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Comparison of Immune Response to the Inuenza Vaccine in Obese and Nonobese Healthcare Workers Michael A. Sweet, Jonathan A. McCullers, Paul R. Lasala, Frank E. Briggs, Anne Smithmyer and Rashida A. Khakoo Infection Control & Hospital Epidemiology / Volume 36 / Issue 03 / March 2015, pp 249 - 253 DOI: 10.1017/ice.2014.59, Published online: 02 January 2015
Link to this article: http://journals.cambridge.org/abstract_S0899823X14000592 How to cite this article: Michael A. Sweet, Jonathan A. McCullers, Paul R. Lasala, Frank E. Briggs, Anne Smithmyer and Rashida A. Khakoo (2015). Comparison of Immune Response to the Inuenza Vaccine in Obese and Nonobese Healthcare Workers. Infection Control & Hospital Epidemiology, 36, pp 249-253 doi:10.1017/ice.2014.59 Request Permissions : Click here
Downloaded from http://journals.cambridge.org/ICE, IP address: 142.66.3.42 on 05 Nov 2015
infection control & hospital epidemiology
march 2015, vol. 36, no. 3
original article
Comparison of Immune Response to the Influenza Vaccine in Obese and Nonobese Healthcare Workers Michael A. Sweet, PharmD;1 Jonathan A. McCullers, MD;4 Paul R. Lasala, MD;3 Frank E. Briggs, PharmD, MPH;1 Anne Smithmyer, FNP-C;2 Rashida A. Khakoo, MD, MACP5
objective. To determine whether there is a difference in antibody titers and functionality after receipt of the influenza vaccine for obese versus nonobese healthcare workers (HCW). design. setting.
Prospective observational study. Tertiary medical center.
participants.
Healthcare workers.
methods. Baseline influenza antibody titers for obese and nonobese HCW were recorded during the hospital’s 2011 annual influenza vaccination day and follow-up antibody titers were measured 4 weeks later. Antibodies were measured using the hemagglutination inhibition assay and functionality was measured using the micro-neutralization method. results. Of 200 initial HCWs, 190 completed the study (97 obese and 93 nonobese). Seroprotection after immunization was not significantly different for nonobese compared with obese HCW for each strain (influenza A [H1N1], 99% and 99%; influenza A [H3N2], 100% and 99%; and influenza B, 67% and 71%, respectively). All geometric mean titers measured by micro-neutralization showed statistically significant increases in activity. In comparison, there was no difference in the 4-fold increase in H1N1 or B titers. There was a significant difference in the 4-fold increase of H3N2 titers between the nonobese and obese HCWs (82/93 [88%] vs 64/97 [66%], P = .003). In an ad hoc analysis we found that obese HCWs had a statistically greater number of 4-fold decreases in titers with H1N1 and H3N2. conclusions.
There was no significant difference in protection from influenza between obese and nonobese HCWs after immunization. Infect Control Hosp Epidemiol 2 01 5; 3 6( 3) :2 4 9– 2 53
Influenza viruses cause significant but potentially preventable morbidity and mortality. Influenza epidemics were associated with more than 450,000 deaths in the United States in the 10-year span of 1989–1999.1 According to the World Health Organization2 it is responsible for 250,000–500,000 mortalities a year globally. Vaccination remains the most effective method for preventing infection.3 During the 2009 influenza A (H1N1) pandemic, there was an observed increased mortality and resource consumption in morbidly obese individuals.4–7 In addition, obese individuals are at increased risk for hospitalization during seasonal influenza.8 West Virginia has the second highest rate of adult obesity in the nation, at 32.5%.9 A prior study demonstrated that obesity was a predictor of poor immunogenic response to hepatitis B vaccination.10 Normal ranges of protection measured by hemagglutination inhibition (HAI) assay are titers of 1:40.11 An effective
response (seroconversion) to the influenza vaccination is typically defined as a 4-fold increase in antibody titer. Another measure to show effectiveness is the functionality of the antibodies once formed, measured by the micro-neutralization method. The current study was designed to measure influenza antibody titers before and after vaccination in obese and nonobese healthcare workers (HCW) to determine whether postvaccine titers are in the protective range and to determine the functionality of the antibodies.
methods This was a prospective observational study of influenza vaccination response. Obese and nonobese HCWs had a prevaccination serum specimen drawn, received the recommended 2011/2012
Affiliations: 1. Center for Quality Outcomes, West Virginia University Hospitals, Morgantown, West Virginia; 2. Employee Health, West Virginia University Hospitals, Morgantown, West Virginia; 3. West Virginia University Pathology, West Virginia University Hospitals, Morgantown, West Virginia; 4. St. Jude Children’s Research Hospital, Memphis, Tennessee; 5. Department of Infectious Diseases, West Virginia University School of Medicine, Morgantown, West Virginia. Received August 25, 2014; accepted November 16, 2014; electronically published January 2, 2015 © 2015 by The Society for Healthcare Epidemiology of America. All rights reserved. 0899-823X/2015/3603-0002. DOI: 10.1017/ice.2014.59
250 infection control & hospital epidemiology
march 2015, vol. 36, no. 3
influenza vaccine, and had a 4-week follow-up serum specimen drawn to determine HAI antibody response. This study was performed at West Virginia University Hospitals (Morgantown) during their 2011 annual influenza vaccination campaign. All HCWs were asked to participate in this study during this time and incentivized with a $35 gift card to complete the study. The only exclusion criterion was receipt of the vaccine by the intranasal route. HCWs were enrolled on a first come, first served basis until 100 workers were enrolled into each of 2 groups consisting of nonobese HCWs with a body mass index (BMI; calculated as weight in kilograms divided by height in meters squared) less than 30 and obese HCWs with a BMI greater than or equal to 30. Demographic and health assessment information was obtained through a questionnaire. The data included on this questionnaire were contact number, age, sex, height, weight, previous year vaccinations, history of influenza in the previous year, diabetes, chronic renal failure, malignancy, liver failure, other comorbidities, chronic steroid use, and other immunosuppressive medications. Height, weight, and an arm circumference were measured before blood collection. Prevaccination blood collection was performed and then influenza vaccine was administered. The HCWs were instructed to return 4 weeks after their vaccination for a second blood collection, after which each received a $35 gift card. HAI and micro-neutralization assays against A/California/ 7/09 (H1N1), A/Perth/16/09 (H3N2), and B/Brisbane/60/08 were performed on the serum samples collected on days 0 and 28–35 as described. The geometric mean titers (GMT) and geometric mean ratio were calculated in the pre- and postvaccination samples for each cohort. Seroconversion was defined as either a postvaccination rate of at least 1:40 with an undetectable (.99 (Fisher) .62 (Fisher) >.99 (Fisher) >.99 (Fisher) .081 (Fisher) .6155 .0001 .0001 .0001
NOTE. All data are number (percentage) unless otherwise indicated. BMI, body mass index (calculated as weight in kilograms divided by height in meters squared).
table 2.
Pre- and Postimmunization Titers and Immunogenicity of Healthcare Workers A (H1N1)
HAI method Before immunization, n GMT (95% CI) (unpaired t test) Seroprotection n, (%) Seroprotection After immunization, n GMT (95% CI) (unpaired t test) GMR Change in GMT Change in seroprotection Seroconversion n, (%) Seroconversion
BMI < 30
A (H3N2) BMI ≥ 30
100 100 165.6 (132–209) 227.8 (180–289) P = .060 93 (93) 100 (100) P = .014 93 97 263.6 (213–327) 313.2 (247–398) P = .30 1.64 1.35 P = .0007 P = .027 P = NS P = NS 30 (32) 32 (33) P > .05
B
BMI < 30
BMI ≥ 30
100 75.7 (62–92)
100 93.8 (78–113) P = .12
83 (83)
89 (89) P = .22
93 187.1 (154–227)
97 201.1 (161–252) P = .64
2.50 P = .0001 P = .001 37 (40)
2.13 P = .0001 P = NS 38 (39) P > .05
BMI < 30
BMI ≥ 30
100 100 23.2 (18–29) 43.5 (36–53) P = .0001 42 (42) 67 (67) P = .0004 93 97 48.3 (40–59) 52.1 (41–66) P = .65 2.14 1.2 P = .0001 P = .0521 P = .001 P = NS 25 (27) 12 (12) P = .012
MN method GMT before immunization (95% CI)
Change in GMT GMR % 4-Fold rise Change in % 4-fold increase between BMI groups % >40 Preimmunization % >40 Postimmunization Change in % >40 between BMI groups % >160 Preimmunization % >160 Postimmunization Change in % >160 between BMI groups
18.9 (14–25) 48.9 (35–68) P = .0001 2.58 43
39.7 (29–54) 932.2 (683–1273) P = .0001 23.5 88
31.0 57.7
55.0 97.9
13.0 33.0
27.0 92.6
P = .56 33.0 57.9
P = .45
7.7 (7–9) 10 (8–12) P = .01 1.3 11
74.0 94.8
6.0 9.5
46.0 84.5
0.0 3.2
P = .003
P = .87 17.0 31.6
110 (77–157) 464 (340–632) P = .0001 4.22 66
P = .39
P = .001 P = .002
6.9 (6–8) 10.8 (9–13) P = .0001 1.56 16 3.0 10.3 P = .62 1.0 1.0 P = .25
NOTE. BMI, body mass index (calculated as weight in kilograms divided by height in meters squared); GMR, geometric mean ratio; GMT, geometric mean titers; HAI, hemagglutination inhibition; NS, not significant.
response to flu vaccine in healthcare workers
GMT after immunization (95% CI)
18.8 (14–26) 46.6 (33–65) P = .0001 2.48 38
251
252 infection control & hospital epidemiology
table 3.
march 2015, vol. 36, no. 3
Comparison of Titers Declining by 4-Fold Postvaccination A (H1N1) BMI < 30
4-Fold declining titers
9.4%
A (H3N2) BMI ≥ 30
BMI < 30
35.5%
1.9%
P = .015 NOTE.
B BMI ≥ 30
BMI < 30
20.3%
0.0%
P = .002
BMI ≥30 0.0% P > .99
BMI, body mass index (calculated as weight in kilograms divided by height in meters squared).
in the nonobese (2.14, P = .0001) but not in the obese (1.2, P = .0521). The change in seroprotection between preand postimmunization phases for H1N1 was not statistically different for the obese and nonobese groups. There was a statistically significant increase with H3N2 with the nonobese group (83/100 [83%] vs 93/93 [100%], P = .001) but not with the obese group (89/100 [89%] vs 96/97 [99%], P = .5). There was a statistically significant increase with B with the nonobese group (42/100 [42%] vs 61/93 [66%], P = .001) but not with the obese group (67/100 [67%] vs 69/97 [71%], P = .5). Seroconversion was not statistically different between the nonobese and obese groups for H1N1 groups. Overall, the changes in micro-neutralization titers measured by the GMT all showed statistically significant increases. Comparing the obese and nonobese groups, there was no difference in rates of 4-fold increases in H1N1 or B titers. There was a statistically significant difference in the rate of 4-fold increase in H3N2 titers for nonobese compared with the obese group (88% [82/93] vs 66% [64/97], respectively; P = .003). There was no difference in the percent of sera achieving titer (% >40 post- after immunization) from microneutralization methods between the 2 groups (Table 2). In an ad hoc analysis we found that the obese group, compared with the nonobese group, had a statistically greater number of HCWs who had a 4-fold decrease in titers from before to after immunization with H1N1 and H3N2, as shown in Table 3.
d i s c u s s io n From the results of this study, it appears that HCWs in our institution are protected from influenza A (H1N1 and H3N2) at greater than 80% before vaccination and 99% after vaccination regardless of weight. This can be partially attributed to the combined 91% of HCWs who received the vaccine the year before. With these initial high rates it is hard to delineate the response differences between the 2 groups. There was a significant increase in seroprotection in response to influenza B vaccine for nonobese but not obese HCWs, but the higher initial rate of seroprotection of the obese HCWs confounds this observation. Historically, the seroconversion rates have been in the range of 42% to 62% after the receipt of the influenza A vaccine.13 Our rates were lower, but this is attributed to the initially high antibody titer rates, especially to the influenza A H1N1 and H3N2 strains. Seroconversion rates for influenza B have been
reported to be between 35% and 58%, compared with our study that showed 27% in the nonobese group and 12% in the obese group.13 Coleman and colleagues14 presented an abstract that suggested that obesity was not independently associated with a lower post–influenza vaccination seroprotection against the 2008–2009 vaccine components. The authors specifically looked at patients who were 50 years or older with a BMI of 30 or greater (obese) or with a BMI of less than 30 (nonobese). Nonobese patients, compared with obese patients, had a lower baseline GMT to the 3 components (H1N1, 10.4 vs 12.1; H3N2, 15 vs 5.3; and B, 51.8 vs 56.5) and a subsequent higher seroconversion rate (H1N1, 28% vs 28%; H3N2, 62% vs 73%; and B, 28% vs 34%) than our data showed. Of note, they did demonstrate a much lower rate of seroprotection for the influenza A strains but not the influenza B (H1N1, 43% vs 47%; H3N2, 76% vs 82%; and B, 95% vs 94%), compared with our study. In an ad hoc analysis of the data, an interesting trend emerged with obese HCWs having a significantly higher rate of 4-fold declining titers in the H1N1 and H3N2 groups. This generates many questions—for example, in the obese population what factors are causing this dramatic decrease in antibody titers in some HCWs who already had a titer of at least 40? Sheridan and colleagues15 reported that the pre- and postvaccination antibody titers for the 3 vaccine strains studied were not significantly different between the obese and nonobese participants. They did, however, report that there was a significantly higher increase to the influenza B component in obese versus nonobese participants. Interestingly, similar to our results, they reported that there was a difference between the 2 groups at the 12-month follow-up with the obese participants showing a greater number of at least 4-fold decreases in HAI titers.
co nclu sio n There were no significant differences between immunity to influenza between obese and nonobese HCWs after immunization. There are some data suggesting the immunization response may be less in some obese HCWs.
acknowledgments Financial support. American Society of Health-System Pharmacists Foundation (Fostering Young Investigators Research Grant to M.S.).
response to flu vaccine in healthcare workers
Potential conflicts of interest. All authors report no conflicts of interest relevant to this article. Address correspondence to Michael A. Sweet, PharmD, Center for Quality Outcomes, West Virginia University Hospitals, PO Box 8242, Morgantown, WV 26506-8242 ([email protected]).
references 1. Thompson WW, Shay DK, Weintraub E, et al. Mortality associated with influenza and respiratory syncytial virus in the United States. JAMA 2003;289:179–186. 2. World Health Organization. WHO factsheet: influenza (seasonal). Available at: http://www.who.int/mediacentre/factsheets/fs211/en. Published April 2009. Accessed February 15, 2012. 3. Cox NJ. Influenza. Lancet 1999;354:1277–1282. 4. Prevention and control of influenza with vaccines; recommendations of the Advisory Committee on Immunization Practices (ACIP), 2010. MMWR Morb Mortal Wkly Rep 2010;59: 1–47. 5. Diaz E, Rodriguez A, Martin-Loeche I, et al. Impact of obesity in patients infected with 2009 A (H1N1). Chest 2011;139: 382–386. 6. Louie JK, Acousta M, Samuel MC, et al. A novel risk factor for a novel virus: obesity and 2009 pandemic influenza A (H1N1). Clin Infect Dis 2011;52:301–312.
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7. Van Kerkhove M, Vandemaele KA, Shinde V, et al. Risk factors for severe outcomes following 2009 Influenza A (H1N1) infection: a global pooled analysis. PLoS Med 2011;8:e1001053. 8. Kwong JC, Campitelli MA, Rosella LC. Obesity and respiratory hospitalizations during influenza seasons in Ontario, Canada: a cohort study. Clin Infect Dis 2011;53:413–421. 9. United States Obesity Statistics for 2010. Available at: http://www. cdc.gov/obesity/data/index.html. Accessed February 15, 2012. 10. Weber DJ, Rutala WA, Samsa GP, et al. Obesity as a predictor of poor antibody response to hepatitis B plasma vaccine. JAMA 1985;254:3187–3189. 11. Potter CW, Oxford JS. Determinants of immunity to influenza infection in man. Br Med Bull 1979;35:69–75. 12. Carr S, Allison KJ, Van De Velde L-A, et al. Safety and immunogenicity of live attenuated and inactivated influenza vaccines in children with cancer. J Infect Dis 2011;204:1475–1482. 13. Goodwin K, Vinoud C, Simonsen L. Antibody response to influenza vaccination in the elderly: a quantitative review. Vaccine 2006;24:1159–1169. 14. Coleman LA, Talbot HK, Crimin K, et al. Effect of body mass index on serologic response to influenza vaccination in older adults. Presented at the Infectious Diseases Society of America 49th Annual Meeting; Boston, MA; October 21, 2011 (Abstract 538). 15. Sheridan PA, Paich HA, Handy J, et al. Obesity is associated with impaired immune response to influenza vaccination in humans. Int J Obes (Lond) 2012;36:1072–1077.
Control & Hospital Epidemiology:
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Comparison of Immune Response to the Inuenza Vaccine in Obese and Nonobese Healthcare Workers Michael A. Sweet, Jonathan A. McCullers, Paul R. Lasala, Frank E. Briggs, Anne Smithmyer and Rashida A. Khakoo Infection Control & Hospital Epidemiology / Volume 36 / Issue 03 / March 2015, pp 249 - 253 DOI: 10.1017/ice.2014.59, Published online: 02 January 2015
Link to this article: http://journals.cambridge.org/abstract_S0899823X14000592 How to cite this article: Michael A. Sweet, Jonathan A. McCullers, Paul R. Lasala, Frank E. Briggs, Anne Smithmyer and Rashida A. Khakoo (2015). Comparison of Immune Response to the Inuenza Vaccine in Obese and Nonobese Healthcare Workers. Infection Control & Hospital Epidemiology, 36, pp 249-253 doi:10.1017/ice.2014.59 Request Permissions : Click here
Downloaded from http://journals.cambridge.org/ICE, IP address: 142.66.3.42 on 05 Nov 2015
infection control & hospital epidemiology
march 2015, vol. 36, no. 3
original article
Comparison of Immune Response to the Influenza Vaccine in Obese and Nonobese Healthcare Workers Michael A. Sweet, PharmD;1 Jonathan A. McCullers, MD;4 Paul R. Lasala, MD;3 Frank E. Briggs, PharmD, MPH;1 Anne Smithmyer, FNP-C;2 Rashida A. Khakoo, MD, MACP5
objective. To determine whether there is a difference in antibody titers and functionality after receipt of the influenza vaccine for obese versus nonobese healthcare workers (HCW). design. setting.
Prospective observational study. Tertiary medical center.
participants.
Healthcare workers.
methods. Baseline influenza antibody titers for obese and nonobese HCW were recorded during the hospital’s 2011 annual influenza vaccination day and follow-up antibody titers were measured 4 weeks later. Antibodies were measured using the hemagglutination inhibition assay and functionality was measured using the micro-neutralization method. results. Of 200 initial HCWs, 190 completed the study (97 obese and 93 nonobese). Seroprotection after immunization was not significantly different for nonobese compared with obese HCW for each strain (influenza A [H1N1], 99% and 99%; influenza A [H3N2], 100% and 99%; and influenza B, 67% and 71%, respectively). All geometric mean titers measured by micro-neutralization showed statistically significant increases in activity. In comparison, there was no difference in the 4-fold increase in H1N1 or B titers. There was a significant difference in the 4-fold increase of H3N2 titers between the nonobese and obese HCWs (82/93 [88%] vs 64/97 [66%], P = .003). In an ad hoc analysis we found that obese HCWs had a statistically greater number of 4-fold decreases in titers with H1N1 and H3N2. conclusions.
There was no significant difference in protection from influenza between obese and nonobese HCWs after immunization. Infect Control Hosp Epidemiol 2 01 5; 3 6( 3) :2 4 9– 2 53
Influenza viruses cause significant but potentially preventable morbidity and mortality. Influenza epidemics were associated with more than 450,000 deaths in the United States in the 10-year span of 1989–1999.1 According to the World Health Organization2 it is responsible for 250,000–500,000 mortalities a year globally. Vaccination remains the most effective method for preventing infection.3 During the 2009 influenza A (H1N1) pandemic, there was an observed increased mortality and resource consumption in morbidly obese individuals.4–7 In addition, obese individuals are at increased risk for hospitalization during seasonal influenza.8 West Virginia has the second highest rate of adult obesity in the nation, at 32.5%.9 A prior study demonstrated that obesity was a predictor of poor immunogenic response to hepatitis B vaccination.10 Normal ranges of protection measured by hemagglutination inhibition (HAI) assay are titers of 1:40.11 An effective
response (seroconversion) to the influenza vaccination is typically defined as a 4-fold increase in antibody titer. Another measure to show effectiveness is the functionality of the antibodies once formed, measured by the micro-neutralization method. The current study was designed to measure influenza antibody titers before and after vaccination in obese and nonobese healthcare workers (HCW) to determine whether postvaccine titers are in the protective range and to determine the functionality of the antibodies.
methods This was a prospective observational study of influenza vaccination response. Obese and nonobese HCWs had a prevaccination serum specimen drawn, received the recommended 2011/2012
Affiliations: 1. Center for Quality Outcomes, West Virginia University Hospitals, Morgantown, West Virginia; 2. Employee Health, West Virginia University Hospitals, Morgantown, West Virginia; 3. West Virginia University Pathology, West Virginia University Hospitals, Morgantown, West Virginia; 4. St. Jude Children’s Research Hospital, Memphis, Tennessee; 5. Department of Infectious Diseases, West Virginia University School of Medicine, Morgantown, West Virginia. Received August 25, 2014; accepted November 16, 2014; electronically published January 2, 2015 © 2015 by The Society for Healthcare Epidemiology of America. All rights reserved. 0899-823X/2015/3603-0002. DOI: 10.1017/ice.2014.59
250 infection control & hospital epidemiology
march 2015, vol. 36, no. 3
influenza vaccine, and had a 4-week follow-up serum specimen drawn to determine HAI antibody response. This study was performed at West Virginia University Hospitals (Morgantown) during their 2011 annual influenza vaccination campaign. All HCWs were asked to participate in this study during this time and incentivized with a $35 gift card to complete the study. The only exclusion criterion was receipt of the vaccine by the intranasal route. HCWs were enrolled on a first come, first served basis until 100 workers were enrolled into each of 2 groups consisting of nonobese HCWs with a body mass index (BMI; calculated as weight in kilograms divided by height in meters squared) less than 30 and obese HCWs with a BMI greater than or equal to 30. Demographic and health assessment information was obtained through a questionnaire. The data included on this questionnaire were contact number, age, sex, height, weight, previous year vaccinations, history of influenza in the previous year, diabetes, chronic renal failure, malignancy, liver failure, other comorbidities, chronic steroid use, and other immunosuppressive medications. Height, weight, and an arm circumference were measured before blood collection. Prevaccination blood collection was performed and then influenza vaccine was administered. The HCWs were instructed to return 4 weeks after their vaccination for a second blood collection, after which each received a $35 gift card. HAI and micro-neutralization assays against A/California/ 7/09 (H1N1), A/Perth/16/09 (H3N2), and B/Brisbane/60/08 were performed on the serum samples collected on days 0 and 28–35 as described. The geometric mean titers (GMT) and geometric mean ratio were calculated in the pre- and postvaccination samples for each cohort. Seroconversion was defined as either a postvaccination rate of at least 1:40 with an undetectable (.99 (Fisher) .62 (Fisher) >.99 (Fisher) >.99 (Fisher) .081 (Fisher) .6155 .0001 .0001 .0001
NOTE. All data are number (percentage) unless otherwise indicated. BMI, body mass index (calculated as weight in kilograms divided by height in meters squared).
table 2.
Pre- and Postimmunization Titers and Immunogenicity of Healthcare Workers A (H1N1)
HAI method Before immunization, n GMT (95% CI) (unpaired t test) Seroprotection n, (%) Seroprotection After immunization, n GMT (95% CI) (unpaired t test) GMR Change in GMT Change in seroprotection Seroconversion n, (%) Seroconversion
BMI < 30
A (H3N2) BMI ≥ 30
100 100 165.6 (132–209) 227.8 (180–289) P = .060 93 (93) 100 (100) P = .014 93 97 263.6 (213–327) 313.2 (247–398) P = .30 1.64 1.35 P = .0007 P = .027 P = NS P = NS 30 (32) 32 (33) P > .05
B
BMI < 30
BMI ≥ 30
100 75.7 (62–92)
100 93.8 (78–113) P = .12
83 (83)
89 (89) P = .22
93 187.1 (154–227)
97 201.1 (161–252) P = .64
2.50 P = .0001 P = .001 37 (40)
2.13 P = .0001 P = NS 38 (39) P > .05
BMI < 30
BMI ≥ 30
100 100 23.2 (18–29) 43.5 (36–53) P = .0001 42 (42) 67 (67) P = .0004 93 97 48.3 (40–59) 52.1 (41–66) P = .65 2.14 1.2 P = .0001 P = .0521 P = .001 P = NS 25 (27) 12 (12) P = .012
MN method GMT before immunization (95% CI)
Change in GMT GMR % 4-Fold rise Change in % 4-fold increase between BMI groups % >40 Preimmunization % >40 Postimmunization Change in % >40 between BMI groups % >160 Preimmunization % >160 Postimmunization Change in % >160 between BMI groups
18.9 (14–25) 48.9 (35–68) P = .0001 2.58 43
39.7 (29–54) 932.2 (683–1273) P = .0001 23.5 88
31.0 57.7
55.0 97.9
13.0 33.0
27.0 92.6
P = .56 33.0 57.9
P = .45
7.7 (7–9) 10 (8–12) P = .01 1.3 11
74.0 94.8
6.0 9.5
46.0 84.5
0.0 3.2
P = .003
P = .87 17.0 31.6
110 (77–157) 464 (340–632) P = .0001 4.22 66
P = .39
P = .001 P = .002
6.9 (6–8) 10.8 (9–13) P = .0001 1.56 16 3.0 10.3 P = .62 1.0 1.0 P = .25
NOTE. BMI, body mass index (calculated as weight in kilograms divided by height in meters squared); GMR, geometric mean ratio; GMT, geometric mean titers; HAI, hemagglutination inhibition; NS, not significant.
response to flu vaccine in healthcare workers
GMT after immunization (95% CI)
18.8 (14–26) 46.6 (33–65) P = .0001 2.48 38
251
252 infection control & hospital epidemiology
table 3.
march 2015, vol. 36, no. 3
Comparison of Titers Declining by 4-Fold Postvaccination A (H1N1) BMI < 30
4-Fold declining titers
9.4%
A (H3N2) BMI ≥ 30
BMI < 30
35.5%
1.9%
P = .015 NOTE.
B BMI ≥ 30
BMI < 30
20.3%
0.0%
P = .002
BMI ≥30 0.0% P > .99
BMI, body mass index (calculated as weight in kilograms divided by height in meters squared).
in the nonobese (2.14, P = .0001) but not in the obese (1.2, P = .0521). The change in seroprotection between preand postimmunization phases for H1N1 was not statistically different for the obese and nonobese groups. There was a statistically significant increase with H3N2 with the nonobese group (83/100 [83%] vs 93/93 [100%], P = .001) but not with the obese group (89/100 [89%] vs 96/97 [99%], P = .5). There was a statistically significant increase with B with the nonobese group (42/100 [42%] vs 61/93 [66%], P = .001) but not with the obese group (67/100 [67%] vs 69/97 [71%], P = .5). Seroconversion was not statistically different between the nonobese and obese groups for H1N1 groups. Overall, the changes in micro-neutralization titers measured by the GMT all showed statistically significant increases. Comparing the obese and nonobese groups, there was no difference in rates of 4-fold increases in H1N1 or B titers. There was a statistically significant difference in the rate of 4-fold increase in H3N2 titers for nonobese compared with the obese group (88% [82/93] vs 66% [64/97], respectively; P = .003). There was no difference in the percent of sera achieving titer (% >40 post- after immunization) from microneutralization methods between the 2 groups (Table 2). In an ad hoc analysis we found that the obese group, compared with the nonobese group, had a statistically greater number of HCWs who had a 4-fold decrease in titers from before to after immunization with H1N1 and H3N2, as shown in Table 3.
d i s c u s s io n From the results of this study, it appears that HCWs in our institution are protected from influenza A (H1N1 and H3N2) at greater than 80% before vaccination and 99% after vaccination regardless of weight. This can be partially attributed to the combined 91% of HCWs who received the vaccine the year before. With these initial high rates it is hard to delineate the response differences between the 2 groups. There was a significant increase in seroprotection in response to influenza B vaccine for nonobese but not obese HCWs, but the higher initial rate of seroprotection of the obese HCWs confounds this observation. Historically, the seroconversion rates have been in the range of 42% to 62% after the receipt of the influenza A vaccine.13 Our rates were lower, but this is attributed to the initially high antibody titer rates, especially to the influenza A H1N1 and H3N2 strains. Seroconversion rates for influenza B have been
reported to be between 35% and 58%, compared with our study that showed 27% in the nonobese group and 12% in the obese group.13 Coleman and colleagues14 presented an abstract that suggested that obesity was not independently associated with a lower post–influenza vaccination seroprotection against the 2008–2009 vaccine components. The authors specifically looked at patients who were 50 years or older with a BMI of 30 or greater (obese) or with a BMI of less than 30 (nonobese). Nonobese patients, compared with obese patients, had a lower baseline GMT to the 3 components (H1N1, 10.4 vs 12.1; H3N2, 15 vs 5.3; and B, 51.8 vs 56.5) and a subsequent higher seroconversion rate (H1N1, 28% vs 28%; H3N2, 62% vs 73%; and B, 28% vs 34%) than our data showed. Of note, they did demonstrate a much lower rate of seroprotection for the influenza A strains but not the influenza B (H1N1, 43% vs 47%; H3N2, 76% vs 82%; and B, 95% vs 94%), compared with our study. In an ad hoc analysis of the data, an interesting trend emerged with obese HCWs having a significantly higher rate of 4-fold declining titers in the H1N1 and H3N2 groups. This generates many questions—for example, in the obese population what factors are causing this dramatic decrease in antibody titers in some HCWs who already had a titer of at least 40? Sheridan and colleagues15 reported that the pre- and postvaccination antibody titers for the 3 vaccine strains studied were not significantly different between the obese and nonobese participants. They did, however, report that there was a significantly higher increase to the influenza B component in obese versus nonobese participants. Interestingly, similar to our results, they reported that there was a difference between the 2 groups at the 12-month follow-up with the obese participants showing a greater number of at least 4-fold decreases in HAI titers.
co nclu sio n There were no significant differences between immunity to influenza between obese and nonobese HCWs after immunization. There are some data suggesting the immunization response may be less in some obese HCWs.
acknowledgments Financial support. American Society of Health-System Pharmacists Foundation (Fostering Young Investigators Research Grant to M.S.).
response to flu vaccine in healthcare workers
Potential conflicts of interest. All authors report no conflicts of interest relevant to this article. Address correspondence to Michael A. Sweet, PharmD, Center for Quality Outcomes, West Virginia University Hospitals, PO Box 8242, Morgantown, WV 26506-8242 ([email protected]).
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