Human Vaccines & Immunotherapeutics
ISSN: 2164-5515 (Print) 2164-554X (Online) Journal homepage: http://www.tandfonline.com/loi/khvi20
Influenza vaccine effectiveness in preventing inpatient and outpatient cases in a season dominated by vaccine-matched influenza B virus Iván Martínez-Baz, Ana Navascués, Francisco Pozo, Judith Chamorro, Esther Albeniz, Itziar Casado, Gabriel Reina, Manuel García Cenoz, Carmen Ezpeleta, Jesús Castilla & Primary Health Care Sentinel Network and Network for Influenza Surveillance in Hospitals of Navarra To cite this article: Iván Martínez-Baz, Ana Navascués, Francisco Pozo, Judith Chamorro, Esther Albeniz, Itziar Casado, Gabriel Reina, Manuel García Cenoz, Carmen Ezpeleta, Jesús Castilla & Primary Health Care Sentinel Network and Network for Influenza Surveillance in Hospitals of Navarra (2015) Influenza vaccine effectiveness in preventing inpatient and outpatient cases in a season dominated by vaccine-matched influenza B virus, Human Vaccines & Immunotherapeutics, 11:7, 1626-1633, DOI: 10.1080/21645515.2015.1038002 To link to this article: http://dx.doi.org/10.1080/21645515.2015.1038002
Accepted author version posted online: 21 May 2015.
Submit your article to this journal
Article views: 68
View related articles
View Crossmark data
Citing articles: 1 View citing articles
Full Terms & Conditions of access and use can be found at http://www.tandfonline.com/action/journalInformation?journalCode=khvi20 Download by: [University of Prince Edward Island]
Date: 05 November 2015, At: 14:01
RESEARCH PAPER Human Vaccines & Immunotherapeutics 11:7, 1626--1633; July 2015; © 2015 Taylor and Francis Group, LLC
Influenza vaccine effectiveness in preventing inpatient and outpatient cases in a season dominated by vaccine-matched influenza B virus Ivan Martínez-Baz1,2,*, Ana Navascu es3, Francisco Pozo4, Judith Chamorro3, Esther Albeniz5, Itziar Casado1, Gabriel Reina6, Manuel García Cenoz1,2, Carmen Ezpeleta3, Jes us Castilla1,2, and Primary Health Care Sentinel Network and Network for Influenza Surveillance in Hospitals of Navarra# Instituto de Salud P ublica de Navarra; Pamplona, Spain; 2CIBER Epidemiología y Salud P ublica (CIBERESP); Madrid, Spain; 3Complejo Hospitalario de Navarra; Pamplona, Spain; 4 Centro Nacional de Microbiología (WHO National Influenza Center - Madrid); Instituto de Salud Carlos III; Majadahonda, Spain; 5Direcci on de Atenci on Primaria; Servicio Navarro de Salud; Pamplona, Spain; 6Clínica Universidad de Navarra; Pamplona, Spain
Downloaded by [University of Prince Edward Island] at 14:02 05 November 2015
1
#
A list of these authors can be found in the Note section.
Keywords: case-control study, effectiveness, influenza, influenza B virus, influenza vaccine, sentinel surveillance Abbreviations: CI, confidence interval; ILI, influenza-like illness; OR, odds ratio; RT-PCR, reverse transcription polymerase chain reaction; VE, vaccine effectiveness
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 laboratoryconfirmed 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 D 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.
Introduction Influenza is an important public health problem that affects a high proportion of the population every year, and its main preventive measure is the vaccine.1 Since influenza vaccine composition is adapted every season to the viruses expected to be in circulation, its effectiveness varies.2 Annual trivalent influenza vaccines contain hemagglutinin (HA) derived from influenza A(H1N1), A(H3N2) and B viruses, intended to be protective against the viruses in circulation each season. Influenza B viruses comprise 2 antigenically distinct lineages, Victoria and Yamagata, and only one of them is included in the trivalent influenza vaccine. When the lineage included in the seasonal vaccine matches the lineage of the circulating virus, the preventive effect of the vaccine is expected to be high against
influenza B, whereas the level of cross-protection between the 2 lineages is not well known, but is assumed to be low,3,4 for that reason a tetravalent vaccine has been recently formulated including both lineages. In the 2012–2013 season the composition recommended for the influenza vaccine in the northern hemisphere included A/California/07/2009(H1N1)pdm09-like, A/Victoria/361/2011 (H3N2)-like and B/Wisconsin/1/2010(Yamagata)-like viruses.5 Virological surveillance of influenza during the 2012–2013 season in Spain detected that the influenza B virus was the predominant circulating influenza virus.6-8 Studies that have evaluated the influenza vaccine effectiveness (VE) to prevent laboratoryconfirmed influenza B cases in a season dominated by this type of virus are uncommon, and few have analyzed the effect in preventing inpatient cases.9-12
*Correspondence to: Ivan Martínez-Baz; Email: [email protected] Submitted: 01/30/2015; Revised: 03/16/2015; Accepted: 04/01/2015 http://dx.doi.org/10.1080/21645515.2015.1038002
1626
Human Vaccines & Immunotherapeutics
Volume 11 Issue 7
The aim of this study was to evaluate the influenza VE in preventing outpatient and hospitalized cases with laboratory-confirmed influenza in the 2012–2013 season in Navarra, Spain, and to provide specific estimates of the VE against influenza B virus using the test-negative case-control design.
Downloaded by [University of Prince Edward Island] at 14:02 05 November 2015
Results Description of cases and controls The weekly distribution of swabbed patients followed a similar pattern to the influenza-like illness (ILI) incidence in the population, peaking in weeks 8 and 7 of 2013, respectively (Fig. 1). The study period was defined as week 50 of 2012 to week 19 of 2013. During this period 744 ILI patients were swabbed and 382 (51%) were confirmed for influenza virus: 268 (70%) with influenza B and 114 (30%) with influenza A. Among influenza A cases, 93 (82%) were subtyped as A(H1N1)pdm09, 20 (18%) as A(H3N2), and 1 strain was not subtyped. In the 97% of patients included in this study the date of symptom onset was recorded, and all of them had been swabbed during the first 5 d. In comparison to test-negative controls, laboratory-confirmed cases with influenza were less frequently children under 5 y and adults aged 65 and over, persons with major chronic conditions and persons in the target population for influenza vaccination (Table 1). Among the 382 laboratory-confirmed cases there were 25 (7%) who had received the influenza vaccine during the 2012– 2013 season compared to 84 (23%) of the 362 influenza-negative controls (P < 0.001).
Center - Madrid laboratory. The 33 isolates of influenza A (H1N1)pdm09 virus were A/StPetersburg/27/2011(nH1N1)like (79%) and A/StPetersburg/100/2011(nH1N1)-like (21%). All 17 A(H3N2) sequenced viruses were characterized as A/Victoria/361/2011(H3N2)-like. Among the 79 influenza B isolates with genetic characterization, the Yamagata lineage included in the trivalent vaccine predominated (92%), and the strains identified were B/Estonia/55669/2011(Yamagata)-like (49%), B/Wisconsin/1/2010(Yamagata)-like (43%) and B/Brisbane/60/2008 (Victoria)-like (8%) (Table 2). VE in preventing laboratory-confirmed influenza The adjusted estimate of the overall influenza VE was 63% (95% CI: 34 to 79). Among primary healthcare patients VE was 55% (95% CI: 1 to 80), while the VE estimate in preventing hospitalizations was 74% (95% CI: 33 to 90). Among persons aged 65 y and older the VE was 75% (95% CI: 22 to 92), and among people younger than 65 it was 59% (95% CI: 17 to 80). The specific estimates of the VE in preventing influenza A(H1N1) pdm09 and A(H3N2) suggested a moderate protective effect, but were not statistically significant (Table 3).
VE in preventing laboratory-confirmed influenza B cases To evaluate the influenza VE in preventing influenza B cases, the study period was defined as week 50 of 2012 to week 15 of 2013. During this period 597 ILI patients were swabbed and 268 (45%) were confirmed for influenza B virus. Among laboratoryconfirmed B cases, 6% had received the influenza vaccine during the 2012–2013 season compared to 22% of the influenza-negative controls (P < 0.001) (Table 1). The overall VE in preventing influenza B cases was 70% (95% Genetic characterization Overall, 129 (34%) isolates obtained from the confirmed cases CI: 41 to 85), similar to the VE among the target population for were further characterized by phylogenetic analysis of the HA1 vaccination (70%; 95% CI: 37 to 86). The point estimate of VE sequence of the haemagglutinin gene in the National Influenza was 89% (95% CI: 53 to 97) in persons aged 65 y and more and 87% (95% CI: 52 to 96) against hospitalizations with influenza B (Table 4). The comparison of vaccination status between inpatient and outpatient cases with laboratory-confirmed influenza B did not show any differences after adjustment for potential confounding factors (odds ratio (OR): 1.13; 95% CI: 0.24– 5.43; p D 0.878). When taking into consideration vaccination in previous seasons in the model, the adjusted estimate of the 2012–2013 seasonal VE against influenza B virus was 69% (95% CI: 23 to 88), and the 2008–2009 influenza season vaccine, which was the last containing Yamagata lineage virus, yielded a residual preventive effect of 25%, although it did not reach statistical significance. Vaccination in previous seasons when Victoria lineage was included Figure 1. Number of influenza cases and test-negative controls, and incidence of influenza-like illin the seasonal vaccine did not show a preness by week, 2012–2013 season in Navarra, Spain. ventive effect (Table 5).
www.tandfonline.com
Human Vaccines & Immunotherapeutics
1627
Downloaded by [University of Prince Edward Island] at 14:02 05 November 2015
Table 1. Baseline characteristics of laboratory-confirmed influenza cases and test-negative controls, 2012–2013 influenza season in Navarra, Spain
Age groups (in years)
ISSN: 2164-5515 (Print) 2164-554X (Online) Journal homepage: http://www.tandfonline.com/loi/khvi20
Influenza vaccine effectiveness in preventing inpatient and outpatient cases in a season dominated by vaccine-matched influenza B virus Iván Martínez-Baz, Ana Navascués, Francisco Pozo, Judith Chamorro, Esther Albeniz, Itziar Casado, Gabriel Reina, Manuel García Cenoz, Carmen Ezpeleta, Jesús Castilla & Primary Health Care Sentinel Network and Network for Influenza Surveillance in Hospitals of Navarra To cite this article: Iván Martínez-Baz, Ana Navascués, Francisco Pozo, Judith Chamorro, Esther Albeniz, Itziar Casado, Gabriel Reina, Manuel García Cenoz, Carmen Ezpeleta, Jesús Castilla & Primary Health Care Sentinel Network and Network for Influenza Surveillance in Hospitals of Navarra (2015) Influenza vaccine effectiveness in preventing inpatient and outpatient cases in a season dominated by vaccine-matched influenza B virus, Human Vaccines & Immunotherapeutics, 11:7, 1626-1633, DOI: 10.1080/21645515.2015.1038002 To link to this article: http://dx.doi.org/10.1080/21645515.2015.1038002
Accepted author version posted online: 21 May 2015.
Submit your article to this journal
Article views: 68
View related articles
View Crossmark data
Citing articles: 1 View citing articles
Full Terms & Conditions of access and use can be found at http://www.tandfonline.com/action/journalInformation?journalCode=khvi20 Download by: [University of Prince Edward Island]
Date: 05 November 2015, At: 14:01
RESEARCH PAPER Human Vaccines & Immunotherapeutics 11:7, 1626--1633; July 2015; © 2015 Taylor and Francis Group, LLC
Influenza vaccine effectiveness in preventing inpatient and outpatient cases in a season dominated by vaccine-matched influenza B virus Ivan Martínez-Baz1,2,*, Ana Navascu es3, Francisco Pozo4, Judith Chamorro3, Esther Albeniz5, Itziar Casado1, Gabriel Reina6, Manuel García Cenoz1,2, Carmen Ezpeleta3, Jes us Castilla1,2, and Primary Health Care Sentinel Network and Network for Influenza Surveillance in Hospitals of Navarra# Instituto de Salud P ublica de Navarra; Pamplona, Spain; 2CIBER Epidemiología y Salud P ublica (CIBERESP); Madrid, Spain; 3Complejo Hospitalario de Navarra; Pamplona, Spain; 4 Centro Nacional de Microbiología (WHO National Influenza Center - Madrid); Instituto de Salud Carlos III; Majadahonda, Spain; 5Direcci on de Atenci on Primaria; Servicio Navarro de Salud; Pamplona, Spain; 6Clínica Universidad de Navarra; Pamplona, Spain
Downloaded by [University of Prince Edward Island] at 14:02 05 November 2015
1
#
A list of these authors can be found in the Note section.
Keywords: case-control study, effectiveness, influenza, influenza B virus, influenza vaccine, sentinel surveillance Abbreviations: CI, confidence interval; ILI, influenza-like illness; OR, odds ratio; RT-PCR, reverse transcription polymerase chain reaction; VE, vaccine effectiveness
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 laboratoryconfirmed 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 D 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.
Introduction Influenza is an important public health problem that affects a high proportion of the population every year, and its main preventive measure is the vaccine.1 Since influenza vaccine composition is adapted every season to the viruses expected to be in circulation, its effectiveness varies.2 Annual trivalent influenza vaccines contain hemagglutinin (HA) derived from influenza A(H1N1), A(H3N2) and B viruses, intended to be protective against the viruses in circulation each season. Influenza B viruses comprise 2 antigenically distinct lineages, Victoria and Yamagata, and only one of them is included in the trivalent influenza vaccine. When the lineage included in the seasonal vaccine matches the lineage of the circulating virus, the preventive effect of the vaccine is expected to be high against
influenza B, whereas the level of cross-protection between the 2 lineages is not well known, but is assumed to be low,3,4 for that reason a tetravalent vaccine has been recently formulated including both lineages. In the 2012–2013 season the composition recommended for the influenza vaccine in the northern hemisphere included A/California/07/2009(H1N1)pdm09-like, A/Victoria/361/2011 (H3N2)-like and B/Wisconsin/1/2010(Yamagata)-like viruses.5 Virological surveillance of influenza during the 2012–2013 season in Spain detected that the influenza B virus was the predominant circulating influenza virus.6-8 Studies that have evaluated the influenza vaccine effectiveness (VE) to prevent laboratoryconfirmed influenza B cases in a season dominated by this type of virus are uncommon, and few have analyzed the effect in preventing inpatient cases.9-12
*Correspondence to: Ivan Martínez-Baz; Email: [email protected] Submitted: 01/30/2015; Revised: 03/16/2015; Accepted: 04/01/2015 http://dx.doi.org/10.1080/21645515.2015.1038002
1626
Human Vaccines & Immunotherapeutics
Volume 11 Issue 7
The aim of this study was to evaluate the influenza VE in preventing outpatient and hospitalized cases with laboratory-confirmed influenza in the 2012–2013 season in Navarra, Spain, and to provide specific estimates of the VE against influenza B virus using the test-negative case-control design.
Downloaded by [University of Prince Edward Island] at 14:02 05 November 2015
Results Description of cases and controls The weekly distribution of swabbed patients followed a similar pattern to the influenza-like illness (ILI) incidence in the population, peaking in weeks 8 and 7 of 2013, respectively (Fig. 1). The study period was defined as week 50 of 2012 to week 19 of 2013. During this period 744 ILI patients were swabbed and 382 (51%) were confirmed for influenza virus: 268 (70%) with influenza B and 114 (30%) with influenza A. Among influenza A cases, 93 (82%) were subtyped as A(H1N1)pdm09, 20 (18%) as A(H3N2), and 1 strain was not subtyped. In the 97% of patients included in this study the date of symptom onset was recorded, and all of them had been swabbed during the first 5 d. In comparison to test-negative controls, laboratory-confirmed cases with influenza were less frequently children under 5 y and adults aged 65 and over, persons with major chronic conditions and persons in the target population for influenza vaccination (Table 1). Among the 382 laboratory-confirmed cases there were 25 (7%) who had received the influenza vaccine during the 2012– 2013 season compared to 84 (23%) of the 362 influenza-negative controls (P < 0.001).
Center - Madrid laboratory. The 33 isolates of influenza A (H1N1)pdm09 virus were A/StPetersburg/27/2011(nH1N1)like (79%) and A/StPetersburg/100/2011(nH1N1)-like (21%). All 17 A(H3N2) sequenced viruses were characterized as A/Victoria/361/2011(H3N2)-like. Among the 79 influenza B isolates with genetic characterization, the Yamagata lineage included in the trivalent vaccine predominated (92%), and the strains identified were B/Estonia/55669/2011(Yamagata)-like (49%), B/Wisconsin/1/2010(Yamagata)-like (43%) and B/Brisbane/60/2008 (Victoria)-like (8%) (Table 2). VE in preventing laboratory-confirmed influenza The adjusted estimate of the overall influenza VE was 63% (95% CI: 34 to 79). Among primary healthcare patients VE was 55% (95% CI: 1 to 80), while the VE estimate in preventing hospitalizations was 74% (95% CI: 33 to 90). Among persons aged 65 y and older the VE was 75% (95% CI: 22 to 92), and among people younger than 65 it was 59% (95% CI: 17 to 80). The specific estimates of the VE in preventing influenza A(H1N1) pdm09 and A(H3N2) suggested a moderate protective effect, but were not statistically significant (Table 3).
VE in preventing laboratory-confirmed influenza B cases To evaluate the influenza VE in preventing influenza B cases, the study period was defined as week 50 of 2012 to week 15 of 2013. During this period 597 ILI patients were swabbed and 268 (45%) were confirmed for influenza B virus. Among laboratoryconfirmed B cases, 6% had received the influenza vaccine during the 2012–2013 season compared to 22% of the influenza-negative controls (P < 0.001) (Table 1). The overall VE in preventing influenza B cases was 70% (95% Genetic characterization Overall, 129 (34%) isolates obtained from the confirmed cases CI: 41 to 85), similar to the VE among the target population for were further characterized by phylogenetic analysis of the HA1 vaccination (70%; 95% CI: 37 to 86). The point estimate of VE sequence of the haemagglutinin gene in the National Influenza was 89% (95% CI: 53 to 97) in persons aged 65 y and more and 87% (95% CI: 52 to 96) against hospitalizations with influenza B (Table 4). The comparison of vaccination status between inpatient and outpatient cases with laboratory-confirmed influenza B did not show any differences after adjustment for potential confounding factors (odds ratio (OR): 1.13; 95% CI: 0.24– 5.43; p D 0.878). When taking into consideration vaccination in previous seasons in the model, the adjusted estimate of the 2012–2013 seasonal VE against influenza B virus was 69% (95% CI: 23 to 88), and the 2008–2009 influenza season vaccine, which was the last containing Yamagata lineage virus, yielded a residual preventive effect of 25%, although it did not reach statistical significance. Vaccination in previous seasons when Victoria lineage was included Figure 1. Number of influenza cases and test-negative controls, and incidence of influenza-like illin the seasonal vaccine did not show a preness by week, 2012–2013 season in Navarra, Spain. ventive effect (Table 5).
www.tandfonline.com
Human Vaccines & Immunotherapeutics
1627
Downloaded by [University of Prince Edward Island] at 14:02 05 November 2015
Table 1. Baseline characteristics of laboratory-confirmed influenza cases and test-negative controls, 2012–2013 influenza season in Navarra, Spain
Age groups (in years)
