Background Evidence regarding the mortality rate after administration of the pandemic influenza A (H1N1) 2009 vaccine on patients with underlying diseases is currently scarce. We conducted a case-control study in Japan to compare the mortality rates of patients with idiopathic interstitial pneumonia after the vaccines were administered and were not administered. Methods Between October 2009 and March 2010, we collected clinical records in Japan and conducted a 1:1 matched case-control study. Patients with idiopathic interstitial pneumonia who died during this period were considered case patients, and those who survived were considered control patients. We determined and compared the proportion of each group that received the pandemic influenza A (H1N1) 2009 vaccine and estimated the odds ratio. Finally, we conducted simulations that compensated for the shortcomings of the study associated with adjusted severity of idiopathic interstitial pneumonia. Results The case and control groups each comprised of 75 patients with idiopathic interstitial pneumonia. The proportion of patients who received the pandemic influenza A (H1N1) 2009 vaccine was 30.7% and 38.7% for the case and control groups, respectively. During that winter, the crude conditional odds ratio of mortality was 0.63 (95% confidence interval, 0.25–1.47) and the adjusted conditional odds ratio was 1.18 (95% confidence interval, 0.33–4.49); neither was significant. The simulation study showed more accurate conditional odds ratios of 0.63–0.71. Conclusions In our study, we detected no evidence that the influenza A (H1N1) 2009 vaccine increased the mortality rate of patients with idiopathic interstitial pneumonia. The results, however, are limited by the small sample size and low statistical power. A larger-scale study is required.
References
[1]
New influenza A (H1N1) virus: global epidemiological situation, June 2009. Wkly Epidemiol Rec 84: 249–257.
[2]
Centers for Disease Control and Prevention (2009) Serum cross-reactive antibody response to a novel influenza A (H1N1) virus after vaccination with seasonal influenza vaccine. MMWR Morb Mortal Wkly Rep 58: 521–524.
Geier MR, Geier DA, Zahalsky AC (2003) Influenza vaccination and Guillain Barre syndrome small star, filled. Clin Immunol 107: 116–121. doi: 10.1016/s1521-6616(03)00046-9
[5]
Saito H, Endo M, Takase S, Itahara K (1980) Acute disseminated encephalomyelitis after influenza vaccination. Arch Neurol 37: 564–566. doi: 10.1001/archneur.1980.00500580060009
[6]
Centers for Disease Control and Prevention (2013) Seasonal flu shot. Available: http://www.cdc.gov/flu/about/qa/flushot.？htm. Accessed 2013 July 31.
[7]
Vellozzi C, Broder KR, Haber P, Guh A, Nguyen M, et al. (2010) Adverse events following influenza A (H1N1) 2009 monovalent vaccines reported to the Vaccine Adverse Event Reporting System, United States, October 1, 2009-January 31, 2010. Vaccine 28: 7248–7255. doi: 10.1016/j.vaccine.2010.09.021
[8]
Jacobsen SJ, Poland GA (2011) Methods in vaccine effectiveness and safety studies: a critical need for vaccine confidence. Vaccine 29: 9573–9574. doi: 10.1016/j.vaccine.2011.10.078
[9]
Ministry of Health, Labour Welfare, Japan (2010 (1)) Available: http://www.mhlw.go.jp/kinkyu/kenkou/infl？uenza/houdou/2010/03/dl/infuh0305-01.pdf. Accessed 31 July 2013.
[10]
Ministry of Health, Labour Welfare, Japan (2010 (2)) Available: http://www.mhlw.go.jp/shingi/2010/03/dl/？s0312-12e.pdf. Accessed 31 July 2013.
Longo DL (2012) Interstitial lung diseases. Harrison’s principles of internal medicine. 18th ed. New York: McGraw-Hill. 2165–2170.
[13]
World Health Organization/SAGE (2009) Experts advise WHO on pandemic vaccine policies and strategies. Geneva: World Health Organization.
[14]
Cecil RL, Goldman L, Ausiello DA (2004) Interstitial lung disease. Cecil textbook of medicine. 22nd ed. Philadelphia.: Saunders. 526–527.
[15]
Rothman KJ, Greenland S, Lash TL (2008) Modern epidemiology. 3rd ed. Philadelphia: Wolters Kluwer Health/Lippincott Williams & Wilkins. pp. x, 758 p.
[16]
Lachin JM (2011) The assessment of relative risks. Biostatistical methods. 2nd ed. New Jersey: John Wiley & Sons, Inc. 201–246.
[17]
Little R, Rubin D (2002) Statistical analysis with missing data. New York: Wiley.
[18]
Nakada H, Narimatsu H, Tsubokura M, Murashige N, Matsumura T, et al. (2010) Risk of fatal adverse events after H1N1 influenza vaccination. Clin Infect Dis 50: 1548–1549. doi: 10.1086/652719
[19]
McNeil MM, Broder KR, Vellozzi C, DeStefano F (2010) Risk of fatal adverse events after H1N1 influenza vaccine: limitations of passive surveillance data. Clin Infect Dis 51: 871–872; author reply 872–873.
[20]
Nakada H, Murashige N, Matsumura T, Kodama Y, Kami M (2010) Informal network of communication tools played an important role in sharing safety information on H1N1 influenza vaccine. Clin Infect Dis 51: 873–874. doi: 10.1086/656297
[21]
Simonsen L, Taylor RJ, Viboud C, Miller MA, Jackson LA (2007) Mortality benefits of influenza vaccination in elderly people: an ongoing controversy. Lancet Infect Dis 7: 658–666. doi: 10.1016/s1473-3099(07)70236-0
[22]
Berlin JA, Glasser SC, Ellenberg SS (2008) Adverse event detection in drug development: recommendations and obligations beyond phase 3. Am J Public Health 98: 1366–1371. doi: 10.2105/ajph.2007.124537
[23]
Folkenberg M, Callréus T, Svanstr？m H, Valentiner-Branth P, Hviid A (2011) Spontaneous reporting of adverse events following immunisation against pandemic influenza in Denmark November 2009–March 2010. Vaccine 29: 1180–1184. doi: 10.1016/j.vaccine.2010.12.008
[24]
Safety of influenza A (H1N1) 2009 monovalent vaccines - United States, October 1-November 24, 2009. MMWR Morb Mortal Wkly Rep 58: 1351–1356.
[25]
Liang XF, Li L, Liu DW, Li KL, Wu WD, et al. (2011) Safety of influenza A (H1N1) vaccine in postmarketing surveillance in China. N Engl J Med 364: 638–647. doi: 10.1056/nejmoa1008553
[26]
Liang XF, Wang HQ, Wang JZ, Fang HH, Wu J, et al. (2010) Safety and immunogenicity of 2009 pandemic influenza A H1N1 vaccines in China: a multicentre, double-blind, randomised, placebo-controlled trial. Lancet 375: 56–66. doi: 10.1016/s0140-6736(09)62003-1
[27]
Vajo Z, Tamas F, Sinka L, Jankovics I (2010) Safety and immunogenicity of a 2009 pandemic influenza A H1N1 vaccine when administered alone or simultaneously with the seasonal influenza vaccine for the 2009–10 influenza season: a multicentre, randomised controlled trial. Lancet 375: 49–55. doi: 10.1016/s0140-6736(09)62039-0
[28]
Greenberg ME, Lai MH, Hartel GF, Wichems CH, Gittleson C, et al. (2009) Response to a monovalent 2009 influenza A (H1N1) vaccine. N Engl J Med 361: 2405–2413. doi: 10.1056/nejmoa0907413
[29]
Plennevaux E, Sheldon E, Blatter M, Reeves-Hoché MK, Denis M (2010) Immune response after a single vaccination against 2009 influenza A H1N1 in USA: a preliminary report of two randomised controlled phase 2 trials. Lancet 375: 41–48. doi: 10.1016/s0140-6736(09)62026-2
[30]
Mallory RM, Malkin E, Ambrose CS, Bellamy T, Shi L, et al. (2010) Safety and immunogenicity following administration of a live, attenuated monovalent 2009 H1N1 influenza vaccine to children and adults in two randomized controlled trials. PLOS ONE 5: e13755. doi: 10.1371/journal.pone.0013755
[31]
Manzoli L, De Vito C, Salanti G, D’Addario M, Villari P, et al. (2011) Meta-analysis of the immunogenicity and tolerability of pandemic influenza A 2009 (H1N1) vaccines. PLOS ONE 6: e24384. doi: 10.1371/journal.pone.0024384
[32]
Lertdumrongluk P, Changsirikulchai S, Limkunakul C, Prachukthum P, Punpiput P, et al. (2012) Safety and immunogenicity of a 2009 influenza A (H1N1) vaccine in hemodialysis patients. Vaccine 30: 1108–1114. doi: 10.1016/j.vaccine.2011.12.023
[33]
Chang YT, Guo CY, Tsai MS, Cheng YY, Lin MT, et al. (2012) Poor immune response to a standard single dose non-adjuvanted vaccination against 2009 pandemic H1N1 influenza virus A in the adult and elder hemodialysis patients. Vaccine 30: 5009–5018. doi: 10.1016/j.vaccine.2012.05.016
[34]
Yanagisawa N, Maeda K, Ajisawa A, Imamura A, Suganuma A, et al. (2011) Reduced immune response to influenza A (H1N1) 2009 monovalent vaccine in HIV-infected Japanese subjects. Vaccine 29: 5694–5698. doi: 10.1016/j.vaccine.2011.06.003
[35]
Flynn PM, Nachman S, Muresan P, Fenton T, Spector SA, et al. (2012) Safety and immunogenicity of 2009 pandemic H1N1 influenza vaccination in perinatally HIV-1-infected children, adolescents, and young adults. J Infect Dis 206: 421–430. doi: 10.1093/infdis/jis360
[36]
Manuel O, Pascual M, Hoschler K, Giulieri S, Alves D, et al. (2011) Humoral response to the influenza A H1N1/09 monovalent AS03-adjuvanted vaccine in immunocompromised patients. Clin Infect Dis 52: 248–256. doi: 10.1093/cid/ciq104
[37]
Launay O, Desaint C, Durier C, Loulergue P, Duval X, et al. (2011) Safety and immunogenicity of a monovalent 2009 influenza A/H1N1v vaccine adjuvanted with AS03A or unadjuvanted in HIV-infected adults: a randomized, controlled trial. J Infect Dis 204: 124–134. doi: 10.1093/infdis/jir211
[38]
Phongsamart W, Sirisanthana V, Wittawatmongkol O, Maleesatharn A, Sudjaritruk T, et al. (2011) Immunogenicity and safety of monovalent influenza A (H1N1) 2009 in HIV-infected Thai children. Vaccine 29: 8705–8711. doi: 10.1016/j.vaccine.2011.08.101
[39]
Lagler H, Grabmeier-Pfistershammer K, Touzeau-Romer V, Tobudic S, Ramharter M, et al. (2012) Immunogenicity and tolerability after two doses of non-adjuvanted, whole-virion pandemic influenza A (H1N1) vaccine in HIV-infected individuals. PLOS ONE 7: e36773. doi: 10.1371/journal.pone.0036773
[40]
Rousseau B, Loulergue P, Mir O, Krivine A, Kotti S, et al. (2012) Immunogenicity and safety of the influenza A H1N1v 2009 vaccine in cancer patients treated with cytotoxic chemotherapy and/or targeted therapy: the VACANCE study. Ann Oncol 23: 450–457. doi: 10.1093/annonc/mdr141
[41]
Lagler H, Tobudic S, Ramharter M, Elandt K, Sperr WR, et al. (2012) Pandemic whole-virion, Vero-cell-derived, adjuvant-free influenza A H1N1 vaccine in patients with solid tumors and hematologic malignancies receiving concurrent anticancer treatment: Immunogenicity, tolerability, and acceptability during the pandemic situation. Vaccine 30: 6864–6870. doi: 10.1016/j.vaccine.2012.09.005
[42]
Lu CC, Wang YC, Lai JH, Lee TSH, Lin HT, et al. (2011) A/H1N1 influenza vaccination in patients with systemic lupus erythematosus: safety and immunity. Vaccine 29: 444–450. doi: 10.1016/j.vaccine.2010.10.081
[43]
Borba EF, Saad CGS, Pasoto SG, Calich ALG, Aikawa NE, et al. (2012) Influenza A/H1N1 vaccination of patients with SLE: can antimalarial drugs restore diminished response under immunosuppressive therapy? Rheumatology 51: 1061–1069. doi: 10.1093/rheumatology/ker427
[44]
Busse WW, Peters SP, Fenton MJ, Mitchell H, Bleecker ER, et al. (2011) Vaccination of patients with mild and severe asthma with a 2009 pandemic H1N1 influenza virus vaccine. J Allergy Clin Immunol 127: 130–U215. doi: 10.1016/j.jaci.2010.11.014
[45]
Ristow SC, Douglas RG Jr, Condemi JJ (1978) Influenza vaccination of patients with systemic lupus erythematosus. Ann Intern Med 88: 786–789. doi: 10.7326/0003-4819-88-6-786
[46]
Williams GW, Steinberg AD, Reinertsen JL, Klassen LW, Decker JL, et al. (1978) Influenza immunization in systemic lupus eruthematosus. A double-blind trial. Ann Intern Med 88: 729–734. doi: 10.7326/0003-4819-88-6-729
[47]
Abu-Shakra M, Press J, Varsano N, Levy V, Mendelson E, et al. (2002) Specific antibody response after influenza immunization in systemic lupus erythematosus. J Rheumatol 29: 2555–2557.
[48]
Holvast A, Huckriede A, Wilschut J, Horst G, De Vries JJ, et al. (2006) Safety and efficacy of influenza vaccination in systemic lupus erythematosus patients with quiescent disease. Ann Rheum Dis 65: 913–918. doi: 10.1136/ard.2005.043943
[49]
Brodman R, Gilfillan R, Glass D, Schur PH (1978) Influenzal vaccine response in systemic lupus erythematosus. Ann Intern Med 88: 735–740. doi: 10.7326/0003-4819-88-6-735
[50]
Louie JS, Nies KM, Shoji KT, Fraback RC, Abrass C, et al. (1978) Clinical and antibody responses after influenza immunization in systemic lupus erythematosus. Ann Intern Med 88: 790–792. doi: 10.7326/0003-4819-88-6-790
[51]
Herron A, Dettleff G, Hixon B, Brandwin L, Ortbals D, et al. (1979) Influenza vaccination in patients with rheumatic diseases. Safety and efficacy. JAMA 242: 53–56. doi: 10.1001/jama.1979.03300010037025
[52]
Chalmers A, Scheifele D, Patterson C, Williams D, Weber J, et al. (1994) Immunization of patients with rheumatoid arthritis against influenza: a study of vaccine safety and immunogenicity. J Rheumatol 21: 1203–1206.
[53]
Del Porto F, Lagana B, Biselli R, Donatelli I, Campitelli L, et al. (2006) Influenza vaccine administration in patients with systemic lupus erythematosus and rheumatoid arthritis. Safety and immunogenicity. Vaccine 24: 3217–3223. doi: 10.1016/j.vaccine.2006.01.028
[54]
Kunisaki KM, Janoff EN (2009) Influenza in immunosuppressed populations: a review of infection frequency, morbidity, mortality, and vaccine responses. Lancet Infect Dis 9: 493–504. doi: 10.1016/s1473-3099(09)70175-6
[55]
de Roux A, Marx A, Burkhardt O, Schweiger B, Borkowski A, et al. (2006) Impact of corticosteroids on the immune response to a MF59-adjuvanted influenza vaccine in elderly COPD-patients. Vaccine 24: 1537–1542. doi: 10.1016/j.vaccine.2005.10.007
[56]
Hanania NA, Sockrider M, Castro M, Holbrook JT, Tonascia J, et al. (2004) Immune response to influenza vaccination in children and adults with asthma: effect of corticosteroid therapy. J Allergy Clin Immunol 113: 717–724. doi: 10.1016/j.jaci.2003.12.584
Parretta E, Ianniello B, Ferrazin F, Rossi F, Capuano A (2011) Italian post-marketing surveillance for adverse event reports after MF59-adjuvanted H1N1v vaccination. Vaccine 29: 3708–3713. doi: 10.1016/j.vaccine.2011.02.097
[59]
Tavares F, Nazareth I, Monegal JS, Kolte I, Verstraeten T, et al. (2011) Pregnancy and safety outcomes in women vaccinated with an AS03-adjuvanted split virion H1N1 (2009) pandemic influenza vaccine during pregnancy: a prospective cohort study. Vaccine 29: 6358–6365. doi: 10.1016/j.vaccine.2011.04.114
[60]
Jackson LA, Patel SM, Swamy GK, Frey SE, Creech CB, et al. (2011) Immunogenicity of an inactivated monovalent 2009 H1N1 influenza vaccine in pregnant women. J Infect Dis 204: 854–863. doi: 10.1093/infdis/jir440
[61]
Munoz FM (2012) Safety of influenza vaccines in pregnant women. Am J Obstet Gynecol 207: S33–S37. doi: 10.1016/j.ajog.2012.06.072
[62]
Amendola A, Boschini A, Colzani D, Anselmi G, Oltolina A, et al. (2001) Influenza vaccination of HIV-1-positive and HIV-1-negative former intravenous drug users. J Med Virol 65: 644–648. doi: 10.1002/jmv.2085
[63]
Mamula P, Markowitz JE, Piccoli DA, Klimov A, Cohen L, et al. (2007) Immune response to influenza vaccine in pediatric patients with inflammatory bowel disease. Clin Gastroenterol Hepatol 5: 851–856. doi: 10.1016/j.cgh.2007.02.035
[64]
World Health Organization (2009) Global Alert and Response (GAR). Pandemic influenza vaccines: current status. briefing note 11. Available: http://www.who.int/csr/disease/swineflu/？notes/pandemic_influenza_vaccines_200909？24/en/index.html. Accessed 2013 July 31.
[65]
Eurich DT, Marrie TJ, Johnstone J, Majumdar SR (2008) Mortality reduction with influenza vaccine in patients with pneumonia outside “flu” season pleiotropic benefits or residual confounding? Am J Respir Criti Care Med 178: 527–533. doi: 10.1164/rccm.200802-282oc
[66]
？rtqvist ？, Granath F, Askling J, Hedlund J (2007) Influenza vaccination and mortality: prospective cohort study of the elderly in a large geographical area. Eur Respir J 30: 414–422. doi: 10.1183/09031936.00135306
[67]
Shrank WH, Patrick AR, Brookhart MA (2011) Healthy user and related biases in observational studies of preventive interventions: a primer for physicians. J Gen Intern Med 26: 546–550. doi: 10.1007/s11606-010-1609-1
