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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.  Protecting patients, protecting healthcare workers: a review of the role of influenza vaccination 
International Nursing Review  2011;59(2):161-167.
MUSIC T. (2012) A review of the role the role of influenza vaccination in protecting patients, protecting healthcare workers the role of influenza vaccination. International Nursing Review59, 161–167
Aim:
Many health authorities recommend routine influenza vaccination for healthcare workers (HCWs), and during the 2009 A (H1N1) pandemic, the World Health Organization (WHO) recommended immunization of all HCWs worldwide. As this remains an important area of policy debate, this paper examines the case for vaccination, the role of local guidelines, barriers to immunization and initiatives to increase uptake.
Background:
Seasonal influenza is a major threat to public health, causing up to 1 million deaths annually. Extensive evidence supports the vaccination of priority groups, including HCWs. Immunization protects HCWs themselves, and their vulnerable patients from nosocomial influenza infections. In addition, influenza can disrupt health services and impact healthcare organizations financially. Immunization can reduce staff absences, offer cost savings and provide economic benefits.
Methods:
This paper reviews official immunization recommendations and HCW vaccination studies, including a recent International Federation of Pharmaceutical Manufacturers and Associations (IFPMA) survey of 26 countries from each region of the world.
Results:
HCW immunization is widely recommended and supported by the WHO. In the IFPMA study, 88% of countries recommended HCW vaccination, and 61% supported this financially (with no correlation to country development status). Overall, coverage can be improved, and research shows that uptake may be impacted by lack of conveniently available vaccines and misconceptions regarding vaccine safety/efficacy and influenza risk.
Conclusions:
Many countries recommend HCW vaccination against influenza. In recent years, there has been an increased uptake rate among HCWs in some countries, but not in others. Several initiatives can increase coverage, including education, easy access to free vaccines and the use of formal declination forms. The case for HCW vaccination is clear, and in an effort to further accelerate uptake as a patient safety measure, an increasing number of healthcare organizations, particularly in the USA, are implementing mandatory immunization policies, similar to other obligatory hygiene measures. However, it would be desirable if similar high vaccination uptake rates could be achieved through voluntary procedures.
doi:10.1111/j.1466-7657.2011.00961.x
PMCID: PMC3418836  PMID: 22591085
Coverage; Education; Guideline; Influenza; Policy; Recommendation; Reimbursement; Seasonal; Vaccine
3.  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
4.  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
5.  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
6.  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
7.  Personal Decision-Making Criteria Related to Seasonal and Pandemic A(H1N1) Influenza-Vaccination Acceptance among French Healthcare Workers 
PLoS ONE  2012;7(7):e38646.
Background
Influenza-vaccination rates among healthcare workers (HCW) remain low worldwide, even during the 2009 A(H1N1) pandemic. In France, this vaccination is free but administered on a voluntary basis. We investigated the factors influencing HCW influenza vaccination.
Methods
In June–July 2010, HCW from wards of five French hospitals completed a cross-sectional survey. A multifaceted campaign aimed at improving vaccination coverage in this hospital group was conducted before and during the 2009 pandemic. Using an anonymous self-administered questionnaire, we assessed the relationships between seasonal (SIV) and pandemic (PIV) influenza vaccinations, and sociodemographic and professional characteristics, previous and current vaccination statuses, and 33 statements investigating 10 sociocognitive domains. The sociocognitive domains describing HCWs' SIV and PIV profiles were analyzed using the classification-and-regression–tree method.
Results
Of the HCWs responding to our survey, 1480 were paramedical and 401 were medical with 2009 vaccination rates of 30% and 58% for SIV and 21% and 71% for PIV, respectively (p<0.0001 for both SIV and PIV vaccinations). Older age, prior SIV, working in emergency departments or intensive care units, being a medical HCW and the hospital they worked in were associated with both vaccinations; while work shift was associated only with PIV. Sociocognitive domains associated with both vaccinations were self-perception of benefits and health motivation for all HCW. For medical HCW, being a role model was an additional domain associated with SIV and PIV.
Conclusions
Both vaccination rates remained low. Vaccination mainly depended on self-determined factors and for medical HCW, being a role model.
doi:10.1371/journal.pone.0038646
PMCID: PMC3407215  PMID: 22848342
8.  BRIEF REPORT: Influenza Vaccination and Health Care Workers in the United States 
OBJECTIVE
To determine influenza vaccination rates among U.S. health care workers (HCWs) by demographic and occupational categories.
DESIGN AND PARTICIPANTS
We analyzed data from the 2000 National Health Interview Survey (NHIS). Weighted multivariable analyses were used to evaluate the association between HCW occupation and other variables potentially related to receipt of influenza vaccination. HCWs were categorized based on standard occupational classifications as health-diagnosing professions, health-assessing professions, health aides, health technicians; or health administrators.
MAIN INDEPENDENT VARIABLES
Demographic characteristics and occupation category.
MAIN OUTCOME VARIABLES
Receipt of influenza vaccination within 12 months of survey.
ANALYSIS
Descriptive statistics and weighted multivariable logistic regression.
RESULTS
There were 1,651 HCWs in the final sample. The overall influenza vaccination rate for HCWs was 38%. After weighted multivariable analyses, HCWs who were under 50 (odds ratio [OR] 0.67%, 95% confidence interval [CI]: 0.50 to 0.89, compared with HCWs 50 to 64), black (OR 0.57 95% CI: 0.42, 0.78, compared with white HCWs), or were health aides (OR 0.73%, 95% CI: 0.51, 1.04, compared with health care administrators and administrative support staff) had lower odds of having been vaccinated against influenza.
CONCLUSIONS
The overall influenza vaccination rate among HCWs in the United States is low. Workers who are under 50, black, or health aides have the lowest rates of vaccinations. Interventions seeking to improve HCW vaccination rates may need to target these specific subgroups.
doi:10.1111/j.1525-1497.2006.00325.x
PMCID: PMC1484661  PMID: 16606378
Influenza vaccinations; health care workers; National Health Interview Survey; nosocomial infection; employee health
9.  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
10.  Impact of the Raising Immunizations Safely and Effectively (RISE) Program on Healthcare Worker Influenza Immunization Rates in Long-Term Care Settings 
Introduction and Rationale
National influenza immunization rates for healthcare workers (HCW) in long-term care (LTC) remain unacceptably low. This poses a serious public health threat to residents. Prior work has suggested high staff turnover rates as a contributing factor to low immunization rates. There is a critical need to identify and deploy successful models of HCW influenza immunization programs to LTC facilities. This report describes one potential model that has been successfully initiated in a network of LTC facilities.
Methods
All facilities served by a single regional LTC pharmacy were invited to participate in a HCW influenza immunization program. This voluntary immunization program began in 2005 and continues to the present. As part of the program, the pharmacy promoted organizational change by assuming oversight and control of HCW immunization policies and processes for all facilities. Primary and secondary outcomes are the number of facilities reaching HCW influenza immunization rates of 60% and 80%.
Results
Fourteen of the sixteen LTC facilities participated. Facilities were diverse and included both nursing and assisted living facilities; unionized and nonunionized facilities; and urban, suburban and rural facilities. The pharmacy provided educational and communication materials, centralized data collection using a standardized definition for HCW immunization rates, and facility feedback. All fourteen LTC facilities achieved the primary goal of 60% and nearly two thirds reached the secondary goal of 80%. Twenty percent reached the new Healthy People 2020 goal of 90%.
Discussion
It is possible for LTC facilities to improve HCW immunization rates using a pharmacy based, voluntary HCW influenza immunization approach. Such an approach may help attenuate the negative influence of staff turnover on HCW immunizations. Attainment of the new Health People 2020 goals still remains a challenge and may require mandatory programs.
doi:10.1016/j.jamda.2012.08.016
PMCID: PMC3650646  PMID: 23031265
healthcare workers; healthcare worker immunization; immunization programs; long-term care; nursing homes; immunizations; influenza
11.  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
12.  Meningococcal, influenza virus, and hepatitis B virus vaccination coverage level among health care workers in Hajj 
Background
The objective of this study was to assess the compliance of health care workers (HCWs) employed in Hajj in receiving the meningococcal, influenza, and hepatitis B vaccines.
Methods
A cross-sectional survey of doctors and nurses working in all Mena and Arafat hospitals and primary health care centers who attended Hajj-medicine training programs immediately before the beginning of Hajj of the lunar Islamic year 1423 (2003) using self-administered structured questionnaire which included demographic data and data on vaccination history.
Results
A total of 392 HCWs were studied including 215 (54.8%) nurses and 177 (45.2%) doctors. One hundred and sixty four (41.8%) HCWs were from Makkah and the rest were recruited from other regions in Saudi Arabia. Three hundred and twenty three (82.4%) HCWs received the quadrivalent (ACYW135) meningococcal meningitis vaccine with 271 (83.9%) HCWs receiving it at least 2 weeks before coming to Hajj, whereas the remaining 52 (16.1%) HCWs received it within < 2 weeks. Only 23 (5.9%) HCWs received the current year's influenza virus vaccine. Two hundred and sixty (66.3%) of HCWs received the three-dose hepatitis B vaccine series, 19.3% received one or two doses, and 14.3% did not receive any dose. There was no statistically significant difference in compliance with the three vaccines between doctors and nurses.
Conclusion
The meningococcal and hepatitis B vaccination coverage level among HCWs in Hajj was suboptimal and the influenza vaccination level was notably low. Strategies to improve vaccination coverage among HCWs should be adopted by all health care facilities in Saudi Arabia.
doi:10.1186/1471-2334-7-80
PMCID: PMC1945029  PMID: 17640374
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.  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
15.  Influenza vaccination in Alberta long-term care facilities 
Background
Canada's National Advisory Committee on Immunization recommends that both staff and residents of long-term care facilities be vaccinated against influenza. This paper describes the influenza vaccination policies and programs, as well as vaccination rates, for staff and residents of long-term care institutions in Alberta. Such data have not previously been reported.
Methods
Data were collected by means of an anonymous mail survey (with 2 reminders) sent to Alberta nursing homes and auxiliary hospitals in spring 1999.
Results
Of 160 facilities providing long-term care during the study period, 136 responded to the survey (85%). Of these, only 85 provided data on staff vaccination rates, whereas 118 provided data on resident vaccination rates. For institutions reporting this information, the median proportion of staff vaccinated was 29.9% and the median proportion of residents vaccinated was 91.0%. Only 2 facilities reported that staff vaccination was mandatory; however, only one of these had a written policy consistent with the self-report period. Using a travelling vaccination cart, offering vaccination on night shift, and monitoring and providing feedback about staff vaccination rates were infrequently employed as elements of staff vaccination programs, although all were positively correlated with staff vaccination rates. Standing orders for resident vaccination were reported by only 84 facilities. Fourteen institutions required written consent for vaccination from the resident or a relative. Facility requirements for consent to vaccinate from the resident or a relative were significantly associated with mean vaccine coverage: 90.5% coverage for institutions requiring verbal consent, 86.5% coverage for institutions requiring written consent and 95.0% for institutions not requiring written or verbal consent.
Interpretation
Staff vaccination rates in Alberta long-term care facilities are unacceptably low. Changes in staff vaccination programs may improve the situation even in the absence of mandatory vaccination or work exclusion rules. Requirements for written consent for vaccination of residents of long-term care facilities may be a barrier to immunization.
PMCID: PMC81068  PMID: 11387914
16.  High effectiveness of pandemic influenza A (H1N1) vaccination in healthcare workers from a Portuguese hospital 
Objectives
Vaccination of healthcare workers (HCWs) was made a high priority during the phase six pandemic of the novel influenza A H1N1 (pH1N1) virus. We surveyed adherence to pH1N1 vaccination and the incidence of pH1N1 infection between vaccinated and unvaccinated HCWs.
Methods
Employees at the S. João Hospital in Porto, Portugal, were offered pH1N1 vaccinations free of charge. Pandemrix® was the vaccine administered. As part of the pandemic plan, employees with influenza-like symptoms (ILS) were called upon to take an RT-PCR H1N1 test. If the test results were positive, they had to stay off work for at least 7 days. Sociodemographic data, vaccination status, contact with infectious patients, ILS and pH1N1 test results were documented in a standardised manner.
Results
The survey population comprised 5,592 employees. The vaccination rate was 30.8% (n = 1,720) for pH1N1 and 50.4% (n = 2,819) for the 2009/2010 seasonal trivalent inactivated influenza vaccine (TIV). One mild anaphylactic reaction occurred after pH1N1 vaccination. Minor local side effects occurred more often after pH1N1 vaccination than after 2009/2010 seasonal TIV (38.0% vs. 12.3%). Pandemic H1N1 infection was diagnosed in 97 HCWs (1.7%). Compared to employees with no regular patient contact, nurses (2.8%) had the highest risk of pH1N1 infection (adjusted OR 3.8; 95% CI 1.2–6.8). Vaccination reduced the pH1N1 infection risk (OR 0.12; 95% CI 0.05–0.29). Vaccine effectiveness was 90.4% (95% CI 73.5–97.3%).
Conclusion
Vaccination reduced the pH1N1 infection risk considerably. The pandemic plan to contain the pH1N1 infection was successful. Nurses had the highest risk of pH1N1 infection and are therefore a target group for vaccination measures.
doi:10.1007/s00420-011-0714-8
PMCID: PMC3440565  PMID: 22045387
Pandemic influenza A H1N1; Healthcare workers; Vaccination
17.  How complete is influenza immunization coverage? A study in 75 nursing and residential homes for elderly people. 
BACKGROUND. Elderly people in residential accommodation are particularly susceptible to outbreaks of influenza. Up to 70% of residents can become ill and many will develop complications or die. Immunization can prevent such outbreaks and is cost-effective. AIM. A study was undertaken to measure influenza immunization coverage in residential accommodation for elderly people and to identify factors that might influence uptake. METHOD. In March 1992, a questionnaire survey was conducted of all 113 registered nursing and residential homes for elderly people, in South Glamorgan. It asked about the demographic characteristics of people resident on 1 October 1991, their influenza immunization history and the homes' arrangements for administering immunizations. RESULTS. Questionnaires were returned by respondents from 75 homes (66%). Mean influenza vaccine uptake was 67%. Uptake was higher in nursing homes (mean of 82% in eight nursing homes) than in homes registered as both nursing and residential homes (mean of 76% in six homes) or in residential homes (mean of 65% in 61 homes). Nearly all of those immunized (94%) had been immunized by the end of November 1991. Residents who were reported to have underlying disease that increased their risk of complications if they contracted influenza were no more likely to have been immunized than those without risk factors. Immunization coverage varied considerably both between homes and between general practices. Most general practices in South Glamorgan had several elderly people in residential accommodation on their list, but only nine out of 64 practices had immunized all the elderly residents on their list and 12 practices had immunized fewer than half. Routine recording of immunization status in nursing and residential homes was variable, often as a consequence of poor communication between the primary health care team and staff at the home. Even where recorded, retrieval of the data was sometimes a problem. CONCLUSION. Influenza immunization coverage could be improved if general practices held a case register of all at-risk patients including elderly residents, and if nursing and residential homes were encouraged to keep better immunization records. These measures would facilitate year-on-year monitoring of influenza immunization coverage and the targeting of homes with low immunization coverage.
PMCID: PMC1239336  PMID: 7576847
18.  Estimates of Pandemic Influenza Vaccine Effectiveness in Europe, 2009–2010: Results of Influenza Monitoring Vaccine Effectiveness in Europe (I-MOVE) Multicentre Case-Control Study 
PLoS Medicine  2011;8(1):e1000388.
Results from a European multicentre case-control study reported by Marta Valenciano and colleagues suggest good protection by the pandemic monovalent H1N1 vaccine against pH1N1 and no effect of the 2009–2010 seasonal influenza vaccine on H1N1.
Background
A multicentre case-control study based on sentinel practitioner surveillance networks from seven European countries was undertaken to estimate the effectiveness of 2009–2010 pandemic and seasonal influenza vaccines against medically attended influenza-like illness (ILI) laboratory-confirmed as pandemic influenza A (H1N1) (pH1N1).
Methods and Findings
Sentinel practitioners swabbed ILI patients using systematic sampling. We included in the study patients meeting the European ILI case definition with onset of symptoms >14 days after the start of national pandemic vaccination campaigns. We compared pH1N1 cases to influenza laboratory-negative controls. A valid vaccination corresponded to >14 days between receiving a dose of vaccine and symptom onset. We estimated pooled vaccine effectiveness (VE) as 1 minus the odds ratio with the study site as a fixed effect. Using logistic regression, we adjusted VE for potential confounding factors (age group, sex, month of onset, chronic diseases and related hospitalizations, smoking history, seasonal influenza vaccinations, practitioner visits in previous year). We conducted a complete case analysis excluding individuals with missing values and a multiple multivariate imputation to estimate missing values. The multivariate imputation (n = 2902) adjusted pandemic VE (PIVE) estimates were 71.9% (95% confidence interval [CI] 45.6–85.5) overall; 78.4% (95% CI 54.4–89.8) in patients <65 years; and 72.9% (95% CI 39.8–87.8) in individuals without chronic disease. The complete case (n = 1,502) adjusted PIVE were 66.0% (95% CI 23.9–84.8), 71.3% (95% CI 29.1–88.4), and 70.2% (95% CI 19.4–89.0), respectively. The adjusted PIVE was 66.0% (95% CI −69.9 to 93.2) if vaccinated 8–14 days before ILI onset. The adjusted 2009–2010 seasonal influenza VE was 9.9% (95% CI −65.2 to 50.9).
Conclusions
Our results suggest good protection of the pandemic monovalent vaccine against medically attended pH1N1 and no effect of the 2009–2010 seasonal influenza vaccine. However, the late availability of the pandemic vaccine and subsequent limited coverage with this vaccine hampered our ability to study vaccine benefits during the outbreak period. Future studies should include estimation of the effectiveness of the new trivalent vaccine in the upcoming 2010–2011 season, when vaccination will occur before the influenza season starts.
Please see later in the article for the Editors' Summary
Editors' Summary
Background
Following the World Health Organization's declaration of pandemic phase six in June 2009, manufacturers developed vaccines against pandemic influenza A 2009 (pH1N1). On the basis of the scientific opinion of the European Medicines Agency, the European Commission initially granted marketing authorization to three pandemic vaccines for use in European countries. During the autumn of 2009, most European countries included the 2009–2010 seasonal influenza vaccine and the pandemic vaccine in their influenza vaccination programs.
The Influenza Monitoring Vaccine Effectiveness in Europe network (established to monitor seasonal and pandemic influenza vaccine effectiveness) conducted seven case-control and three cohort studies in seven European countries in 2009–2010 to estimate the effectiveness of the pandemic and seasonal vaccines. Data from the seven pilot case-control studies were pooled to provide overall adjusted estimates of vaccine effectiveness.
Why Was This Study Done?
After seasonal and pandemic vaccines are made available to populations, it is necessary to estimate the effectiveness of the vaccines at the population level during every influenza season. Therefore, this study was conducted in European countries to estimate the pandemic influenza vaccine effectiveness and seasonal influenza vaccine effectiveness against people presenting to their doctor with influenza-like illness who were confirmed (by laboratory tests) to be infected with pH1N1.
What Did the Researchers Do and Find?
The researchers conducted a multicenter case-control study on the basis of practitioner surveillance networks from seven countries—France, Hungary, Ireland, Italy, Romania, Portugal, and Spain. Patients consulting a participating practitioner for influenza-like illness had a nasal or throat swab taken within 8 days of symptom onset. Cases were swabbed patients who tested positive for pH1N1. Patients presenting with influenza-like illness whose swab tested negative for any influenza virus were controls.
Individuals were considered vaccinated if they had received a dose of the vaccine more than 14 days before the date of onset of influenza-like illness and unvaccinated if they were not vaccinated at all, or if the vaccine was given less than 15 days before the onset of symptoms. The researchers analyzed pandemic influenza vaccination effectiveness in those vaccinated less than 8 days, those vaccinated between and including 8 and 14 days, and those vaccinated more than 14 days before onset of symptoms compared to those who had never been vaccinated.
The researchers used modeling (taking account of all potential confounding factors) to estimate adjusted vaccine effectiveness and stratified the adjusted pandemic influenza vaccine effectiveness and the adjusted seasonal influenza vaccine effectiveness in three age groups (<15, 15–64, and ≥65 years of age).
The adjusted results suggest that the 2009–2010 seasonal influenza vaccine did not protect against pH1N1 illness. However, one dose of the pandemic vaccines used in the participating countries conferred good protection (65.5%–100% according to various stratifications performed) against pH1N1 in people who attended their practitioner with influenza-like illness, especially in people aged <65 years and in those without any chronic disease. Furthermore, good pandemic influenza vaccine effectiveness was observed as early as 8 days after vaccination.
What Do These Findings Mean?
The results of this study provide early estimates of the pandemic influenza vaccine effectiveness suggesting that the monovalent pandemic vaccines have been effective. The findings also give an indication of the vaccine effectiveness for the Influenza A (H1N1) 2009 strain included in the 2010–2011 seasonal vaccines, although specific vaccine effectiveness studies will have to be conducted to verify if similar good effectiveness are observed with 2010–2011 trivalent vaccines. However, the results of this study should be interpreted with caution because of limitations in the pandemic context (late timing of the studies, low incidence, low vaccine coverage leading to imprecise estimates) and potential biases due the study design, confounding factors, and missing values. The researchers recommend that in future season studies, the sample size per country should be enlarged in order to allow for precise pooled and stratified analyses.
Additional Information
Please access these websites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.1000388.
The World Health Organization has information on H1N1 vaccination
The US Centers for Disease Control and Prevention provides a fact sheet on the 2009 H1N1 influenza virus
The US Department of Health and Human services has a comprehensive website on flu
The European Centre for Disease Prevention and Control provides information on 2009 H1N1 pandemic
The European Centre for Disease Prevention and Control presents a summary of the 2009 H1N1 pandemic in Europe and elsewhere
doi:10.1371/journal.pmed.1000388
PMCID: PMC3019108  PMID: 21379316
19.  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
20.  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
21.  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
22.  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
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.  Healthcare workers as parents: attitudes toward vaccinating their children against pandemic influenza A/H1N1 
BMC Public Health  2010;10:596.
Background
Both the health care workers (HCWs) and children are target groups for pandemic influenza vaccination. The coverage of the target populations is an important determinant for impact of mass vaccination. The objective of this study is to determine the attitudes of HCWs as parents, toward vaccinating their children with pandemic influenza A/H1N1 vaccine.
Methods
A cross-sectional questionnaire survey was conducted with health care workers (HCWs) in a public hospital during December 2009 in Istanbul. All persons employed in the hospital with or without a health-care occupation are accepted as HCW. The HCWs who are parents of children 6 months to 18 years of age were included in the study. Pearson's chi-square test and logistic regression analysis was applied for the statistical analyses.
Results
A total of 389 HCWs who were parents of children aged 6 months-18 years participated study. Among all participants 27.0% (n = 105) reported that themselves had been vaccinated against pandemic influenza A/H1N1. Two third (66.1%) of the parents answered that they will not vaccinate their children, 21.1% already vaccinated and 12.9% were still undecided. Concern about side effect was most reported reason among who had been not vaccinated their children and among undecided parents. The second reason for refusing the pandemic vaccine was concerns efficacy of the vaccine. Media was the only source of information about pandemic influenza in nearly one third of HCWs. Agreement with vaccine safety, self receipt of pandemic influenza A/H1N1 vaccine, and trust in Ministry of Health were found to be associated with the positive attitude toward vaccinating their children against pandemic influenza A/H1N1.
Conclusions
Persuading parents to accept a new vaccine seems not be easy even if they are HCWs. In order to overcome the barriers among HCWs related to pandemic vaccines, determination of their misinformation, attitudes and behaviors regarding the pandemic influenza vaccination is necessary. Efforts for orienting the HCWs to use evidence based scientific sources, rather than the media for information should be considered by the authorities.
doi:10.1186/1471-2458-10-596
PMCID: PMC3091558  PMID: 20932342
25.  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

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