the primary cause of death in HIV-infected people, and mortality due to hepatic diseases and drug overdose is high. Early diagnosis of HIV-infection would reduce the incidence of deaths due to AIDS.