1. Annual influenza vaccination affects the development of heterosubtypic immunity
Abstract
“Annual vaccination of healthy children >6 months of age against seasonal influenza has been recommended by public health authorities of some countries. However, currently used seasonal vaccines provide only limited protection against (potentially) pandemic influenza viruses. Furthermore, we recently hypothesized that annual vaccination may hamper the development of cross-reactive immunity against influenza A viruses of novel subtypes, that would otherwise be induced by natural infection. Here we summarize our findings in animal models in which we demonstrated that vaccination against influenza A/H3N2 virus reduced the induction of heterosubtypic immunity against highly pathogenic avian influenza A/H5N1 virus, otherwise induced by a prior infection with influenza A/H3N2 virus. The reduction of heterosubtypic immunity correlated with reduced virus-specific CD8+ T cell responses. An additional study was performed in humans, in which we collected peripheral blood mononuclear cells from annually vaccinated children with cystic fibrosis (CF) and age-matched unvaccinated healthy control children to study the virus-specific T cell response. An age-related increase of the virus-specific CD8+ T cell response was observed in unvaccinated children that was absent in vaccinated children with CF. These findings highlight the importance of the development of vaccines that provide protection against influenza A viruses of all subtypes.”
Link
https://www.ncbi.nlm.nih.gov/pubmed/22643217
Citation
Kahan, Dan M., Donald Braman, Geoffrey L. Cohen, John Gastil, and Paul Slovic. "Who Fears the HPV Vaccine, Who Doesnât, and Why? An Experimental Study of the Mechanisms of Cultural Cognition." Law and Human Behavior 34.6 (2010): 501-16.
“Annual vaccination of healthy children >6 months of age against seasonal influenza has been recommended by public health authorities of some countries. However, currently used seasonal vaccines provide only limited protection against (potentially) pandemic influenza viruses. Furthermore, we recently hypothesized that annual vaccination may hamper the development of cross-reactive immunity against influenza A viruses of novel subtypes, that would otherwise be induced by natural infection. Here we summarize our findings in animal models in which we demonstrated that vaccination against influenza A/H3N2 virus reduced the induction of heterosubtypic immunity against highly pathogenic avian influenza A/H5N1 virus, otherwise induced by a prior infection with influenza A/H3N2 virus. The reduction of heterosubtypic immunity correlated with reduced virus-specific CD8+ T cell responses. An additional study was performed in humans, in which we collected peripheral blood mononuclear cells from annually vaccinated children with cystic fibrosis (CF) and age-matched unvaccinated healthy control children to study the virus-specific T cell response. An age-related increase of the virus-specific CD8+ T cell response was observed in unvaccinated children that was absent in vaccinated children with CF. These findings highlight the importance of the development of vaccines that provide protection against influenza A viruses of all subtypes.”
Link
https://www.ncbi.nlm.nih.gov/pubmed/22643217
Citation
Kahan, Dan M., Donald Braman, Geoffrey L. Cohen, John Gastil, and Paul Slovic. "Who Fears the HPV Vaccine, Who Doesnât, and Why? An Experimental Study of the Mechanisms of Cultural Cognition." Law and Human Behavior 34.6 (2010): 501-16.
2. Effectiveness of Trivalent Inactivated Influenza Vaccine in Children Estimated by a Test-Negative Case-Control Design Study Based on Influenza Rapid Diagnostic Test Results
Abstract
“We assessed vaccine effectiveness (VE) against medically attended, laboratory-confirmed influenza in children 6 months to 15 years of age in 22 hospitals in Japan during the 2013– 14 season. Our study was conducted according to a test-negative case-control design based on influenza rapid diagnostic test (IRDT) results. Outpatients who came to our clinics with a fever of 38°C or over and had undergone an IRDT were enrolled in this study. Patients with positive IRDT results were recorded as cases, and patients with negative results were recorded as controls. Between November 2013 and March 2014, a total of 4727 pediatric patients (6 months to 15 years of age) were enrolled: 876 were positive for influenza A, 66 for A(H1N1)pdm09 and in the other 810 the subtype was unknown; 1405 were positive for influenza B; and 2445 were negative for influenza. Overall VE was 46% (95% confidence interval [CI], 39–52). Adjusted VE against influenza A, influenza A(H1N1) pdm09, and influenza B was 63% (95% CI, 56–69), 77% (95% CI, 59–87), and 26% (95% CI, 14–36), respectively. Influenza vaccine was not effective against either influenza A or influenza B in infants 6 to 11 months of age. Two doses of influenza vaccine provided better protection against influenza A infection than a single dose did. VE against hospitalization influenza A infection was 76%. Influenza vaccine was effective against influenza A, especially against influenza A(H1N1)pdm09, but was much less effective against influenza B.”
Link
http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0136539
Citation
Shinjoh, Masayoshi, Norio Sugaya, Yoshio Yamaguchi, Yuka Tomidokoro, Shinichiro Sekiguchi, Keiko Mitamura, Motoko Fujino, Hiroyuki Shiro, Osamu Komiyama, Nobuhiko Taguchi, Yuji Nakata, Naoko Yoshida, Atsushi Narabayashi, Michiko Myokai, Masanori Sato, Munehiro Furuichi, Hiroaki Baba, Hisayo Fujita, Akihiro Sato, Ichiro Ookawara, Kenichiro Tsunematsu, Makoto Yoshida, Mio Kono, Fumie Tanaka, Chiharu Kawakami, Takahisa Kimiya, Takao Takahashi, and Satoshi Iwata. "Effectiveness of Trivalent Inactivated Influenza Vaccine in Children Estimated by a Test-Negative Case-Control Design Study Based on Influenza Rapid Diagnostic Test Results." Plos One 10.8 (2015)
“We assessed vaccine effectiveness (VE) against medically attended, laboratory-confirmed influenza in children 6 months to 15 years of age in 22 hospitals in Japan during the 2013– 14 season. Our study was conducted according to a test-negative case-control design based on influenza rapid diagnostic test (IRDT) results. Outpatients who came to our clinics with a fever of 38°C or over and had undergone an IRDT were enrolled in this study. Patients with positive IRDT results were recorded as cases, and patients with negative results were recorded as controls. Between November 2013 and March 2014, a total of 4727 pediatric patients (6 months to 15 years of age) were enrolled: 876 were positive for influenza A, 66 for A(H1N1)pdm09 and in the other 810 the subtype was unknown; 1405 were positive for influenza B; and 2445 were negative for influenza. Overall VE was 46% (95% confidence interval [CI], 39–52). Adjusted VE against influenza A, influenza A(H1N1) pdm09, and influenza B was 63% (95% CI, 56–69), 77% (95% CI, 59–87), and 26% (95% CI, 14–36), respectively. Influenza vaccine was not effective against either influenza A or influenza B in infants 6 to 11 months of age. Two doses of influenza vaccine provided better protection against influenza A infection than a single dose did. VE against hospitalization influenza A infection was 76%. Influenza vaccine was effective against influenza A, especially against influenza A(H1N1)pdm09, but was much less effective against influenza B.”
Link
http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0136539
Citation
Shinjoh, Masayoshi, Norio Sugaya, Yoshio Yamaguchi, Yuka Tomidokoro, Shinichiro Sekiguchi, Keiko Mitamura, Motoko Fujino, Hiroyuki Shiro, Osamu Komiyama, Nobuhiko Taguchi, Yuji Nakata, Naoko Yoshida, Atsushi Narabayashi, Michiko Myokai, Masanori Sato, Munehiro Furuichi, Hiroaki Baba, Hisayo Fujita, Akihiro Sato, Ichiro Ookawara, Kenichiro Tsunematsu, Makoto Yoshida, Mio Kono, Fumie Tanaka, Chiharu Kawakami, Takahisa Kimiya, Takao Takahashi, and Satoshi Iwata. "Effectiveness of Trivalent Inactivated Influenza Vaccine in Children Estimated by a Test-Negative Case-Control Design Study Based on Influenza Rapid Diagnostic Test Results." Plos One 10.8 (2015)
3. Clinical and Epidemiologic Characteristics of an Outbreak of Novel H1N1 (Swine Origin) Influenza A Virus among United States Military Beneficiaries
Abstract
“Background
A novel swine-origin influenza A (H1N1) virus was identified in March 2009 and subsequently caused worldwide outbreaks. The San Diego region was an early focal point of the emerging pandemic. We describe the clinical and epidemiologic characteristics of this novel strain in a military population to assist in future outbreak prevention and control efforts.
Methods
We performed an epidemiologic evaluation of novel H1N1 virus infections diagnosed in San Diego County among 96,258 local US military beneficiaries. The structured military medical system afforded the ability to obtain precise epidemiologic information on the impact on H1N1 virus infection in a population. The novel H1N1 virus was confirmed using real-time reverse transcriptase polymerase chain reaction (rRT-PCR).
Results
From 21 April through 8 May 2009, 761 patients presented with influenza-like illness and underwent rRT-PCR testing. Of these patients, 97 had confirmed novel H1N1 virus infection, with an incidence rate of 101 cases per 100,000 persons. The median age of H1N1 patients with H1N1 virus infection was 21 years (interquartile range, 15–25 years). Fever was a universal symptom in patients with H1N1 virus infection; other symptoms included cough (present in 96% of patients), myalgia or arthralgia (57%), and sore throat (51%). Sixty-eight (70%) of our patients had an identifiable epidemiologic link to another confirmed patient. The largest cluster of cases of H1N1 virus infection occurred on a Navy ship and involved 32 (8%) of 402 crew members; the secondary attack rate was 6%–14%. The rapid influenza testing that was used during this outbreak had a sensitivity of 51% and specificity of 98%, compared with rRT-PCR. Only 1 patient was hospitalized, and there were no deaths. ‘
Conclusions
A novel H1N1 influenza A virus caused a significant outbreak among military beneficiaries in San Diego County, including a significant cluster of cases onboard a Navy ship. The outbreak described here primarily affected adolescents and young adults and resulted in a febrile illness without sequelae.”
Link
https://www.ncbi.nlm.nih.gov/pubmed/19911946
Citation
Crum-Cianflone, Nancy F., Patrick J. Blair, Dennis Faix, John Arnold, Sara Echols, Sterling S. Sherman, John E. Tueller, Tyler Warkentien, Gabriela Sanguineti, Mary Bavaro, and Braden R. Hale. "Clinical and Epidemiologic Characteristics of an Outbreak of Novel H1N1 (Swine Origin) Influenza A Virus among United States Military Beneficiaries." Clinical Infectious Diseases 49.12 (2009): 1801-810.
“Background
A novel swine-origin influenza A (H1N1) virus was identified in March 2009 and subsequently caused worldwide outbreaks. The San Diego region was an early focal point of the emerging pandemic. We describe the clinical and epidemiologic characteristics of this novel strain in a military population to assist in future outbreak prevention and control efforts.
Methods
We performed an epidemiologic evaluation of novel H1N1 virus infections diagnosed in San Diego County among 96,258 local US military beneficiaries. The structured military medical system afforded the ability to obtain precise epidemiologic information on the impact on H1N1 virus infection in a population. The novel H1N1 virus was confirmed using real-time reverse transcriptase polymerase chain reaction (rRT-PCR).
Results
From 21 April through 8 May 2009, 761 patients presented with influenza-like illness and underwent rRT-PCR testing. Of these patients, 97 had confirmed novel H1N1 virus infection, with an incidence rate of 101 cases per 100,000 persons. The median age of H1N1 patients with H1N1 virus infection was 21 years (interquartile range, 15–25 years). Fever was a universal symptom in patients with H1N1 virus infection; other symptoms included cough (present in 96% of patients), myalgia or arthralgia (57%), and sore throat (51%). Sixty-eight (70%) of our patients had an identifiable epidemiologic link to another confirmed patient. The largest cluster of cases of H1N1 virus infection occurred on a Navy ship and involved 32 (8%) of 402 crew members; the secondary attack rate was 6%–14%. The rapid influenza testing that was used during this outbreak had a sensitivity of 51% and specificity of 98%, compared with rRT-PCR. Only 1 patient was hospitalized, and there were no deaths. ‘
Conclusions
A novel H1N1 influenza A virus caused a significant outbreak among military beneficiaries in San Diego County, including a significant cluster of cases onboard a Navy ship. The outbreak described here primarily affected adolescents and young adults and resulted in a febrile illness without sequelae.”
Link
https://www.ncbi.nlm.nih.gov/pubmed/19911946
Citation
Crum-Cianflone, Nancy F., Patrick J. Blair, Dennis Faix, John Arnold, Sara Echols, Sterling S. Sherman, John E. Tueller, Tyler Warkentien, Gabriela Sanguineti, Mary Bavaro, and Braden R. Hale. "Clinical and Epidemiologic Characteristics of an Outbreak of Novel H1N1 (Swine Origin) Influenza A Virus among United States Military Beneficiaries." Clinical Infectious Diseases 49.12 (2009): 1801-810.
4. Assessment of the efficacy and effectiveness of influenza vaccines in healthy children: systematic review
Abstract
“Background
We aimed to assess evidence of efficacy and effectiveness of live attenuated and inactivated influenza vaccines in children up to 16 years of age.
Methods
We searched the Cochrane Library, MEDLINE, EMBASE Biological Abstracts, and Science Citation Index to June, 2004, in any language, and contacted vaccine manufacturers and authors of relevant studies to identify additional data. We included randomised, cohort, and case-control studies comparing efficacy of vaccines against influenza (reduction in laboratory-confirmed cases), effectiveness of vaccines against influenza-like illness (reduction in symptomatic cases), or both, with placebo or no intervention. We analysed the following outcomes: influenza, influenza-like illness, admissions, school absences, complications, and secondary transmission.
Findings
We included 14 randomised controlled trials, eight cohort studies, one case-control study, and one randomised controlled trial of intraepidemic use of the vaccines. Live attenuated influenza vaccines had 79% efficacy and 38% effectiveness in children older than 2 years compared with placebo or no immunisation. Inactivated vaccines had lower efficacy (65%) than live attenuated vaccines, and in children aged 2 years or younger they had similar effects to placebo. Effectiveness of inactivated vaccines was about 28% in children older than 2 years. Vaccines were effective in reducing long school absences (relative risk 0·14 [95% CI 0·07–0·27]). Studies assessing the effects of vaccines against secondary cases, lower-respiratory tract disease, acute otitis media, and hospital stay suggested no difference with placebo or standard care, but lacked statistical power.
Interpretation
Influenza vaccines (especially two-dose live attenuated vaccines) are efficacious in children older than 2 years. Efficacy and effectiveness of the vaccines differed strikingly. Only two small studies assessed the effects of influenza vaccines on hospital admissions and no studies assessed reductions in mortality, serious complications, and community transmission of influenza. If influenza immunisation in children is to be recommended as publichealth policy, large-scale studies assessing such important outcomes and undertaking direct comparisons of vaccines are urgently needed.”
Link
https://www.ncbi.nlm.nih.gov/pubmed/15733718
Citation
Jefferson, T., S. Smith, V. Demicheli, A. Harnden, A. Rivetti, and C. Di Pietrantonj. "Assessment of the Efficacy and Effectiveness of Influenza Vaccines in Healthy Children: Systematic Review." The Lancet 365.9461 (2005): 773-80.
“Background
We aimed to assess evidence of efficacy and effectiveness of live attenuated and inactivated influenza vaccines in children up to 16 years of age.
Methods
We searched the Cochrane Library, MEDLINE, EMBASE Biological Abstracts, and Science Citation Index to June, 2004, in any language, and contacted vaccine manufacturers and authors of relevant studies to identify additional data. We included randomised, cohort, and case-control studies comparing efficacy of vaccines against influenza (reduction in laboratory-confirmed cases), effectiveness of vaccines against influenza-like illness (reduction in symptomatic cases), or both, with placebo or no intervention. We analysed the following outcomes: influenza, influenza-like illness, admissions, school absences, complications, and secondary transmission.
Findings
We included 14 randomised controlled trials, eight cohort studies, one case-control study, and one randomised controlled trial of intraepidemic use of the vaccines. Live attenuated influenza vaccines had 79% efficacy and 38% effectiveness in children older than 2 years compared with placebo or no immunisation. Inactivated vaccines had lower efficacy (65%) than live attenuated vaccines, and in children aged 2 years or younger they had similar effects to placebo. Effectiveness of inactivated vaccines was about 28% in children older than 2 years. Vaccines were effective in reducing long school absences (relative risk 0·14 [95% CI 0·07–0·27]). Studies assessing the effects of vaccines against secondary cases, lower-respiratory tract disease, acute otitis media, and hospital stay suggested no difference with placebo or standard care, but lacked statistical power.
Interpretation
Influenza vaccines (especially two-dose live attenuated vaccines) are efficacious in children older than 2 years. Efficacy and effectiveness of the vaccines differed strikingly. Only two small studies assessed the effects of influenza vaccines on hospital admissions and no studies assessed reductions in mortality, serious complications, and community transmission of influenza. If influenza immunisation in children is to be recommended as publichealth policy, large-scale studies assessing such important outcomes and undertaking direct comparisons of vaccines are urgently needed.”
Link
https://www.ncbi.nlm.nih.gov/pubmed/15733718
Citation
Jefferson, T., S. Smith, V. Demicheli, A. Harnden, A. Rivetti, and C. Di Pietrantonj. "Assessment of the Efficacy and Effectiveness of Influenza Vaccines in Healthy Children: Systematic Review." The Lancet 365.9461 (2005): 773-80.
5. Comparison of VAERS fetal-loss reports during three consecutive influenza seasons: Was there a synergistic fetal toxicity associated with the two-vaccine 2009/2010 season?
Abstract
“The aim of this study was to compare the number of inactivated-influenza vaccine–related spontaneous abortion and stillbirth (SB) reports in the Vaccine Adverse Event Reporting System (VAERS) database during three consecutive flu seasons beginning 2008/2009 and assess the relative fetal death reports associated with the two-vaccine 2009/2010 season. The VAERS database was searched for reports of fetal demise following administration of the influenza vaccine/vaccines to pregnant women. Utilization of an independent surveillance survey and VAERS, two-source capture–recapture analysis estimated the reporting completeness in the 2009/2010 flu season. Capture–recapture demonstrated that the VAERS database captured about 13.2% of the total 1321 (95% confidence interval (CI): 815–2795) estimated reports, yielding an ascertainment-corrected rate of 590 fetal-loss reports per million pregnant women vaccinated (or 1 per 1695). The unadjusted fetal-loss report rates for the three consecutive influenza seasons beginning 2008/2009 were 6.8 (95% CI: 0.1–13.1), 77.8 (95% CI: 66.3–89.4), and 12.6 (95% CI: 7.2–18.0) cases per million pregnant women vaccinated, respectively. The observed reporting bias was too low to explain the magnitude increase in fetal-demise reporting rates in the VAERS database relative to the reported annual trends. Thus, a synergistic fetal toxicity likely resulted from the administration of both the pandemic (A-H1N1) and seasonal influenza vaccines during the 2009/2010 season.”
Link
https://www.ncbi.nlm.nih.gov/pubmed/23023030
Citation
Goldman, G. "Comparison of VAERS Fetal-loss Reports during Three Consecutive Influenza Seasons: Was There a Synergistic Fetal Toxicity Associated with the Two-vaccine 2009/2010 Season?" Human & Experimental Toxicology 32.5 (2012): 464-75.
“The aim of this study was to compare the number of inactivated-influenza vaccine–related spontaneous abortion and stillbirth (SB) reports in the Vaccine Adverse Event Reporting System (VAERS) database during three consecutive flu seasons beginning 2008/2009 and assess the relative fetal death reports associated with the two-vaccine 2009/2010 season. The VAERS database was searched for reports of fetal demise following administration of the influenza vaccine/vaccines to pregnant women. Utilization of an independent surveillance survey and VAERS, two-source capture–recapture analysis estimated the reporting completeness in the 2009/2010 flu season. Capture–recapture demonstrated that the VAERS database captured about 13.2% of the total 1321 (95% confidence interval (CI): 815–2795) estimated reports, yielding an ascertainment-corrected rate of 590 fetal-loss reports per million pregnant women vaccinated (or 1 per 1695). The unadjusted fetal-loss report rates for the three consecutive influenza seasons beginning 2008/2009 were 6.8 (95% CI: 0.1–13.1), 77.8 (95% CI: 66.3–89.4), and 12.6 (95% CI: 7.2–18.0) cases per million pregnant women vaccinated, respectively. The observed reporting bias was too low to explain the magnitude increase in fetal-demise reporting rates in the VAERS database relative to the reported annual trends. Thus, a synergistic fetal toxicity likely resulted from the administration of both the pandemic (A-H1N1) and seasonal influenza vaccines during the 2009/2010 season.”
Link
https://www.ncbi.nlm.nih.gov/pubmed/23023030
Citation
Goldman, G. "Comparison of VAERS Fetal-loss Reports during Three Consecutive Influenza Seasons: Was There a Synergistic Fetal Toxicity Associated with the Two-vaccine 2009/2010 Season?" Human & Experimental Toxicology 32.5 (2012): 464-75.
6. Impact of Influenza Vaccination on Seasonal Mortality in the US Elderly Population
Abstract
“Background:
Observational studies report that influenza vaccination reduces winter mortality risk from any cause by 50% among the elderly. Influenza vaccination coverage among elderly persons (65 years) in the United States increased from between 15% and 20% before 1980 to 65% in 2001. Unexpectedly, estimates of influenzarelated mortality in this age group also increased during this period. We tried to reconcile these conflicting findings by adjusting excess mortality estimates for aging and increased circulation of influenza A(H3N2) viruses.
Methods:
We used a cyclical regression model to generate seasonal estimates of national influenza-related mortality (excess mortality) among the elderly in both pneumonia and influenza and all-cause deaths for the 33 seasons from 1968 to 2001. We stratified the data by 5-year age group and separated seasons dominated by A(H3N2) viruses from other seasons.
Results:
For people aged 65 to 74 years, excess mortality rates in A(H3N2)-dominated seasons fell between 1968 and the early 1980s but remained approximately constant thereafter. For persons 85 years or older, the mortality rate remained flat throughout. Excess mortality in A(H1N1) and B seasons did not change. All-cause excess mortality for persons 65 years or older never exceeded 10% of all winter deaths.
Conclusions:
We attribute the decline in influenzarelated mortality among people aged 65 to 74 years in the decade after the 1968 pandemic to the acquisition of immunity to the emerging A(H3N2) virus. We could not correlate increasing vaccination coverage after 1980 with declining mortality rates in any age group. Because fewer than 10% of all winter deaths were attributable to influenza in any season, we conclude that observational studies substantially overestimate vaccination benefit.”
Link
https://www.ncbi.nlm.nih.gov/pubmed/15710788
Citation
"Impact of Influenza Vaccination on Seasonal Mortality in the US Elderly Population." Archives of Internal Medicine 165.3 (2005): 265.
“Background:
Observational studies report that influenza vaccination reduces winter mortality risk from any cause by 50% among the elderly. Influenza vaccination coverage among elderly persons (65 years) in the United States increased from between 15% and 20% before 1980 to 65% in 2001. Unexpectedly, estimates of influenzarelated mortality in this age group also increased during this period. We tried to reconcile these conflicting findings by adjusting excess mortality estimates for aging and increased circulation of influenza A(H3N2) viruses.
Methods:
We used a cyclical regression model to generate seasonal estimates of national influenza-related mortality (excess mortality) among the elderly in both pneumonia and influenza and all-cause deaths for the 33 seasons from 1968 to 2001. We stratified the data by 5-year age group and separated seasons dominated by A(H3N2) viruses from other seasons.
Results:
For people aged 65 to 74 years, excess mortality rates in A(H3N2)-dominated seasons fell between 1968 and the early 1980s but remained approximately constant thereafter. For persons 85 years or older, the mortality rate remained flat throughout. Excess mortality in A(H1N1) and B seasons did not change. All-cause excess mortality for persons 65 years or older never exceeded 10% of all winter deaths.
Conclusions:
We attribute the decline in influenzarelated mortality among people aged 65 to 74 years in the decade after the 1968 pandemic to the acquisition of immunity to the emerging A(H3N2) virus. We could not correlate increasing vaccination coverage after 1980 with declining mortality rates in any age group. Because fewer than 10% of all winter deaths were attributable to influenza in any season, we conclude that observational studies substantially overestimate vaccination benefit.”
Link
https://www.ncbi.nlm.nih.gov/pubmed/15710788
Citation
"Impact of Influenza Vaccination on Seasonal Mortality in the US Elderly Population." Archives of Internal Medicine 165.3 (2005): 265.
7. Influenza vaccination and mortality benefits: New insights, new opportunities
Abstract
“Influenza vaccination control strategies in most countries rely on vaccination of seniors and other high risk groups. Although placebo-controlled randomized trials show influenza vaccine is effective in younger age groups, few seniors >70 years were studied even though they suffer >90% of influenza-related deaths. Excess mortality studies could not confirm a national decline in influenza-related mortality while vaccine coverage quadrupled. Cohort studies have consistently reported that vaccination reduces all-cause winter mortality by ∼50%, an astonishing claim given only ∼5% of all winter deaths are attributable to influenza. This VE overestimation has now been attributed to profound confounding frailty selection bias. A way forward includes a new generation of unbiased studies with laboratory endpoints, and requires an agreement that the evidence base was flawed. The latter may clear the way for more immunogenic vaccines for seniors and exploration of other influenza control strategies.”
Link
https://www.ncbi.nlm.nih.gov/pubmed/19840664
Citation
Simonsen, Lone, Cecile Viboud, Robert J. Taylor, Mark A. Miller, and Lisa Jackson. "Influenza Vaccination and Mortality Benefits: New Insights, New Opportunities." Vaccine 27.45 (2009): 6300-304
“Influenza vaccination control strategies in most countries rely on vaccination of seniors and other high risk groups. Although placebo-controlled randomized trials show influenza vaccine is effective in younger age groups, few seniors >70 years were studied even though they suffer >90% of influenza-related deaths. Excess mortality studies could not confirm a national decline in influenza-related mortality while vaccine coverage quadrupled. Cohort studies have consistently reported that vaccination reduces all-cause winter mortality by ∼50%, an astonishing claim given only ∼5% of all winter deaths are attributable to influenza. This VE overestimation has now been attributed to profound confounding frailty selection bias. A way forward includes a new generation of unbiased studies with laboratory endpoints, and requires an agreement that the evidence base was flawed. The latter may clear the way for more immunogenic vaccines for seniors and exploration of other influenza control strategies.”
Link
https://www.ncbi.nlm.nih.gov/pubmed/19840664
Citation
Simonsen, Lone, Cecile Viboud, Robert J. Taylor, Mark A. Miller, and Lisa Jackson. "Influenza Vaccination and Mortality Benefits: New Insights, New Opportunities." Vaccine 27.45 (2009): 6300-304
8. Primary influenza A virus infection induces cross-protective immunity against a lethal infection with a heterosubtypic virus strain in mice
Abstract
“In order to assess the level of protection against a lethal influenza virus infection provided by a primary infection with a virus strain of another subtype, C57BL/6 mice were infected with the sublethal influenza virus X-31 (H3N2) and subsequently challenged with the lethal strain A/PR/8/34 (H1N1). The outcome of the challenge infection was compared with that in mice that did not experience an infection with influenza virus X-31 prior to the challenge infection. The X-31 experienced mice cleared the infection with influenza virus A/PR/8/34 in an accelerated fashion, displayed less clinical signs and a reduction of lesions in the lungs resulting in improved survival rates of these mice compared to the naive mice. The improved outcome of the challenge infection with influenza virus A/PR/8/34 in the X-31 experienced mice correlated with priming for anamnestic virus-specific CD8+ cytotoxic T lymphocyte (CTL) responses as was demonstrated by the detection of CTL specific for the H-2Db restricted NP366–374 epitope that was shared by the influenza viruses X-31 and A/PR/8/34. Thus previous exposure to influenza A viruses affords partial protection against infection in the absence of virus-neutralizing antibodies specific for the hemagglutinin and the neuraminidase. The implications of these observations are discussed in the light of the current pandemic threat and development of vaccines that aim at the induction of virus-specific CTL.”
Link
http://www.jpands.org/vol11no2/ayoub.pdf
Citation
Kreijtz, J.h.c.m., R. Bodewes, G. Van Amerongen, T. Kuiken, R.a.m. Fouchier, A.d.m.e. Osterhaus, and G.f. Rimmelzwaan. "Primary Influenza A Virus Infection Induces Cross-protective Immunity against a Lethal Infection with a Heterosubtypic Virus Strain in Mice." Vaccine 25.4 (2007): 612-20
“In order to assess the level of protection against a lethal influenza virus infection provided by a primary infection with a virus strain of another subtype, C57BL/6 mice were infected with the sublethal influenza virus X-31 (H3N2) and subsequently challenged with the lethal strain A/PR/8/34 (H1N1). The outcome of the challenge infection was compared with that in mice that did not experience an infection with influenza virus X-31 prior to the challenge infection. The X-31 experienced mice cleared the infection with influenza virus A/PR/8/34 in an accelerated fashion, displayed less clinical signs and a reduction of lesions in the lungs resulting in improved survival rates of these mice compared to the naive mice. The improved outcome of the challenge infection with influenza virus A/PR/8/34 in the X-31 experienced mice correlated with priming for anamnestic virus-specific CD8+ cytotoxic T lymphocyte (CTL) responses as was demonstrated by the detection of CTL specific for the H-2Db restricted NP366–374 epitope that was shared by the influenza viruses X-31 and A/PR/8/34. Thus previous exposure to influenza A viruses affords partial protection against infection in the absence of virus-neutralizing antibodies specific for the hemagglutinin and the neuraminidase. The implications of these observations are discussed in the light of the current pandemic threat and development of vaccines that aim at the induction of virus-specific CTL.”
Link
http://www.jpands.org/vol11no2/ayoub.pdf
Citation
Kreijtz, J.h.c.m., R. Bodewes, G. Van Amerongen, T. Kuiken, R.a.m. Fouchier, A.d.m.e. Osterhaus, and G.f. Rimmelzwaan. "Primary Influenza A Virus Infection Induces Cross-protective Immunity against a Lethal Infection with a Heterosubtypic Virus Strain in Mice." Vaccine 25.4 (2007): 612-20
9. Relation of study quality, concordance, take home message, funding, and impact in studies of influenza vaccines: systematic review
Abstract
“Objective
To explore the relation between study concordance, take home message, funding, and dissemination of comparative studies assessing the effects of influenza vaccines.
Design
Systematic review without meta-analysis.
Data extraction
Search of the Cochrane Library, PubMed, Embase, and the web, without language restriction, for any studies comparing the effects of influenza vaccines against placebo or no intervention. Abstraction and assessment of quality of methods were carried out.
Data synthesis
We identified 259 primary studies (274 datasets). Higher quality studies were significantly more likely to show concordance between data presented and conclusions (odds ratio 16.35, 95% confidence interval 4.24 to 63.04) and less likely to favour effectiveness of vaccines (0.04, 0.02 to 0.09). Government funded studies were lesslikely to have conclusionsfavouring the vaccines (0.45, 0.26 to 0.90). A higher mean journal impact factor was associated with complete or partial industry funding compared with government or private funding and no funding (differences betweenmeans 5.04). Study sizewas not associated with concordance, content of take home message,funding, and study quality. Higher citation index factor was associated with partial or complete industry funding. This was sensitive to the exclusion from the analysis of studies with undeclared funding.
Conclusion
Publication in prestigious journals is associated with partial or total industry funding, and this association is not explained by study quality or size.”
Link
http://www.bmj.com/content/338/bmj.b354
Citation
Jefferson, T., C. Di Pietrantonj, M. G. Debalini, A. Rivetti, and V. Demicheli. "Relation of Study Quality, Concordance, Take Home Message, Funding, and Impact in Studies of Influenza Vaccines: Systematic Review." Bmj 338.Feb12 2 (2009)
“Objective
To explore the relation between study concordance, take home message, funding, and dissemination of comparative studies assessing the effects of influenza vaccines.
Design
Systematic review without meta-analysis.
Data extraction
Search of the Cochrane Library, PubMed, Embase, and the web, without language restriction, for any studies comparing the effects of influenza vaccines against placebo or no intervention. Abstraction and assessment of quality of methods were carried out.
Data synthesis
We identified 259 primary studies (274 datasets). Higher quality studies were significantly more likely to show concordance between data presented and conclusions (odds ratio 16.35, 95% confidence interval 4.24 to 63.04) and less likely to favour effectiveness of vaccines (0.04, 0.02 to 0.09). Government funded studies were lesslikely to have conclusionsfavouring the vaccines (0.45, 0.26 to 0.90). A higher mean journal impact factor was associated with complete or partial industry funding compared with government or private funding and no funding (differences betweenmeans 5.04). Study sizewas not associated with concordance, content of take home message,funding, and study quality. Higher citation index factor was associated with partial or complete industry funding. This was sensitive to the exclusion from the analysis of studies with undeclared funding.
Conclusion
Publication in prestigious journals is associated with partial or total industry funding, and this association is not explained by study quality or size.”
Link
http://www.bmj.com/content/338/bmj.b354
Citation
Jefferson, T., C. Di Pietrantonj, M. G. Debalini, A. Rivetti, and V. Demicheli. "Relation of Study Quality, Concordance, Take Home Message, Funding, and Impact in Studies of Influenza Vaccines: Systematic Review." Bmj 338.Feb12 2 (2009)
10.
Abstract
“Background and Methods
Vaccination of all healthcare workers is widely recommended by health authorities and medical institutions and support for mandatory vaccination is increasing. This paper presents the relevant literature and examines the evidence for patient benefit from healthcare worker vaccination. Articles identified by Medline searches and citation lists were inspected for internal and external validity. Emphasis was put on RCTs. The literature on self-protection from vaccination is also presented.
Results
Published research shows that personal benefit from vaccinating healthy nonelderly adults is small and there is no evidence that it is any different for HCWs. The studies aiming to prove the widespread belief that healthcare worker vaccination decreases patient morbidity and mortality are heavily flawed and the recommendations for vaccination biased. No reliable published evidence shows that healthcare workers’ vaccination has substantial benefit for their patients—not in reducing patient morbidity or mortality and not even in increasing patient vaccination rates.
Conclusion
The arguments for uniform healthcare worker influenza vaccination are not supported by existing literature. The decision whether to get vaccinated should, except possibly in extreme situations, be that of the individual healthcare worker, without legal, institutional, or peer coercion.”
Link
https://www.hindawi.com/journals/ijfm/2012/205464/
Citation
Abramson, Zvi Howard. "What, in Fact, Is the Evidence That Vaccinating Healthcare Workers against Seasonal Influenza Protects Their Patients? A Critical Review." International Journal of Family Medicine 2012 (2012): 1-6.
“Background and Methods
Vaccination of all healthcare workers is widely recommended by health authorities and medical institutions and support for mandatory vaccination is increasing. This paper presents the relevant literature and examines the evidence for patient benefit from healthcare worker vaccination. Articles identified by Medline searches and citation lists were inspected for internal and external validity. Emphasis was put on RCTs. The literature on self-protection from vaccination is also presented.
Results
Published research shows that personal benefit from vaccinating healthy nonelderly adults is small and there is no evidence that it is any different for HCWs. The studies aiming to prove the widespread belief that healthcare worker vaccination decreases patient morbidity and mortality are heavily flawed and the recommendations for vaccination biased. No reliable published evidence shows that healthcare workers’ vaccination has substantial benefit for their patients—not in reducing patient morbidity or mortality and not even in increasing patient vaccination rates.
Conclusion
The arguments for uniform healthcare worker influenza vaccination are not supported by existing literature. The decision whether to get vaccinated should, except possibly in extreme situations, be that of the individual healthcare worker, without legal, institutional, or peer coercion.”
Link
https://www.hindawi.com/journals/ijfm/2012/205464/
Citation
Abramson, Zvi Howard. "What, in Fact, Is the Evidence That Vaccinating Healthcare Workers against Seasonal Influenza Protects Their Patients? A Critical Review." International Journal of Family Medicine 2012 (2012): 1-6.