Emily
Editor, Senior Moderator
http://jama.ama-assn.org/cgi/content/full/2009.265v1?hits=10&FIRSTINDEX=0&FULLTEXT=zhong&SEARCHID=1&gca=jama%3B2009.265v1&
Early Release Article, posted March 2, 2009 JAMA
Live Attenuated or Inactivated Influenza Vaccines and Medical Encounters for Respiratory Illnesses Among US Military Personnel
Zhong Wang, PhD, MPH; Steven Tobler, MD, MPH; Jean Roayaei, PhD; Angelia Eick, PhD, ScM
JAMA. 2009;301(9)
ABSTRACT
Context Since 2004, increasing numbers of military personnel have been immunized with the intranasal live attenuated influenza vaccine (LAIV) while most others received the trivalent inactivated vaccine (TIV). However, data about live virus vaccine effectiveness among healthy adults are limited.
Objective
To monitor the effectiveness of vaccines to better inform military vaccination policy.
Design, Setting, and Participants
Surveillance of population-based, propensity-matched, and/or vaccine-naive cohorts of more than a million active-duty, nonrecruit military service members aged 17 to 49 years stationed in the United States during the 2004-2005, 2005-2006, or 2006-2007 influenza season.
Main Outcome Measures
Incidence of health care encounters resulting in a primary diagnostic code consistent with pneumonia or influenza. Incident hospitalizations was a secondary outcome.
Results
In all 3 seasons, immunization with TIV was associated with lower incidence rates of health care encounters for pneumonia and influenza when compared with no immunization: 8.6 vs 19.4 for 2004-2005, 7.8 vs 10.9 for 2005-2006, and 8.0 vs. 11.7 per 1000 person-years for 2006-2007 (all P < .001). Similar estimates were obtained from propensity-matched and/or vaccine-naive cohorts. Consistently lower vaccine effect following LAIV immunization was only seen during the 2006-2007 influenza season in the total (10.7; 95% confidence interval [CI], 2.72 to 18.1; P = .03) and propensity-matched cohorts (11.8; 95% CI, 0.85 to 21.5; P = .04), and was less than effect from TIV (TIV vs LAIV, 19.8; 95% CI, 13.6 to 25.5; P < .001). Among vaccine-naive service members, however, estimates for LAIV effect were more robust for both the 2005-2006 and 2006-2007 seasons (P = .01) and were comparable with TIV (eg, LAIV, 30.2; 95% CI, 11.2 to 45.2; vs TIV, 35.3; 95% CI, 25.9 to 43.6; in 2005-2006).
Conclusions
Vaccination with TIV was associated with fewer medical encounters related to pneumonia and influenza compared with LAIV or no immunization. In this annually immunized population, this effect was less apparent in those vaccinated with LAIV.
....
The incidence rate of health care encounters for pneumonia and influenza was highest in the unimmunized group each season (19.4, 10.9, and 11.7 per 1000 person-years for the 2004-2005, 2005-2006, and 2006-2007 seasons, respectively) (Table 2). The LAIV immunized group had the next highest incidence with rates of 18.3, 10.6, and 11.1 per 1000 person-years for the 2004-2005, 2005-2006, and 2006-2007 influenza seasons, respectively (P < .001). The lowest incidence was found in the TIV immunized group (8.6, 7.8, and 8.0 per 1000 person-years for the 2004-2005, 2005-2006, and 2006-2007 seasons, respectively; P < .001).
....
The incidence rates of hospitalizations for pneumonia and influenza were highest in the LAIV immunized group for each of the 3 seasons, and the adjusted incidence rate in this group was significantly higher than that in the unimmunized group during the 2004-2005 season (adjusted IRR, 2.14; 95% CI, 1.30 to 3.54; P = .01) but not during 2005-2006 (IRR, 1.18; 95% CI, 0.69 to 2.01; P = .49) or 2006-2007 (IRR, 1.11; 95% CI, 0.71 to 1.74; P = .53).
The effect of vaccination for each individual vaccine group was highest during the 2004-2005 influenza season, followed by the 2005-2006 season, and lowest during the 2006-2007 season. The estimated effect of vaccination with LAIV ranged from 10.7 (95% CI, 2.72 to 18.1; P = .03) in 2006-2007 to 20.8 (95% CI, 12.3 to 28.5) in 2004-2005 using the adjusted Poisson regression model and 5.9 (95% CI, –9.2 to 18.9) in 2005-2006 to 11.8 (95% CI, 0.85 to 21.5; P = .04) in 2006-2007 using propensity-based matching (Table 3). In reference to the unimmunized group, the effect of vaccination with TIV was higher than LAIV, with an estimated effect ranging from 28.4 (95% CI, 21.9 to 34.3) to 54.8 (95% CI, 51.3 to 58.1) for TIV and from 10.7 (95% CI, 2.7 to 18.1) to 20.8 (95% CI, 12.3 to 28.5) for LAIV.
The effect of vaccination was also analyzed in vaccine-naive cohorts. For the 2005-2006 and 2006-2007 seasons, there were 329 471 and 168 663 persons, respectively, in these cohorts. The incidence rates of pneumonia and influenza were similar between the vaccine-naive cohort and the total cohort for the unimmunized group (Table 2). However, incidence rates were lower among LAIV or TIV recipients in the vaccine-naive cohort compared with the total cohort (eg, LAIV during 2005-2006 season, 7.7 per 1000 person-years in vaccine-naive cohort vs 10.6 per 1000 person-years in total cohort). This yielded a higher effect of vaccination for both LAIV and TIV in the vaccine-naive cohort compared with the total cohort, particularly for LAIV. Among the vaccine-naive cohorts, estimates for LAIV and TIV effect were statistically similar in both the 2005-2006 (P = .53) and 2006-2007 (P = .56) seasons.
The effect of vaccination was compared with vaccination history (years of being vaccine-naive, 2 years vs 1 year vs none) for the 2006-2007 season. The estimates were obtained from the total cohort and vaccine-naive cohorts during the 2006-2007 season (Table 3). The correlation between years of being vaccine-naive and the effect of vaccination was statistically significant for LAIV (P = .04) but not for TIV (P = .63). Similar correlations were seen in propensity-matched cohorts (data not shown).
We followed a large healthy population through 3 influenza seasons and assessed health care use, immunization status, demographic information, and person-time at risk. To the best of our knowledge, this is the first systematic assessment and comparison of the effect of influenza vaccination in a population of healthy young adults with high vaccination coverage. Results of this multiseason surveillance report suggest that annual immunization could reduce influenza-related morbidity during seasons with varying levels of influenza activity.
Immunization with TIV was associated with a significantly lower incidence rate of clinical encounters for pneumonia and influenza during the 2004-2005 through 2006-2007 seasons. In an attempt to reduce the selection bias in observational studies, we performed a propensity-matched cohort analysis.20 The consistent estimates for TIV between the total and propensity-matched cohorts argue that TIV administration was not biased among the known covariates included in the model. This was expected because TIV was the predominant vaccine and ubiquitously distributed in most military treatment facilities for use in the event of a local outbreak. On the other hand, LAIV was used only in select services in the 2004-2005 influenza season and did not equal the level of TIV administration until the 2006-2007 season. Thus, we observed a similar reduction in the incidence rate for the LAIV immunized group only during the 2006-2007 season, in either the total or propensity-matched cohort. In addition to limited LAIV administration, other factors might have affected the effectiveness of LAIV, such as the change in formulary from frozen to refrigerated form before the 2006-2007 season. Our results from 2006-2007 were consistent with the findings of the pivotal efficacy trial for LAIV in healthy adults.21 Furthermore, our design enabled us to compare TIV and LAIV effect in the same setting.
A recent meta-analysis review of influenza vaccine effectiveness in healthy adults suggested that the intranasal vaccine is less effective than TIV.22 Similarly, Ohmit et al12, 23 recently reported LAIV to be less efficacious in reducing culture-confirmed influenza infection compared with TIV in a randomized control trial conducted during the 2004-200512 and 2005-200623 influenza seasons. It is worth noting that approximately 50% of the members in the Ohmit et al trial were immunized in the prior season (comparable with our propensity-score matched cohort) (Table 1). These findings are supported by our results. Reports of equal efficacy or effectiveness for LAIV were mostly from infants and young children with limited history of influenza vaccination.8-10
Live attenuated influenza vaccine was found to have an effect similar to TIV in the vaccine-naive cohort. This suggests that preexisting vaccine-induced immunity may play a role in determining the effectiveness of LAIV. We think that this modulation may occur because the attenuated virus from LAIV must undergo self-replication in the individual receiving the vaccine in the presence of neutralizing antibodies. Previous studies have reported that children and adults who were seropositive at baseline were less likely to have a serologic response to LAIV compared with those who were seronegative participants.24-26
......
We found that hospitalization rates related to pneumonia and influenza were higher in the LAIV-immunized group compared with the unimmunized or TIV group in the 2004-2005, 2005-2006, and 2006-2007 seasons. This has been reported previously for the 2004-2005 season.8, 35 Our report further revealed that the hospitalization risk decreased to insignificant levels in the later 2 seasons. It is not possible to know if the increased risk in hospitalization seen during the 2004-2005 season was causally linked to LAIV immunization, but it is biologically plausible to have a severe outcome as a result of mild respiratory infection.36 In any case, this elevated risk is countered by the overall low rate of hospitalization in the military health system such that, on average, around 30 excess incident hospitalizations were expected to occur among those who took LAIV compared with TIV.
These results suggest that in a highly immunized adult population, TIV may be more effective than LAIV for the prevention of pneumonia- and influenza-related morbidity. Live attenuated influenza vaccine may be more appropriate for those with no prior immunization, such as military recruits. Continued assessment is needed of TIV and LAIV effectiveness during influenza seasons with a mismatch between circulating virus strains and the vaccine components. Because our population is highly immunized against influenza on an annual basis, results from this report may not be generalizable to the entire US adult population but could be useful for nonmilitary adult populations where vaccination rates are high. Additional efficacy trials in this population or effectiveness studies using laboratory-confirmed influenza infections may be warranted.
Early Release Article, posted March 2, 2009 JAMA
Live Attenuated or Inactivated Influenza Vaccines and Medical Encounters for Respiratory Illnesses Among US Military Personnel
Zhong Wang, PhD, MPH; Steven Tobler, MD, MPH; Jean Roayaei, PhD; Angelia Eick, PhD, ScM
JAMA. 2009;301(9)
ABSTRACT
Context Since 2004, increasing numbers of military personnel have been immunized with the intranasal live attenuated influenza vaccine (LAIV) while most others received the trivalent inactivated vaccine (TIV). However, data about live virus vaccine effectiveness among healthy adults are limited.
Objective
To monitor the effectiveness of vaccines to better inform military vaccination policy.
Design, Setting, and Participants
Surveillance of population-based, propensity-matched, and/or vaccine-naive cohorts of more than a million active-duty, nonrecruit military service members aged 17 to 49 years stationed in the United States during the 2004-2005, 2005-2006, or 2006-2007 influenza season.
Main Outcome Measures
Incidence of health care encounters resulting in a primary diagnostic code consistent with pneumonia or influenza. Incident hospitalizations was a secondary outcome.
Results
In all 3 seasons, immunization with TIV was associated with lower incidence rates of health care encounters for pneumonia and influenza when compared with no immunization: 8.6 vs 19.4 for 2004-2005, 7.8 vs 10.9 for 2005-2006, and 8.0 vs. 11.7 per 1000 person-years for 2006-2007 (all P < .001). Similar estimates were obtained from propensity-matched and/or vaccine-naive cohorts. Consistently lower vaccine effect following LAIV immunization was only seen during the 2006-2007 influenza season in the total (10.7; 95% confidence interval [CI], 2.72 to 18.1; P = .03) and propensity-matched cohorts (11.8; 95% CI, 0.85 to 21.5; P = .04), and was less than effect from TIV (TIV vs LAIV, 19.8; 95% CI, 13.6 to 25.5; P < .001). Among vaccine-naive service members, however, estimates for LAIV effect were more robust for both the 2005-2006 and 2006-2007 seasons (P = .01) and were comparable with TIV (eg, LAIV, 30.2; 95% CI, 11.2 to 45.2; vs TIV, 35.3; 95% CI, 25.9 to 43.6; in 2005-2006).
Conclusions
Vaccination with TIV was associated with fewer medical encounters related to pneumonia and influenza compared with LAIV or no immunization. In this annually immunized population, this effect was less apparent in those vaccinated with LAIV.
....
The incidence rate of health care encounters for pneumonia and influenza was highest in the unimmunized group each season (19.4, 10.9, and 11.7 per 1000 person-years for the 2004-2005, 2005-2006, and 2006-2007 seasons, respectively) (Table 2). The LAIV immunized group had the next highest incidence with rates of 18.3, 10.6, and 11.1 per 1000 person-years for the 2004-2005, 2005-2006, and 2006-2007 influenza seasons, respectively (P < .001). The lowest incidence was found in the TIV immunized group (8.6, 7.8, and 8.0 per 1000 person-years for the 2004-2005, 2005-2006, and 2006-2007 seasons, respectively; P < .001).
....
The incidence rates of hospitalizations for pneumonia and influenza were highest in the LAIV immunized group for each of the 3 seasons, and the adjusted incidence rate in this group was significantly higher than that in the unimmunized group during the 2004-2005 season (adjusted IRR, 2.14; 95% CI, 1.30 to 3.54; P = .01) but not during 2005-2006 (IRR, 1.18; 95% CI, 0.69 to 2.01; P = .49) or 2006-2007 (IRR, 1.11; 95% CI, 0.71 to 1.74; P = .53).
The effect of vaccination for each individual vaccine group was highest during the 2004-2005 influenza season, followed by the 2005-2006 season, and lowest during the 2006-2007 season. The estimated effect of vaccination with LAIV ranged from 10.7 (95% CI, 2.72 to 18.1; P = .03) in 2006-2007 to 20.8 (95% CI, 12.3 to 28.5) in 2004-2005 using the adjusted Poisson regression model and 5.9 (95% CI, –9.2 to 18.9) in 2005-2006 to 11.8 (95% CI, 0.85 to 21.5; P = .04) in 2006-2007 using propensity-based matching (Table 3). In reference to the unimmunized group, the effect of vaccination with TIV was higher than LAIV, with an estimated effect ranging from 28.4 (95% CI, 21.9 to 34.3) to 54.8 (95% CI, 51.3 to 58.1) for TIV and from 10.7 (95% CI, 2.7 to 18.1) to 20.8 (95% CI, 12.3 to 28.5) for LAIV.
The effect of vaccination was also analyzed in vaccine-naive cohorts. For the 2005-2006 and 2006-2007 seasons, there were 329 471 and 168 663 persons, respectively, in these cohorts. The incidence rates of pneumonia and influenza were similar between the vaccine-naive cohort and the total cohort for the unimmunized group (Table 2). However, incidence rates were lower among LAIV or TIV recipients in the vaccine-naive cohort compared with the total cohort (eg, LAIV during 2005-2006 season, 7.7 per 1000 person-years in vaccine-naive cohort vs 10.6 per 1000 person-years in total cohort). This yielded a higher effect of vaccination for both LAIV and TIV in the vaccine-naive cohort compared with the total cohort, particularly for LAIV. Among the vaccine-naive cohorts, estimates for LAIV and TIV effect were statistically similar in both the 2005-2006 (P = .53) and 2006-2007 (P = .56) seasons.
The effect of vaccination was compared with vaccination history (years of being vaccine-naive, 2 years vs 1 year vs none) for the 2006-2007 season. The estimates were obtained from the total cohort and vaccine-naive cohorts during the 2006-2007 season (Table 3). The correlation between years of being vaccine-naive and the effect of vaccination was statistically significant for LAIV (P = .04) but not for TIV (P = .63). Similar correlations were seen in propensity-matched cohorts (data not shown).
We followed a large healthy population through 3 influenza seasons and assessed health care use, immunization status, demographic information, and person-time at risk. To the best of our knowledge, this is the first systematic assessment and comparison of the effect of influenza vaccination in a population of healthy young adults with high vaccination coverage. Results of this multiseason surveillance report suggest that annual immunization could reduce influenza-related morbidity during seasons with varying levels of influenza activity.
Immunization with TIV was associated with a significantly lower incidence rate of clinical encounters for pneumonia and influenza during the 2004-2005 through 2006-2007 seasons. In an attempt to reduce the selection bias in observational studies, we performed a propensity-matched cohort analysis.20 The consistent estimates for TIV between the total and propensity-matched cohorts argue that TIV administration was not biased among the known covariates included in the model. This was expected because TIV was the predominant vaccine and ubiquitously distributed in most military treatment facilities for use in the event of a local outbreak. On the other hand, LAIV was used only in select services in the 2004-2005 influenza season and did not equal the level of TIV administration until the 2006-2007 season. Thus, we observed a similar reduction in the incidence rate for the LAIV immunized group only during the 2006-2007 season, in either the total or propensity-matched cohort. In addition to limited LAIV administration, other factors might have affected the effectiveness of LAIV, such as the change in formulary from frozen to refrigerated form before the 2006-2007 season. Our results from 2006-2007 were consistent with the findings of the pivotal efficacy trial for LAIV in healthy adults.21 Furthermore, our design enabled us to compare TIV and LAIV effect in the same setting.
A recent meta-analysis review of influenza vaccine effectiveness in healthy adults suggested that the intranasal vaccine is less effective than TIV.22 Similarly, Ohmit et al12, 23 recently reported LAIV to be less efficacious in reducing culture-confirmed influenza infection compared with TIV in a randomized control trial conducted during the 2004-200512 and 2005-200623 influenza seasons. It is worth noting that approximately 50% of the members in the Ohmit et al trial were immunized in the prior season (comparable with our propensity-score matched cohort) (Table 1). These findings are supported by our results. Reports of equal efficacy or effectiveness for LAIV were mostly from infants and young children with limited history of influenza vaccination.8-10
Live attenuated influenza vaccine was found to have an effect similar to TIV in the vaccine-naive cohort. This suggests that preexisting vaccine-induced immunity may play a role in determining the effectiveness of LAIV. We think that this modulation may occur because the attenuated virus from LAIV must undergo self-replication in the individual receiving the vaccine in the presence of neutralizing antibodies. Previous studies have reported that children and adults who were seropositive at baseline were less likely to have a serologic response to LAIV compared with those who were seronegative participants.24-26
......
We found that hospitalization rates related to pneumonia and influenza were higher in the LAIV-immunized group compared with the unimmunized or TIV group in the 2004-2005, 2005-2006, and 2006-2007 seasons. This has been reported previously for the 2004-2005 season.8, 35 Our report further revealed that the hospitalization risk decreased to insignificant levels in the later 2 seasons. It is not possible to know if the increased risk in hospitalization seen during the 2004-2005 season was causally linked to LAIV immunization, but it is biologically plausible to have a severe outcome as a result of mild respiratory infection.36 In any case, this elevated risk is countered by the overall low rate of hospitalization in the military health system such that, on average, around 30 excess incident hospitalizations were expected to occur among those who took LAIV compared with TIV.
These results suggest that in a highly immunized adult population, TIV may be more effective than LAIV for the prevention of pneumonia- and influenza-related morbidity. Live attenuated influenza vaccine may be more appropriate for those with no prior immunization, such as military recruits. Continued assessment is needed of TIV and LAIV effectiveness during influenza seasons with a mismatch between circulating virus strains and the vaccine components. Because our population is highly immunized against influenza on an annual basis, results from this report may not be generalizable to the entire US adult population but could be useful for nonmilitary adult populations where vaccination rates are high. Additional efficacy trials in this population or effectiveness studies using laboratory-confirmed influenza infections may be warranted.
I had run across this study earlier, so was surprised that LAIV swine flu nasal mist was going to be given to health care workers. I just read, (and lost link now), that they think this may work out OK since the health care workers should be immunlogically naive to swine flu. (Though I know of one nurse that just retired that got the swine flu vaccine back in 1976.)