Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress
Clinical Collections
Advances in Alzheimer’s

At a glance: The ONWARDS insulin icodec trials

A round-up of the ONWARDS phase 3 clinical trials evaluating the novel weekly insulin icodec in people with diabetes.
ADVANCED SEARCH
Log in
Top
BMC Infectious Diseases
Published in: BMC Infectious Diseases 1/2012

Open Access 01-12-2012 | Research article

Prospective hospital-based case–control study to assess the effectiveness of pandemic influenza A(H1N1)pdm09 vaccination and risk factors for hospitalization in 2009–2010 using matched hospital and test-negative controls

Authors: Wiebke Hellenbrand, Pernille Jorgensen, Brunhilde Schweiger, Gerhard Falkenhorst, Matthias Nachtnebel, Benedikt Greutélaers, Christian Traeder, Ole Wichmann

Published in: BMC Infectious Diseases | Issue 1/2012

Login to get access

Abstract

Background

We performed a case–control study to estimate vaccine effectiveness (VE) for prevention of hospitalization due to pandemic influenza A(H1N1)pdm09 (pH1N1) and to identify risk factors for pH1N1 and acute respiratory infection (ARI) in 10 hospitals in Berlin from December 2009 to April 2010.

Methods

Cases were patients aged 18–65 years with onset of ARI ≤10 days before admission testing positive for pH1N1 by PCR performed on nasal and throat swabs or by serological testing. Cases were compared to (1) matched hospital controls with acute surgical, traumatological or other diagnoses matched on age, sex and vaccination probability, and (2) ARI patients testing negative for pH1N1. Additionally, ARI cases were compared to matched hospital controls. A standardized interview and chart review elicited demographic and clinical data as well as potential risk factors for pH1N1/ARI. VE was estimated by 1-(Odds ratio) for pH1N1-vaccination ≥10 days before symptom onset using exact logistic regression analysis.

Results

Of 177 ARI cases recruited, 27 tested pH1N1 positive. A monovalent AS03-adjuvanted pH1N1 vaccine was the only pandemic vaccine type identified among cases and controls (vaccination coverage in control group 1 and 2: 15% and 5.9%). The only breakthrough infections were observed in 2 of 3 vaccinated HIV positive pH1N1 patients. After exclusion of HIV positive participants, VE was 96% (95%CI: 26-100%) in the matched multivariate analysis and 46% (95%CI: -376-100%) in the test-negative analysis. Exposure to children in the household was independently associated with hospitalization for pH1N1 and ARI.

Conclusions

Though limited by low vaccination coverage and number of pH1N1 cases, our results suggest a protective effect of the AS03-adjuvanted pH1N1 vaccine for the prevention of pH1N1 hospitalization. The use of hospital but not test-negative controls showed a statistically protective effect of pH1N1-vaccination and permitted the integrated assessment of risk factors for pH1N1-infection. To increase statistical power and to permit stratified analyses (e.g. VE for specific risk groups), the authors suggest pooling of future studies assessing effectiveness of influenza vaccines for prevention of severe disease from different centres.
Appendix
Available only for authorised users
Literature
1.
2.
Perez-Padilla R, de la Rosa-Zamboni D, Ponce de Leon S, Hernandez M, Quinones-Falconi F, Bautista E, Ramirez-Venegas A, Rojas-Serrano J, Ormsby CE, Corrales A, et al: Pneumonia and respiratory failure from swine-origin influenza A (H1N1) in Mexico. N Engl J Med. 2009, 361: 680-689. 10.1056/NEJMoa0904252.CrossRefPubMed
3.
Poggensee G, Gilsdorf A, Buda S, Eckmanns T, Claus H, Altmann D, Krause G, Haas W, RKI Working Group: The first wave of pandemic influenza (H1N1) 2009 in Germany: from initiation to acceleration. BMC Infect Dis. 2010, 10: 155-10.1186/1471-2334-10-155.CrossRefPubMedPubMedCentral
4.
Roman F, Vaman T, Gerlach B, Markendorf A, Gillard P, Devaster JM: Immunogenicity and safety in adults of one dose of influenza A H1N1v 2009 vaccine formulated with and without AS03A-adjuvant: preliminary report of an observer-blind, randomised trial. Vaccine. 2010, 28: 1740-1745. 10.1016/j.vaccine.2009.12.014.CrossRefPubMed
5.
Roman F, Vaman T, Kafeja F, Hanon E, Van Damme P: AS03A-adjuvanted influenza A (H1N1) 2009 vaccine for adults up to 85 years of age. Clin Infect Dis. 2010, 51: 668-677. 10.1086/655830.CrossRefPubMed
6.
Gilsdorf A, Poggensee G: Working group pandemic influenza A(H1N1)v: influenza A(H1N1)v in Germany: the first 10,000 cases. Euro Surveill. 2009, 14: 1-4.
7.
Walter D, Heiden Mad, Reiter S, Krause G, Wichmann O: Monitoring pandemic influenza A(H1N1) vaccination coverage in Germany 2009/10 - results from thirteen consecutive cross-sectional surveys. Vaccine. 2011, 29: 4008-4012. 10.1016/j.vaccine.2011.03.069.CrossRefPubMed
8.
9.
Demicheli V, Di PC, Jefferson T, Rivetti A, Rivetti D: Vaccines for preventing influenza in healthy adults. Cochrane Database Syst Rev. 2007, CD001269-2
10.
Jefferson T, DiPietrantonj C, Rivetti A, Bawazeer GA, Al-Ansary LA, Ferroni E: Vaccines for preventing influenza in the elderly (Review). Cochrane Database Syst Rev. 2010, CD004876-7
11.
Koch-Institut R: Telefonische Erhebung zur Impfung gegen die pandemische Influenza (H1N1) 2009 [Telephone survey regarding vaccination against pandemic influenza (H1N1) 2009]. Epidemiol Bull. 2010, 13: 114-115.
12.
Schulze M, Nitsche A, Schweiger B, Biere B: Diagnostic approach for the differentiation of the pandemic influenza A(H1N1)v virus from recent human influenza viruses by real-time PCR. PLoS One. 2010, 5: e9966-10.1371/journal.pone.0009966.CrossRefPubMedPubMedCentral
13.
Biere B, Bauer B, Schweiger B: Differentiation of influenza B virus lineages yamagata and victoria by real-time PCR. J Clin Microbiol. 2010, 48: 1425-1427. 10.1128/JCM.02116-09.CrossRefPubMedPubMedCentral
14.
Rowe T, Abernathy RA, Hu-Primmer J, Thompson WW, Lu X, Lim W, Fukuda K, Cox NJ, Katz JM: Detection of antibody to avian influenza A (H5N1) virus in human serum by using a combination of serologic assays. J Clin Microbiol. 1999, 37: 937-943.PubMedPubMedCentral
15.
Cowling BJ, Chan KH, Fang VJ, Lau LLH, So HC, Fung ROP, Ma ESK, Kwong ASK, Chan CW, Tsui WWS, et al: Comparative epidemiology of pandemic and seasonal influenza A in households. N Engl J Med. 2010, 362: 2175-2184. 10.1056/NEJMoa0911530.CrossRefPubMedPubMedCentral
16.
De Serres G, Rouleau I, Hamelin M-È, Quach C, Skworonski D, Flamand L, Boulianne N, Li Y, Carbonneau J, Bourgault A-M, et al: Contagious period for pandemic (H1N1) 2009. Emerg Infect Dis. 2010, 16: 783-788. 10.3201/eid1605.091894.CrossRefPubMedPubMedCentral
17.
Suess T, Buchholz U, Dupke S, Grunow R, Matthias an dH, Heider A, Biere B, Schweiger B, Haas W, Krause G, et al: Shedding and transmission of novel influenza virus A/H1N1 infection in households--Germany, 2009. Am J Epidemiol. 2010, 171: 1157-1164. 10.1093/aje/kwq071.CrossRefPubMed
18.
Lee N, Chan PK, Hui D, Rainer TH, Wong E, Choi K-W, Lui GC, Wong BC, Wong RY, Lam W-Y, et al: Viral loads and duration of viral shedding in adult patients hospitalized with influenza. J Infect Dis. 2009, 200: 492-500. 10.1086/600383.CrossRefPubMed
19.
Leekha S, Zitterkopf NL, Espy MJ, Smith TF, Thompson RL, Sampathkumar P: Duration of Influenza A shedding in hospitalized patients and implications for infection control. Infect Control Hosp Epidemiol. 2007, 28: 1071-1076. 10.1086/520101.CrossRefPubMed
20.
Arbeitsgemeinschaft Influenza: Bericht zur Epidemiologie der Influenza in Deutschland Saison 2009/10. 2011, Robert Koch-Institute, Berlin
21.
Puig-Barberà J, Arnedo-Pena A, Pardo-Serrano F, Tirado-Balaguer MD, Pérez-Vilar S, Silvestre-Silvestre E, Calvo-Mas C, Safont-Adsuara L, Ruiz-García M: Effectiveness of seasonal 2008–2009, 2009–2010 and pandemic vaccines, to prevent influenza hospitalizations during the autumn 2009 influenza pandemic wave in Castellón, Spain. A test-negative, hospital-based, case–control study. Vaccine. 2010, 28: 7460-7467. 10.1016/j.vaccine.2010.09.042.CrossRefPubMed
22.
Nicholson KG, Abrams KR, Batham S, Clark TW, Hoschler K, Lim WS, Medina MJ, Nguyen-Van-Tam JS, Read RC, Warren FC, et al: Immunogenicity and safety of a two-dose schedule of whole-virion and AS03A-adjuvanted 2009 influenza A (H1N1) vaccines: a randomised, multicentre, age-stratified, head-to-head trial. Lancet Infect Dis. 2011, 11: 91-101. 10.1016/S1473-3099(10)70296-6.CrossRefPubMed
23.
24.
Van Buynder PG, Dhaliwal JK, Van Buynder JL, Couturier C, Minville-Leblanc M, Garceau R, Tremblay FW: Protective effect of single-dose adjuvanted pandemic influenza vaccine in children. Influenza Other Respi Viruses. 2010, 4: 171-178. 10.1111/j.1750-2659.2010.00146.x.CrossRef
25.
Valenciano M, Kissling E, Cohen JM, Oroszi B, Barret AS, Rizzo C, Nunes B, Pitigoi D, Larrauri Cámara A, Mosnier A, et al: Estimates of pandemic influenza vaccine effectiveness in Europe, 2009–2010: results of influenza monitoring vaccine effectiveness in Europe (I-MOVE) multicentre case–control study. PLoS Med. 2011, 8: e1000388-10.1371/journal.pmed.1000388.CrossRefPubMedPubMedCentral
26.
Simpson CR, Ritchie LD, Robertson C, Sheikh A, McMenamin J: Vaccine effectiveness in pandemic influenza – primary care reporting (VIPER): an observational study to assess the effectiveness of the pandemic influenza A (H1N1)v vaccine. Health Technol Assess. 2010, 14: 313-346.PubMed
27.
Williams C, Schweiger B, Diner G, Gerlach F, Haaman F, Krause G, Nienhaus A, Buchholz U: Seasonal influenza risk in hospital healthcare workers is more strongly associated with household than occupational exposures: results from a prospective cohort study in Berlin, Germany, 2006/07. BMC Infect Dis. 2010, 10: 8-10.1186/1471-2334-10-8.CrossRefPubMedPubMedCentral
28.
Emborg H-D, Krause TG, Hviid A, Simonsen J, Molbak K: Effectiveness of vaccine against pandemic influenza A/H1N1 among people with underlying chronic diseases: cohort study, Denmark, 2009–10. BMJ. 2012, 344: d7901-CrossRef
29.
Skowronski DM, Janjua NZ, De Serres G, Hottes TS, Dickinson JA, Crowcroft N, Kwindt TL, Tang P, Charest H, Fonseca K, et al: Effectiveness of AS03 adjuvanted pandemic H1N1 vaccine: case–control evaluation based on sentinel surveillance system in Canada, autumn 2009. BMJ. 2011, 342: c7297-10.1136/bmj.c7297.CrossRefPubMedPubMedCentral
30.
Andrews N, Waight P, Yung CF, Miller E: Age-specific effectiveness of an oil-in-water adjuvanted pandemic (H1N1) 2009 vaccine against confirmed infection in high risk groups in England. J Infect Dis. 2011, 203: 32-39. 10.1093/infdis/jiq014.CrossRefPubMedPubMedCentral
31.
Ortqvist A, Berggren I, Insulander M, de Jong B, Svenungsson B: Effectiveness of an adjuvanted monovalent vaccine against the 2009 pandemic strain of influenza a(H1N1)v in stockholm county, Sweden. Clin Infect Dis. 2011, 52: 1203-1211. 10.1093/cid/cir182.CrossRefPubMed
32.
Castilla J, Morán J, Martinez-Artola V, Fernández-Alonso M, Guevara M, Cenoz MG, Reina G, Alvarez N, Arriazu M, Elía F, et al: Effectiveness of the monovalent influenza A(H1N1)2009 vaccine in Navarre, Spain, 2009–2010: cohort and case–control study. Vaccine. 2011, 29: 5919-5924. 10.1016/j.vaccine.2011.06.063.CrossRefPubMed
33.
Bickel M, Wieters I, Khaykin P, Nisius G, Haberl A, Stephan C, Von HN, Herrmann E, Doerr HW, Brodt HR, et al: Low rate of seroconversion after vaccination with a split virion, adjuvanted pandemic H1N1 influenza vaccine in HIV-1-infected patients. AIDS. 2010, 24: F31-F35. 10.1097/QAD.0b013e3283398da1.CrossRefPubMed
34.
Tremblay CL, Rouleau D, Fortin C, Toma E, Sylla M, Cyr L, Cote S, Baz M, Sampalis J, Trautman L, et al: Immunogenicity and tolerability of an inactivated and adjuvanted pandemic H1N1 influenza vaccine, in HIV-1-infected patients. Vaccine. 2011, 29: 1359-1363. 10.1016/j.vaccine.2010.12.023.CrossRefPubMed
35.
Robert Koch-Institut: Repräsentative telefonische Erhebung zur Impfung gegen die pandemische Influenza (H1N1) 2009. Ergebnisse aus Befragungen bis April 2010 [Representative telephone survey on vaccination against pandemic influenza (H1N1) 2009. Results to April 2010]. Epidemiol Bull. 2010, 25: 237-238.
36.
Skull SA, Andrews RM, Byrnes GB, Kelly HA, Nolan TM, Brown GV, Campbell DA: Validity of self-reported influenza and pneumococcal vaccination status among a cohort of hospitalized elderly inpatients. Vaccine. 2007, 25: 4775-4783. 10.1016/j.vaccine.2007.04.015.CrossRefPubMed
37.
Grimes DA, Schulz KF: Compared to what? Finding controls for case–control studies. Lancet. 2005, 365: 1429-1433. 10.1016/S0140-6736(05)66379-9.CrossRefPubMed
38.
Wacholder S, McLaughlin JK, Silverman DK, Mandel JS: Selection of controls in case–control studies I.Principles. Am J Epidemiol. 1992, 135: 1019-1028.PubMed
39.
Wacholder S, Silverman DK, McLaughlin JK, Mandel JS: Selection of Controls in Case–control Studies II. Types of Controls. Am J Epidemiol. 1992, 135: 1029-1041.PubMed
40.
Valenciano M, Kissling E, Ciancio BC, Moren A: Study designs for timely estimation of influenza vaccine effectiveness using European sentinel practitioner networks. Vaccine. 2010, 28: 7381-7388. 10.1016/j.vaccine.2010.09.010.CrossRefPubMed
41.
Orenstein EW, De Serres G, Haber MJ, Shay DK, Bridges CB, Gargiullo P, Orenstein WA: Methodologic issues regarding the use of three observational study designs to assess influenza vaccine effectiveness. Int J Epidemiol. 2007, 36: 623-631. 10.1093/ije/dym021.CrossRefPubMed
42.
Skowronski DM, De SG, Crowcroft NS, Janjua NZ, Boulianne N, Hottes TS, Rosella LC, Dickinson JA, Gilca R, Sethi P, et al: Association between the 2008–09 seasonal influenza vaccine and pandemic H1N1 illness during Spring-Summer 2009: four observational studies from Canada. PLoS Med. 2010, 7: e1000258-10.1371/journal.pmed.1000258.CrossRefPubMedPubMedCentral
43.
Janjua NZ, Skowronski DM, Hottes TS, Osei W, Adams E, Petric M, Sabaiduc S, Chan T, Mak A, Lem M, et al: Seasonal influenza vaccine and increased risk of pandemic A/H1N1-related illness: first detection of the association in British Columbia, Canada. Clin Infect Dis. 2010, 51: 1017-1027. 10.1086/656586.CrossRefPubMed
44.
45.
Iuliano AD, Reed C, Guh A, Desai M, Dee DL, Kutty P, Gould LH, Sotir M, Grant G, Lynch M, et al: Notes from the field: outbreak of 2009 pandemic influenza a (H1N1) virus at a large public university in Delaware, April-May 2009. Clin Infect Dis. 2009, 49: 1811-1820. 10.1086/649555.CrossRefPubMed
46.
Kelly HA, Grant KA, Fielding JE, Carville KS, Looker CO, Tran T, Jacoby P: Pandemic influenza H1N1 2009 infection in Victoria, Australia: no evidence for harm or benefit following receipt of seasonal influenza vaccine in 2009. Vaccine. 2011, 29: 6419-6426. 10.1016/j.vaccine.2011.03.055.CrossRefPubMed
47.
Pebody R, Andrews N, Waight P, Malkani R, McCartney C, Ellis J, Miller E: No effect of 2008/09 seasonal influenza vaccination on the risk of pandemic H1N1 2009 influenza infection in England. Vaccine. 2011, 29: 2613-2618. 10.1016/j.vaccine.2011.01.046.CrossRefPubMed
48.
Echevarría-Zuno S, Mejía-Aranguré JM, Mar-Obeso AJ, Grajales-Muniz C, Robles-Pérez E, González-León M, Ortega-Alvarez MC, Gonzalez-Bonilla C, Rascón-Pacheco RA, Borja-Aburto VH: Infection and death from influenza A H1N1 virus in Mexico: a retrospective analysis. Lancet. 2009, 374: 2072-2079. 10.1016/S0140-6736(09)61638-X.CrossRefPubMed
49.
Garcia-Garcia L, Valdespino-Gomez JL, Lazcano-Ponce E, Jimenez-Corona A, Higuera-Iglesias A, Cruz-Hervert P, Cano-Arellano B, Garcia-Anaya A, Ferreira-Guerrero E, Baez-Saldana R, et al: Partial protection of seasonal trivalent inactivated vaccine against novel pandemic influenza A/H1N1 2009: case–control study in Mexico City. BMJ. 2009, 339: b3928-10.1136/bmj.b3928.CrossRefPubMedPubMedCentral
50.
Glezen WP: How did the 2008−2009 seasonal influenza vaccine affect the pandemic?. Clin Infect Dis. 2010, 51: 1380-1382. 10.1086/657312.CrossRefPubMed
51.
52.
Mercer G, Kelly H: Seasonal influenza vaccination and the 2009 pandemic. Clin Infect Dis. 2011, 52: 828-829. 10.1093/cid/cir035.CrossRefPubMed
53.
Buda S, Köpke K, Haas W: Epidemiologischer Steckbrief der pandemischen Influenza (H1N1) 2009 basierend auf Einzelfallmeldungen nach Infektionsschutzgesetz. Bundesgesundheitsbl - Gesundheitsforsch - Gesundheitsschutz. 2010, 53: 1223-1230. 10.1007/s00103-010-1158-0.CrossRef
54.
Jain S, Kamimoto L, Bramley AM, Schmitz AM, Benoit SR, Louie J, Sugerman DE, Druckenmiller JK, Ritger KA, Chugh R, et al: Hospitalized patients with 2009 H1N1 influenza in the United States, April-June 2009. N Engl J Med. 2009, 361: 1935-1944. 10.1056/NEJMoa0906695.CrossRefPubMed
55.
Morgan OW, Bramley A, Fowlkes A, Freedman DS, Taylor TH, Gargiullo P, Belay B, Jain S, Cox C, Kamimoto L, et al: Morbid Obesity as a Risk Factor for Hospitalization and Death Due to 2009 Pandemic Influenza A(H1N1) Disease. PLoS One. 2010, 5: e9694-10.1371/journal.pone.0009694.CrossRefPubMedPubMedCentral
56.
Louie JK, Acosta M, Samuel MC, Schechter R, Vugia DJ, Harriman K, Matyas BT, the CP: A novel risk factor for a novel virus: obesity and 2009 pandemic influenza A (H1N1). Clin Infect Dis. 2011, 52: 1-12.CrossRef
57.
Murin S, Bilello KS: Respiratory Tract Infections: another reason not to smoke. Cleve Clin J Med. 2005, 72: 916-920. 10.3949/ccjm.72.10.916.CrossRefPubMed
58.
59.
Brownstein JS, Mandl KD: Pediatric population size is associated with geographic patterns of Acute Respiratory Infections among adults. Ann Emerg Med. 2008, 52: 63-68. 10.1016/j.annemergmed.2008.02.009.CrossRefPubMedPubMedCentral
60.
Brownstein JS, Kleinman KP, Mandl KD: Identifying pediatric age groups for influenza vaccination using a real-time regional surveillance system. Am J Epidemiol. 2005, 162: 686-693. 10.1093/aje/kwi257.CrossRefPubMedPubMedCentral
61.
Musher DM: How contagious are common respiratory tract infections?. N Engl J Med. 2003, 348: 1256-1266. 10.1056/NEJMra021771.CrossRefPubMed
62.
Viboud C, Boelle P, Cauchemez S, Lavenu A, Valleron A, Antoine F, Carrat F: Risk factors of influenza transmission in households. Br J Gen Pract. 2004, 54: 684-689.PubMedPubMedCentral
Metadata
Title
Prospective hospital-based case–control study to assess the effectiveness of pandemic influenza A(H1N1)pdm09 vaccination and risk factors for hospitalization in 2009–2010 using matched hospital and test-negative controls
Authors
Wiebke Hellenbrand
Pernille Jorgensen
Brunhilde Schweiger
Gerhard Falkenhorst
Matthias Nachtnebel
Benedikt Greutélaers
Christian Traeder
Ole Wichmann
Publication date
01-12-2012
Publisher
BioMed Central
Published in
BMC Infectious Diseases / Issue 1/2012
Electronic ISSN: 1471-2334
DOI
https://doi.org/10.1186/1471-2334-12-127

Other articles of this Issue 1/2012

BMC Infectious Diseases 1/2012 Go to the issue

Research article

Differences in characteristics between healthcare-associated and community-acquired infection in community-onset Klebsiella pneumoniae bloodstream infection in Korea

Case report

Clostridium septicum growth from a total knee arthroplasty associated with intestinal malignancy: a case report

Research article

Cross-sectional assessment of prevalence and correlates of blood-borne and sexually-transmitted infections among Afghan National Army recruits

Study protocol

Multivitamin supplementation in HIV infected adults initiating antiretroviral therapy in Uganda: the protocol for a randomized double blinded placebo controlled efficacy trial

Research article

Pandemic influenza A/H1N1 virus infection and TNF, LTA, IL1B, IL6, IL8, and CCLpolymorphisms in Mexican population: a case–control study

Research article

Non-capsulated and capsulated Haemophilus influenzaein children with acute otitis media in Venezuela: a prospective epidemiological study

ACC 2024 Congress Coverage

Heart Failure Video

Year in Review: Heart failure and cardiomyopathies

Watch now

Watch this official video from ACC.24. Dr. Biykem Bozkurt discuss last year's major advances in heart failure and cardiomyopathies.

Semaglutide benefits people with type 2 diabetes and obesity-related heart failure

16-04-2024 Type 2 Diabetes News

Incentivised to exercise

11-04-2024 Lifestyle Modifications News

New intervention for STEMI-related cardiogenic shock

10-04-2024 Myocardial Infarction News

» View more highlights on the ACC 2024 congress hub page

Image Credits