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Influenza vaccination for elderly people and their care workers
Comment
Influenza vaccination for elderly people and their care workers People aged 65 years and older incur substantial morbidity and mortality every year because of influenza.1,2 To reduce the effect of influenza on health, in 2003 the World Health Assembly encouraged member states with influenza-vaccination policies to increase coverage of elderly people to at least 50% by 2006, and to 75% by 2010.3 By 2005, about 50 countries had recommendations to vaccinate high-risk groups, including elderly people.3 Two Cochrane Collaboration systematic reviews have assessed the efficacy, effectiveness, and safety of influenza vaccination for elderly people4 and the health workers who care for them.5 The reviewers concluded that vaccination of elderly people, although safe, gives only modest reduction of complications from influenza, and that additional data are needed to document the benefit of vaccinating health-care workers to reduce influenza and influenza-associated complications in their elderly patients. These reviews highlight important challenges in the assessment of interventions to prevent influenza. Many factors affect the potential benefits of annual influenza vaccination, including recipients (eg, age and previous immunity), timing and intensity of influenza circulation, the degree of match between vaccine strains and wild circulating strains during a particular season, and the outcome measured. When the vaccine is poorly matched to circulating strains, the effect of the vaccine (irrespective of the outcome being measured) will be lower than in seasons with better antigenic matches. Furthermore, use of non-standard terms to define vaccine effects can complicate the interpretation of
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The printed journal includes an image merely for illustration
1752
studies. In standard epidemiological use, as introduced by Cochrane, efficacy is the extent to which an intervention leads to a specific outcome under ideal conditions (typically those in a randomised clinical trial), whereas effectiveness is the extent to which this intervention leads to the desired effect in the field during an observational study.6 However, in the recent Cochrane reviews,4,5 efficacy was defined as the effect of vaccination against laboratory-confirmed influenza infection, whereas effectiveness was the effect against influenza-like illness—a clinical diagnosis with various definitions—irrespective of whether results were derived from observational or randomised studies. The reviews4,5 assessed the effect of influenza vaccines against various outcomes, including clinically defined influenza-like illness, laboratory-confirmed influenza infection, admissions to hospital associated with influenza, and influenza-associated death. Influenza-like illness is a particularly problematic outcome because of its variable specificity for influenza infection. Symptoms of influenza-like illness might be caused by infection with respiratory pathogens other than influenza. The causes of influenza-like illness vary both across seasons and during a particular season depending on the co-circulation of influenza and non-influenza pathogens. For example, during clinical trials of the neuraminidase inhibitors oseltamivir7 and zanamivir,8 for which participants were recruited during periods when influenza viruses were known to be circulating, about 60% and 70%, respectively, of participants with influenza-like illness tested positive for influenza. By contrast, during surveillance of about 75 sentinel practices in England and Wales in the UK over three consecutive winters, only 32% of nasopharyngeal swab samples from patients with influenza-like illness tested positive for influenza, ranging from 20% to 50% during the three seasons.9 Thus influenza-like illness is a non-specific outcome, the degree of which varies by respiratory season (ie, the time between late autumn and spring, when respiratory pathogens show a seasonal peak), making results of meta-analyses that assessed influenza-like illness difficult to interpret. The use of internationally standardised case definitions for influenza outcomes would assist the formation and interpretation of meta-analyses that assess vaccines.10 In addition, future reviewers should address specifically the relative strengths of the outcomes used. The Cochrane www.thelancet.com Vol 368 November 18, 2006
Comment
reviews of influenza vaccines in elderly people may have been more helpful if they prioritised summary results by study type and outcome. For example,4 in analysis 13·02 of three randomised trials11–13 of people older than 60 years who lived in the community or in a nursing home, relative risk after vaccination against illness from laboratory-confirmed influenza was 0·42 (95% CI 0·27–0·66). This result suggests a substantial effect against a well defined specific outcome in a high-risk population. More emphasis should be placed on results from clinical trials with specific outcomes than on results from observational studies with less-specific outcomes, such as influenza-like illness. When observational studies are summarised, control for confounding factors is most important, and whenever possible needs to be described and standardised. Given the burden of influenza in elderly people every season, and the evidence suggesting that influenza vaccination of healthy adults is beneficial, the justification of further randomised clinical trials of existing vaccines for elderly or health-care workers is difficult ethically. However, the development of vaccines with greater immunogenicity for older adults will give opportunities for randomised clinical trials that compare new vaccines with current inactivated vaccines. These trials can address some of the issues related to the methods of studies, which have complicated the assessment of influenza vaccination in this population. We agree that more data would help assess fully the benefits of vaccinating health professionals who care for elderly people. Furthermore, researchers should assess potential indirect benefits on the health of older people of vaccinating other caregivers,
household contacts, and children, so that the risks and benefits of vaccine programmes can be understood fully. Nicole M Smith, *David K Shay Influenza Branch, US Centers for Disease Control and Prevention, Atlanta, GA 30333, USA [email protected] We declare that we have no conflicts of interest. The findings and conclusions of this Comment are those of the authors and do not necessarily represent the views of the US Centers for Disease Control and Prevention. 1 2
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Thompson WW, Shay DK, Weintraub E, et al. Influenza-associated hospitalizations in the United States. JAMA 2004; 292: 1333–40. Thompson WW. Shay DK, Weintraub E, et al. Mortality associated with influenza and respiratory syncytial virus in the United States. JAMA 2003; 289: 179–86. World Health Organization. Influenza vaccines: position paper. Wkly Epidemiol Rec 2005; 80: 279–87. Rivetti D, Jefferson T, Thomas R, et al. Vaccines for preventing influenza in the elderly. Cochrane Database Syst Rev 2006; 3: CD004876. Thomas RE, Jefferson T, Demicheli V, Rivetti D. Influenza vaccination for healthcare workers who work with the elderly. Cochrane Database Syst Rev 2006; 3: CD005187. Cochrane AL. Effectiveness and efficiency: random reflections on health services. London: Nuffield Provincial Hospitals Trust, 1972. Treanor JJ, Hayden FG, Vrooman PS, et al. Efficacy and safety of the oral neuraminidase inhibitor oseltamivir in treating acute influenza: a randomized controlled trial. JAMA 2000; 283: 1016–24. Monto AS, Webster A, Keene O. Randomized, placebo controlled trials of inhaled zanamivir in the treatment of influenza A and B: pooled efficacy analysis. J Antimicrob Chemother 1999; 44: 23–29. Zambon MC, Stockton JD, Clewley JP, Fleming DM. Contribution of influenza and respiratory syncytial virus to community cases of influenza-like illness: an observational study. Lancet 2001; 358: 1410–16. Beyer WE. Heterogeneity of case definitions used in vaccine effectiveness studies—and its impact on meta-analysis. Vaccine 2006; 24: 6602–04. Edmondson WP Jr, Rothenberg R, White PW, Gwaltney JM Jr. A comparison of subcutaneous, nasal, and combined influenza vaccination, II: protection against natural challenge. Am J Epidemiol 1971; 93: 480–86. Govaert TM, Thijs CT, Masurel N, Sprenger MJ, Dinant GJ, Knotterus JA. The efficacy of influenza vaccination in elderly individuals: a randomized double-blinded placebo-controlled trial. JAMA 1994; 272: 1661–65. Rudenko LG, Arden NH, Grigorieva E, et al. Immunogenicity and efficacy of Russian live attenuated and US inactivated influenza vaccines used alone and in combination in nursing home residents. Vaccine 2000; 19: 308–18.
A gendered look at Mexico’s health-sector reform The strong links between health and development have been increasingly articulated by leaders in health policy and economic development: investments in health systems help to reduce poverty and promote sustainable development, while national development contributes to improved public health.1 The connection between health and development is clearly articulated in the Millennium Development Goals, which provide a global framework for current development efforts. Gender—the social, cultural, and political constructs that prescribe feminine and masculine roles and www.thelancet.com Vol 368 November 18, 2006
which often lead to power imbalances between women and men2—also strongly affects health and development. Gender-related disadvantages, in addition to undermining human rights and social justice, contribute to poverty and poor health. Health policies and social systems that ensure women’s equal access to information and services not only contribute to their wellbeing, but also affect economic growth and reduction of poverty by raising productivity, improving efficiency, and enabling the female half of the population to reach its full potential.3
Published Online October 25, 2006 DOI:10.1016/S01406736(06)69527-5
1753
Influenza vaccination for elderly people and their care workers People aged 65 years and older incur substantial morbidity and mortality every year because of influenza.1,2 To reduce the effect of influenza on health, in 2003 the World Health Assembly encouraged member states with influenza-vaccination policies to increase coverage of elderly people to at least 50% by 2006, and to 75% by 2010.3 By 2005, about 50 countries had recommendations to vaccinate high-risk groups, including elderly people.3 Two Cochrane Collaboration systematic reviews have assessed the efficacy, effectiveness, and safety of influenza vaccination for elderly people4 and the health workers who care for them.5 The reviewers concluded that vaccination of elderly people, although safe, gives only modest reduction of complications from influenza, and that additional data are needed to document the benefit of vaccinating health-care workers to reduce influenza and influenza-associated complications in their elderly patients. These reviews highlight important challenges in the assessment of interventions to prevent influenza. Many factors affect the potential benefits of annual influenza vaccination, including recipients (eg, age and previous immunity), timing and intensity of influenza circulation, the degree of match between vaccine strains and wild circulating strains during a particular season, and the outcome measured. When the vaccine is poorly matched to circulating strains, the effect of the vaccine (irrespective of the outcome being measured) will be lower than in seasons with better antigenic matches. Furthermore, use of non-standard terms to define vaccine effects can complicate the interpretation of
Science Photo Library
The printed journal includes an image merely for illustration
1752
studies. In standard epidemiological use, as introduced by Cochrane, efficacy is the extent to which an intervention leads to a specific outcome under ideal conditions (typically those in a randomised clinical trial), whereas effectiveness is the extent to which this intervention leads to the desired effect in the field during an observational study.6 However, in the recent Cochrane reviews,4,5 efficacy was defined as the effect of vaccination against laboratory-confirmed influenza infection, whereas effectiveness was the effect against influenza-like illness—a clinical diagnosis with various definitions—irrespective of whether results were derived from observational or randomised studies. The reviews4,5 assessed the effect of influenza vaccines against various outcomes, including clinically defined influenza-like illness, laboratory-confirmed influenza infection, admissions to hospital associated with influenza, and influenza-associated death. Influenza-like illness is a particularly problematic outcome because of its variable specificity for influenza infection. Symptoms of influenza-like illness might be caused by infection with respiratory pathogens other than influenza. The causes of influenza-like illness vary both across seasons and during a particular season depending on the co-circulation of influenza and non-influenza pathogens. For example, during clinical trials of the neuraminidase inhibitors oseltamivir7 and zanamivir,8 for which participants were recruited during periods when influenza viruses were known to be circulating, about 60% and 70%, respectively, of participants with influenza-like illness tested positive for influenza. By contrast, during surveillance of about 75 sentinel practices in England and Wales in the UK over three consecutive winters, only 32% of nasopharyngeal swab samples from patients with influenza-like illness tested positive for influenza, ranging from 20% to 50% during the three seasons.9 Thus influenza-like illness is a non-specific outcome, the degree of which varies by respiratory season (ie, the time between late autumn and spring, when respiratory pathogens show a seasonal peak), making results of meta-analyses that assessed influenza-like illness difficult to interpret. The use of internationally standardised case definitions for influenza outcomes would assist the formation and interpretation of meta-analyses that assess vaccines.10 In addition, future reviewers should address specifically the relative strengths of the outcomes used. The Cochrane www.thelancet.com Vol 368 November 18, 2006
Comment
reviews of influenza vaccines in elderly people may have been more helpful if they prioritised summary results by study type and outcome. For example,4 in analysis 13·02 of three randomised trials11–13 of people older than 60 years who lived in the community or in a nursing home, relative risk after vaccination against illness from laboratory-confirmed influenza was 0·42 (95% CI 0·27–0·66). This result suggests a substantial effect against a well defined specific outcome in a high-risk population. More emphasis should be placed on results from clinical trials with specific outcomes than on results from observational studies with less-specific outcomes, such as influenza-like illness. When observational studies are summarised, control for confounding factors is most important, and whenever possible needs to be described and standardised. Given the burden of influenza in elderly people every season, and the evidence suggesting that influenza vaccination of healthy adults is beneficial, the justification of further randomised clinical trials of existing vaccines for elderly or health-care workers is difficult ethically. However, the development of vaccines with greater immunogenicity for older adults will give opportunities for randomised clinical trials that compare new vaccines with current inactivated vaccines. These trials can address some of the issues related to the methods of studies, which have complicated the assessment of influenza vaccination in this population. We agree that more data would help assess fully the benefits of vaccinating health professionals who care for elderly people. Furthermore, researchers should assess potential indirect benefits on the health of older people of vaccinating other caregivers,
household contacts, and children, so that the risks and benefits of vaccine programmes can be understood fully. Nicole M Smith, *David K Shay Influenza Branch, US Centers for Disease Control and Prevention, Atlanta, GA 30333, USA [email protected] We declare that we have no conflicts of interest. The findings and conclusions of this Comment are those of the authors and do not necessarily represent the views of the US Centers for Disease Control and Prevention. 1 2
3 4 5
6 7
8
9
10 11
12
13
Thompson WW, Shay DK, Weintraub E, et al. Influenza-associated hospitalizations in the United States. JAMA 2004; 292: 1333–40. Thompson WW. Shay DK, Weintraub E, et al. Mortality associated with influenza and respiratory syncytial virus in the United States. JAMA 2003; 289: 179–86. World Health Organization. Influenza vaccines: position paper. Wkly Epidemiol Rec 2005; 80: 279–87. Rivetti D, Jefferson T, Thomas R, et al. Vaccines for preventing influenza in the elderly. Cochrane Database Syst Rev 2006; 3: CD004876. Thomas RE, Jefferson T, Demicheli V, Rivetti D. Influenza vaccination for healthcare workers who work with the elderly. Cochrane Database Syst Rev 2006; 3: CD005187. Cochrane AL. Effectiveness and efficiency: random reflections on health services. London: Nuffield Provincial Hospitals Trust, 1972. Treanor JJ, Hayden FG, Vrooman PS, et al. Efficacy and safety of the oral neuraminidase inhibitor oseltamivir in treating acute influenza: a randomized controlled trial. JAMA 2000; 283: 1016–24. Monto AS, Webster A, Keene O. Randomized, placebo controlled trials of inhaled zanamivir in the treatment of influenza A and B: pooled efficacy analysis. J Antimicrob Chemother 1999; 44: 23–29. Zambon MC, Stockton JD, Clewley JP, Fleming DM. Contribution of influenza and respiratory syncytial virus to community cases of influenza-like illness: an observational study. Lancet 2001; 358: 1410–16. Beyer WE. Heterogeneity of case definitions used in vaccine effectiveness studies—and its impact on meta-analysis. Vaccine 2006; 24: 6602–04. Edmondson WP Jr, Rothenberg R, White PW, Gwaltney JM Jr. A comparison of subcutaneous, nasal, and combined influenza vaccination, II: protection against natural challenge. Am J Epidemiol 1971; 93: 480–86. Govaert TM, Thijs CT, Masurel N, Sprenger MJ, Dinant GJ, Knotterus JA. The efficacy of influenza vaccination in elderly individuals: a randomized double-blinded placebo-controlled trial. JAMA 1994; 272: 1661–65. Rudenko LG, Arden NH, Grigorieva E, et al. Immunogenicity and efficacy of Russian live attenuated and US inactivated influenza vaccines used alone and in combination in nursing home residents. Vaccine 2000; 19: 308–18.
A gendered look at Mexico’s health-sector reform The strong links between health and development have been increasingly articulated by leaders in health policy and economic development: investments in health systems help to reduce poverty and promote sustainable development, while national development contributes to improved public health.1 The connection between health and development is clearly articulated in the Millennium Development Goals, which provide a global framework for current development efforts. Gender—the social, cultural, and political constructs that prescribe feminine and masculine roles and www.thelancet.com Vol 368 November 18, 2006
which often lead to power imbalances between women and men2—also strongly affects health and development. Gender-related disadvantages, in addition to undermining human rights and social justice, contribute to poverty and poor health. Health policies and social systems that ensure women’s equal access to information and services not only contribute to their wellbeing, but also affect economic growth and reduction of poverty by raising productivity, improving efficiency, and enabling the female half of the population to reach its full potential.3
Published Online October 25, 2006 DOI:10.1016/S01406736(06)69527-5
1753