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1.  The Effects of Influenza Vaccination of Health Care Workers in Nursing Homes: Insights from a Mathematical Model 
PLoS Medicine  2008;5(10):e200.
Background
Annual influenza vaccination of institutional health care workers (HCWs) is advised in most Western countries, but adherence to this recommendation is generally low. Although protective effects of this intervention for nursing home patients have been demonstrated in some clinical trials, the exact relationship between increased vaccine uptake among HCWs and protection of patients remains unknown owing to variations between study designs, settings, intensity of influenza seasons, and failure to control all effect modifiers. Therefore, we use a mathematical model to estimate the effects of HCW vaccination in different scenarios and to identify a herd immunity threshold in a nursing home department.
Methods and Findings
We use a stochastic individual-based model with discrete time intervals to simulate influenza virus transmission in a 30-bed long-term care nursing home department. We simulate different levels of HCW vaccine uptake and study the effect on influenza virus attack rates among patients for different institutional and seasonal scenarios. Our model reveals a robust linear relationship between the number of HCWs vaccinated and the expected number of influenza virus infections among patients. In a realistic scenario, approximately 60% of influenza virus infections among patients can be prevented when the HCW vaccination rate increases from 0 to 1. A threshold for herd immunity is not detected. Due to stochastic variations, the differences in patient attack rates between departments are high and large outbreaks can occur for every level of HCW vaccine uptake.
Conclusions
The absence of herd immunity in nursing homes implies that vaccination of every additional HCW protects an additional fraction of patients. Because of large stochastic variations, results of small-sized clinical trials on the effects of HCW vaccination should be interpreted with great care. Moreover, the large variations in attack rates should be taken into account when designing future studies.
Using a mathematical model to simulate influenza transmission in nursing homes, Carline van den Dool and colleagues find that each additional staff member vaccinated further reduces the risk to patients.
Editors' Summary
Background.
Every winter, millions of people catch influenza, a contagious viral disease of the nose, throat, and airways. Most people recover completely from influenza within a week or two but some develop life-threatening complications such as bacterial pneumonia. As a result, influenza outbreaks kill about half a million people—mainly infants, elderly people, and chronically ill individuals—each year. To minimize influenza-related deaths, the World Health Organization recommends that vulnerable people be vaccinated against influenza every autumn. Annual vaccination is necessary because flu viruses continually make small changes to the viral proteins (antigens) that the immune system recognizes. This means that an immune response produced one year provides only partial protection against influenza the next year. To provide maximum protection against influenza, each year's vaccine contains disabled versions of the major circulating strains of influenza viruses.
Why Was This Study Done?
Most Western countries also recommend annual flu vaccination for health care workers (HCWs) in hospitals and other institutions to reduce the transmission of influenza to vulnerable patients. However, many HCWs don't get a regular flu shot, so should efforts be made to increase their rate of vaccine uptake? To answer this question, public-health experts need to know more about the relationship between vaccine uptake among HCWs and patient protection. In particular, they need to know whether a high rate of vaccine uptake by HCWs will provide “herd immunity.” Herd immunity occurs because, when a sufficient fraction of a population is immune to a disease that passes from person to person, infected people rarely come into contact with susceptible people, which means that both vaccinated and unvaccinated people are protected from the disease. In this study, the researchers develop a mathematical model to investigate the relationship between vaccine uptake among HCWs and patient protection in a nursing home department.
What Did the Researchers Do and Find?
To predict influenza virus attack rates (the number of patient infections divided by the number of patients in a nursing home department during an influenza season) at different levels of HCW vaccine uptake, the researchers develop a stochastic transmission model to simulate epidemics on a computer. This model predicts that as the HCW vaccination rate increases from 0 (no HCWs vaccinated) to 1 (all the HCWs vaccinated), the expected average influenza virus attack rate decreases at a constant rate. In the researchers' baseline scenario—a nursing home department with 30 beds where patients come into contact with other patients, HCWs, and visitors—the model predicts that about 60% of the patients who would have been infected if no HCWs had been vaccinated are protected when all the HCWs are vaccinated, and that seven HCWs would have to be vaccinated to protect one patient. This last figure does not change with increasing vaccine uptake, which indicates that there is no level of HCW vaccination that completely stops the spread of influenza among the patients; that is, there is no herd immunity. Finally, the researchers show that large influenza outbreaks can happen by chance at every level of HCW vaccine uptake.
What Do These Findings Mean?
As with all mathematical models, the accuracy of these predictions may depend on the specific assumptions built into the model. Therefore the researchers verified that their findings hold for a wide range of plausible assumptions. These findings have two important practical implications. First, the direct relationship between HCW vaccination and patient protection and the lack of any herd immunity suggest that any increase in HCW vaccine uptake will be beneficial to patients in nursing homes. That is, increasing the HCW vaccination rate from 80% to 90% is likely to be as important as increasing it from 10% to 20%. Second, even 100% HCW vaccination cannot guarantee that influenza outbreaks will not occasionally occur in nursing homes. Because of the large variation in attack rates, the results of small clinical trials on the effects of HCW vaccination may be inaccurate and future studies will need to be very large if they are to provide reliable estimates of the amount of protection that HCW vaccination provides to vulnerable patients.
Additional Information.
Please access these Web sites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.0050200.
Read the related PLoSMedicine Perspective by Cécile Viboud and Mark Miller
A related PLoSMedicine Research Article by Jeffrey Kwong and colleagues is also available
The World Health Organization provides information on influenza and on influenza vaccines (in several languages)
The US Centers for Disease Control and Prevention provide information for patients and professionals on all aspects of influenza (in English and Spanish)
The UK Health Protection Agency also provides information on influenza
MedlinePlus provides a list of links to other information about influenza (in English and Spanish)
The UK National Health Service provides information about herd immunity, including a simple explanatory animation
The European Centre for Disease Prevention and Control provides an overview on the types of influenza
doi:10.1371/journal.pmed.0050200
PMCID: PMC2573905  PMID: 18959470
2.  Planning and process evaluation of a multi-faceted influenza vaccination implementation strategy for health care workers in acute health care settings 
BMC Infectious Diseases  2013;13:235.
Background
Influenza transmitted by health care workers (HCWs) is a potential threat to frail patients in acute health care settings. Therefore, immunizing HCWs against influenza should receive high priority. Despite recommendations of the World Health Organization, vaccine coverage of HCWs remains low in all European countries. This study explores the use of intervention strategies and methods to improve influenza vaccination rates among HCWs in an acute care setting.
Methods
The Intervention Mapping (IM) method was used to systematically develop and implement an intervention strategy aimed at changing influenza vaccination behaviour among HCWs in Dutch University Medical Centres (UMCs). Carried out during the influenza seasons 2009/2010 and 2010/2011, the interventions were then qualitatively and quantitatively evaluated by way of feedback from participating UMCs and the completion of a web-based staff questionnaire in the following spring of each season.
Results
The IM method resulted in the development of a transparent influenza vaccination intervention implementation strategy. The intervention strategy was offered to six Dutch UMCs in a randomized in a clustered Randomized Controlled Trial (RCT), where three UMCs were chosen for intervention, and three UMCs acted as controls. A further two UMCs elected to have the intervention. The qualitative process evaluation showed that HCWs at four of the five intervention UMCs were responsive to the majority of the 11 relevant behavioural determinants resulting from the needs assessment in their intervention strategy compared with only one of three control UMCs. The quantitative evaluation among a sample of HCWs revealed that of all the developed communication materials, HCWs reported the posters as the most noticeable.
Conclusions
Our study demonstrates that it is possible to develop a structured implementation strategy for increasing the rate of influenza vaccination by HCWs in acute health care settings. The evaluation also showed that it is impossible to expose all HCWs to all intervention methods (which would have been the best case scenario). Further study is needed to (1) improve HCW exposure to intervention methods; (2) determine the effect of such interventions on vaccine uptake among HCWs; and (3) assess the impact on clinical outcomes among patients when such interventions are enacted.
doi:10.1186/1471-2334-13-235
PMCID: PMC3680164  PMID: 23701921
Influenza vaccination; Health care workers; Intervention mapping; Intervention implementation; Acute health care
3.  Assessing Optimal Target Populations for Influenza Vaccination Programmes: An Evidence Synthesis and Modelling Study 
PLoS Medicine  2013;10(10):e1001527.
Marc Baguelin and colleagues use virological, clinical, epidemiological, and behavioral data to estimate how policies for influenza vaccination programs may be optimized in England and Wales.
Please see later in the article for the Editors' Summary
Background
Influenza vaccine policies that maximise health benefit through efficient use of limited resources are needed. Generally, influenza vaccination programmes have targeted individuals 65 y and over and those at risk, according to World Health Organization recommendations. We developed methods to synthesise the multiplicity of surveillance datasets in order to evaluate how changing target populations in the seasonal vaccination programme would affect infection rate and mortality.
Methods and Findings
Using a contemporary evidence-synthesis approach, we use virological, clinical, epidemiological, and behavioural data to develop an age- and risk-stratified transmission model that reproduces the strain-specific behaviour of influenza over 14 seasons in England and Wales, having accounted for the vaccination uptake over this period. We estimate the reduction in infections and deaths achieved by the historical programme compared with no vaccination, and the reduction had different policies been in place over the period. We find that the current programme has averted 0.39 (95% credible interval 0.34–0.45) infections per dose of vaccine and 1.74 (1.16–3.02) deaths per 1,000 doses. Targeting transmitters by extending the current programme to 5–16-y-old children would increase the efficiency of the total programme, resulting in an overall reduction of 0.70 (0.52–0.81) infections per dose and 1.95 (1.28–3.39) deaths per 1,000 doses. In comparison, choosing the next group most at risk (50–64-y-olds) would prevent only 0.43 (0.35–0.52) infections per dose and 1.77 (1.15–3.14) deaths per 1,000 doses.
Conclusions
This study proposes a framework to integrate influenza surveillance data into transmission models. Application to data from England and Wales confirms the role of children as key infection spreaders. The most efficient use of vaccine to reduce overall influenza morbidity and mortality is thus to target children in addition to older adults.
Please see later in the article for the Editors' Summary
Editors' Summary
Background
Every winter, millions of people catch influenza, a viral infection of the airways. Most infected individuals recover quickly, but seasonal influenza outbreaks (epidemics) kill about half a million people annually. In countries with advanced health systems, these deaths occur mainly among elderly people and among individuals with long-term illnesses such as asthma and heart disease that increase the risk of complications occurring after influenza virus infection. Epidemics of influenza occur because small but frequent changes in the influenza virus mean that an immune response produced one year through infection provides only partial protection against influenza the following year. Annual immunization with a vaccine that contains killed influenza viruses of the major circulating strains can greatly reduce a person's risk of catching influenza by preparing the immune system to respond quickly when challenged by a live influenza virus. Consequently, many countries run seasonal influenza vaccination programs that, in line with World Health Organization recommendations, target individuals 65 years old and older and people in high-risk groups.
Why Was This Study Done?
Is this approach the best use of available resources? Might, for example, vaccination of children—the main transmitters of influenza—provide more benefit to the whole population than vaccination of elderly people? Vaccination of children would not directly prevent as many influenza-related deaths as vaccination of elderly people, but it might indirectly prevent deaths in elderly adults by inducing herd immunity—vaccination of a large part of a population can protect unvaccinated members of the population by reducing the chances of an infection spreading. Policy makers need to know whether a change to an influenza vaccination program is likely to provide additional population benefits before altering the program. In this evidence synthesis and modeling study, the researchers combine (synthesize) longitudinal influenza surveillance datasets (data collected over time) from England and Wales, develop a mathematical model for influenza transmission based on these data using a Bayesian statistical approach, and use the model to evaluate the impact on influenza infections and deaths of changes to the seasonal influenza vaccination program in England and Wales.
What Did the Researchers Do and Find?
The researchers developed an influenza transmission model using clinical data on influenza-like illness consultations collected in a primary care surveillance scheme for each week of 14 influenza seasons in England and Wales, virological information on respiratory viruses detected in a subset of patients presenting with clinically suspected influenza, and data on vaccination coverage in the whole population (epidemiological data). They also incorporated data on social contacts (behavioral data) and on immunity to influenza viruses in the population (seroepidemiological data) into their model. To estimate the impact of potential changes to the current vaccination strategy in England and Wales, the researchers used their model, which replicated the patterns of disease observed in the surveillance data, to run simulated epidemics for each influenza season and for three strains of influenza virus under various vaccination scenarios. Compared to no vaccination, the current program (vaccination of people 65 years old and older and people in high-risk groups) averted 0.39 infections per dose of vaccine and 1.74 deaths per 1,000 doses. Notably, the model predicted that extension of the program to target 5–16-year-old children would increase the efficiency of the program and would avert 0.70 infections per dose and 1.95 deaths per 1,000 doses.
What Do These Findings Mean?
The finding that the transmission model developed by the researchers closely fit the available surveillance data suggests that the model should be able to predict what would have happened in England and Wales over the study period if an alternative vaccination regimen had been in place. The accuracy of such predictions may be limited, however, because the vaccination model is based on a series of simplifying assumptions. Importantly, given that influenza vaccination for children is being rolled out in England and Wales from September 2013, the model confirms that children are key spreaders of influenza and suggests that a vaccination program targeting children will reduce influenza infections and potentially influenza deaths in the whole population. More generally, the findings of this study support wider adoption of national vaccination strategies designed to block influenza transmission and to target those individuals most at risk from the complications of influenza infection.
Additional Information
Please access these websites via the online version of this summary at http://dx.doi.org/10.1371.journal.pmed.1001527.
The UK National Health Service Choices website provides information for patients about seasonal influenza and about vaccination; Public Health England (formerly the Health Protection Agency) provides information on influenza surveillance in the UK, including information about the primary care surveillance database used in this study
The World Health Organization provides information on seasonal influenza (in several languages)
The European Influenzanet is a system to monitor the activity of influenza-like illness with the aid of volunteers via the Internet
The US Centers for Disease Control and Prevention also provides information for patients and health professionals on all aspects of seasonal influenza, including information about vaccination and about the US influenza surveillance system; its website contains a short video about personal experiences of influenza
Flu.gov, a US government website, provides access to information on seasonal influenza and vaccination
MedlinePlus has links to further information about influenza and about immunization (in English and Spanish)
doi:10.1371/journal.pmed.1001527
PMCID: PMC3793005  PMID: 24115913
4.  Tuberculosis among Health-Care Workers in Low- and Middle-Income Countries: A Systematic Review 
PLoS Medicine  2006;3(12):e494.
Background
The risk of transmission of Mycobacterium tuberculosis from patients to health-care workers (HCWs) is a neglected problem in many low- and middle-income countries (LMICs). Most health-care facilities in these countries lack resources to prevent nosocomial transmission of tuberculosis (TB).
Methods and Findings
We conducted a systematic review to summarize the evidence on the incidence and prevalence of latent TB infection (LTBI) and disease among HCWs in LMICs, and to evaluate the impact of various preventive strategies that have been attempted. To identify relevant studies, we searched electronic databases and journals, and contacted experts in the field. We identified 42 articles, consisting of 51 studies, and extracted data on incidence, prevalence, and risk factors for LTBI and disease among HCWs. The prevalence of LTBI among HCWs was, on average, 54% (range 33% to 79%). Estimates of the annual risk of LTBI ranged from 0.5% to 14.3%, and the annual incidence of TB disease in HCWs ranged from 69 to 5,780 per 100,000. The attributable risk for TB disease in HCWs, compared to the risk in the general population, ranged from 25 to 5,361 per 100,000 per year. A higher risk of acquiring TB disease was associated with certain work locations (inpatient TB facility, laboratory, internal medicine, and emergency facilities) and occupational categories (radiology technicians, patient attendants, nurses, ward attendants, paramedics, and clinical officers).
Conclusions
In summary, our review demonstrates that TB is a significant occupational problem among HCWs in LMICs. Available evidence reinforces the need to design and implement simple, effective, and affordable TB infection-control programs in health-care facilities in these countries.
A systematic review demonstrates that tuberculosis is an important occupational problem among health care workers in low and middle-income countries.
Editors' Summary
Background.
One third of the world's population is infected with Mycobacterium tuberculosis, the bacterium that causes tuberculosis (TB). In many people, the bug causes no health problems—it remains latent. But about 10% of infected people develop active, potentially fatal TB, often in their lungs. People with active pulmonary TB readily spread the infection to other people, including health-care workers (HCWs), in small airborne droplets produced when they cough or sneeze. In high-income countries such as the US, guidelines are in place to minimize the transmission of TB in health-care facilities. Administrative controls (for example, standard treatment plans for people with suspected or confirmed TB) aim to reduce the exposure of HCWs to people with TB. Environmental controls (for example, the use of special isolation rooms) aim to prevent the spread and to reduce the concentration of infectious droplets in the air. Finally, respiratory-protection controls (for example, personal respirators for nursing staff) aim to reduce the risk of infection when exposure to M. tuberculosis is unavoidably high. Together, these three layers of control have reduced the incidence of TB in HCWs (the number who catch TB annually) in high-income countries.
Why Was This Study Done?
But what about low- and middle-income countries (LMICs) where more than 90% of the world's cases of TB occur? Here, there is little money available to implement even low-cost strategies to reduce TB transmission in health-care facilities—so how important an occupational disease is TB in HCWs in these countries? In this study, the researchers have systematically reviewed published papers to find out the incidence and prevalence (how many people in a population have a specific disease) of active TB and latent TB infections (LTBIs) in HCWs in LMICs. They have also investigated whether any of the preventative strategies used in high-income countries have been shown to reduce the TB burden in HCWs in poorer countries.
What Did the Researchers Do and Find?
To identify studies on TB transmission to HCWs in LMICs, the researchers searched electronic databases and journals, and also contacted experts on TB transmission. They then extracted and analyzed the relevant data on TB incidence, prevalence, risk factors, and control measures. Averaged-out over the 51 identified studies, 54% of HCWs had LTBI. In most of the studies, increasing age and duration of employment in health-care facilities, indicating a longer cumulative exposure to infection, was associated with a higher prevalence of LTBI. The same trend was seen in a subgroup of medical and nursing students. After accounting for the incidence of TB in the relevant general population, the excess incidence of TB in the different studies that was attributable to being a HCW ranged from 25 to 5,361 cases per 100, 000 people per year. In addition, a higher risk of acquiring TB was associated with working in specific locations (for example, inpatient TB facilities or diagnostic laboratories) and with specific occupations, including nurses and radiology attendants; most of the health-care facilities examined in the published studies had no specific TB infection-control programs in place.
What Do These Findings Mean?
As with all systematic reviews, the accuracy of these findings may be limited by some aspects of the original studies, such as how the incidence of LTBI was measured. In addition, the possibility that the researchers missed some relevant published studies, or that only studies where there was a high incidence of TB in HCWs were published, may also affect the findings of this study. Nevertheless, they suggest that TB is an important occupational disease in HCWs in LMICs and that the HCWs most at risk of TB are those exposed to the most patients with TB. Reduction of that risk should be a high priority because occupational TB leads to the loss of essential, skilled HCWs. Unfortunately, there are few data available to indicate how this should be done. Thus, the researchers conclude, well-designed field studies are urgently needed to evaluate whether the TB-control measures that have reduced TB transmission to HCWs in high-income countries will work and be affordable in LMICs.
Additional Information.
Please access these Web sites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.0030494.
• US National Institute of Allergy and Infectious Diseases patient fact sheet on tuberculosis
• US Centers for Disease Control and Prevention information for patients and professionals on tuberculosis
• MedlinePlus encyclopedia entry on tuberculosis
• NHS Direct Online, from the UK National Health Service, patient information on tuberculosis
• US National Institute for Occupational Health and Safety, information about tuberculosis for health-care workers
• American Lung Association information on tuberculosis and health-care workers
doi:10.1371/journal.pmed.0030494
PMCID: PMC1716189  PMID: 17194191
5.  Accelerating Policy Decisions to Adopt Haemophilus influenzae Type b Vaccine: A Global, Multivariable Analysis 
PLoS Medicine  2010;7(3):e1000249.
Jessica Shearer and colleagues analyze data from 147 countries to identify factors that influence the time taken to introduce routine vaccination against Haemophilus influenzae type b (Hib).
Background
Adoption of new and underutilized vaccines by national immunization programs is an essential step towards reducing child mortality. Policy decisions to adopt new vaccines in high mortality countries often lag behind decisions in high-income countries. Using the case of Haemophilus influenzae type b (Hib) vaccine, this paper endeavors to explain these delays through the analysis of country-level economic, epidemiological, programmatic and policy-related factors, as well as the role of the Global Alliance for Vaccines and Immunisation (GAVI Alliance).
Methods and Findings
Data for 147 countries from 1990 to 2007 were analyzed in accelerated failure time models to identify factors that are associated with the time to decision to adopt Hib vaccine. In multivariable models that control for Gross National Income, region, and burden of Hib disease, the receipt of GAVI support speeded the time to decision by a factor of 0.37 (95% CI 0.18–0.76), or 63%. The presence of two or more neighboring country adopters accelerated decisions to adopt by a factor of 0.50 (95% CI 0.33–0.75). For each 1% increase in vaccine price, decisions to adopt are delayed by a factor of 1.02 (95% CI 1.00–1.04). Global recommendations and local studies were not associated with time to decision.
Conclusions
This study substantiates previous findings related to vaccine price and presents new evidence to suggest that GAVI eligibility is associated with accelerated decisions to adopt Hib vaccine. The influence of neighboring country decisions was also highly significant, suggesting that approaches to support the adoption of new vaccines should consider supply- and demand-side factors.
Please see later in the article for the Editors' Summary
Editors' Summary
Background
Every year, immunization averts more than 2 million deaths by preparing people's immune systems to recognize and attack disease-causing organisms (pathogens) rapidly and effectively. Although the immune system is designed to protect the human body against infections, the first time a person is exposed to a pathogen (usually during early childhood) their immune system can take some time to respond. As a result, they can become seriously ill or even die. However, the immune system “learns” from the experience and when the pathogen is encountered again, the immune system swings into action much more quickly. Immunization or vaccination is a safe way to make individuals resistant to infectious diseases. It works by exposing them to weakened or dead pathogens or to pathogen molecules (antigens) that the immune system recognizes as foreign. Widespread, routine immunization of children is, therefore, an essential component of national and global strategies to reduce childhood illnesses and deaths.
Why Was This Study Done?
Although many factors affect the uptake of immunization (in particular, vaccine prices), national policy decisions to adopt new vaccines are an essential step toward improving coverage. Unfortunately, these decisions are often delayed in developing countries. Thus, although many industrialized countries have routinely immunized their children with the highly effective Haemophilus influenza type b (Hib) conjugate vaccine since it became available in the early 1990s, only 13 low-income countries were using the vaccine in 2004. Hib bacteria, which cause pneumonia (lung infection) and meningitis (brain inflammation), kill about 370,000 unvaccinated young children every year. In this study, the researchers try to explain delays in the adoption of routine Hib vaccination in developing countries by analyzing the associations between Hib vaccination and factors such as national economic status, local Hib burden, and eligibility for support from the Global Alliance for Vaccines and Immunisation (GAVI Alliance; a public–private partnership that offers financial, technical, and health systems support for the introduction of national immunization programs to developing countries that meet certain eligibility criteria).
What Did the Researchers Do and Find?
The researchers used a statistical approach called accelerated failure time analysis to analyze data collected in 147 countries between 1990 and 2007 on vaccine costs, Hib disease incidence, GAVI eligibility, and other factors that could influence decision-makers' perceptions of the costs and benefits of Hib vaccination. After allowing for gross national income, region, and burden of Hib disease, the researchers identified several factors that influenced the time between the availability of a Hib conjugate vaccine in a country and a decision being made to introduce routine Hib vaccination. The receipt of GAVI support speeded the decision to adopt vaccination by 63%, for example, and sharing borders with two or more countries that had adopted the vaccine speeded the decision by 50%. By contrast, for each 1% increase in vaccine costs, the time to decision to adopt vaccination was delayed by 2%. The 1998 and 2006 World Health Organization recommendations on routine Hib vaccination and the existence of local studies on Hib disease had no influence on the time to decision.
What Do These Findings Mean?
These findings confirm previous studies that showed that increases in the price of Hib vaccine increase the time to adoption. In addition, they suggest that GAVI eligibility accelerates decisions to adopt this vaccine and show that the decisions made by neighboring countries are important, which suggests that policy diffusion may occur. Thus, in the case of adoption of the Hib vaccine, both supply-side and demand-side factors seem to be important. Its is relevant to note that during writing of the article, JCS, MLS, MRR, APB, and RAH were employed by the Hib Initiative, which was funded by the GAVI Alliance. The findings do not necessarily represent the views, policies or decisions of the Hib Initiative or the GAVI Alliance. Importantly, these findings are explanatory, not predictive, so they cannot be applied directly to new vaccines to improve their rate of adoption. Nevertheless, these findings highlight the potential importance of setting up formal and informal networks to facilitate policy diffusion and suggest that long-term price and supply certainty might be factors that could help to accelerate national decisions to adopt new and/or underutilized vaccines and other public-health technologies.
Additional Information
Please access these Web sites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.1000249.
The World Health Organization provides information on immunization and on Haemophilus influenza type b (in several languages)
The GAVI Alliance Web site describes the work of this public–private partnership and provides details of developing countries eligible for Hib vaccination support
The Hib Initiative aims to reduce the risk of childhood death and disability through sustained use of Hib vaccine
MedlinePlus provides links to further resources on immunization and information on the Haemophilus influenzae type b vaccine (in English and Spanish)
doi:10.1371/journal.pmed.1000249
PMCID: PMC2838745  PMID: 20305714
6.  Determinants of influenza vaccination uptake among Italian healthcare workers 
We analyzed seasonal influenza vaccination coverage among the Italian healthcare workers (HCW) in order to identify socio-demographic and clinical determinants of vaccination.
We used data from the survey “Health and health care use in Italy,” which comprised interviews of 5,336 HCWs For each respondent, information on socioeconomic, health conditions, self-perceived health and smoking status were obtained. After bivariate analysis, we used multilevel regression models to assess determinants of immunization. Overall 20.8% of HCWs (95%CI 19.7–21.9) reported being vaccinated against seasonal influenza.
After controlling for potential confounders, multilevel regression revealed that older workers have a higher likelihood of vaccine uptake (OR = 6.07; 95% CI 4.72–7.79). Conversely, higher education was associated with lower vaccine uptake (OR = 0.65; 95% IC 0.50–0.83). Those suffering from diabetes (OR = 2.07; 95% CI 1.19–1.69), COPD (OR = 1.95; 95% CI 1.31–2.89) and cardiovascular diseases (OR = 1.48 95% CI 1.11–1.96) were more likely to be vaccinated. Likewise, smokers, or former smokers receive more frequently the vaccination (OR = 1.40; 95% CI 1.15–1.70; OR = 1.54; 95% CI 1.24–1.91, respectively) compared with never-smokers as well as those HCWs reporting fair or poor perceived health status (ORs of 1.68, 95% CI 1.30–2.18).
Vaccine coverage among HCWs in Italy remains low, especially among those with no comorbidities and being younger than 44 y old. This behavior not only raises questions regarding healthcare organization, infection control in healthcare settings and clinical costs, but also brings up ethical issues concerning physicians who seem not to be very concerned about the impact of the flu on themselves, as well as on their patients. Influenza vaccination campaigns will only be effective if HCWs understand their role in influenza transmission and prevention, and realize the importance of vaccination as a preventive measure
doi:10.4161/hv.22997
PMCID: PMC3903913  PMID: 24064543
administration and dosage; attitude of health personnel; health behavior; human prevention and control; influenza; influenza vaccines; socioeconomic factors
7.  Optimizing the Dose of Pre-Pandemic Influenza Vaccines to Reduce the Infection Attack Rate 
PLoS Medicine  2007;4(6):e218.
Background
The recent spread of avian influenza in wild birds and poultry may be a precursor to the emergence of a 1918-like human pandemic. Therefore, stockpiles of human pre-pandemic vaccine (targeted at avian strains) are being considered. For many countries, the principal constraint for these vaccine stockpiles will be the total mass of antigen maintained. We tested the hypothesis that lower individual doses (i.e., less than the recommended dose for maximum protection) may provide substantial extra community-level benefits because they would permit wider vaccine coverage for a given total size of antigen stockpile.
Methods and Findings
We used a mathematical model to predict infection attack rates under different policies. The model incorporated both an individual's response to vaccination at different doses and the process of person-to-person transmission of pandemic influenza. We found that substantial reductions in the attack rate are likely if vaccines are given to more people at lower doses. These results are applicable to all three vaccine candidates for which data are available. As a guide to the magnitude of the effect, we simulated epidemics based on historical studies of immunogenicity. For example, for one of the vaccines for which data are available, the attack rate would drop from 67.6% to 58.7% if 160 out of the total US population of 300 million were given an optimal dose rather than 20 out of 300 million given the maximally protective dose (as promulgated in the US National Pandemic Preparedness Plan). Our results are conservative with respect to a number of alternative assumptions about the precise nature of vaccine protection. We also considered a model variant that includes a single high-risk subgroup representing children. For smaller stockpile sizes that allow vaccine to be offered only to the high-risk group at the optimal dose, the predicted benefits of using the homogenous model formed a lower bound in the presence of a risk group, even when the high-risk group was twice as infective and twice as susceptible.
Conclusions
In addition to individual-level protection (i.e., vaccine efficacy), the population-level implications of pre-pandemic vaccine programs should be considered when deciding on stockpile size and dose. Our results suggest that a lower vaccine dose may be justified in order to increase population coverage, thereby reducing the infection attack rate overall.
Steven Riley and colleagues examine the potential benefits of "stretching" a limited supply of vaccine and suggest that substantial reductions in the attack rate are possible if vaccines are given to more people at lower doses.
Editors' Summary
Background.
Every winter, millions of people catch influenza, a viral infection of the nose, throat, and airways. Most recover quickly, but the disease can be deadly. In the US, seasonal influenza outbreaks (epidemics) cause 36,000 excess deaths annually. And now there are fears that an avian (bird) influenza virus might trigger a human influenza pandemic—a global epidemic that could kill millions. Seasonal epidemics occur because flu viruses continually make small changes to their hemagglutinin and neuraminidase molecules, the viral proteins (antigens) that the immune system recognizes. Because of this “antigenic drift,” an immune system response (which can be induced by catching flu or by vaccination with disabled circulating influenza strains) that combats flu one year may provide only partial protection the next year. “Antigenic shift” (large changes in flu antigens) can cause pandemics because communities have no immunity to the changed virus.
Why Was This Study Done?
Although avian influenza virus, which contains a hemagglutinin type that differs from currently circulating human flu viruses, has caused a few cases of human influenza, it has not started a human pandemic yet because it cannot move easily between people. If it acquires this property, which will probably involve further small antigenic changes, it could kill millions of people before scientists can develop an effective vaccine against it. To provide some interim protection, many countries are preparing stockpiles of “pre-pandemic” vaccines targeted against the avian virus. The US, for example, plans to store enough pre-pandemic vaccine to provide maximum protection to 20 million people (including key health workers) out of its population of 300 million. But, given a limited stockpile of pre-pandemic vaccine, might giving more people a lower dose of vaccine, which might reduce the number of people susceptible to infection and induce herd immunity by preventing efficient transmission of the flu virus, be a better way to limit the spread of pandemic influenza? In this study, the researchers have used mathematical modeling to investigate this question.
What Did the Researchers Do and Find?
To predict the infection rates associated with different vaccination policies, the researchers developed a mathematical model that incorporates data on human immune responses induced with three experimental vaccines against the avian virus and historical data on the person–person transmission of previous pandemic influenza viruses. For all the vaccines, the model predicts that giving more people a low dose of the vaccine would limit the spread of influenza better than giving fewer people the high dose needed for full individual protection. For example, the researchers estimate that dividing the planned US stockpile of one experimental vaccine equally between 160 million people instead of giving it at the fully protective dose to 20 million people might avert about 27 million influenza cases in less than year. However, giving the maximally protective dose to the 9 million US health-care workers and using the remaining vaccine at a lower dose to optimize protection within the general population might avert only 14 million infections.
What Do These Findings Mean?
These findings suggest that, given a limited stockpile of pre-pandemic vaccine, increasing the population coverage of vaccination by using low doses of vaccine might reduce the overall influenza infection rate more effectively than vaccinating fewer people with fully protective doses of vaccine. However, because the researchers' model includes many assumptions, it can only give an indication of how different strategies might perform, not firm numbers for how many influenza cases each strategy is likely to avert. Before public-health officials use this or a similar model to help them decide the best way to use pre-pandemic vaccines to control a human influenza pandemic, they will need more information about the efficacy of these vaccines and about transmission rates of currently circulating viruses. They will also need to know whether pre-pandemic vaccines actually provide good protection against the pandemic virus, as assumed in this study, before they can recommend mass immunization with low doses of pre-pandemic vaccine, selective vaccination with high doses, or a mixed strategy.
Additional Information.
Please access these Web sites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.0040218.
US Centers for Disease Control and Prevention provide information on influenza and influenza vaccination for patients and health professionals (in English, Spanish, Filipino, Chinese, and Vietnamese)
The World Health Organization has a fact sheet on influenza and on the global response to avian influenza (in English, Spanish, French, Russian, Arabic, and Chinese)
The MedlinePlus online encyclopedia devotes a page to flu (in English and Spanish)
The UK Health Protection Agency information on avian, pandemic, and seasonal influenza
The US National Institute of Allergy and Infectious Diseases has a comprehensive feature called “focus on the flu”
doi:10.1371/journal.pmed.0040218
PMCID: PMC1892041  PMID: 17579511
8.  INFLUENZA VACCINATION IN HEALTHCARE WORKERS: 10-YEAR EXPERIENCE OF A LARGE HEALTHCARE ORGANIZATION 
Objective
To describe the results of different measures implemented to improve compliance with the healthcare worker (HCW) influenza immunization program at BJC HealthCare between 1997 and 2007.
Design
Descriptive retrospective study.
Setting
BJC HealthCare, a 13-hospital nonprofit healthcare organization in the Midwest.
Methods
Review and analysis of HCW influenza vaccination data from all BJC HealthCare Occupational Health Services and hospitals between 1997 and 2007. Occupational health staff, infection prevention personnel and key influenza vaccine campaign leaders were also interviewed regarding implementation measures during the study years.
Results
At the end of 2007, BJC HealthCare had approximately 26,000 employees. Using multiple progressive interventions, influenza vaccination rates among BJC employees increased from 45% in 1997 to 71.9% in 2007 (p<0.001). The influenza vaccination rate in 2007 was significantly higher than in 2006, 71.9% versus 54.2% (p<0.001). Five hospitals had influenza vaccination rates over the target goal of 80% in 2007. The most successful interventions were adding influenza vaccination rates to the incented quality scorecard and declination statements, both implemented in 2007. The most important barriers identified in the interviews related to HCWs’ misconceptions about influenza vaccination and a perceived lack of leadership support.
Conclusions
Influenza vaccination rates in HCWs significantly improved with multiple interventions over the years. However, the BJC HealthCare influenza vaccination target of 80% was not attained at all hospitals with these measures. More aggressive interventions such as implementing mandatory influenza vaccination policies are needed to achieve higher vaccination rates.
doi:10.1086/650449
PMCID: PMC3919446  PMID: 20055666
9.  Influenza vaccination coverage of healthcare workers and residents and their determinants in nursing homes for elderly people in France: a cross-sectional survey 
BMC Public Health  2010;10:159.
Background
Nursing home residents bear a substantial burden of influenza morbidity and mortality. Vaccination of residents and healthcare workers (HCWs) is the main strategy for prevention. Despite recommendations, influenza vaccination coverage among HCWs remains generally low.
Methods
During the 2007-2008 influenza season, we conducted a nationwide survey to estimate influenza vaccination coverage of HCWs and residents in nursing homes for elderly people in France and to identify determinants of vaccination rates. Multivariate analysis were performed with a negative binomial regression.
Results
Influenza vaccination coverage rates were 33.6% (95% CI: 31.9-35.4) for HCWs and 91% (95% CI: 90-92) for residents. Influenza vaccination uptake of HCWs varied by occupational category. Higher vaccination coverage was found in private elderly care residences, when free vaccination was offered (RR: 1.89, 1.35-2.64), in small nursing homes (RR: 1.54, 1.31-1.81) and when training sessions and staff meetings on influenza were organized (RR: 1.20, 1.11-1.29). The analysis by occupational category showed that some determinants were shared by all categories of professionals (type of nursing homes, organization of training and staff meetings on influenza). Higher influenza vaccination coverage was found when free vaccination was offered to recreational, cleaning, administrative staff, nurses and nurse assistants, but not for physicians.
Conclusions
This nationwide study assessed for the first time the rate of influenza vaccination among residents and HCWs in nursing homes for elderly in France. Better communication on the current recommendations regarding influenza vaccination is needed to increase compliance of HCWs. Vaccination programmes should include free vaccination and education campaigns targeting in priority nurses and nurse assistants.
doi:10.1186/1471-2458-10-159
PMCID: PMC2850345  PMID: 20338028
10.  Association between the 2008–09 Seasonal Influenza Vaccine and Pandemic H1N1 Illness during Spring–Summer 2009: Four Observational Studies from Canada 
PLoS Medicine  2010;7(4):e1000258.
In three case-control studies and a household transmission cohort, Danuta Skowronski and colleagues find an association between prior seasonal flu vaccination and increased risk of 2009 pandemic H1N1 flu.
Background
In late spring 2009, concern was raised in Canada that prior vaccination with the 2008–09 trivalent inactivated influenza vaccine (TIV) was associated with increased risk of pandemic influenza A (H1N1) (pH1N1) illness. Several epidemiologic investigations were conducted through the summer to assess this putative association.
Methods and Findings
Studies included: (1) test-negative case-control design based on Canada's sentinel vaccine effectiveness monitoring system in British Columbia, Alberta, Ontario, and Quebec; (2) conventional case-control design using population controls in Quebec; (3) test-negative case-control design in Ontario; and (4) prospective household transmission (cohort) study in Quebec. Logistic regression was used to estimate odds ratios for TIV effect on community- or hospital-based laboratory-confirmed seasonal or pH1N1 influenza cases compared to controls with restriction, stratification, and adjustment for covariates including combinations of age, sex, comorbidity, timeliness of medical visit, prior physician visits, and/or health care worker (HCW) status. For the prospective study risk ratios were computed. Based on the sentinel study of 672 cases and 857 controls, 2008–09 TIV was associated with statistically significant protection against seasonal influenza (odds ratio 0.44, 95% CI 0.33–0.59). In contrast, estimates from the sentinel and three other observational studies, involving a total of 1,226 laboratory-confirmed pH1N1 cases and 1,505 controls, indicated that prior receipt of 2008–09 TIV was associated with increased risk of medically attended pH1N1 illness during the spring–summer 2009, with estimated risk or odds ratios ranging from 1.4 to 2.5. Risk of pH1N1 hospitalization was not further increased among vaccinated people when comparing hospitalized to community cases.
Conclusions
Prior receipt of 2008–09 TIV was associated with increased risk of medically attended pH1N1 illness during the spring–summer 2009 in Canada. The occurrence of bias (selection, information) or confounding cannot be ruled out. Further experimental and epidemiological assessment is warranted. Possible biological mechanisms and immunoepidemiologic implications are considered.
Please see later in the article for the Editors' Summary
Editors' Summary
Background
Every winter, millions of people catch influenza—a viral infection of the airways—and hundreds of thousands of people die as a result. These seasonal epidemics occur because small but frequent changes in the influenza virus mean that an immune response produced one year through infection or vaccination provides only partial protection against influenza the next year. Annual vaccination with killed influenza viruses of the major circulating strains can greatly reduce a person's risk of catching influenza. Consequently, many countries run seasonal influenza vaccination programs. In most of Canada, vaccination with a mixture of three inactivated viruses (a trivalent inactivated vaccine or TIV) is provided free to children aged 6–23 months, to elderly people, to people with long-term conditions that increase their risk of influenza-related complications, and those who provide care for them; in Ontario, free vaccination is offered to everyone older than 6 months.
In addition, influenza viruses occasionally emerge that are very different and to which human populations have virtually no immunity. These viruses can start global epidemics (pandemics) that can kill millions of people. Experts have been warning for some time that an influenza pandemic is long overdue and, in March 2009, the first cases of influenza caused by a new virus called pandemic A/H1N1 2009 (pH1N1; swine flu) occurred in Mexico. The virus spread rapidly and on 11 June 2009, the World Health Organization declared that a global pandemic of pH1N1 influenza was underway. By the end of February 2010, more than 16,000 people around the world had died from pH1N1.
Why Was This Study Done?
During an investigation of a school outbreak of pH1N1 in the late spring 2009 in Canada, investigators noted that people with illness characterized by fever and coughing had been vaccinated against seasonal influenza more often than individuals without such illness. To assess whether this association between prior vaccination with seasonal 2008–09 TIV and subsequent pH1N1 illness was evident in other settings, researchers in Canada therefore conducted additional studies using different methods. In this paper, the researchers report the results of four additional studies conducted in Canada during the summer of 2009 to assess this possible association.
What Did the Researchers Do and Find?
The researchers conducted four epidemiologic studies. Epidemiology is the study of the causes, distribution, and control of diseases in populations.
Three of the four studies were case-control studies in which the researchers assessed the frequency of prior vaccination with the 2008–09 TIV in people with pH1N1 influenza compared to the frequency among healthy members of the general population or among individuals who had an influenza-like illness but no sign of infection with an influenza virus. The researchers also did a household transmission study in which they collected information about vaccination with TIV among the additional cases of influenza that were identified in 47 households in which a case of laboratory-confirmed pH1N1 influenza had occurred. The first of the case-control studies, which was based on Canada's vaccine effectiveness monitoring system, showed that, as expected, the 2008–09 TIV provided protection against seasonal influenza. However, estimates from all four studies (which included about 1,200 laboratory-confirmed pH1N1 cases and 1,500 controls) showed that prior recipients of the 2008–09 TIV had approximately 1.4–2.5 times increased chances of developing pH1N1 illness that needed medical attention during the spring–summer of 2009 compared to people who had not received the TIV. Prior seasonal vaccination was not associated with an increase in the severity of pH1N1 illness, however. That is, it did not increase the risk of being hospitalized among those with pH1N1 illness.
What Do These Findings Mean?
Because all the investigations in this study are “observational,” the people who had been vaccinated might share another unknown characteristic that is actually responsible for increasing their risk of developing pH1N1 illness (“confounding”). Furthermore, the results reported in this study might have arisen by chance, although the consistency of results across the studies makes this unlikely. Thus, the finding of an association between prior receipt of 2008–09 TIV and an increased risk of pH1N1 illness is not conclusive and needs to be investigated further, particularly since some other observational studies conducted in other countries have reported that seasonal vaccination had no influence or may have been associated with reduced chances of pH1N1 illness. If the findings in the current study are real, however, they raise important questions about the biological interactions between seasonal and pandemic influenza strains and vaccines, and about the best way to prevent and control both types of influenza in future.
Additional Information
Please access these Web sites via the online version of this summary at http://dx.doi.org/ 10.1371/journal.pmed.1000258.
This article is further discussed in a PLoS Medicine Perspective by Cécile Viboud and Lone Simonsen
FightFlu.ca, a Canadian government Web site, provides access to information on pH1N1 influenza
The US Centers for Disease Control and Prevention provides information about influenza for patients and professionals, including specific information on H1N1 influenza
Flu.gov, a US government website, provides access to information on H1N1, avian and pandemic influenza
The World Health Organization provides information on seasonal influenza and has detailed information on pH1N1 influenza (in several languages)
The UK Health Protection Agency provides information on pandemic influenza and on pH1N1 influenza
doi:10.1371/journal.pmed.1000258
PMCID: PMC2850386  PMID: 20386731
11.  Vaccination coverage for seasonal influenza among residents and health care workers in Norwegian nursing homes during the 2012/13 season, a cross-sectional study 
BMC Public Health  2014;14:434.
Background
WHO has set a goal of 75% vaccination coverage (VC) for seasonal influenza for residents and also recommends immunization for all healthcare workers (HCWs) in nursing homes (NHs). We conducted a cross-sectional study to estimate the VC for seasonal influenza vaccination in Norwegian NHs in 2012/2013 since the VC in NHs and HCWs is unknown.
Methods
We gathered information from NHs concerning VC for residents and HCWs, and vaccination costs for HCWs, using a web-based questionnaire. We calculated VC among NH residents by dividing the number of residents vaccinated by the total number of residents for each NH. VC among HCWs was similarly calculated by dividing the number of HCWs vaccinated by the total number of HCWs for each NH. The association between VC and possible demographic variables were explored.
Results
Of 910 NHs, 354 (38.9%) responded. Median VC per NH was 71.7% (range 0-100) among residents and 0% (range 0-100) among HCWs, with 214 (60%) NHs reporting that none of their HCWs was vaccinated. Median VC for HCWs in NHs with an annual vaccination campaign was 0% (range 0-53), compared to when they did not have an annual vaccination campaign 0% (range 0-12); the distributions in the two groups differed significantly (Mann–Whitney U, P = 0.006 two tailed).
Conclusion
Median influenza VC in Norwegian NHs was marginally lower than recommended among residents and exceptionally low among HCWs. The VC in HCWs was significantly higher when NHs had an annual vaccination campaign. We recommend that NHs implement measures to increase VC among residents and HCWs, including vaccination campaigns and studies to identify potential barriers to vaccination.
doi:10.1186/1471-2458-14-434
PMCID: PMC4049507  PMID: 24885662
12.  Characterization of Regional Influenza Seasonality Patterns in China and Implications for Vaccination Strategies: Spatio-Temporal Modeling of Surveillance Data 
PLoS Medicine  2013;10(11):e1001552.
Cécile Viboud and colleagues describe epidemiological patterns of influenza incidence across China to support the design of a national vaccination program.
Please see later in the article for the Editors' Summary
Background
The complexity of influenza seasonal patterns in the inter-tropical zone impedes the establishment of effective routine immunization programs. China is a climatologically and economically diverse country, which has yet to establish a national influenza vaccination program. Here we characterize the diversity of influenza seasonality in China and make recommendations to guide future vaccination programs.
Methods and Findings
We compiled weekly reports of laboratory-confirmed influenza A and B infections from sentinel hospitals in cities representing 30 Chinese provinces, 2005–2011, and data on population demographics, mobility patterns, socio-economic, and climate factors. We applied linear regression models with harmonic terms to estimate influenza seasonal characteristics, including the amplitude of annual and semi-annual periodicities, their ratio, and peak timing. Hierarchical Bayesian modeling and hierarchical clustering were used to identify predictors of influenza seasonal characteristics and define epidemiologically-relevant regions. The annual periodicity of influenza A epidemics increased with latitude (mean amplitude of annual cycle standardized by mean incidence, 140% [95% CI 128%–151%] in the north versus 37% [95% CI 27%–47%] in the south, p<0.0001). Epidemics peaked in January–February in Northern China (latitude ≥33°N) and April–June in southernmost regions (latitude <27°N). Provinces at intermediate latitudes experienced dominant semi-annual influenza A periodicity with peaks in January–February and June–August (periodicity ratio >0.6 in provinces located within 27.4°N–31.3°N, slope of latitudinal gradient with latitude −0.016 [95% CI −0.025 to −0.008], p<0.001). In contrast, influenza B activity predominated in colder months throughout most of China. Climate factors were the strongest predictors of influenza seasonality, including minimum temperature, hours of sunshine, and maximum rainfall. Our main study limitations include a short surveillance period and sparse influenza sampling in some of the southern provinces.
Conclusions
Regional-specific influenza vaccination strategies would be optimal in China; in particular, annual campaigns should be initiated 4–6 months apart in Northern and Southern China. Influenza surveillance should be strengthened in mid-latitude provinces, given the complexity of seasonal patterns in this region. More broadly, our findings are consistent with the role of climatic factors on influenza transmission dynamics.
Please see later in the article for the Editors' Summary
Editors' Summary
Background
Every year, millions of people worldwide catch influenza, a viral disease of the airways. Most infected individuals recover quickly but seasonal influenza outbreaks (epidemics) kill about half a million people annually. These epidemics occur because antigenic drift—frequent small changes in the viral proteins to which the immune system responds—means that an immune response produced one year provides only partial protection against influenza the next year. Annual vaccination with a mixture of killed influenza viruses of the major circulating strains boosts this natural immunity and greatly reduces the risk of catching influenza. Consequently, many countries run seasonal influenza vaccination programs. Because the immune response induced by vaccination decays within 4–8 months of vaccination and because of antigenic drift, it is important that these programs are initiated only a few weeks before the onset of local influenza activity. Thus, vaccination starts in early autumn in temperate zones (regions of the world that have a mild climate, part way between a tropical and a polar climate), because seasonal influenza outbreaks occur in the winter months when low humidity and low temperatures favor the transmission of the influenza virus.
Why Was This Study Done?
Unlike temperate regions, seasonal influenza patterns are very diverse in tropical countries, which lie between latitudes 23.5°N and 23.5°S, and in the subtropical countries slightly north and south of these latitudes. In some of these countries, there is year-round influenza activity, in others influenza epidemics occur annually or semi-annually (twice yearly). This complexity, which is perhaps driven by rainfall fluctuations, complicates the establishment of effective routine immunization programs in tropical and subtropical countries. Take China as an example. Before a national influenza vaccination program can be established in this large, climatologically diverse country, public-health experts need a clear picture of influenza seasonality across the country. Here, the researchers use spatio-temporal modeling of influenza surveillance data to characterize the seasonality of influenza A and B (the two types of influenza that usually cause epidemics) in China, to assess the role of putative drivers of seasonality, and to identify broad epidemiological regions (areas with specific patterns of disease) that could be used as a basis to optimize the timing of future Chinese vaccination programs.
What Did the Researchers Do and Find?
The researchers collected together the weekly reports of laboratory-confirmed influenza prepared by the Chinese national sentinel hospital-based surveillance network between 2005 and 2011, data on population size and density, mobility patterns, and socio-economic factors, and daily meteorological data for the cities participating in the surveillance network. They then used various statistical modeling approaches to estimate influenza seasonal characteristics, to assess predictors of influenza seasonal characteristics, and to identify epidemiologically relevant regions. These analyses indicate that, over the study period, northern provinces (latitudes greater than 33°N) experienced winter epidemics of influenza A in January–February, southern provinces (latitudes less than 27°N) experienced peak viral activity in the spring (April–June), and provinces at intermediate latitudes experienced semi-annual epidemic cycles with infection peaks in January–February and June–August. By contrast, influenza B activity predominated in the colder months throughout China. The researchers also report that minimum temperatures, hours of sunshine, and maximum rainfall were the strongest predictors of influenza seasonality.
What Do These Findings Mean?
These findings show that influenza seasonality in China varies between regions and between influenza virus types and suggest that, as in other settings, some of these variations might be associated with specific climatic factors. The accuracy of these findings is limited by the short surveillance period, by sparse surveillance data from some southern and mid-latitude provinces, and by some aspects of the modeling approach used in the study. Further surveillance studies need to be undertaken to confirm influenza seasonality patterns in China. Overall, these findings suggest that, to optimize routine influenza vaccination in China, it will be necessary to stagger the timing of vaccination over three broad geographical regions. More generally, given that there is growing interest in rolling out national influenza immunization programs in low- and middle-income countries, these findings highlight the importance of ensuring that vaccination strategies are optimized by taking into account local disease patterns.
Additional Information
Please access these websites via the online version of this summary at http://dx.doi.org/ 10.1371/journal.pmed.1001552.
This study is further discussed in a PLOS Medicine Perspective by Steven Riley
The UK National Health Service Choices website provides information for patients about seasonal influenza and about influenza vaccination
The World Health Organization provides information on seasonal influenza (in several languages) and on influenza surveillance and monitoring
The US Centers for Disease Control and Prevention also provides information for patients and health professionals on all aspects of seasonal influenza, including information about vaccination; its website contains a short video about personal experiences of influenza.
Flu.gov, a US government website, provides access to information on seasonal influenza and vaccination
Information about the Chinese National Influenza Center, which is part of the Chinese Center for Disease Control and Prevention: and which runs influenza surveillance in China, is available (in English and Chinese)
MedlinePlus has links to further information about influenza and about vaccination (in English and Spanish)
A recent PLOS Pathogens Research Article by James D. Tamerius et al. investigates environmental predictors of seasonal influenza epidemics across temperate and tropical climates
A study published in PLOS ONE by Wyller Alencar de Mello et al. indicates that Brazil, like China, requires staggered timing of vaccination from Northern to Southern states to account for different timings of influenza activity.
doi:10.1371/journal.pmed.1001552
PMCID: PMC3864611  PMID: 24348203
13.  Barriers to Provider-Initiated Testing and Counselling for Children in a High HIV Prevalence Setting: A Mixed Methods Study 
PLoS Medicine  2014;11(5):e1001649.
Rashida Ferrand and colleagues combine quantitative and qualitative methods to investigate HIV prevalence among older children receiving primary care in Harare, Zimbabwe, and reasons why providers did not pursue testing.
Please see later in the article for the Editors' Summary
Background
There is a substantial burden of HIV infection among older children in sub-Saharan Africa, the majority of whom are diagnosed after presentation with advanced disease. We investigated the provision and uptake of provider-initiated HIV testing and counselling (PITC) among children in primary health care facilities, and explored health care worker (HCW) perspectives on providing HIV testing to children.
Methods and Findings
Children aged 6 to 15 y attending six primary care clinics in Harare, Zimbabwe, were offered PITC, with guardian consent and child assent. The reasons why testing did not occur in eligible children were recorded, and factors associated with HCWs offering and children/guardians refusing HIV testing were investigated using multivariable logistic regression. Semi-structured interviews were conducted with clinic nurses and counsellors to explore these factors. Among 2,831 eligible children, 2,151 (76%) were offered PITC, of whom 1,534 (54.2%) consented to HIV testing. The main reasons HCWs gave for not offering PITC were the perceived unsuitability of the accompanying guardian to provide consent for HIV testing on behalf of the child and lack of availability of staff or HIV testing kits. Children who were asymptomatic, older, or attending with a male or a younger guardian had significantly lower odds of being offered HIV testing. Male guardians were less likely to consent to their child being tested. 82 (5.3%) children tested HIV-positive, with 95% linking to care. Of the 940 guardians who tested with the child, 186 (19.8%) were HIV-positive.
Conclusions
The HIV prevalence among children tested was high, highlighting the need for PITC. For PITC to be successfully implemented, clear legislation about consent and guardianship needs to be developed, and structural issues addressed. HCWs require training on counselling children and guardians, particularly male guardians, who are less likely to engage with health care services. Increased awareness of the risk of HIV infection in asymptomatic older children is needed.
Please see later in the article for the Editors' Summary
Editors' Summary
Background
Over 3 million children globally are estimated to be living with HIV (the virus that causes AIDS). While HIV infection is most commonly spread through unprotected sex with an infected person, most HIV infections among children are the result of mother-to-child HIV transmission during pregnancy, delivery, or breastfeeding. Mother-to-child transmission can be prevented by administering antiretroviral therapy to mothers with HIV during pregnancy, delivery, and breast feeding, and to their newborn babies. According to a report by the Joint United Nations Programme on HIV/AIDS published in 2012, 92% of pregnant women with HIV were living in sub-Saharan Africa and just under 60% were receiving antiretroviral therapy. Consequently, sub-Saharan Africa is the region where most children infected with HIV live.
Why Was This Study Done?
If an opportunity to prevent mother-to-child transmission around the time of birth is missed, diagnosis of HIV infection in a child or adolescent is likely to depend on HIV testing in health care facilities. Health care provider–initiated HIV testing and counselling (PITC) for children is important in areas where HIV infection is common because earlier diagnosis allows children to benefit from care that can prevent the development of advanced HIV disease. Even if a child or adolescent appears to be in good health, access to care and antiretroviral therapy provides a health benefit to the individual over the long term. The administration of HIV testing (and counselling) to children relies not only on health care workers (HCWs) offering HIV testing but also on parents or guardians consenting for a child to be tested. However, more than 30% of children in countries with severe HIV epidemics are AIDS orphans, and economic conditions in these countries cause many adults to migrate for work, leaving children under the care of extended families. This study aimed to investigate the reasons for acceptance and rejection of PITC in primary health care settings in Harare, Zimbabwe. By exploring HCW perspectives on providing HIV testing to children and adolescents, the study also sought to gain insight into factors that could be hindering implementation of testing procedures.
What Did the Researchers Do and Find?
The researchers identified all children aged 6 to 15 years old at six primary care clinics in Harare, who were offered HIV testing as part of routine care between 22 January and 31 May 2013. Study fieldworkers collected data on numbers of child attendances, numbers offered testing, numbers who underwent HIV testing, and reasons why HIV testing did not occur. During the study 2,831 children attending the health clinics were eligible for PITC, and just over half (1,534, 54.2%) underwent HIV testing. Eighty-two children tested HIV-positive, and nearly all of them received counselling, medication, and follow-up care. HCWs offered the test to around 75% of those eligible. The most frequent explanation given by HCWs for a diagnostic test not being offered was that the child was accompanied by a guardian not appropriate for providing consent (401 occasions, 59%); Other reasons given were a lack of available counsellors or test kits and counsellors refusing to conduct the test. The likelihood of being offered the test was lower for children not exhibiting symptoms (such as persistent skin problems), older children, or those attending with a male or a younger guardian. In addition, over 100 guardians or parents provided consent but left before the child could be tested.
The researchers also conducted semi-structured interviews with 12 clinic nurses and counsellors (two from each clinic) to explore challenges to implementation of PITC. The researchers recorded the factors associated with testing not taking place, either when offered to eligible children or when HCWs declined to offer the test. The interviewees identified the frequent absence or unavailability of parents or legal guardians as an obstacle, and showed uncertainty or misconceptions around whether testing of the guardian was mandatory (versus recommended) and whether specifically a parent (if one was living) must provide consent. The interviews also revealed HCW concerns about the availability of adequate counselling and child services, and fears that a child might experience maltreatment if he or she tested positive. HCWs also noted long waiting times and test kits being out of stock as practical hindrances to testing.
What Do These Findings Mean?
Prevalence of HIV was high among the children tested, validating the need for PITC in sub-Saharan health care settings. Although 76% of eligible attendees were offered testing, the authors note that this is likely higher than in routine settings because the researchers were actively recording reasons for not offering testing and counselling, which may have encouraged heath care staff to offer PITC more often than usual. The researchers outline strategies that may improve PITC rates and testing acceptance for Zimbabwe and other sub-Saharan settings. These strategies include developing clear laws and guidance concerning guardianship and proxy consent when testing older children for HIV, training HCWs around these policies, strengthening legislation to address discrimination, and increasing public awareness about HIV infection in older children.
Additional Information
Please access these websites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.1001649.
This study is further discussed in a PLOS Medicine Perspective by Davies and Kalk
The Joint United Nations Programme on HIV/AIDS publishes an annual report on the global AIDS epidemic, which provides information on progress towards eliminating new HIV infections
The World Health Organization has more information on mother-to-child transmission of HIV
The World Health Organization's website also has information about treatment for children living with HIV
Personal stories about living with HIV/AIDS, including stories from young people infected with HIV, are available through Avert, through NAM/aidsmap, and through the charity website Healthtalkonline
doi:10.1371/journal.pmed.1001649
PMCID: PMC4035250  PMID: 24866209
14.  Influenza Vaccination: Healthcare Workers Attitude in Three Middle East Countries 
Background: Healthcare workers (HCWs) pose a potential risk of transmitting communicable diseases in the hospital settings where they usually work. This study aims to determine the current influenza vaccination rates among HCWs in three Middle East countries namely United Arab Emirates (UAE), Kuwait and Oman, and also to identify the different variables associated with the noncompliance of HCWs to the recommendations of the Advisory Committee on Immunization Practices (ACIP) set in those countries. Methods: 1500 questionnaires were distributed to health care workers in the three countries during the period of July-October 2009. Results: Among 993 respondents, the vaccination rate was 24.7%, 67.2% and 46.4% in UAE, Kuwait and Oman, respectively. The different motivating factors that influenced the health care workers to take the vaccine was assessed and found that the most common factor that influenced their decision to take the vaccine was for their self protection (59%). On the other hand, the most common reason that discouraged HCWs to take the vaccine was “lack of time” as reported by 31.8% of the respondents. Other reasons for not taking the vaccine were unawareness of vaccine availability (29.4%), unavailability of vaccine (25.4%), doubts about vaccine efficacy (24.9%), lack of information about importance (20.1%) and concerns about its side effects (17.3%). Conclusions: influenza immunization by healthcare workers in the studied countries was suboptimal which could be improved by setting different interventions and educational programs to increase vaccination acceptance among HCWs.
PMCID: PMC2948215  PMID: 20922053
Influenza; healthcare workers; vaccination
15.  Vaccinating to Protect a Vulnerable Subpopulation 
PLoS Medicine  2007;4(5):e174.
Background
Epidemic influenza causes serious mortality and morbidity in temperate countries each winter. Research suggests that schoolchildren are critical in the spread of influenza virus, while the elderly and the very young are most vulnerable to the disease. Under these conditions, it is unclear how best to focus prevention efforts in order to protect the population. Here we investigate the question of how to protect a population against a disease when one group is particularly effective at spreading disease and another group is more vulnerable to the effects of the disease.
Methods and Findings
We developed a simple mathematical model of an epidemic that includes assortative mixing between groups of hosts. We evaluate the impact of different vaccine allocation strategies across a wide range of parameter values. With this model we demonstrate that the optimal vaccination strategy is extremely sensitive to the assortativity of population mixing, as well as to the reproductive number of the disease in each group. Small differences in parameter values can change the best vaccination strategy from one focused on the most vulnerable individuals to one focused on the most transmissive individuals.
Conclusions
Given the limited amount of information about relevant parameters, we suggest that changes in vaccination strategy, while potentially promising, should be approached with caution. In particular, we find that, while switching vaccine to more active groups may protect vulnerable groups in many cases, switching too much vaccine, or switching vaccine under slightly different conditions, may lead to large increases in disease in the vulnerable group. This outcome is more likely when vaccine limitation is stringent, when mixing is highly structured, or when transmission levels are high.
Jonathan Dushoff and colleagues model the benefits of different vaccination strategies and suggest that small differences in how populations mix can change the best vaccination strategy from one focused on the most vulnerable individuals to one focused on the most transmissive individuals.
Editors' Summary
Background.
Every winter, millions of people take to their beds with influenza—a viral infection of the nose, throat, and airways that is transmitted in airborne droplets released by coughing and sneezing. Most people who catch flu recover within a few days, but some develop serious complications such as pneumonia, and in the US alone, about 36,000 people—mainly infants, elderly, and chronically ill individuals—die every year. To minimize the morbidity (illness) and mortality (death) associated with seasonal (epidemic) influenza, the World Health Organization recommends that these vulnerable people be vaccinated against influenza every autumn. Annual vaccination is necessary because flu viruses continually make small changes to the viral proteins that the immune system recognizes.
Why Was This Study Done?
Although infants and the elderly are particularly vulnerable to influenza, schoolchildren are more likely to spread the flu virus. Also, vaccination is more effective in schoolchildren than in elderly people. So could vaccination of schoolchildren be the best way to reduce influenza morbidity and mortality? Some Japanese and US data suggest that it might be, but policymakers need to know more about the likely effects of changing the current influenza vaccination strategy. They need to know in what circumstances the direct effects of vaccination (protection of vaccinated individuals from disease) outweigh its indirect effects (reduced infection in vulnerable individuals caused by the reduced spread of disease in the whole population) and when the opposite is true. In this study, the researchers have used mathematical modeling to investigate how vaccination affects the spread of diseases such as influenza for which a “core” group in the population spreads the disease and a distinct “vulnerable” group is sensitive to its effects.
What Did the Researchers Do and Find?
The researchers developed a mathematical model in which members of each group mixed mainly with their own group (assortative mixing) and used it to predict how changing the proportion of a limited amount of vaccine given to each group might affect disease spread under different conditions. For example, they report that in a population in which the two groups were very unlikely to mix and viral transmission was low, switching vaccine from the vulnerable group to the core group initially increased infections in the vulnerable group because fewer individuals were directly protected but, as more vaccine was allocated to the core group, fewer vulnerable people became infected because the size of the epidemic decreased. When viral transmission was high, vaccination of the vulnerable group was always best. However, when viral transmission was moderate, shifting vaccine from the vulnerable group first increased, then decreased infections in this group before increasing them again. This last change occurred when vaccination in the vulnerable group was so low that viral transmission was sufficient to maintain the epidemic within this group.
What Do These Findings Mean?
As with all mathematical modeling, the researchers' findings depend on the assumptions included in the model, many of which are based on limited information. The model also considers a population that contains only two groups, an unlikely situation in real life. Nevertheless, these findings indicate that in a population in which one group of people is mainly responsible for the spread of a disease and another is most vulnerable to its effects, the best vaccination strategy is very sensitive to how the groups mix and how well the disease spreads in each group. Small changes in these poorly understood parameters can change the optimal vaccination strategy from one that vaccinates vulnerable individuals to one that mainly vaccinates the people who spread the disease. Importantly, a beneficial change in strategy can become deleterious if taken too far, so policy makers need to approach potentially promising changes in vaccination policy cautiously. Finally, for influenza, the model supports the idea that using some vaccine stocks in schoolchildren might decrease morbidity and mortality among elderly people but suggests that—even if this turns out to be correct—if all the vaccine were given to schoolchildren, more old people might die. Thus, the most prudent policy would be to supplement rather than replace vaccination of the elderly with vaccination of children.
Additional Information.
Please access these Web sites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.0040174.
US Centers for Disease Control and Prevention provide information about influenza for patients and professionals, including key facts about the flu vaccine (in English and Spanish)
World Health Organization, fact sheet on influenza and information on vaccination (in English, Spanish, French, Arabic, Chinese and Russian)
UK Health Protection Agency, information on seasonal influenza
MedlinePlus encyclopedia entries on influenza and the influenza vaccine (in English and Spanish)
Public disease mortality and morbidity data at the International Infectious Disease Data Archive (IIDDA)
doi:10.1371/journal.pmed.0040174
PMCID: PMC1872043  PMID: 17518515
16.  Seroprevalence of Pandemic H1N1 Antibody among Health Care Workers in Hong Kong Following Receipt of Monovalent 2009 H1N1 Influenza Vaccine 
PLoS ONE  2011;6(11):e27169.
Background
Healthcare workers in many countries are recommended to receive influenza vaccine to protect themselves as well as patients. A monovalent H1N1 vaccine became available in Hong Kong in December 2009 and around 10% of local healthcare workers had received the vaccine by February 2010.
Methods
We conducted a cross-sectional study of the prevalence of antibody to pandemic (H1N1) 2009 among HCWs in Hong Kong in February–March 2010 following the first pandemic wave and the pH1N1 vaccination campaign. In this study we focus on the subset of healthcare workers who reported receipt of non-adjuvanted monovalent 2009 H1N1 vaccine (Panenza, Sanofi Pasteur). Sera collected from HCWs were tested for antibody against the pH1N1 virus by hemagglutination inhibition (HI) and viral neutralization (VN) assays.
Results
We enrolled 703 HCWs. Among 104 HCWs who reported receipt of pH1N1 vaccine, 54% (95% confidence interval (CI): 44%–63%) had antibody titer ≥1∶40 by HI and 42% (95% CI: 33%–52%) had antibody titer ≥1∶40 by VN. The proportion of HCWs with antibody titer ≥1∶40 by HI and VN significantly decreased with age, and the proportion with antibody titer ≥1∶40 by VN was marginally significantly lower among HCWs who reported prior receipt of 2007–08 seasonal influenza vaccine (odds ratio: 0.43; 95% CI: 0.19–1.00). After adjustment for age, the effect of prior seasonal vaccine receipt was not statistically significant.
Conclusions
Our findings suggest that monovalent H1N1 vaccine may have had suboptimal immunogenicity in HCWs in Hong Kong. Larger studies are required to confirm whether influenza vaccine maintains high efficacy and effectiveness in HCWs.
doi:10.1371/journal.pone.0027169
PMCID: PMC3213124  PMID: 22102878
17.  Prioritization strategies for pandemic influenza vaccine in 27 countries of the European Union and the Global Health Security Action Group: a review 
BMC Public Health  2007;7:236.
Background
Although there is rapid progress in vaccine research regarding influenza pandemic vaccines it is expected that pandemic influenza vaccine production can only start once the pandemic virus has been recognized. Therefore, pandemic vaccine capacity will be limited at least during the first phase of an influenza pandemic, requiring vaccine prioritization strategies. WHO recommends developing preliminary priorities for pandemic vaccine use. The goal of this review is to provide a thorough overview of pandemic vaccine prioritization concepts in the 27 European Union (EU) member states and the four non-EU countries of the Global Health Security Action Group.
Methods
Between September and December 2006 data was collected for each country through two data sources: (i) the national influenza pandemic plan; (ii) contacting key persons involved in pandemic planning by email and/or phone and/or fax
Results
Twenty-six (84%) countries had established at least one vaccine priority group. Most common reported vaccine priority groups were health care workers (HCW) (100%), essential service providers (ESP) (92%) and high risk individuals (HRI) (92%). Ranking of at least one vaccine priority group was done by 17 (65%) of 26 countries. Fifteen (88%) of these 17 countries including a ranking strategy, decided that HCW with close contact to influenza patients should be vaccinated first; in most countries followed and/or ranked equally by ESP and subsequently HRI. Rationales for prioritization were provided by 22 (85%) of 26 countries that established vaccine priority groups. There was large variation in the phrasing and level of detailed specification of rationales. Seven (32%) of 22 countries providing rationales clearly associated each vaccine priority group with the specific rationale. Ten (32% of the 31 countries studied) countries have consulted and involved ethical experts to guide decisions related to vaccine prioritization.
Conclusion
In the majority of the countries the establishment of vaccine priority groups, ranking and underlying rationales are in line with WHO recommendations. In most public plans the criteria by which prioritized groups are identified are not easily recognizable. Clarity however, may be necessary to assure public acceptability of the prioritization. Ethical experts, results of modelling exercises could play an increasing role in the future decision making process.
doi:10.1186/1471-2458-7-236
PMCID: PMC2048949  PMID: 17825095
18.  How to develop a program to increase influenza vaccine uptake among workers in health care settings? 
Background
Apart from direct protection and reduced productivity loss during epidemics, the main reason to immunize healthcare workers (HCWs) against influenza is to provide indirect protection of frail patients through reduced transmission in healthcare settings. Because the vaccine uptake among HCWs remains far below the health objectives, systematic programs are needed to take full advantage of such vaccination. In an earlier report, we showed a mean 9% increase of vaccine uptake among HCWs in nursing homes that implemented a systematic program compared with control homes, with higher rates in those homes that implemented more program elements. Here, we report in detail the process of the development of the implementation program to enable researchers and practitioners to develop intervention programs tailored to their setting.
Methods
We applied the intervention mapping (IM) method to develop a theory- and evidence-based intervention program to change vaccination behaviour among HCWs in nursing homes.
Results
After a comprehensive needs assessment, we were able to specify proximal program objectives and selected methods and strategies for inducing behavioural change. By consensus, we decided on planning of three main program components, i.e., an outreach visit to all nursing homes, plenary information meetings, and the appointment of a program coordinator -- preferably a physician -- in each home. Finally, we planned program adoption, implementation, and evaluation.
Conclusion
The IM methodology resulted in a systematic, comprehensive, and transparent procedure of program development. A potentially effective intervention program to change influenza vaccination behaviour among HCWs was developed, and its impact was assessed in a clustered randomised controlled trial.
doi:10.1186/1748-5908-6-47
PMCID: PMC3115899  PMID: 21595877
19.  Barriers to pandemic influenza vaccination and uptake of seasonal influenza vaccine in the post-pandemic season in Germany 
BMC Public Health  2012;12:938.
Background
In Germany, annual vaccination against seasonal influenza is recommended for certain target groups (e.g. persons aged ≥60 years, chronically ill persons, healthcare workers (HCW)). In season 2009/10, vaccination against pandemic influenza A(H1N1)pdm09, which was controversially discussed in the public, was recommended for the whole population. The objectives of this study were to assess vaccination coverage for seasonal (seasons 2008/09-2010/11) and pandemic influenza (season 2009/10), to identify predictors of and barriers to pandemic vaccine uptake and whether the controversial discussions on pandemic vaccination has had a negative impact on seasonal influenza vaccine uptake in Germany.
Methods
We analysed data from the ‘German Health Update’ (GEDA10) telephone survey (n=22,050) and a smaller GEDA10-follow-up survey (n=2,493), which were both representative of the general population aged ≥18 years living in Germany.
Results
Overall only 8.8% of the adult population in Germany received a vaccination against pandemic influenza. High socioeconomic status, having received a seasonal influenza shot in the previous season, and belonging to a target group for seasonal influenza vaccination were independently associated with the uptake of pandemic vaccines. The main reasons for not receiving a pandemic vaccination were ‘fear of side effects’ and the opinion that ‘vaccination was not necessary’. Seasonal influenza vaccine uptake in the pre-pandemic season 2008/09 was 52.8% among persons aged ≥60 years; 30.5% among HCW, and 43.3% among chronically ill persons. A decrease in vaccination coverage was observed across all target groups in the first post-pandemic season 2010/11 (50.6%, 25.8%, and 41.0% vaccination coverage, respectively).
Conclusions
Seasonal influenza vaccination coverage in Germany remains in all target groups below 75%, which is a declared goal of the European Union. Our results suggest that controversial public discussions about safety and the benefits of pandemic influenza vaccination may have contributed to both a very low uptake of pandemic vaccines and a decreased uptake of seasonal influenza vaccines in the first post-pandemic season. In the upcoming years, the uptake of seasonal influenza vaccines should be carefully monitored in all target groups to identify if this trend continues and to guide public health authorities in developing more effective vaccination and communication strategies for seasonal influenza vaccination.
doi:10.1186/1471-2458-12-938
PMCID: PMC3527143  PMID: 23113995
Vaccination; Influenza; Coverage; Pandemic; Germany
20.  Influenza and hepatitis B vaccination coverage among healthcare workers in Croatian hospitals: a series of cross-sectional surveys, 2006–2011 
BMC Infectious Diseases  2013;13:520.
Background
Healthcare workers (HCWs) are at an increased risk of exposure to and transmission of infectious diseases. Vaccination lowers morbidity and mortality of HCWs and their patients. To assess vaccination coverage for influenza and hepatitis B virus (HBV) among HCWs in Croatian hospitals, we conducted yearly nationwide surveys.
Methods
From 2006 to 2011, all 66 Croatian public hospitals, representing 43–60% of all the HCWs in Croatia, were included. Statistical analysis was performed using the Kruskal–Wallis analysis of variance, Dunn’s multiple comparison analysis and the chi-square test, as appropriate.
Results
The median seasonal influenza vaccination coverage rates in pre-pandemic (2006–2008) seasons were 36%, 25% and 29%, respectively. By occupation, influenza vaccination rates among physicians were 33 ± 21%, 33 ± 22% among graduate nurses, 30±34% among other HCWs, 26 ± 21% among housekeeping and the lowest, 23 ± 17%, among practical nurses (p < 0.01). In 2009–2010 season, seasonal influenza vaccination coverage was 30%, while overall vaccination coverage against pandemic influenza was fewer than 5%. Median vaccination coverage in the post-pandemic seasons of 2010–2011 and 2011–2012 decreased to 15% and 14%, respectively (reduction of 24% and 35%, respectively, p < 0.0001). Meanwhile, the median mandatory HBV vaccination coverage was 98%, albeit with considerable differences according to work setting (range 19–100%) and occupation (range 4–100%).
Conclusions
We found substantial year-on-year variations in seasonal influenza vaccination rates, with reduction in post pandemic influenza seasons. HBV vaccination is satisfactory compared to seasonal influenza vaccination coverage, although substantial variations by occupation and work setting were observed. These findings highlight the need for national strategies that optimize vaccination coverage among HCWs in Croatian hospitals. Further studies are needed to establish the potential role of mandatory vaccination for seasonal influenza.
doi:10.1186/1471-2334-13-520
PMCID: PMC3840606  PMID: 24192278
Influenza; Hepatitis B; Healthcare workers; Vaccination
21.  Influenza and Pneumococcal Vaccinations for Patients With Chronic Obstructive Pulmonary Disease (COPD) 
Executive Summary
In July 2010, the Medical Advisory Secretariat (MAS) began work on a Chronic Obstructive Pulmonary Disease (COPD) evidentiary framework, an evidence-based review of the literature surrounding treatment strategies for patients with COPD. This project emerged from a request by the Health System Strategy Division of the Ministry of Health and Long-Term Care that MAS provide them with an evidentiary platform on the effectiveness and cost-effectiveness of COPD interventions.
After an initial review of health technology assessments and systematic reviews of COPD literature, and consultation with experts, MAS identified the following topics for analysis: vaccinations (influenza and pneumococcal), smoking cessation, multidisciplinary care, pulmonary rehabilitation, long-term oxygen therapy, noninvasive positive pressure ventilation for acute and chronic respiratory failure, hospital-at-home for acute exacerbations of COPD, and telehealth (including telemonitoring and telephone support). Evidence-based analyses were prepared for each of these topics. For each technology, an economic analysis was also completed where appropriate. In addition, a review of the qualitative literature on patient, caregiver, and provider perspectives on living and dying with COPD was conducted, as were reviews of the qualitative literature on each of the technologies included in these analyses.
The Chronic Obstructive Pulmonary Disease Mega-Analysis series is made up of the following reports, which can be publicly accessed at the MAS website at: http://www.hqontario.ca/en/mas/mas_ohtas_mn.html.
Chronic Obstructive Pulmonary Disease (COPD) Evidentiary Framework
Influenza and Pneumococcal Vaccinations for Patients With Chronic Obstructive Pulmonary Disease (COPD): An Evidence-Based Analysis
Smoking Cessation for Patients With Chronic Obstructive Pulmonary Disease (COPD): An Evidence-Based Analysis
Community-Based Multidisciplinary Care for Patients With Stable Chronic Obstructive Pulmonary Disease (COPD): An Evidence-Based Analysis
Pulmonary Rehabilitation for Patients With Chronic Obstructive Pulmonary Disease (COPD): An Evidence-Based Analysis
Long-term Oxygen Therapy for Patients With Chronic Obstructive Pulmonary Disease (COPD): An Evidence-Based Analysis
Noninvasive Positive Pressure Ventilation for Acute Respiratory Failure Patients With Chronic Obstructive Pulmonary Disease (COPD): An Evidence-Based Analysis
Noninvasive Positive Pressure Ventilation for Chronic Respiratory Failure Patients With Stable Chronic Obstructive Pulmonary Disease (COPD): An Evidence-Based Analysis
Hospital-at-Home Programs for Patients with Acute Exacerbations of Chronic Obstructive Pulmonary Disease (COPD): An Evidence-Based Analysis
Home Telehealth for Patients With Chronic Obstructive Pulmonary Disease (COPD): An Evidence-Based Analysis
Cost-Effectiveness of Interventions for Chronic Obstructive Pulmonary Disease Using an Ontario Policy Model
Experiences of Living and Dying With COPD: A Systematic Review and Synthesis of the Qualitative Empirical Literature
For more information on the qualitative review, please contact Mita Giacomini at: http://fhs.mcmaster.ca/ceb/faculty_member_giacomini.htm.
For more information on the economic analysis, please visit the PATH website: http://www.path-hta.ca/About-Us/Contact-Us.aspx.
The Toronto Health Economics and Technology Assessment (THETA) collaborative has produced an associated report on patient preference for mechanical ventilation. For more information, please visit the THETA website: http://theta.utoronto.ca/static/contact.
Objective
The objective of this analysis was to determine the effectiveness of the influenza vaccination and the pneumococcal vaccination in patients with chronic obstructive pulmonary disease (COPD) in reducing the incidence of influenza-related illness or pneumococcal pneumonia.
Clinical Need: Condition and Target Population
Influenza Disease
Influenza is a global threat. It is believed that the risk of a pandemic of influenza still exists. Three pandemics occurred in the 20th century which resulted in millions of deaths worldwide. The fourth pandemic of H1N1 influenza occurred in 2009 and affected countries in all continents.
Rates of serious illness due to influenza viruses are high among older people and patients with chronic conditions such as COPD. The influenza viruses spread from person to person through sneezing and coughing. Infected persons can transfer the virus even a day before their symptoms start. The incubation period is 1 to 4 days with a mean of 2 days. Symptoms of influenza infection include fever, shivering, dry cough, headache, runny or stuffy nose, muscle ache, and sore throat. Other symptoms such as nausea, vomiting, and diarrhea can occur.
Complications of influenza infection include viral pneumonia, secondary bacterial pneumonia, and other secondary bacterial infections such as bronchitis, sinusitis, and otitis media. In viral pneumonia, patients develop acute fever and dyspnea, and may further show signs and symptoms of hypoxia. The organisms involved in bacterial pneumonia are commonly identified as Staphylococcus aureus and Hemophilus influenza. The incidence of secondary bacterial pneumonia is most common in the elderly and those with underlying conditions such as congestive heart disease and chronic bronchitis.
Healthy people usually recover within one week but in very young or very old people and those with underlying medical conditions such as COPD, heart disease, diabetes, and cancer, influenza is associated with higher risks and may lead to hospitalization and in some cases death. The cause of hospitalization or death in many cases is viral pneumonia or secondary bacterial pneumonia. Influenza infection can lead to the exacerbation of COPD or an underlying heart disease.
Streptococcal Pneumonia
Streptococcus pneumoniae, also known as pneumococcus, is an encapsulated Gram-positive bacterium that often colonizes in the nasopharynx of healthy children and adults. Pneumococcus can be transmitted from person to person during close contact. The bacteria can cause illnesses such as otitis media and sinusitis, and may become more aggressive and affect other areas of the body such as the lungs, brain, joints, and blood stream. More severe infections caused by pneumococcus are pneumonia, bacterial sepsis, meningitis, peritonitis, arthritis, osteomyelitis, and in rare cases, endocarditis and pericarditis.
People with impaired immune systems are susceptible to pneumococcal infection. Young children, elderly people, patients with underlying medical conditions including chronic lung or heart disease, human immunodeficiency virus (HIV) infection, sickle cell disease, and people who have undergone a splenectomy are at a higher risk for acquiring pneumococcal pneumonia.
Technology
Influenza and Pneumococcal Vaccines
Trivalent Influenza Vaccines in Canada
In Canada, 5 trivalent influenza vaccines are currently authorized for use by injection. Four of these are formulated for intramuscular use and the fifth product (Intanza®) is formulated for intradermal use.
The 4 vaccines for intramuscular use are:
Fluviral (GlaxoSmithKline), split virus, inactivated vaccine, for use in adults and children ≥ 6 months;
Vaxigrip (Sanofi Pasteur), split virus inactivated vaccine, for use in adults and children ≥ 6 months;
Agriflu (Novartis), surface antigen inactivated vaccine, for use in adults and children ≥ 6 months; and
Influvac (Abbott), surface antigen inactivated vaccine, for use in persons ≥ 18 years of age.
FluMist is a live attenuated virus in the form of an intranasal spray for persons aged 2 to 59 years. Immunization with current available influenza vaccines is not recommended for infants less than 6 months of age.
Pneumococcal Vaccine
Pneumococcal polysaccharide vaccines were developed more than 50 years ago and have progressed from 2-valent vaccines to the current 23-valent vaccines to prevent diseases caused by 23 of the most common serotypes of S pneumoniae. Canada-wide estimates suggest that approximately 90% of cases of pneumococcal bacteremia and meningitis are caused by these 23 serotypes. Health Canada has issued licenses for 2 types of 23-valent vaccines to be injected intramuscularly or subcutaneously:
Pneumovax 23® (Merck & Co Inc. Whitehouse Station, NJ, USA), and
Pneumo 23® (Sanofi Pasteur SA, Lion, France) for persons 2 years of age and older.
Other types of pneumococcal vaccines licensed in Canada are for pediatric use. Pneumococcal polysaccharide vaccine is injected only once. A second dose is applied only in some conditions.
Research Questions
What is the effectiveness of the influenza vaccination and the pneumococcal vaccination compared with no vaccination in COPD patients?
What is the safety of these 2 vaccines in COPD patients?
What is the budget impact and cost-effectiveness of these 2 vaccines in COPD patients?
Research Methods
Literature search
Search Strategy
A literature search was performed on July 5, 2010 using OVID MEDLINE, MEDLINE In-Process and Other Non-Indexed Citations, EMBASE, the Cumulative Index to Nursing & Allied Health Literature (CINAHL), the Cochrane Library, and the International Agency for Health Technology Assessment (INAHTA) for studies published from January 1, 2000 to July 5, 2010. The search was updated monthly through the AutoAlert function of the search up to January 31, 2011. Abstracts were reviewed by a single reviewer and, for those studies meeting the eligibility criteria, full-text articles were obtained. Articles with an unknown eligibility were reviewed with a second clinical epidemiologist and then a group of epidemiologists until consensus was established. Data extraction was carried out by the author.
Inclusion Criteria
studies comparing clinical efficacy of the influenza vaccine or the pneumococcal vaccine with no vaccine or placebo;
randomized controlled trials published between January 1, 2000 and January 31, 2011;
studies including patients with COPD only;
studies investigating the efficacy of types of vaccines approved by Health Canada;
English language studies.
Exclusion Criteria
non-randomized controlled trials;
studies investigating vaccines for other diseases;
studies comparing different variations of vaccines;
studies in which patients received 2 or more types of vaccines;
studies comparing different routes of administering vaccines;
studies not reporting clinical efficacy of the vaccine or reporting immune response only;
studies investigating the efficacy of vaccines not approved by Health Canada.
Outcomes of Interest
Primary Outcomes
Influenza vaccination: Episodes of acute respiratory illness due to the influenza virus.
Pneumococcal vaccination: Time to the first episode of community-acquired pneumonia either due to pneumococcus or of unknown etiology.
Secondary Outcomes
rate of hospitalization and mechanical ventilation
mortality rate
adverse events
Quality of Evidence
The quality of each included study was assessed taking into consideration allocation concealment, randomization, blinding, power/sample size, withdrawals/dropouts, and intention-to-treat analyses. The quality of the body of evidence was assessed as high, moderate, low, or very low according to the GRADE Working Group criteria. The following definitions of quality were used in grading the quality of the evidence:
Summary of Efficacy of the Influenza Vaccination in Immunocompetent Patients With COPD
Clinical Effectiveness
The influenza vaccination was associated with significantly fewer episodes of influenza-related acute respiratory illness (ARI). The incidence density of influenza-related ARI was:
All patients: vaccine group: (total of 4 cases) = 6.8 episodes per 100 person-years; placebo group: (total of 17 cases) = 28.1 episodes per 100 person-years, (relative risk [RR], 0.2; 95% confidence interval [CI], 0.06−0.70; P = 0.005).
Patients with severe airflow obstruction (forced expiratory volume in 1 second [FEV1] < 50% predicted): vaccine group: (total of 1 case) = 4.6 episodes per 100 person-years; placebo group: (total of 7 cases) = 31.2 episodes per 100 person-years, (RR, 0.1; 95% CI, 0.003−1.1; P = 0.04).
Patients with moderate airflow obstruction (FEV1 50%−69% predicted): vaccine group: (total of 2 cases) = 13.2 episodes per 100 person-years; placebo group: (total of 4 cases) = 23.8 episodes per 100 person-years, (RR, 0.5; 95% CI, 0.05−3.8; P = 0.5).
Patients with mild airflow obstruction (FEV1 ≥ 70% predicted): vaccine group: (total of 1 case) = 4.5 episodes per 100 person-years; placebo group: (total of 6 cases) = 28.2 episodes per 100 person-years, (RR, 0.2; 95% CI, 0.003−1.3; P = 0.06).
The Kaplan-Meier survival analysis showed a significant difference between the vaccinated group and the placebo group regarding the probability of not acquiring influenza-related ARI (log-rank test P value = 0.003). Overall, the vaccine effectiveness was 76%. For categories of mild, moderate, or severe COPD the vaccine effectiveness was 84%, 45%, and 85% respectively.
With respect to hospitalization, fewer patients in the vaccine group compared with the placebo group were hospitalized due to influenza-related ARIs, although these differences were not statistically significant. The incidence density of influenza-related ARIs that required hospitalization was 3.4 episodes per 100 person-years in the vaccine group and 8.3 episodes per 100 person-years in the placebo group (RR, 0.4; 95% CI, 0.04−2.5; P = 0.3; log-rank test P value = 0.2). Also, no statistically significant differences between the 2 groups were observed for the 3 categories of severity of COPD.
Fewer patients in the vaccine group compared with the placebo group required mechanical ventilation due to influenza-related ARIs. However, these differences were not statistically significant. The incidence density of influenza-related ARIs that required mechanical ventilation was 0 episodes per 100 person-years in the vaccine group and 5 episodes per 100 person-years in the placebo group (RR, 0.0; 95% CI, 0−2.5; P = 0.1; log-rank test P value = 0.4). In addition, no statistically significant differences between the 2 groups were observed for the 3 categories of severity of COPD. The effectiveness of the influenza vaccine in preventing influenza-related ARIs and influenza-related hospitalization was not related to age, sex, severity of COPD, smoking status, or comorbid diseases.
safety
Overall, significantly more patients in the vaccine group than the placebo group experienced local adverse reactions (vaccine: 17 [27%], placebo: 4 [6%]; P = 0.002). Significantly more patients in the vaccine group than the placebo group experienced swelling (vaccine 4, placebo 0; P = 0.04) and itching (vaccine 4, placebo 0; P = 0.04). Systemic reactions included headache, myalgia, fever, and skin rash and there were no significant differences between the 2 groups for these reactions (vaccine: 47 [76%], placebo: 51 [81%], P = 0.5).
With respect to lung function, dyspneic symptoms, and exercise capacity, there were no significant differences between the 2 groups at 1 week and at 4 weeks in: FEV1, maximum inspiratory pressure at residual volume, oxygen saturation level of arterial blood, visual analogue scale for dyspneic symptoms, and the 6 Minute Walking Test for exercise capacity.
There was no significant difference between the 2 groups with regard to the probability of not acquiring total ARIs (influenza-related and/or non-influenza-related); (log-rank test P value = 0.6).
Summary of Efficacy of the Pneumococcal Vaccination in Immunocompetent Patients With COPD
Clinical Effectiveness
The Kaplan-Meier survival analysis showed no significant differences between the group receiving the penumoccocal vaccination and the control group for time to the first episode of community-acquired pneumonia due to pneumococcus or of unknown etiology (log-rank test 1.15; P = 0.28). Overall, vaccine efficacy was 24% (95% CI, −24 to 54; P = 0.33).
With respect to the incidence of pneumococcal pneumonia, the Kaplan-Meier survival analysis showed a significant difference between the 2 groups (vaccine: 0/298; control: 5/298; log-rank test 5.03; P = 0.03).
Hospital admission rates and median length of hospital stays were lower in the vaccine group, but the difference was not statistically significant. The mortality rate was not different between the 2 groups.
Subgroup Analysis
The Kaplan-Meier survival analysis showed significant differences between the vaccine and control groups for pneumonia due to pneumococcus and pneumonia of unknown etiology, and when data were analyzed according to subgroups of patients (age < 65 years, and severe airflow obstruction FEV1 < 40% predicted). The accumulated percentage of patients without pneumonia (due to pneumococcus and of unknown etiology) across time was significantly lower in the vaccine group than in the control group in patients younger than 65 years of age (log-rank test 6.68; P = 0.0097) and patients with a FEV1 less than 40% predicted (log-rank test 3.85; P = 0.0498).
Vaccine effectiveness was 76% (95% CI, 20−93; P = 0.01) for patients who were less than 65 years of age and −14% (95% CI, −107 to 38; P = 0.8) for those who were 65 years of age or older. Vaccine effectiveness for patients with a FEV1 less than 40% predicted and FEV1 greater than or equal to 40% predicted was 48% (95% CI, −7 to 80; P = 0.08) and −11% (95% CI, −132 to 47; P = 0.95), respectively. For patients who were less than 65 years of age (FEV1 < 40% predicted), vaccine effectiveness was 91% (95% CI, 35−99; P = 0.002).
Cox modelling showed that the effectiveness of the vaccine was dependent on the age of the patient. The vaccine was not effective in patients 65 years of age or older (hazard ratio, 1.53; 95% CI, 0.61−a2.17; P = 0.66) but it reduced the risk of acquiring pneumonia by 80% in patients less than 65 years of age (hazard ratio, 0.19; 95% CI, 0.06−0.66; P = 0.01).
safety
No patients reported any local or systemic adverse reactions to the vaccine.
PMCID: PMC3384373  PMID: 23074431
22.  The Effect of Universal Influenza Immunization on Mortality and Health Care Use 
PLoS Medicine  2008;5(10):e211.
Background
In 2000, Ontario, Canada, initiated a universal influenza immunization program (UIIP) to provide free influenza vaccines for the entire population aged 6 mo or older. Influenza immunization increased more rapidly in younger age groups in Ontario compared to other Canadian provinces, which all maintained targeted immunization programs. We evaluated the effect of Ontario's UIIP on influenza-associated mortality, hospitalizations, emergency department (ED) use, and visits to doctors' offices.
Methods and Findings
Mortality and hospitalization data from 1997 to 2004 for all ten Canadian provinces were obtained from national datasets. Physician billing claims for visits to EDs and doctors' offices were obtained from provincial administrative datasets for four provinces with comprehensive data. Since outcomes coded as influenza are known to underestimate the true burden of influenza, we studied more broadly defined conditions. Hospitalizations, ED use, doctors' office visits for pneumonia and influenza, and all-cause mortality from 1997 to 2004 were modelled using Poisson regression, controlling for age, sex, province, influenza surveillance data, and temporal trends, and used to estimate the expected baseline outcome rates in the absence of influenza activity. The primary outcome was then defined as influenza-associated events, or the difference between the observed events and the expected baseline events. Changes in influenza-associated outcome rates before and after UIIP introduction in Ontario were compared to the corresponding changes in other provinces. After UIIP introduction, influenza-associated mortality decreased more in Ontario (relative rate [RR] = 0.26) than in other provinces (RR = 0.43) (ratio of RRs = 0.61, p = 0.002). Similar differences between Ontario and other provinces were observed for influenza-associated hospitalizations (RR = 0.25 versus 0.44, ratio of RRs = 0.58, p < 0.001), ED use (RR = 0.31 versus 0.69, ratio of RRs = 0.45, p < 0.001), and doctors' office visits (RR = 0.21 versus 0.52, ratio of RRs = 0.41, p < 0.001). Sensitivity analyses were carried out to assess consistency, specificity, and the presence of a dose-response relationship. Limitations of this study include the ecological study design, the nonspecific outcomes, difficulty in modeling baseline events, data quality and availability, and the inability to control for potentially important confounders.
Conclusions
Compared to targeted programs in other provinces, introduction of universal vaccination in Ontario in 2000 was associated with relative reductions in influenza-associated mortality and health care use. The results of this large-scale natural experiment suggest that universal vaccination may be an effective public health measure for reducing the annual burden of influenza.
Comparing influenza-related mortality and health care use between Ontario and other Canadian provinces, Jeffrey Kwong and colleagues find evidence that Ontario's universal vaccination program has reduced the burden of influenza.
Editors' Summary
Background.
Seasonal outbreaks (epidemics) of influenza—a viral disease of the nose, throat, and airways—affect millions of people and kill about 500,000 individuals every year. These epidemics occur because of “antigenic drift”: small but frequent changes in the viral proteins to which the human immune system responds mean that an immune response produced one year by exposure to an influenza virus provides only partial protection against influenza the next year. Immunization can boost this natural immunity and reduce a person's chances of catching influenza. That is, an injection of killed influenza viruses can be used to prime the immune system so that it responds quickly and efficiently when exposed to live virus. However, because of antigenic drift, for influenza immunization to be effective, it has to be repeated annually with a vaccine that contains the major circulating strains of the influenza virus.
Why Was This Study Done?
Public-health organizations recommend targeted vaccination programs, so that elderly people, infants, and chronically ill individuals—the people most likely to die from pneumonia and other complications of influenza—receive annual influenza vaccination. Some experts argue, however, that universal vaccination might provide populations with better protection from influenza, both directly by increasing the number of vaccinated people and indirectly through “herd immunity,” which occurs when a high proportion of the population is immune to an infectious disease, so that even unvaccinated people are unlikely to become infected (because infected people rarely come into contact with susceptible people). In this study, the researchers compare the effects of the world's first free universal influenza immunization program (UIIP), which started in 2000 in the Canadian province of Ontario, on influenza-associated deaths and health care use with the effects of targeted vaccine programs on the same outcomes elsewhere in Canada.
What Did the Researchers Do and Find?
Using national records, the researchers collected data on influenza vaccination, on all deaths, and on hospitalizations for pneumonia and influenza in all Canadian provinces between 1997 and 2004. They also collected data on emergency department and doctors' office visits for pneumonia and influenza for Ontario, Quebec, Alberta, and Manitoba. They then used a mathematical model to estimate the baseline rates for these outcomes in the absence of influenza activity, and from these calculated weekly rates for deaths and health care use specifically resulting from influenza. In 1996–1997, 18% of the population was vaccinated against influenza in Ontario whereas in the other provinces combined the vaccination rate was 13%. On average, since 2000—the year in which UIIP was introduced in Ontario—vaccination rates have risen to 38% and 24% in Ontario and the other provinces, respectively. Since the introduction of UIIP, the researchers report, influenza-associated deaths have decreased by 74% in Ontario but by only 57% in the other provinces combined. Influenza-associated use of health care facilities has also decreased more in Ontario than in the other provinces over the same period.
What Do These Findings Mean?
These findings are limited by some aspects of the study design. For example, they depend on the accuracy of the assumptions made when calculating events due specifically to influenza, and on the availability and accuracy of vaccination and clinical outcome data. In addition, it is possible that influenza-associated deaths and health care use may have decreased more in Ontario than in the other Canadian provinces because of some unrecognized health care changes specific to Ontario but unrelated to the introduction of universal influenza vaccination. Nevertheless, these findings indicate that, compared to the targeted vaccination programs in the other Canadian provinces, the Ontarian UIIP is associated with reductions in influenza-associated deaths and health care use, particularly in people younger than 65 years old. This effect is seen at a level of vaccination unlikely to produce herd immunity so might be more marked if the uptake of vaccination could be further increased. Thus, although it is possible that Canada is a special case, these findings suggest that universal influenza vaccination might be an effective way to reduce the global burden of influenza.
Additional Information.
Please access these Web sites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.0050211.
Read the related PLoSMedicine Perspective by Cécile Viboud and Mark Miller
A related PLoSMedicine Research Article by Carline van den Dool and colleagues is also available
The Ontario Ministry of Health provides information on its universal influenza immunization program (in English and French)
The World Health Organization provides information on influenza and on influenza vaccines (in several languages)
The US Centers for Disease Control and Prevention provide information for patients and professionals on all aspects of influenza (in English and Spanish)
MedlinePlus provides a list of links to other information about influenza (in English and Spanish)
The UK National Health Service provides information about the science of immunization, including a simple explanatory animation of immunity
doi:10.1371/journal.pmed.0050211
PMCID: PMC2573914  PMID: 18959473
23.  Acceptance of a Vaccine Against Novel Influenza A (H1N1) Virus Among Health Care Workers in Two Major Cities in Mexico 
Archives of medical research  2009;40(8):705-711.
Background and Aims
Further cases of novel influenza A (H1N1) outbreak are expected in the coming months. Vaccination has been proven to be essential to control a pandemic of influenza; therefore, considerable efforts and resources have been devoted to develop a vaccine against the influenza A (H1N1) virus. With the current availability of the vaccine, it will be important to immunize as many people as possible. However, previous data with seasonal influenza vaccines have shown that there are multiple barriers related to perceptions and attitudes of the population that influence vaccine use. The aim of the study was to evaluate the acceptance of a newly developed vaccine against pandemic (H1N1) 2009 influenza A among healthcare workers (HCW) in Mexico.
Methods
We conducted a cross-sectional study among HCW in three hospitals in the two largest cities in Mexico—Mexico City and Guadalajara—between June and September 2009.
Results
A total of 1097 HCW participated in the survey. Overall, 80% (n = 880) intended to accept the H1N1 pandemic vaccine and 71.6% (n = 786) reported they would recommend the vaccine to their patients. Doctors were more likely to accept and recommend the vaccine than nurses. HCWs who intend to be immunized will be more likely to do so if they know that the vaccine is safe and effective.
Conclusions
Knowledge of the willingness to accept the vaccine can be used to plan strategies that will effectively respond to the needs of the population studied, reducing the health and economic impact of novel influenza A (H1N1) virus.
doi:10.1016/j.arcmed.2010.01.004
PMCID: PMC2854164  PMID: 20304260
Vaccine acceptance; Influenza A (H1N1) virus; Health care workers
24.  Did the pandemic have an impact on influenza vaccination attitude? a survey among health care workers 
Background
Health care workers' (HCWs) influenza vaccination attitude is known to be negative. The H1N1 epidemic had started in mid 2009 and made a peak in October-November in Turkey. A national vaccination campaign began on November 2nd, 2009. Despite the diligent efforts of the Ministry of Health and NGOs, the attitudes of the media and politicians were mostly negative. The aim of this study was to evaluate whether HCWs' vaccination attitudes improved during the pandemic and to assess the related factors.
Methods
This cross-sectional survey was carried out at the largest university hospital of the Aegean Region-Turkey. A self-administered questionnaire with 12 structured questions was applied to 807 HCWs (sample coverage 91.3%) before the onset of the vaccination programme. Their final vaccination status was tracked one week afterwards, using immunization records. Factors influencing vaccination rates were analyzed using ANOVA, t-test, chi-square test and logistic regression.
Results
Among 807 participants, 363 (45.3%) were doctors and 293 (36.6%) nurses. A total of 153 (19.0%) had been vaccinated against seasonal influenza in the 2008-2009 season. Regarding H1N1 vaccination, 143 (17.7%) were willing to be vaccinated vs. 357 (44.2%) unwilling. The number of indecisive HCWs was 307 (38.0%) one week prior to vaccination. Only 53 (11.1%) stated that they would vaccinate their children. Possible side effects (78%, n = 519) and lack of comprehensive field evaluation before marketing (77%, n = 508) were the most common reasons underlying unwillingness or hesitation.
Among the 749 staff whose vaccination status could be tracked, 228 (30.4%) actually received the H1N1 vaccine. Some of the 'decided' staff members had changed their mind one week later. Only 82 (60%) of those willing, 108 (37%) of those indecisive and 38 (12%) of those unwilling were vaccinated.
Indecisive HCWs were significantly younger (p = 0.017). Females, nurses, and HCWs working in surgical departments were more likely to reject vaccination (p < 0.05). Doctors, HCWs working in medical departments, and HCWs previously vaccinated against seasonal influenza were more likely to accept vaccination (p < 0.05). Being younger than 50 and having been vaccinated in the previous season were important predictors of attitude towards pandemic influenza vaccination.
Conclusions
Vaccination rates increased substantially in comparison to the previous influenza season. However, vaccination rates could have been even higher since hesitation to be vaccinated increased dramatically within one week (only 60% of those willing and the minority of those indecisive were finally vaccinated). We speculate that this may be connected with negative media at the time.
doi:10.1186/1471-2334-11-87
PMCID: PMC3084177  PMID: 21473763
25.  Influenza vaccination among healthcare workers in a multidisciplinary University hospital in Italy 
BMC Public Health  2008;8:422.
Background
Annual influenza vaccination is recommended for healthcare workers (HCWs) in order to reduce the morbidity associated with influenza in healthcare settings. The aim of this study was to evaluate the current vaccination status of the HCWs in one of Italy's largest multidisciplinary University Hospitals.
Methods
Between February 1 and March 31, 2006, we carried out a cross-sectional study of influenza vaccination coverage among HCWs at the University Hospital Fondazione IRCCS "Ospedale Maggiore Policlinico, Mangiagalli e Regina Elena", Milan, Italy. After receiving a brief description of the aim of the study, 2,143 (95%: 1,064 physicians; 855 nurses; 224 paramedics) of 2,240 HCWs self-completed an anonymous questionnaire.
Results
Influenza vaccination coverage was very low in all specialties, varying from 17.6% in the Emergency Department to 24.3% in the Surgery Department, and knowledge of influenza epidemiology and prevention was poor. The factors positively associated with being vaccinated were an age of ≥ 45 years, considering influenza a potentially severe disease, and being aware of the high-risk categories for which influenza vaccination is strongly recommended; those that negatively associated with being vaccinated were being female, working in the Medicine Department, and being a nurse or paramedic.
Conclusion
Despite strong recommendations, influenza vaccination coverage seemed to be very low among HCWs of all specialties, with differences between areas and types of employment. Specific continuous educational and vaccination programs for different targets should be urgently organized to reduce morbidity and mortality in high-risk patients, contain nosocomial outbreaks, and ensure an appropriate socioeconomic impact.
doi:10.1186/1471-2458-8-422
PMCID: PMC2651144  PMID: 19105838

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