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1.  A Population-Based Evaluation of a Publicly Funded, School-Based HPV Vaccine Program in British Columbia, Canada: Parental Factors Associated with HPV Vaccine Receipt 
PLoS Medicine  2010;7(5):e1000270.
Analysis of a telephone survey by Gina Ogilvie and colleagues identifies the parental factors associated with HPV vaccine uptake in a school-based program in Canada.
Information on factors that influence parental decisions for actual human papillomavirus (HPV) vaccine receipt in publicly funded, school-based HPV vaccine programs for girls is limited. We report on the level of uptake of the first dose of the HPV vaccine, and determine parental factors associated with receipt of the HPV vaccine, in a publicly funded school-based HPV vaccine program in British Columbia, Canada.
Methods and Findings
All parents of girls enrolled in grade 6 during the academic year of September 2008–June 2009 in the province of British Columbia were eligible to participate. Eligible households identified through the provincial public health information system were randomly selected and those who consented completed a validated survey exploring factors associated with HPV vaccine uptake. Bivariate and multivariate analyses were conducted to calculate adjusted odds ratios to identify the factors that were associated with parents' decision to vaccinate their daughter(s) against HPV. 2,025 parents agreed to complete the survey, and 65.1% (95% confidence interval [CI] 63.1–67.1) of parents in the survey reported that their daughters received the first dose of the HPV vaccine. In the same school-based vaccine program, 88.4% (95% CI 87.1–89.7) consented to the hepatitis B vaccine, and 86.5% (95% CI 85.1–87.9) consented to the meningococcal C vaccine. The main reasons for having a daughter receive the HPV vaccine were the effectiveness of the vaccine (47.9%), advice from a physician (8.7%), and concerns about daughter's health (8.4%). The main reasons for not having a daughter receive the HPV vaccine were concerns about HPV vaccine safety (29.2%), preference to wait until the daughter is older (15.6%), and not enough information to make an informed decision (12.6%). In multivariate analysis, overall attitudes to vaccines, the impact of the HPV vaccine on sexual practices, and childhood vaccine history were predictive of parents having a daughter receive the HPV vaccine in a publicly funded school-based HPV vaccine program. By contrast, having a family with two parents, having three or more children, and having more education was associated with a decreased likelihood of having a daughter receive the HPV vaccine.
This study is, to our knowledge, one of the first population-based assessments of factors associated with HPV vaccine uptake in a publicly funded school-based program worldwide. Policy makers need to consider that even with the removal of financial and health care barriers, parents, who are key decision makers in the uptake of this vaccine, are still hesitant to have their daughters receive the HPV vaccine, and strategies to ensure optimal HPV vaccine uptake need to be employed.
Please see later in the article for the Editors' Summary
Editors' Summary
About 10% of cancers in women occur in the cervix, the structure that connects the womb to the vagina. Every year, globally, more than a quarter of a million women die because of cervical cancer, which only occurs after the cervix has been infected with a human papillomavirus (HPV) through sexual intercourse. There are many types of HPV, a virus that infects the skin and the mucosa (the moist membranes that line various parts of the body, including the cervix). Although most people become infected with HPV at some time in their life, most never know they are infected. However, some HPV types cause harmless warts on the skin or around the genital area and several—in particular, HPV 16 and HPV 18, so-called high-risk HPVs—can cause cervical cancer. HPV infections are usually cleared by the immune system, but about 10% of women infected with a high-risk HPV develop a long-term infection that puts them at risk of developing cervical cancer.
Why Was This Study Done?
Screening programs have greatly reduced cervical cancer deaths in developed countries in recent decades by detecting the cancer early when it can be treated; but it would be better to prevent cervical cancer ever developing. Because HPV is necessary for the development of cervical cancer, vaccination of girls against HPV infection before the onset of sexual activity might be one way to do this. Scientists recently developed a vaccine that prevents infection with HPV 16 and HPV 18 (and with two HPVs that cause genital warts) and that should, therefore, reduce the incidence of cervical cancer. Publicly funded HPV vaccination programs are now planned or underway in several countries; but before girls can receive the HPV vaccine, parental consent is usually needed, so it is important to know what influences parental decisions about HPV vaccination. In this study, the researchers undertake a telephone survey to determine the uptake of the HPV vaccine by 11-year-old girls (grade 6) in British Columbia, Canada, and to determine the parental factors associated with vaccine uptake; British Columbia started a voluntary school-based HPV vaccine program in September 2008.
What Did the Researchers Do and Find?
In early 2009, the researchers contacted randomly selected parents of girls enrolled in grade 6 during the 2008–2009 academic year and asked them to complete a telephone survey that explored factors associated with HPV vaccine uptake. 65.1% of the 2,025 parents who completed the survey had consented to their daughter receiving the first dose of HPV vaccine. By contrast, more than 85% of the parents had consented to hepatitis B and meningitis C vaccination of their daughters. Nearly half of the parents surveyed said their main reason for consenting to HPV vaccination was the effectiveness of the vaccine. Conversely, nearly a third of the parents said concern about the vaccine's safety was their main reason for not consenting to vaccination and one in eight said they had been given insufficient information to make an informed decision. In a statistical analysis of the survey data, the researchers found that a positive parental attitude towards vaccination, a parental belief that HPV vaccination had limited impact on sexual practices, and completed childhood vaccination increased the likelihood of a daughter receiving the HPV vaccine. Having a family with two parents or three or more children and having well-educated parents decreased the likelihood of a daughter receiving the vaccine.
What Do These Findings Mean?
These findings provide one of the first population-based assessments of the factors that affect HPV vaccine uptake in a setting where there are no financial or health care barriers to vaccination. By identifying the factors associated with parental reluctance to agree to HPV vaccination for their daughters, these findings should help public-health officials design strategies to ensure optimal HPV vaccine uptake, although further studies are needed to discover why, for example, parents with more education are less likely to agree to vaccination than parents with less education. Importantly, the findings of this study, which are likely to be generalizable to other high-income countries, indicate that there is a continued need to ensure that the public receives credible, clear information about both the benefits and long-term safety of HPV vaccination.
Additional Information
Please access these Web sites via the online version of this summary at
The US National Cancer Institute provides information about cervical cancer for patients and for health professionals, including information on HPV vaccines (in English and Spanish)
The US Centers for Disease Control and Prevention also has information about cervical cancer and about HPV
The UK National Health Service Choices website has pages on cervical cancer and on HPV vaccination
More information about cervical cancer and HPV vaccination is available from the Macmillan cancer charity
ImmunizeBC provides general information about vaccination and information about HPV vaccination in British Columbia
MedlinePlus provides links to additional resources about cervical cancer (in English and Spanish)
PMCID: PMC2864299  PMID: 20454567
2.  Frequency of Adverse Events after Vaccination with Different Vaccinia Strains 
PLoS Medicine  2006;3(8):e272.
Large quantities of smallpox vaccine have been stockpiled to protect entire nations against a possible reintroduction of smallpox. Planning for an appropriate use of these stockpiled vaccines in response to a smallpox outbreak requires a rational assessment of the risks of vaccination-related adverse events, compared to the risk of contracting an infection. Although considerable effort has been made to understand the dynamics of smallpox transmission in modern societies, little attention has been paid to estimating the frequency of adverse events due to smallpox vaccination. Studies exploring the consequences of smallpox vaccination strategies have commonly used a frequency of approximately one death per million vaccinations, which is based on a study of vaccination with the New York City Board of Health (NYCBH) strain of vaccinia virus. However, a multitude of historical studies of smallpox vaccination with other vaccinia strains suggest that there are strain-related differences in the frequency of adverse events after vaccination. Because many countries have stockpiled vaccine based on the Lister strain of vaccinia virus, a quantitative evaluation of the adverse effects of such vaccines is essential for emergency response planning. We conducted a systematic review and statistical analysis of historical data concerning vaccination against smallpox with different strains of vaccinia virus.
Methods and Findings
We analyzed historical vaccination data extracted from the literature. We extracted data on the frequency of postvaccinal encephalitis and death with respect to vaccinia strain and age of vaccinees. Using a hierarchical Bayesian approach for meta-analysis, we estimated the expected frequencies of postvaccinal encephalitis and death with respect to age at vaccination for smallpox vaccines based on the NYCBH and Lister vaccinia strains. We found large heterogeneity between findings from different studies and a time-period effect that showed decreasing incidences of adverse events over several decades. To estimate death rates, we then restricted our analysis to more-recent studies. We estimated that vaccination with the NYCBH strain leads to an average of 1.4 deaths per million vaccinations (95% credible interval, 0–6) and that vaccination with Lister vaccine leads to an average of 8.4 deaths per million vaccinations (95% credible interval, 0–31). We combined age-dependent estimates of the frequency of death after vaccination and revaccination with demographic data to obtain estimates of the expected number of deaths in present societies due to vaccination with the NYCBH and Lister vaccinia strains.
Previous analyses of smallpox vaccination policies, which rely on the commonly assumed value of one death per million vaccinations, may give serious underestimates of the number of deaths resulting from vaccination. Moreover, because there are large, strain-dependent differences in the frequency of adverse events due to smallpox vaccination, it is difficult to extrapolate from predictions for the NYCBH-derived vaccines (stockpiled in countries such as the US) to predictions for the Lister-derived vaccines (stockpiled in countries such as Germany). In planning for an effective response to a possible smallpox outbreak, public-health decision makers should reconsider their strategies of when to opt for ring vaccination and when to opt for mass vaccination.
Analysis of historical data for adverse events suggests that the commonly assumed number of one death per million vaccinations is inaccurate. Large differences between different vaccinia strains used should be taken into account when mass vaccinations are considered.
Editors' Summary
For thousands of years, smallpox was one of the world's most-feared diseases. This contagious disease, caused by the variola virus, historically killed about 30 percent of the people it infected. Over the centuries, it probably killed more people than all other infectious diseases combined, but it was also the first disease to be prevented by vaccination. In 1796, the English physician Edward Jenner rubbed pus from the spots of a milkmaid with cowpox into scratches on a young boy's arm; according to folklore, people who caught cowpox, a related but mild disease of cows, were protected against smallpox. Six weeks later, after a mild bout of cowpox, when the boy was challenged with pus from a smallpox patient, he did not develop smallpox. This vaccination procedure was later refined so that people were inoculated with pure preparations of live vaccinia virus, which is closely related to the smallpox and cowpox viruses, and by 1979 a global vaccination campaign had totally eradicated the disease.
Why Was This Study Done?
Smallpox vaccination has some adverse effects. In particular, vaccinia virus occasionally infects the brain. This so-called post-vaccination encephalitis can cause permanent brain damage and, it has been estimated, kills one vaccinee in every million. Consequently, as smallpox became rarer, the dangers of vaccination began to outweigh its benefits. Routine smallpox vaccination stopped in the US in 1972, and in 1980 the World Health Organization recommended that all countries stop vaccination. Now, however, there are fears that smallpox may be used for bioterrorism. If this did happen, exposed individuals and their contacts, possibly even whole populations, would have to be vaccinated as quickly as possible (very few people now have strong immunity to smallpox). Many countries have stockpiles of smallpox vaccines for this eventuality, but these contain different vaccinia virus strains. In this study, the researchers examined historical data to discover whether these strains differ in their potential to cause encephalitis and death. This information should help public-health officials plan their vaccination strategies in response to a bioterrorism attack with smallpox.
What Did the Researchers Do and Find?
The researchers collected data from published studies on smallpox vaccination and adverse events from several countries from the late 1950s onwards. They then used these data to extrapolate how often the different vaccinia strains might cause encephalitis and death if they were used today in vaccination programs. They estimate that vaccinating with the New York City Board of Health (NYCBH) strain, which is stockpiled in the US, might cause 2.9 cases of post-vaccination encephalitis and 1.4 deaths per million vaccinated individuals. In contrast, the Lister strain, which is stockpiled in many European countries, might cause 26.2 cases of post-vaccination encephalitis and 2.5 deaths per million vaccinees. For both strains, vaccination of children younger than 1 year old would cause the highest death rate, and individuals being re-vaccinated would be less likely to die than those being vaccinated for the first time. Finally, the researchers use their figures to estimate that about ten people would die if mass vaccination with the NYCBH strain were used in the Netherlands (population 16 million), whereas 55 people would die if the Lister strain were used.
What Do These Findings Mean?
The data used in this study are of variable quality, so the figures calculated by the researchers are only estimates. For instance, given the scatter of the original data, mass vaccination in the Netherlands with the Lister strain might cause anywhere between seven and nearly 200 deaths. However, the study clearly suggests that more serious adverse events would occur after vaccination with the Lister strain than after vaccination with the NYCBH strain. It also indicates that even in the US, where the NYCBH vaccine strain is stockpiled, previous analyses of the effects of vaccination in response to a bioterrorist attack have probably underestimated how many people might die from post-vaccination encephalitis. Public-health decision makers should incorporate these new estimates into their planning for a smallpox outbreak. These increased estimates of adverse events after vaccination might, for example, make mass vaccination with the Lister strain of vaccinia virus less acceptable. Instead, public-health officials might decide to rely on vaccination of only the people directly exposed to released smallpox virus and their close contacts (ring vaccination) to contain a smallpox outbreak.
Additional Information.
Please access these Web sites via the online version of this summary at
World Health Organization, information on smallpox and preparedness in the event of a smallpox outbreak
MedlinePlus encyclopedia entry on smallpox
US National Institute of Allergy and Infectious Diseases, patient fact sheet on smallpox
US Centers for Disease Control and Prevention, information for patients and professionals on smallpox
Wikipedia page on smallpox (note that Wikipedia is a free online encyclopedia that anyone can edit)
Wellcome Library MedHist, links to information on the history of smallpox vaccination
PMCID: PMC1551910  PMID: 16933957
3.  Canadian family physicians' and paediatricians' knowledge, attitudes and practices regarding A(H1N1) pandemic vaccine 
BMC Research Notes  2010;3:102.
One of the main determinants of public immunization success is health professionals' support and recommendations. Little is known about the physicians' level of support and intentions regarding A(H1N1) pandemic influenza vaccination. The aim of this survey was to document Canadian family physicians' and paediatricians' knowledge, attitudes and practices (KAP) as well as their intentions regarding A(H1N1) pandemic influenza vaccines right before the beginning of the largest immunization campaign in Canadian history.
A self-administered, anonymous, mail-based questionnaire was sent to a random sample of family physicians and to all paediatricians practicing in Canada. All 921 questionnaires received by October 29 2009 were included in the analysis. Between 72% and 92% of respondents agreed with the statements regarding vaccine safety, effectiveness and acceptability. More than 75% of respondents intended to recommend the A(H1N1) pandemic influenza vaccine to their patients and to get vaccinated themselves. The most significant factors associated with the intention to recommend A(H1N1) pandemic vaccines were physicians' intention to be vaccinated against influenza themselves and the perceived acceptability of the vaccine by the vaccinators.
Most Canadian family physicians and paediatricians surveyed were supportive of the A(H1N1) pandemic influenza vaccination before its implementation and large media coverage.
PMCID: PMC2864287  PMID: 20398265
4.  A(H1N1) pandemic influenza and its prevention by vaccination: Paediatricians' opinions before and after the beginning of the vaccination campaign 
BMC Public Health  2011;11:128.
In June 2009, the World Health Organization declared an A(H1N1) influenza pandemic. In October 2009, the largest vaccination campaign in Canadian history began. The aim of this study was to document paediatricians' knowledge, attitudes and practices (KAP) regarding A(H1N1) pandemic influenza and its prevention by vaccination just after the beginning of the A(H1N1) vaccination campaign and to compare the results with those obtained before campaign initiation.
A self-administered mail-based questionnaire was sent to all Canadian paediatricians. Questionnaires were analyzed in two subsets: those received before and after the beginning of the vaccination campaign.
Overall the response rate was 50%. Respondents' characteristics were comparable between the two subsets. Before the beginning of the campaign, 63% of paediatricians perceived A(H1N1) pandemic infection as a serious disease, that would occur frequently without vaccination compared to more than 75% after. Before the vaccination campaign, half of respondents or less thought that the A(H1N1) vaccine was safe (50%) and effective (35%) compared to 77% and 72% after. The proportion of paediatricians who reported they had received sufficient information on A(H1N1) vaccine increased from 31% before to 73% after the beginning of the vaccination campaign. The majority of respondents intended to get vaccinated against A(H1N1) influenza themselves (84% before and 92% after). Respondents' intention to recommend the A(H1N1) vaccine to their patients increased from 80% before the beginning of the campaign to 92% after. In multivariate analysis, the main determinants of paediatricians' intention to recommend the A(H1N1) vaccine were their intention to get vaccinated against A(H1N1) influenza themselves and a belief that A(H1N1) vaccine would be well accepted by health professionals who administer vaccines to the public.
Results of this study show important increases in physicians' level of confidence about A(H1N1) vaccine's safety and immunogenicity and their willingness to recommend this vaccine to their patients. These changes could be explained, at least partially, by the important effort done by public health authorities to disseminate information regarding A(H1N1) vaccination.
PMCID: PMC3050752  PMID: 21342511
5.  Measuring the Performance of Vaccination Programs Using Cross-Sectional Surveys: A Likelihood Framework and Retrospective Analysis 
PLoS Medicine  2011;8(10):e1001110.
Justin Lessler and colleagues describe a method that estimates the fraction of a population accessible to vaccination activities, and they apply it to measles vaccination in three African countries: Ghana, Madagascar, and Sierra Leone.
The performance of routine and supplemental immunization activities is usually measured by the administrative method: dividing the number of doses distributed by the size of the target population. This method leads to coverage estimates that are sometimes impossible (e.g., vaccination of 102% of the target population), and are generally inconsistent with the proportion found to be vaccinated in Demographic and Health Surveys (DHS). We describe a method that estimates the fraction of the population accessible to vaccination activities, as well as within-campaign inefficiencies, thus providing a consistent estimate of vaccination coverage.
Methods and Findings
We developed a likelihood framework for estimating the effective coverage of vaccination programs using cross-sectional surveys of vaccine coverage combined with administrative data. We applied our method to measles vaccination in three African countries: Ghana, Madagascar, and Sierra Leone, using data from each country's most recent DHS survey and administrative coverage data reported to the World Health Organization. We estimate that 93% (95% CI: 91, 94) of the population in Ghana was ever covered by any measles vaccination activity, 77% (95% CI: 78, 81) in Madagascar, and 69% (95% CI: 67, 70) in Sierra Leone. “Within-activity” inefficiencies were estimated to be low in Ghana, and higher in Sierra Leone and Madagascar. Our model successfully fits age-specific vaccination coverage levels seen in DHS data, which differ markedly from those predicted by naïve extrapolation from country-reported and World Health Organization–adjusted vaccination coverage.
Combining administrative data with survey data substantially improves estimates of vaccination coverage. Estimates of the inefficiency of past vaccination activities and the proportion not covered by any activity allow us to more accurately predict the results of future activities and provide insight into the ways in which vaccination programs are failing to meet their goals.
Please see later in the article for the Editors' Summary
Editors' Summary
Immunization (vaccination) is a proven, cost-effective tool for controlling life-threatening infectious diseases. It provides protection against infectious diseases by priming the human immune system to respond quickly and efficiently to bacteria, viruses, and other disease-causing organisms (pathogens). Whenever the human body is exposed to a pathogen, the immune system—a network of cells, tissues, and organs—mounts an attack against the foreign invader. Importantly, the immune system “learns” from the encounter, and the next time the body is exposed to the same pathogen, the immune system responds much faster to the threat. Immunization exposes the body to a very small amount of a pathogen, thereby safely providing protection against subsequent infection. More than two billion deaths are averted every year through routine childhood immunization and supplemental immunization activities (mass vaccination campaigns designed to increase vaccination coverage where immunization goals have not been reached by routine vaccination). Indeed, these two types of vaccination activities have eliminated smallpox from the world and are close to doing the same for several other infectious diseases.
Why Was This Study Done?
To reduce deaths from infectious diseases even further, it is important to know the proportion of the population reached by vaccination activities. At present, countries report vaccination coverage to the World Health Organization (WHO) that is calculated by dividing the number of vaccine doses delivered during the activity by the size of the target population. However, estimates arrived at through this “administrative method” do not account for vaccine doses that were not actually delivered, and can only reflect a single vaccination activity, which prevents us from identifying populations that may be systematically missed by all vaccination activities (for example, children living in remote areas, or children whose parents refuse vaccination). Moreover, estimates of coverage obtained by the administrative method rarely agree with estimates obtained through cross-sectional surveys such as Demographic and Health Surveys (DHS), which are household surveys of family circumstances and health undertaken at a single time point. In this study, the researchers developed a method for measuring the performance of vaccination activities that estimates the fraction of the population accessible to these activities and within-activity inefficiencies. They then tested their method by applying it to measles vaccination in three African countries; before 1980, measles killed about 2.6 million children worldwide every year, but vaccination activities have reduced this death toll to about 164,000 per year.
What Did the Researchers Do and Find?
The researchers developed a set of formulae (a “likelihood framework”) to estimate the effective coverage of vaccination activities using data on vaccine coverage from cross-sectional surveys and administrative data. They then applied their method to measles vaccination in Ghana, Madagascar, and Sierra Leone using data obtained in each country's most recent DHS survey and administrative data reported to WHO. The researchers estimate that 93%, 77%, and 65% of the target populations in Ghana, Madagascar, and Sierra Leone, respectively, were ever covered by any vaccination activity, and that inefficiencies within vaccination activities were low for Ghana, but higher for Madagascar and Sierra Leone. Consequently, the researchers' estimates of vaccination activity coverage were substantially lower than the administrative estimates for Madagascar and Sierra Leone but only slightly lower than that for Ghana. Finally, the researchers' estimates of routine vaccination coverage were generally lower than WHO-adjusted estimates but broadly agreed with age-specific vaccination coverage levels from DHS surveys.
What Do These Findings Mean?
Although the accuracy of the estimates provided by this likelihood framework depends on the assumptions included in the framework and the quality of the data fed into it, these findings show that, by combining administrative data with survey data, estimates of vaccine coverage can be substantially improved. By providing estimates of both the inefficiency of past vaccination activities and the proportion of the target population inaccessible to any vaccination activity, this method should help public health experts predict the results of future activities and help them understand why some vaccination programs fail to meet their goals. Importantly, knowing both the size of the inaccessible population and the inefficiency level of past programs makes it possible to estimate the effect of providing additional doses of vaccine on vaccination coverage. Finally, the application of this new method might help individual countries understand how susceptibility to specific infectious diseases is building up in their population and enable them to avoid outbreaks similar to the measles outbreaks that have recently occurred in several African countries.
Additional Information
Please access these Web sites via the online version of this summary at
WHO provides information about immunization and details of its Expanded Program on Immunization and its Global Immunization Vision and Strategy; WHO Africa provides details about measles immunization in Africa; a photo story about mass measles vaccination in Côte d’Ivoire is available (some material in several languages)
The UK National Health Service Choices website provides information for members of the public about immunization
The Measles Initiative is a collaborative effort that aims to reduce global measles mortality through mass vaccination campaigns and by strengthening routine immunization; its website includes information on measles and measles vaccination, including photos and videos of vaccination activities
MedlinePlus provides links to additional resources about immunization and about measles (in English and Spanish)
The charity website Healthtalkonline has interviews with UK parents about their experience of immunizing their children
PMCID: PMC3201935  PMID: 22039353
6.  The Effect of Universal Influenza Immunization on Mortality and Health Care Use 
PLoS Medicine  2008;5(10):e211.
In 2000, Ontario, Canada, initiated a universal influenza immunization program (UIIP) to provide free influenza vaccines for the entire population aged 6 mo or older. Influenza immunization increased more rapidly in younger age groups in Ontario compared to other Canadian provinces, which all maintained targeted immunization programs. We evaluated the effect of Ontario's UIIP on influenza-associated mortality, hospitalizations, emergency department (ED) use, and visits to doctors' offices.
Methods and Findings
Mortality and hospitalization data from 1997 to 2004 for all ten Canadian provinces were obtained from national datasets. Physician billing claims for visits to EDs and doctors' offices were obtained from provincial administrative datasets for four provinces with comprehensive data. Since outcomes coded as influenza are known to underestimate the true burden of influenza, we studied more broadly defined conditions. Hospitalizations, ED use, doctors' office visits for pneumonia and influenza, and all-cause mortality from 1997 to 2004 were modelled using Poisson regression, controlling for age, sex, province, influenza surveillance data, and temporal trends, and used to estimate the expected baseline outcome rates in the absence of influenza activity. The primary outcome was then defined as influenza-associated events, or the difference between the observed events and the expected baseline events. Changes in influenza-associated outcome rates before and after UIIP introduction in Ontario were compared to the corresponding changes in other provinces. After UIIP introduction, influenza-associated mortality decreased more in Ontario (relative rate [RR] = 0.26) than in other provinces (RR = 0.43) (ratio of RRs = 0.61, p = 0.002). Similar differences between Ontario and other provinces were observed for influenza-associated hospitalizations (RR = 0.25 versus 0.44, ratio of RRs = 0.58, p < 0.001), ED use (RR = 0.31 versus 0.69, ratio of RRs = 0.45, p < 0.001), and doctors' office visits (RR = 0.21 versus 0.52, ratio of RRs = 0.41, p < 0.001). Sensitivity analyses were carried out to assess consistency, specificity, and the presence of a dose-response relationship. Limitations of this study include the ecological study design, the nonspecific outcomes, difficulty in modeling baseline events, data quality and availability, and the inability to control for potentially important confounders.
Compared to targeted programs in other provinces, introduction of universal vaccination in Ontario in 2000 was associated with relative reductions in influenza-associated mortality and health care use. The results of this large-scale natural experiment suggest that universal vaccination may be an effective public health measure for reducing the annual burden of influenza.
Comparing influenza-related mortality and health care use between Ontario and other Canadian provinces, Jeffrey Kwong and colleagues find evidence that Ontario's universal vaccination program has reduced the burden of influenza.
Editors' Summary
Seasonal outbreaks (epidemics) of influenza—a viral disease of the nose, throat, and airways—affect millions of people and kill about 500,000 individuals every year. These epidemics occur because of “antigenic drift”: small but frequent changes in the viral proteins to which the human immune system responds mean that an immune response produced one year by exposure to an influenza virus provides only partial protection against influenza the next year. Immunization can boost this natural immunity and reduce a person's chances of catching influenza. That is, an injection of killed influenza viruses can be used to prime the immune system so that it responds quickly and efficiently when exposed to live virus. However, because of antigenic drift, for influenza immunization to be effective, it has to be repeated annually with a vaccine that contains the major circulating strains of the influenza virus.
Why Was This Study Done?
Public-health organizations recommend targeted vaccination programs, so that elderly people, infants, and chronically ill individuals—the people most likely to die from pneumonia and other complications of influenza—receive annual influenza vaccination. Some experts argue, however, that universal vaccination might provide populations with better protection from influenza, both directly by increasing the number of vaccinated people and indirectly through “herd immunity,” which occurs when a high proportion of the population is immune to an infectious disease, so that even unvaccinated people are unlikely to become infected (because infected people rarely come into contact with susceptible people). In this study, the researchers compare the effects of the world's first free universal influenza immunization program (UIIP), which started in 2000 in the Canadian province of Ontario, on influenza-associated deaths and health care use with the effects of targeted vaccine programs on the same outcomes elsewhere in Canada.
What Did the Researchers Do and Find?
Using national records, the researchers collected data on influenza vaccination, on all deaths, and on hospitalizations for pneumonia and influenza in all Canadian provinces between 1997 and 2004. They also collected data on emergency department and doctors' office visits for pneumonia and influenza for Ontario, Quebec, Alberta, and Manitoba. They then used a mathematical model to estimate the baseline rates for these outcomes in the absence of influenza activity, and from these calculated weekly rates for deaths and health care use specifically resulting from influenza. In 1996–1997, 18% of the population was vaccinated against influenza in Ontario whereas in the other provinces combined the vaccination rate was 13%. On average, since 2000—the year in which UIIP was introduced in Ontario—vaccination rates have risen to 38% and 24% in Ontario and the other provinces, respectively. Since the introduction of UIIP, the researchers report, influenza-associated deaths have decreased by 74% in Ontario but by only 57% in the other provinces combined. Influenza-associated use of health care facilities has also decreased more in Ontario than in the other provinces over the same period.
What Do These Findings Mean?
These findings are limited by some aspects of the study design. For example, they depend on the accuracy of the assumptions made when calculating events due specifically to influenza, and on the availability and accuracy of vaccination and clinical outcome data. In addition, it is possible that influenza-associated deaths and health care use may have decreased more in Ontario than in the other Canadian provinces because of some unrecognized health care changes specific to Ontario but unrelated to the introduction of universal influenza vaccination. Nevertheless, these findings indicate that, compared to the targeted vaccination programs in the other Canadian provinces, the Ontarian UIIP is associated with reductions in influenza-associated deaths and health care use, particularly in people younger than 65 years old. This effect is seen at a level of vaccination unlikely to produce herd immunity so might be more marked if the uptake of vaccination could be further increased. Thus, although it is possible that Canada is a special case, these findings suggest that universal influenza vaccination might be an effective way to reduce the global burden of influenza.
Additional Information.
Please access these Web sites via the online version of this summary at
Read the related PLoSMedicine Perspective by Cécile Viboud and Mark Miller
A related PLoSMedicine Research Article by Carline van den Dool and colleagues is also available
The Ontario Ministry of Health provides information on its universal influenza immunization program (in English and French)
The World Health Organization provides information on influenza and on influenza vaccines (in several languages)
The US Centers for Disease Control and Prevention provide information for patients and professionals on all aspects of influenza (in English and Spanish)
MedlinePlus provides a list of links to other information about influenza (in English and Spanish)
The UK National Health Service provides information about the science of immunization, including a simple explanatory animation of immunity
PMCID: PMC2573914  PMID: 18959473
7.  Yellow Fever in Africa: Estimating the Burden of Disease and Impact of Mass Vaccination from Outbreak and Serological Data 
PLoS Medicine  2014;11(5):e1001638.
Neil Ferguson and colleagues estimate the disease burden of yellow fever in Africa, as well as the impact of mass vaccination campaigns.
Please see later in the article for the Editors' Summary
Yellow fever is a vector-borne disease affecting humans and non-human primates in tropical areas of Africa and South America. While eradication is not feasible due to the wildlife reservoir, large scale vaccination activities in Africa during the 1940s to 1960s reduced yellow fever incidence for several decades. However, after a period of low vaccination coverage, yellow fever has resurged in the continent. Since 2006 there has been substantial funding for large preventive mass vaccination campaigns in the most affected countries in Africa to curb the rising burden of disease and control future outbreaks. Contemporary estimates of the yellow fever disease burden are lacking, and the present study aimed to update the previous estimates on the basis of more recent yellow fever occurrence data and improved estimation methods.
Methods and Findings
Generalised linear regression models were fitted to a dataset of the locations of yellow fever outbreaks within the last 25 years to estimate the probability of outbreak reports across the endemic zone. Environmental variables and indicators for the surveillance quality in the affected countries were used as covariates. By comparing probabilities of outbreak reports estimated in the regression with the force of infection estimated for a limited set of locations for which serological surveys were available, the detection probability per case and the force of infection were estimated across the endemic zone.
The yellow fever burden in Africa was estimated for the year 2013 as 130,000 (95% CI 51,000–380,000) cases with fever and jaundice or haemorrhage including 78,000 (95% CI 19,000–180,000) deaths, taking into account the current level of vaccination coverage. The impact of the recent mass vaccination campaigns was assessed by evaluating the difference between the estimates obtained for the current vaccination coverage and for a hypothetical scenario excluding these vaccination campaigns. Vaccination campaigns were estimated to have reduced the number of cases and deaths by 27% (95% CI 22%–31%) across the region, achieving up to an 82% reduction in countries targeted by these campaigns. A limitation of our study is the high level of uncertainty in our estimates arising from the sparseness of data available from both surveillance and serological surveys.
With the estimation method presented here, spatial estimates of transmission intensity can be combined with vaccination coverage levels to evaluate the impact of past or proposed vaccination campaigns, thereby helping to allocate resources efficiently for yellow fever control. This method has been used by the Global Alliance for Vaccines and Immunization (GAVI Alliance) to estimate the potential impact of future vaccination campaigns.
Please see later in the article for the Editors' Summary
Editors' Summary
Yellow fever is a flavivirus infection that is transmitted to people and to non-human primates through the bites of infected mosquitoes. This serious viral disease affects people living in and visiting tropical regions of Africa and Central and South America. In rural areas next to forests, the virus typically causes sporadic cases or even small-scale epidemics (outbreaks) but, if it is introduced into urban areas, it can cause large explosive epidemics that are hard to control. Although many people who contract yellow fever do not develop any symptoms, some have mild flu-like symptoms, and others develop a high fever with jaundice (yellowing of the skin and eyes) or hemorrhaging (bleeding) from the mouth, nose, eyes, or stomach. Half of patients who develop these severe symptoms die. Because of this wide spectrum of symptoms, which overlap with those of other tropical diseases, it is hard to diagnose yellow fever from symptoms alone. However, serological tests that detect antibodies to the virus in the blood can help in diagnosis. There is no specific antiviral treatment for yellow fever but its symptoms can be treated.
Why Was This Study Done?
Eradication of yellow fever is not feasible because of the wildlife reservoir for the virus but there is a safe, affordable, and highly effective vaccine against the disease. Large-scale vaccination efforts during the 1940s, 1950s, and 1960s reduced the yellow fever burden for several decades but, after a period of low vaccination coverage, the number of cases rebounded. In 2005, the Yellow Fever Initiative—a collaboration between the World Health Organization (WHO) and the United Nations Children Fund supported by the Global Alliance for Vaccines and Immunization (GAVI Alliance)—was launched to create a vaccine stockpile for use in epidemics and to implement preventive mass vaccination campaigns in the 12 most affected countries in West Africa. Campaigns have now been implemented in all these countries except Nigeria. However, without an estimate of the current yellow fever burden, it is hard to determine the impact of these campaigns. Here, the researchers use recent yellow fever occurrence data, serological survey data, and improved estimation methods to update estimates of the yellow fever burden and to determine the impact of mass vaccination on this burden.
What Did the Researchers Do and Find?
The researchers developed a generalized linear statistical model and used data on the locations where yellow fever was reported between 1987 and 2011 in Africa, force of infection estimates for a limited set of locations where serological surveys were available (the force of infection is the rate at which susceptible individuals acquire a disease), data on vaccination coverage, and demographic and environmental data for their calculations. They estimate that about 130,000 yellow fever cases with fever and jaundice or hemorrhage occurred in Africa in 2013 and that about 78,000 people died from the disease. By evaluating the difference between this estimate, which takes into account the current vaccination coverage, and a hypothetical scenario that excluded the mass vaccination campaigns, the researchers estimate that these campaigns have reduced the burden of disease by 27% across Africa and by up to 82% in the countries targeted by the campaigns (an overall reduction of 57% in the 12 targeted countries).
What Do These Findings Mean?
These findings provide a contemporary estimate of the burden of yellow fever in Africa. This estimate is broadly similar to the historic estimate of 200,000 cases and 30,000 deaths annually, which was based on serological survey data obtained from children in Nigeria between 1945 and 1971. Notably, both disease burden estimates are several hundred-fold higher than the average number of yellow fever cases reported annually to WHO, which reflects the difficulties associated with the diagnosis of yellow fever. Importantly, these findings also provide an estimate of the impact of recent mass vaccination campaigns. All these findings have a high level of uncertainty, however, because of the lack of data from both surveillance and serological surveys. Other assumptions incorporated in the researchers' model may also affect the accuracy of these findings. Nevertheless, the framework for burden estimation developed here provides essential new information about the yellow fever burden and the impact of vaccination campaigns and should help the partners of the Yellow Fever Initiative estimate the potential impact of future vaccination campaigns and ensure the efficient allocation of resources for yellow fever control.
Additional Information
Please access these websites via the online version of this summary at
The World Health Organization provides detailed information about yellow fever (in several languages), including photo stories about vaccination campaigns in the Sudan and Mali; it also provides information about the Yellow Fever Initiative (in English and French)
The GAVI Alliance website includes detailed of its support for yellow fever vaccination
The US Centers for Disease Control and Prevention provides information about yellow fever for the public, travelers, and health care providers
The UK National Health Service Choices website also has information about yellow fever
Wikipedia has a page on yellow fever that includes information about the history of the disease (note that Wikipedia is a free online encyclopedia that anyone can edit; available in several languages)
PMCID: PMC4011853  PMID: 24800812
8.  Will Dengue Vaccines Be Used in the Public Sector and if so, How? Findings from an 8-country Survey of Policymakers and Opinion Leaders 
A face-to-face survey of 158 policymakers and other influential professionals was conducted in eight dengue-endemic countries in Asia (India, Sri Lanka, Thailand, Vietnam) and Latin America (Brazil, Colombia, Mexico, Nicaragua) to provide an indication of the potential demand for dengue vaccination in endemic countries, and to anticipate their research and other requirements in order to make decisions about the introduction of dengue vaccines. The study took place in anticipation of the licensure of the first dengue vaccine in the next several years.
Methods/Principal Findings
Semi-structured interviews were conducted on an individual or small group basis with government health officials, research scientists, medical association officers, vaccine producers, local-level health authorities, and others considered to have a role in influencing decisions about dengue control and vaccines. Most informants across countries considered dengue a priority disease and expressed interest in the public sector use of dengue vaccines, with a major driver being the political pressure from the public and the medical community to control the disease. There was interest in a vaccine that protects children as young as possible and that can fit into existing childhood immunization schedules. Dengue vaccination in most countries surveyed will likely be targeted to high-risk areas and begin with routine immunization of infants and young children, followed by catch-up campaigns for older age groups, as funding permits. Key data requirements for decision-making were additional local dengue surveillance data, vaccine cost-effectiveness estimates, post-marketing safety surveillance data and, in some countries vaccine safety and immunogenicity data in the local population.
The lookout for the public sector use of dengue vaccines in the eight countries appears quite favorable. Major determinants of whether and when countries will introduce dengue vaccines include whether WHO recommends the vaccines, their price, the availability of external financing for lower income countries, and whether they can be incorporated into countries' routine immunization schedules.
Author Summary
Information gleaned from surveys of country-level policymakers and other opinion leaders can assist in planning the development, production and introduction of new or upcoming vaccines into public sector immunization programs. In the case of dengue vaccines, prevailing views among these leaders about the importance of the disease, their expressed level of interest in the government's use of the vaccine, and preferred strategies for vaccine introduction (e.g., geographically-targeted vs. nation-wide vaccination, specific age groups to target) can help to identify “early adopter” countries and indicate the level of demand for the vaccine. This information can be critical to current producers of the vaccine in planning their production capacity and to potential future producers in deciding whether to pursue development of the vaccine. This information also helps donors and international technical agencies, such as WHO and UNICEF, in setting their priorities and determining their level of technical and financial support to countries for the introduction of dengue vaccines. In addition, these surveys can provide crucial information to national governments and the above stakeholders about potential barriers to introducing dengue vaccines into national immunization programs, and what additional studies and data countries will require in order to make decisions about use of the vaccines in the public sector.
PMCID: PMC3597493  PMID: 23516658
9.  Vesicular Stomatitis Virus-Based Ebola Vaccine Is Well-Tolerated and Protects Immunocompromised Nonhuman Primates 
PLoS Pathogens  2008;4(11):e1000225.
Ebola virus (EBOV) is a significant human pathogen that presents a public health concern as an emerging/re-emerging virus and as a potential biological weapon. Substantial progress has been made over the last decade in developing candidate preventive vaccines that can protect nonhuman primates against EBOV. Among these prospects, a vaccine based on recombinant vesicular stomatitis virus (VSV) is particularly robust, as it can also confer protection when administered as a postexposure treatment. A concern that has been raised regarding the replication-competent VSV vectors that express EBOV glycoproteins is how these vectors would be tolerated by individuals with altered or compromised immune systems such as patients infected with HIV. This is especially important as all EBOV outbreaks to date have occurred in areas of Central and Western Africa with high HIV incidence rates in the population. In order to address this concern, we evaluated the safety of the recombinant VSV vector expressing the Zaire ebolavirus glycoprotein (VSVΔG/ZEBOVGP) in six rhesus macaques infected with simian-human immunodeficiency virus (SHIV). All six animals showed no evidence of illness associated with the VSVΔG/ZEBOVGP vaccine, suggesting that this vaccine may be safe in immunocompromised populations. While one goal of the study was to evaluate the safety of the candidate vaccine platform, it was also of interest to determine if altered immune status would affect vaccine efficacy. The vaccine protected 4 of 6 SHIV-infected macaques from death following ZEBOV challenge. Evaluation of CD4+ T cells in all animals showed that the animals that succumbed to lethal ZEBOV challenge had the lowest CD4+ counts, suggesting that CD4+ T cells may play a role in mediating protection against ZEBOV.
Author Summary
Ebola virus is among the most lethal microbes known to man, with case fatality rates often exceeding 80%. Since its discovery in 1976, outbreaks have been sporadic and geographically restricted, primarily to areas of Central Africa. However, concern about the natural or unnatural introduction of Ebola outside of the endemic areas has dramatically increased both research interest and public awareness. A number of candidate vaccines have been developed to combat Ebola virus, and these vaccines have shown varying degrees of success in nonhuman primate models. Safety is a significant concern for any vaccine and in particular for vaccines that replicate in the host. Here, we evaluated the safety of our replication-competent vesicular stomatitus virus (VSV)-based Ebola vaccine in SHIV-infected rhesus monkeys. We found that the vaccine caused no evidence of overt illness in any of these immunocompromised animals. We also demonstrated that this vaccine partially protected the SHIV-infected monkeys against a lethal Ebola challenge and that there appears to be an association with levels of CD4+ lymphocytes and survival. Our study suggests that the VSV-based Ebola vaccine will be safe in immunocompromised populations and supports further study and development of this promising vaccine platform for its use in humans.
PMCID: PMC2582959  PMID: 19043556
10.  Factors influencing H1N1 vaccine behavior among Manitoba Metis in Canada: a qualitative study 
BMC Public Health  2015;15:128.
During the first wave of the H1N1 influenza pandemic in 2009, Aboriginal populations in Canada experienced disproportionate rates of infection, particularly in the province of Manitoba. To protect those thought to be most at-risk, health authorities in Manitoba listed all Aboriginal people, including Metis, among those able to receive priority access to the novel vaccine when it first became available. Currently, no studies exist that have investigated the attitudes, influences, and vaccine behaviors among Aboriginal communities in Canada. This paper is the first to systematically connect vaccine behavior with the attitudes and beliefs that influenced Metis study participants’ H1N1 vaccine decision-making.
Researchers held focus groups (n = 17) with Metis participants in urban, rural, and remote locations of Manitoba following the conclusion of the H1N1 pandemic. Participants were asked about their vaccination decisions and about the factors that influenced their decisions. Following data collection, responses were coded into the broad categories of a social-ecological model, nuanced by categories stemming from earlier research. Responses were then quantified to show the most influential factors in positively or negatively affecting the vaccine decision.
Media reporting, the influence of peer groups, and prioritization all had positive and negative influential effects on decision making. Whether vaccinated or not, the most negatively influential factors cited by participants were a lack of knowledge about the vaccine and the pandemic as well as concerns about vaccine safety. Risk of contracting H1N1 influenza was the biggest factor in positively influencing a vaccine decision, which in many cases trumped any co-existing negative influencers.
Metis experiences of colonialism in Canada deeply affected their perceptions of the vaccine and pandemic, a context that health systems need to take into account when planning response activities in the future. Participants felt under-informed about most aspects of the vaccine and the pandemic, and many vaccine related misconceptions and fears existed. Recommendations include leveraging doctor-patient interactions as a site for sharing vaccine-related knowledge, as well as targeted, culturally-appropriate, and empowering public information strategies to supply reliable vaccine and pandemic information to potentially at-risk Aboriginal populations.
PMCID: PMC4334920
Infectious disease; Influenza; Immunization; Vaccination; Uptake; Perceptions; Aboriginal; Canada; Colonialism; Focus groups
11.  Pandemic influenza is a strong motivator for participation in vaccine clinical trials among HIV-positive Canadian adults 
HIV-positive patients represent an immunosuppressed population at risk for severe influenza. In the event of a pandemic, such as 2009 H1N1, rapid implementation of vaccine clinical trials in target populations will be critical. In the present paper, knowledge and attitudes of HIV-positive adults regarding seasonal/pandemic influenza vaccination were evaluated, and facilitators and barriers to participation in vaccine clinical trials were explored.
A validated, 70-item, self-administered questionnaire was distributed to all HIV patients presenting for routine follow-up at eight Canadian Institutes of Health Research Canadian HIV Trials Network (CTN) sites from October 2008 to February 2009, as well as all participants in CTN trial 237. This study has representation from all Canadian provinces.
In total, 610 HIV-positive adults responded (298 CTN 237 participants; 312 non-CTN 237 participants). Most reported receiving influenza vaccine last season (83% of CTN 237 participants versus 83% non-CTN 237 participants; P not significant) and most would receive a pandemic influenza vaccine if offered (76% versus 73%; P not significant). A majority believed that it was important to include HIV patients in vaccine clinical trials (65% versus 53%; P<0.001) and would agree to participate in trials of a pandemic vaccine if invited (86% versus 51%; P≤0.0001). Predictors of willingness to participate in a pandemic vaccine trial were ‘desire to be protected from pandemic flu’, OR 4.5 (95% CI 2 to 8) and ‘desire to help others’, OR 2.3 (95% CI 1.3 to 4.5). ‘Fear of needles’, OR 0.49 (95% CI 0.1 to 1.5) and ‘need for extra blood tests’, OR 0.49 (95% CI 0.2 to 1.4) were key barriers to participation.
Most HIV-positive Canadian adults surveyed receive influenza vaccination. Protection from pandemic influenza is considered important and is a motivator for receiving influenza vaccine and future trial participation. Modifiable barriers to these objectives identified in the present study should be the focus of efforts to increase influenza immunization in this population.
PMCID: PMC2807248  PMID: 21119788
HIV-positive adult attitudes; Pandemic influenza; Public health; Vaccine uptake
12.  Vaccination of children with a live-attenuated, intranasal influenza vaccine – analysis and evaluation through a Health Technology Assessment 
Background: Influenza is a worldwide prevalent infectious disease of the respiratory tract annually causing high morbidity and mortality in Germany. Influenza is preventable by vaccination and this vaccination is so far recommended by the The German Standing Committee on Vaccination (STIKO) as a standard vaccination for people from the age of 60 onwards. Up to date a parenterally administered trivalent inactivated vaccine (TIV) has been in use almost exclusively. Since 2011 however a live-attenuated vaccine (LAIV) has been approved additionally. Consecutively, since 2013 the STIKO recommends LAIV (besides TIV) for children from 2 to 17 years of age, within the scope of vaccination by specified indications. LAIV should be preferred administered in children from 2 to 6 of age. The objective of this Health Technology Assessment (HTA) is to address various research issues regarding the vaccination of children with LAIV. The analysis was performed from a medical, epidemiological and health economic perspective, as well as from an ethical, social and legal point of view.
Method: An extensive systematic database research was performed to obtain relevant information. In addition a supplementary research by hand was done. Identified literature was screened in two passes by two independent reviewers using predefined inclusion and exclusion criteria. Included literature was evaluated in full-text using acknowledged standards. Studies were graded with the highest level of evidence (1++), if they met the criteria of European Medicines Agency (EMA)-Guidance: Points to consider on applications with 1. meta-analyses; 2. one pivotal study.
Results: For the medical section, the age of the study participants ranges from 6 months to 17 years. Regarding study efficacy, in children aged 6 months to ≤7 years, LAIV is superior to placebo as well as to a vac-cination with TIV (Relative Risk Reduction – RRR – of laboratory confirmed influenza infection approx. 80% and 50%, respectively). In children aged >7 to 17 years (= 18th year of their lives), LAIV is superior to a vaccination with TIV (RRR 32%). For this age group, no studies that compared LAIV with placebo were identified. It can be concluded that there is high evidence for superior efficacy of LAIV (compared to placebo or TIV) among children aged 6 months to ≤7 years. For children from >7 to 17 years, there is moderate evidence for superiority of LAIV for children with asthma, while direct evidence for children from the general population is lacking for this age group. Due to the efficacy of LAIV in children aged 6 months to ≤7 years (high evidence) and the efficacy of LAIV in children with asthma aged >7 to 17 years (moderate evidence), LAIV is also very likely to be efficacious among children in the general population aged >7 to 17 years (indirect evidence). In the included studies with children aged 2 to 17 years, LAIV was safe and well-tolerated; while in younger children LAIV may increase the risk of obstruction of the airways (e.g. wheezing).
In the majority of the evaluated epidemiological studies, LAIV proved to be effective in the prevention of influenza among children aged 2–17 years under everyday conditions (effectiveness). The trend appears to indicate that LAIV is more effective than TIV, although this can only be based on limited evidence for methodological reasons (observational studies). In addition to a direct protective effect for vaccinated children themselves, indirect protective ("herd protection") effects were reported among non-vaccinated elderly population groups, even at relatively low vaccination coverage of children. With regard to safety, LAIV generally can be considered equivalent to TIV. This also applies to the use among children with mild chronically obstructive conditions, from whom LAIV therefore does not have to be withheld. In all included epidemiological studies, there was some risk of bias identified, e.g. due to residual confounding or other methodology-related sources of error.
In the evaluated studies, both the vaccination of children with previous illnesses and the routine vaccination of (healthy) children frequently involve cost savings. This is especially the case if one includes indirect costs from a societal perspective. From a payer perspective, a routine vaccination of children is often regarded as a highly cost-effective intervention. However, not all of the studies arrive at consistent results. In isolated cases, relatively high levels of cost-effectiveness are reported that make it difficult to perform a conclusive assessment from an economic perspective. Based on the included studies, it is not possible to make a clear statement about the budget impact of using LAIV. None of the evaluated studies provides results for the context of the German healthcare setting.
The efficacy of the vaccine, physicians' recommendations, and a potential reduction in influenza symptoms appear to play a role in the vaccination decision taken by parents/custodians on behalf of their children. Major barriers to the utilization of influenza vaccination services are a low level of perception and an underestimation of the disease risk, reservations concerning the safety and efficacy of the vaccine, and potential side effects of the vaccine. For some of the parents surveyed, the question as to whether the vaccine is administered as an injection or nasal spray might also be important.
Conclusion: In children aged 2 to 17 years, the use of LAIV can lead to a reduction of the number of influenza cases and the associated burden of disease. In addition, indirect preventive effects may be expected, especially among elderly age groups. Currently there are no data available for the German healthcare setting. Long-term direct and indirect effectiveness and safety should be supported by surveillance programs with a broader use of LAIV.
Since there is no general model available for the German healthcare setting, statements concerning the cost-effectiveness can be made only with precaution. Beside this there is a need to conduct health eco-nomic studies to show the impact of influenza vaccination for children in Germany. Such studies should be based on a dynamic transmission model. Only these models are able to include the indirect protective effects of vaccination correctly.
With regard to ethical, social and legal aspects, physicians should discuss with parents the motivations for vaccinating their children and upcoming barriers in order to achieve broader vaccination coverage.
The present HTA provides an extensive basis for further scientific approaches and pending decisions relating to health policy.
PMCID: PMC4219018  PMID: 25371764
Health Technology Assessment; HTA; LAIV; live attenuated vaccine; TIV; trivalent inactivated vaccine
13.  Healthcare workers as parents: attitudes toward vaccinating their children against pandemic influenza A/H1N1 
BMC Public Health  2010;10:596.
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.
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.
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.
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.
PMCID: PMC3091558  PMID: 20932342
14.  Drivers and barriers to acceptance of human-papillomavirus vaccination among young women: a qualitative and quantitative study 
BMC Public Health  2010;10:68.
Human papillomavirus (HPV) is a necessary cause of cervical dysplasia and cancer, and of genital warts. Few studies have examined attitudes to HPV vaccination since the introduction of HPV vaccines. We aimed to investigate the reasons for young women's acceptance or rejection of the quadrivalent HPV vaccine after its general availability in Denmark.
A literature review assessed attitudes towards HPV vaccination and the information was used to identify relevant questions for telephone and focus group interviews with women aged 16-26 who had decided to receive or reject HPV vaccination. 435 women across Denmark were interviewed by telephone. Qualitative interviews were undertaken in focus groups with 33 women living in Odense who had completed the telephone survey. Four focus groups were set up according to age (16-20 and 21-26 years of age) and acceptance/rejection of the vaccine.
Of 839 women initially contacted by telephone, 794 were included, 411 (49%) said they accepted vaccination but only 201 (24%) had actually received the vaccine and these latter were interviewed. 242 women said they refused vaccination of which 234 were interviewed. Women who were undecided were excluded from the study. Prevention of cervical cancer was the main driver for acceptance of the vaccine, followed by parental encouragement and financial support, personal experience of someone with cancer and recommendation by health-care professionals. The greatest barrier to vaccination was its cost. A lack of information about the benefits of vaccination for sexually active women was also an important barrier and the older participants in particular considered that they were too old to be vaccinated. Knowledge about HPV and its role in the development of cervical cancer and genital warts was poor.
The difference between intention to be vaccinated and starting vaccination was considerable, and a large proportion of women aged 16-26 did not wish to be vaccinated. If the most important barriers to vaccination were addressed (cost and a lack of information about vaccination benefits), it is likely that the uptake of vaccination in Denmark would increase substantially.
PMCID: PMC2829006  PMID: 20152055
15.  Reasons for non-vaccination against HPV and future vaccination intentions among 19-26 year-old women 
BMC Women's Health  2010;10:27.
Despite CDC recommendations regarding universal catch-up vaccination against human papillomavirus (HPV), only about ten percent of young adult women in the United States have been vaccinated. The purpose of this study was to better understand reasons for non-vaccination among insured 19-26 year-old women and to evaluate future vaccination intentions.
We used an administrative claims database from a large US managed care plan to identify women aged 19-26 for receipt of a mailed survey. From a sample of 1,375 women with no evidence of HPV vaccination from June 1, 2006 through April 30, 2007, 222 completed surveys were received, of which 185 were eligible for this analysis. The main outcome measures were unvaccinated women's attitudes and vaccine awareness, likelihood of future action regarding the vaccine, and reasons for inaction.
Among the 185 non-vaccinees, 25.4% were married, 83.2% were white, and 89.2% had a college or higher level education. The vaccine was described as very important by 32.4% of subjects, and 30.1% had discussed the vaccine with a doctor and received a doctor's recommendation. Half or fewer of respondents were "very" or "extremely" likely to discuss the vaccine with their doctor (50.0%), do additional research on the vaccine (42.6%), ask a doctor to get the vaccine (37.5%), or make an appointment to get the vaccine (27.8%), while 48.0% were "somewhat", "very", or "extremely" likely to do nothing to get the vaccine. Among the latter, reasons for taking no action included being married or in a monogamous relationship (54.9%), belief that the vaccine is too new (35.4%), not having enough information about the vaccine (31.7%), concerns about side effects (24.4%), and uncertainty about insurance coverage (24.4%).
Educational interventions may be needed to enhance HPV vaccination rates among 19-26 year-old women, particularly regarding information about vaccine safety, vaccine efficacy, insurance coverage, and the value of vaccination to women in monogamous relationships.
PMCID: PMC2941477  PMID: 20809965
16.  Decline in Diarrhea Mortality and Admissions after Routine Childhood Rotavirus Immunization in Brazil: A Time-Series Analysis 
PLoS Medicine  2011;8(4):e1001024.
A time series analysis by Manish Patel and colleagues shows that the introduction of rotavirus vaccination in Brazil is associated with reduced diarrhea-related deaths and hospital admissions in children under 5 years of age.
In 2006, Brazil began routine immunization of infants <15 wk of age with a single-strain rotavirus vaccine. We evaluated whether the rotavirus vaccination program was associated with declines in childhood diarrhea deaths and hospital admissions by monitoring disease trends before and after vaccine introduction in all five regions of Brazil with varying disease burden and distinct socioeconomic and health indicators.
Methods and Findings
National data were analyzed with an interrupted time-series analysis that used diarrhea-related mortality or hospitalization rates as the main outcomes. Monthly mortality and admission rates estimated for the years after rotavirus vaccination (2007–2009) were compared with expected rates calculated from pre-vaccine years (2002–2005), adjusting for secular and seasonal trends. During the three years following rotavirus vaccination in Brazil, rates for diarrhea-related mortality and admissions among children <5 y of age were 22% (95% confidence interval 6%–44%) and 17% (95% confidence interval 5%–27%) lower than expected, respectively. A cumulative total of ∼1,500 fewer diarrhea deaths and 130,000 fewer admissions were observed among children <5 y during the three years after rotavirus vaccination. The largest reductions in deaths (22%–28%) and admissions (21%–25%) were among children younger than 2 y, who had the highest rates of vaccination. In contrast, lower reductions in deaths (4%) and admissions (7%) were noted among children two years of age and older, who were not age-eligible for vaccination during the study period.
After the introduction of rotavirus vaccination for infants, significant declines for three full years were observed in under-5-y diarrhea-related mortality and hospital admissions for diarrhea in Brazil. The largest reductions in diarrhea-related mortality and hospital admissions for diarrhea were among children younger than 2 y, who were eligible for vaccination as infants, which suggests that the reduced diarrhea burden in this age group was associated with introduction of the rotavirus vaccine. These real-world data are consistent with evidence obtained from clinical trials and strengthen the evidence base for the introduction of rotavirus vaccination as an effective measure for controlling severe and fatal childhood diarrhea.
Please see later in the article for the Editors' Summary
Editors' Summary
Diarrheal disease, usually caused by infectious agents, is the second major cause of death in children aged under five years. As highlighted in a recent PLoS Medicine series, access to clean water and improved sanitation is the key to the primary prevention of diarrheal illnesses. Yet despite the targets of Millennium Development Goal 7 to half the number of people without access to clean water or improved sanitation by 2015, over one billion people worldwide do not currently have access to clean water and over two billion do not currently have access to improved sanitation.
Since enteric viruses are primarily transmitted directly from one person to another, they cannot be controlled completely by improvements in sanitation. Therefore, although not replacing the urgent need to provide access to clean water and improved sanitation for all, vaccination programs that protect young children against some infections that cause diarrhea, such as rotavirus, which accounts for one-third of all child deaths caused by diarrhea, are a pragmatic way forward. As large clinical trials have shown the safety and efficacy of rotavirus vaccines in population settings, in July 2009, the World Health Organization recommended including rotavirus vaccines into every country's national immunization programs.
Why Was This Study Done?
Although the protective effect of rotavirus vaccines has been assessed in various high-, middle-, and low-income settings, for reasons that remain unclear, the efficacy of live, oral rotavirus vaccines appears to be dependent on geographical location and correlated to the socioeconomic status of the population. Because of these concerns, evaluating the health impact of large-scale rotavirus vaccine programs and ensuring their equity in a real-world setting (rather than in clinical trial conditions) is important.
Therefore, the researchers addressed this issue by conducting this study to evaluate the effect of rotavirus vaccination on mortality and hospital admissions for diarrhea due to all causes among young children in the five regions of Brazil. The researchers chose to do this study in Brazil because of the high incidence of diarrhea-related deaths and hospital admissions and because five years ago, in July 2006, the Brazilian Ministry of Health introduced the single-strain rotavirus vaccine simultaneously in all 27 states through its national immunization program—allowing for “before” and “after” intervention analysis.
What Did the Researchers Do and Find?
The researchers obtained data on diarrheal deaths and hospital admissions in children aged under five years for the period 2002–2005 and 2007–2009 and data on rotavirus vaccination rates. The researchers got the data on diarrhea deaths from the Brazilian Mortality Information System—the national database of information collected from death certificates that covers 90% of all deaths in Brazil. The data on hospital admissions came from the electronic Hospital Information System of Brazil's Unified Health System (Sistema Unico de Saúde, SUS)—the publicly funded health-care system that covers roughly 70% of the hospitalizations and includes information on all admissions (from public hospitals and some private hospitals) authorized for payment by the Unified Health System. The researchers got regional rotavirus vaccination coverage estimates for 2007–2009 from the information department of the Ministry of Health, and estimated coverage of the two doses of oral rotavirus vaccine by taking the annual number of second doses administered divided by the number of infants in the region.
In 2007, an estimated 80% of infants received two doses of rotavirus vaccine, and by 2009, this proportion rose to 84% of children younger than one year of age. The researchers found that in the three years following the introduction of rotavirus vaccination, diarrhea-related mortality rates and admissions among children aged under five years were respectively 22% and 17% lower than expected, with a cumulative total of 1,500 fewer diarrhea deaths and 130,000 fewer admissions. Furthermore, the largest reductions in deaths and admissions were among children who had the highest rates of vaccination (less than two years of age), and the lowest reductions were among children who were not eligible for vaccination during the study period (aged 2–4 years).
What Do These Findings Mean?
These findings suggest that the introduction of rotavirus vaccination in all areas of Brazil is associated with reduced diarrhea-related deaths and hospital admissions in children aged under five years. These real-world impact data are consistent with the clinical trials and strengthen the evidence base for rotavirus vaccination as an effective measure for controlling severe and fatal childhood diarrhea.
These findings have important global policy implications. In middle-income countries, such as Brazil, that are not eligible for financial support from donors, the potential reductions in admissions and other health-care costs will be important for cost-effectiveness considerations to justify the purchase of these still relatively expensive vaccines.
Additional Information
Please access these Web sites via the online version of this summary at
PLoS Medicine has published a series on water and sanitation
More information is available from the World Health Organization on diarrheal illness in children
More information is available about rotavirus vaccines from the World Health Organization, the US Centers for Disease Control and Prevention, and the Rotavirus Vaccine Program
PMCID: PMC3079643  PMID: 21526228
17.  Low HPV Vaccine Coverage among Female Community College Students 
Journal of community health  2012;37(6):1136-1144.
This study assessed HPV vaccination and its correlates among culturally diverse 18–26 year-old community college women in Los Angeles. Specific research questions were: (1) What proportion of respondents have initiated the HPV vaccine, and what proportion have completed the three-dose series? (2) What demographic (e.g., age, ethnicity), psychosocial (e.g., vaccine-related beliefs, perceived social norms), and health care-related variables (e.g., health insurance status, provider recommendation, health care trust and satisfaction) are associated with vaccine initiation for this sample?
Participants were recruited from the campus of a community college in central Los Angeles. All female students between 18 and 26 were eligible to participate. An anonymous web-based survey assessed number of HPV vaccine doses received as well as demographic information, HPV- and HPV vaccine-related knowledge, attitudes, and behavior, perceived social norms, provider & health care system factors, sexual behavior, cervical health, and mother-daughter communication about sex. Analyses were conducted using 178 surveys. Multivariate logistic regression tested the relationships of statistically significant bivariate predictors to vaccine initiation.
Those who initiated the vaccine were younger, more often had a health-related academic major, thought the vaccine to be safer, perceived HPV severity lower, and perceived higher social approval for HPV vaccination than those unvaccinated. All who had initiated the vaccine had a doctor’s recommendation.
To increase uptake among 18–26-year-old women, research should explore provider interventions to increase vaccine recommendation, and also identify individuals and groups who may have negative beliefs about vaccine safety and efficacy to provide support in vaccine decision-making.
PMCID: PMC3747828  PMID: 22669623
HPV vaccine; cervical cancer prevention; college women; community college; ethnic minority women
18.  Canadian national surveys on pandemic influenza preparations: pre-pandemic and peri-pandemic findings 
BMC Public Health  2013;13:271.
Prior to the 2009 H1N1 Influenza pandemic, public health authorities in Canada and elsewhere prepared for the future outbreak, partly guided by an ethical framework developed within the Canadian Program of Research on Ethics in a Pandemic (CanPREP). We developed a telephone-based survey based on that framework, which was delivered across Canada in late 2008. In June, 2009, the WHO declared pandemic Phase 6 status and from the subsequent October (2009) until May 2010, the CanPREP team fielded a second (revised) survey, collecting another 1,000 opinions from Canadians during a period of pre-pandemic anticipation and peri-pandemic experience.
Surveys were administered by telephone with random sampling achieved via random digit dialing. Eligible participants were adults, 18 years or older, with per province stratification approximating provincial percentages of national population. Descriptive results were tabulated and logistic regression analyses used to assess whether demographic factors were significantly associated with outcomes, and to identify divergences (between the pre-pandemic and intra-pandemic surveys).
N = 1,029 interviews were completed from 1,986 households, yielding a gross response rate of 52% (AAPOR Standard Definition 3). Over 90% of subjects indicated the most important goal of pandemic influenza preparations was saving lives, with 41% indicating that saving lives solely in Canada was the highest priority and 50% indicating saving lives globally was the highest priority. About 90% of respondents supported the obligation of health care workers to report to work and face influenza pandemic risks excepting those with serious health conditions which that increased risks. Strong majorities favoured stocking adequate protective antiviral dosages for all Canadians (92%) and, if effective, influenza vaccinations (95%). Over 70% agreed Canada should provide international assistance to poorer countries for pandemic preparation, even if resources for Canadians were reduced.
Results suggest Canadians trust public health officials to make difficult decisions, providing emphasis is maintained on reciprocity and respect for individual rights. Canadians also support international obligations to help poorer countries and associated efforts to save lives outside the country, even if intra-national efforts are reduced.
PMCID: PMC3627899  PMID: 23530550
Pandemic influenza; Canada; Survey research; Public health ethics; Bioethics; H1N1
19.  Live Attenuated Influenza Vaccine, Trivalent, Is Safe in Healthy Children 18 Months to 4 Years, 5 to 9 Years, and 10 to 18 Years of Age in a Community-Based, Nonrandomized, Open-Label Trial 
Pediatrics  2005;116(3):e397-e407.
Influenza-associated deaths in healthy children that were reported during the 2003–2004 influenza season heightened the public awareness of the seriousness of influenza in children. In 1996–1998, a pivotal phase III trial was conducted in children who were 15 to 71 months of age. Live attenuated influenza vaccine, trivalent (LAIV-T), was shown to be safe and efficacious. In a subsequent randomized, double-blind, placebo-controlled LAIV-T trial in children who were 1 to 17 years of age, a statistically significant increase in asthma encounters was observed for children who were younger than 59 months. LAIV-T was not licensed to children who were younger than 5 years because of the concern for asthma. We report on the largest safety study to date of the recently licensed LAIV-T in children 18 months to 4 years, 5 to 9 years, and 10 to 18 years of age in a 4-year (1998–2002) community-based trial that was conducted at Scott & White Memorial Hospital and Clinic (Temple, TX).
An open-label, nonrandomized, community-based trial of LAIV-T was conducted before its licensure. Medical records of all children were surveyed for serious adverse events (SAEs) 6 weeks after vaccination. Health care utilization was evaluated by determining the relative risk (RR) of medically attended acute respiratory illness (MAARI) and asthma rates at 0 to 14 and 15 to 42 days after vaccination compared with the rates before vaccination. Medical charts of all visits coded as asthma were reviewed for appropriate classification of events: acute asthma or other. We evaluated the risk for MAARI (health care utilization for acute respiratory illness) 0 to 14 and 15 to 42 days after LAIV-T by a method similar to the postlicensure safety analysis conducted on measles, mumps, and rubella and on diphtheria, tetanus, and whole-cell pertussis vaccines.
All children regardless of age were administered a single intranasal dose of LAIV-T in each vaccine year. In the 4 years of the study, we administered 18 780 doses of LAIV-T to 11 096 children. A total of 4529, 7036, and 7215 doses of LAIV-T were administered to children who were 18 months to 4 years, 5 to 9 years, and 10 to 18 years of age, respectively. In vaccination years 1, 2, 3, and 4, we identified 10, 15, 11, and 6 SAEs, respectively. None of the SAEs was attributed to LAIV-T. In vaccination years 1, 2, 3, and 4, we identified 3, 2, 1, and 0 pregnancies, respectively, among adolescents. All delivered healthy infants. The RR for MAARI from 0 to 14 and 15 to 42 days after LAIV-T was assessed in vaccinees during the 4 vaccine years. Compared with the prevaccination period, there was no significant increase in risk in health care utilization attributed to MAARI from 0 to 14 and 15 to 42 days after vaccination in children who were 18 months to 4 years, 5 to 9 years, and 10 to 18 years of age in the 4 vaccine years. In children who were 18 months to 4 years of age, there was no significant increase in the risk in health care utilization for MAARI, MAARI subcategories (otitis media/sinusitis, upper respiratory tract illness, and lower respiratory tract illness), and asthma during the 0 to 14 days after vaccination compared with the prevaccination period. No significant increase in the risk in health care utilization for MAARI, MAARI subcategories, and asthma was detected when the risk period was extended to 15 to 42 days after vaccination, except for asthma events in vaccine year 1. A RR of 2.85 (95% confidence interval [CI]: 1.01–8.03) for asthma events was detected in children who were 18 months to 4 years of age but was not significantly increased for the other 3 vaccine years (vaccine year 2, RR: 1.42 [95% CI: 0.59–3.42]; vaccine year 3, RR: 0.47 [95% CI: 0.12–1.83]; vaccine year 4, RR: 0.20 [95% CI: 0.03–1.54]). No significant increase in the risk in health care utilization for MAARI or asthma was observed in children who were 18 months to 18 years of age and received 1, 2, 3, or 4 annual sequential doses of LAIV-T. Children who were 18 months to 4 years of age and received 1, 2, 3, or 4 annual doses of LAIV-T did not experience a significant increase in the RR for MAARI 0 to 14 days after vaccination; this was also true for children who were 5 to 9 and 10 to 18 years of age.
We observed no increased risk for asthma events 0 to 14 days after vaccination in children who were 18 months to 4 years, 5 to 9 years, and 10 to 18 years of age, In vaccine year 1, children who were 18 months to 4 years of age did have a significantly higher RR (2.85; 95% CI: 1.01–8.03) for asthma events 15 to 42 days after vaccination. In vaccine year 2, the formulation of LAIV-T was identical to the vaccine formulation used in vaccine year 1; however, in children who were 18 months to 4 years of age, no statistically significant increased risk was detected for asthma events 15 to 42 days after vaccination. Similarly, in vaccine years 3 and 4, children who were 18 months to 4 years of age did not have a statistically significant increased risk for asthma events 15 to 42 days after vaccination. Also, LAIV-T did not increase the risk for asthma in children who received 1, 2, 3, or 4 annual doses of LAIV-T. Although the possibility for a true increased risk for asthma was observed in 1 of 4 years in children who were 18 months to 4 years at 15 to 42 days after vaccination, it is more likely that the association is a chance effect because of the 190 comparisons made without adjustment for multiple comparisons. We conclude that LAIV-T is safe in children who are 18 months to 4 years, 5 to 9 years, and 10 to 18 years of age. The hypothesis that LAIV-T is associated with an increase in asthma events in children who are younger than 5 years is not supported by our data. Reassessment of the lower age limit for use of LAIV-T in children is indicated.
PMCID: PMC1361119  PMID: 16140685
asthma exacerbation; children and adolescents; health service utilization; influenza vaccine; outcome assessment; RSV, respiratory syncytial virus; LAIV-T, live attenuated influenza vaccine, trivalent; MAARI, medically attended acute respiratory illness; FDA, Food and Drug Administration; SAE, serious adverse event; SWHP, Scott & White Health Plan; RR, relative risk; ICD-9, International Classification of Diseases, Ninth Revision; CI, confidence interval
20.  Participation in and attitude towards the national immunization program in the Netherlands: data from population-based questionnaires 
BMC Public Health  2012;12:57.
Knowledge about the determinants of participation and attitude towards the National Immunisation Program (NIP) may be helpful in tailoring information campaigns for this program. Our aim was to determine which factors were associated with nonparticipation in the NIP and which ones were associated with parents' intention to accept remaining vaccinations. Further, we analyzed possible changes in opinion on vaccination over a 10 year period.
We used questionnaire data from two independent, population-based, cross-sectional surveys performed in 1995-96 and 2006-07. For the 2006-07 survey, logistic regression modelling was used to evaluate what factors were associated with nonparticipation and with parents' intention to accept remaining vaccinations. We used multivariate multinomial logistic regression modelling to compare the results between the two surveys.
Ninety-five percent of parents reported that they or their child (had) participated in the NIP. Similarly, 95% reported they intended to accept remaining vaccinations. Ethnicity, religion, income, educational level and anthroposophic beliefs were important determinants of nonparticipation in the NIP. Parental concerns that played a role in whether or not they would accept remaining vaccinations included safety of vaccinations, maximum number of injections, whether vaccinations protect the health of one's child and whether vaccinating healthy children is necessary. Although about 90% reported their opinion towards vaccination had not changed, a larger proportion of participants reported to be less inclined to accept vaccination in 2006-07 than in 1995-96.
Most participants had a positive attitude towards vaccination, although some had doubts. Groups with a lower income or educational level or of non-Western descent participated less in the NIP than those with a high income or educational level or indigenous Dutch and have been less well identified previously. Particular attention ought to be given to these groups as they contribute in large measure to the rate of nonparticipation in the NIP, i.e., to a greater extent than well-known vaccine refusers such as specific religious groups and anthroposophics. Our finding that the proportion of the population inclined to accept vaccinations is smaller than it was 10 years ago highlights the need to increase knowledge about attitudes and beliefs regarding the NIP.
PMCID: PMC3298495  PMID: 22264347
21.  Knowledge, Attitude, Practice and Barriers on Vaccination against Human Papillomavirus Infection: A Cross-Sectional Study among Primary Care Physicians in Hong Kong 
PLoS ONE  2013;8(8):e71827.
This study explored the knowledge, attitude, practice and barriers to prescribe human papillomavirus (HPV) vaccines among private primary care physicians in Hong Kong. A self-administered questionnaire survey was conducted by sending letters to doctors who had joined a vaccination program for school girls. From 720 surveys sent, 444 (61.7%) completed questionnaires were returned and analyzed. For knowledge, few responded to questions accurately on the prevalence of cervical HPV (27.9%) and genital wart infection (13.1%) among sexually active young women in Hong Kong, and only 44.4% correctly answered the percentage of cervical cancers caused by HPV. For attitude, most agreed that HPV vaccination should be fully paid by the Government (68.3%) as an important public health strategy. Vaccination against HPV was perceived as more important than those for genital herpes (52.2%) and Chlamydia (50.1%) for adolescent health, and the majority selected adolescents aged 12–14 years as the ideal group for vaccination. Gardasil® (30.9%) and Cervarix® (28.0%) were almost equally preferred. For practice, the factors influencing the choice of vaccine included strength of vaccine protection (61.1%), long-lasting immunity (56.8%) and good antibody response (55.6%). The most significant barriers to prescribe HPV vaccines consisted of parental refusal due to safety concerns (48.2%), and their practice of advising vaccination was mostly affected by local Governmental recommendations (78.7%). A substantial proportion of physicians had recommended HPV vaccines for their female clients/patients aged 18–26 years for protection of cervical cancer (83.8%) or both cervical cancer and genital warts (85.5%). The knowledge on HPV infection was low among physicians in Hong Kong. Prescription of HPV vaccine was hindered by the perceived parental concerns and was mostly relied on Governmental recommendations. Educational initiatives should be targeted towards both physicians and parents, and the Government should consider full subsidy to enhance vaccine uptake rate.
PMCID: PMC3749199  PMID: 23990994
22.  Challenges to immunization: the experiences of homeless youth 
BMC Public Health  2012;12:338.
Homelessness is a critical social issue, both a product of, and contributing to, poor mental and physical health. Over 150,000 young Canadians live on the streets. Homeless youth experience a high incidence of infectious diseases, many of which are vaccine preventable. Early departure from school and limited access to public health services makes them a particularly vulnerable high-risk group. This study explores challenges to obtaining essential vaccines experienced by homeless youth.
A qualitative research study to explore knowledge, attitudes, beliefs, and experiences surrounding immunization of hard-to-reach homeless youth was designed. Participants were recruited for focus groups from Phoenix House and Shelter, a non-profit, community-based organization assisting homeless youth in Halifax, Nova Scotia, Canada. An experienced facilitator guided the recorded discussions. Transcripts of audiotapes were analyzed using a constant comparative method until data revealed a set of exemplars and themes that best captured participants’ knowledge, attitudes, beliefs and experiences surrounding immunization and infectious diseases.
Important themes emerged from our analysis. Considerable variability in knowledge about immunization and vaccine preventable diseases was found. The homeless youth in the study had limited awareness of meningitis in contrast to a greater knowledge about sexually transmitted infections and influenza, gained during the H1N1/09 public health campaign. They recognized their poverty as a risk for contracting infectious diseases, along with their inability to always employ known strategies to prevent infectious diseases, due to circumstances. They showed considerable insight into the detrimental effects of poor hygiene, sleeping locations and risk behaviour. Interviewed homeless youth regarded themselves as good compliers of health professional advice and offered valuable suggestions to improve immunization in their population.
To provide effective public health interventions, it is necessary to consider the knowledge, attitudes, beliefs, and experiences of hard to reach, high risk groups. Our study shows that homeless youth are interested and capable in discussing immunization. Active targeting of homeless youth for public health immunization programs is needed. Working collaboratively with non-profit organizations that assist homeless youth provides an opportunity to increase their knowledge of infectious risks and to improve immunization strategies in this vulnerable group.
PMCID: PMC3390266  PMID: 22568937
Homeless youth; Hard to reach population; Vaccines; Immunization programs; Infectious diseases; Invasive meningococcal disease
23.  Accelerating Policy Decisions to Adopt Haemophilus influenzae Type b Vaccine: A Global, Multivariable Analysis 
PLoS Medicine  2010;7(3):e1000249.
Jessica Shearer and colleagues analyze data from 147 countries to identify factors that influence the time taken to introduce routine vaccination against Haemophilus influenzae type b (Hib).
Adoption of new and underutilized vaccines by national immunization programs is an essential step towards reducing child mortality. Policy decisions to adopt new vaccines in high mortality countries often lag behind decisions in high-income countries. Using the case of Haemophilus influenzae type b (Hib) vaccine, this paper endeavors to explain these delays through the analysis of country-level economic, epidemiological, programmatic and policy-related factors, as well as the role of the Global Alliance for Vaccines and Immunisation (GAVI Alliance).
Methods and Findings
Data for 147 countries from 1990 to 2007 were analyzed in accelerated failure time models to identify factors that are associated with the time to decision to adopt Hib vaccine. In multivariable models that control for Gross National Income, region, and burden of Hib disease, the receipt of GAVI support speeded the time to decision by a factor of 0.37 (95% CI 0.18–0.76), or 63%. The presence of two or more neighboring country adopters accelerated decisions to adopt by a factor of 0.50 (95% CI 0.33–0.75). For each 1% increase in vaccine price, decisions to adopt are delayed by a factor of 1.02 (95% CI 1.00–1.04). Global recommendations and local studies were not associated with time to decision.
This study substantiates previous findings related to vaccine price and presents new evidence to suggest that GAVI eligibility is associated with accelerated decisions to adopt Hib vaccine. The influence of neighboring country decisions was also highly significant, suggesting that approaches to support the adoption of new vaccines should consider supply- and demand-side factors.
Please see later in the article for the Editors' Summary
Editors' Summary
Every year, immunization averts more than 2 million deaths by preparing people's immune systems to recognize and attack disease-causing organisms (pathogens) rapidly and effectively. Although the immune system is designed to protect the human body against infections, the first time a person is exposed to a pathogen (usually during early childhood) their immune system can take some time to respond. As a result, they can become seriously ill or even die. However, the immune system “learns” from the experience and when the pathogen is encountered again, the immune system swings into action much more quickly. Immunization or vaccination is a safe way to make individuals resistant to infectious diseases. It works by exposing them to weakened or dead pathogens or to pathogen molecules (antigens) that the immune system recognizes as foreign. Widespread, routine immunization of children is, therefore, an essential component of national and global strategies to reduce childhood illnesses and deaths.
Why Was This Study Done?
Although many factors affect the uptake of immunization (in particular, vaccine prices), national policy decisions to adopt new vaccines are an essential step toward improving coverage. Unfortunately, these decisions are often delayed in developing countries. Thus, although many industrialized countries have routinely immunized their children with the highly effective Haemophilus influenza type b (Hib) conjugate vaccine since it became available in the early 1990s, only 13 low-income countries were using the vaccine in 2004. Hib bacteria, which cause pneumonia (lung infection) and meningitis (brain inflammation), kill about 370,000 unvaccinated young children every year. In this study, the researchers try to explain delays in the adoption of routine Hib vaccination in developing countries by analyzing the associations between Hib vaccination and factors such as national economic status, local Hib burden, and eligibility for support from the Global Alliance for Vaccines and Immunisation (GAVI Alliance; a public–private partnership that offers financial, technical, and health systems support for the introduction of national immunization programs to developing countries that meet certain eligibility criteria).
What Did the Researchers Do and Find?
The researchers used a statistical approach called accelerated failure time analysis to analyze data collected in 147 countries between 1990 and 2007 on vaccine costs, Hib disease incidence, GAVI eligibility, and other factors that could influence decision-makers' perceptions of the costs and benefits of Hib vaccination. After allowing for gross national income, region, and burden of Hib disease, the researchers identified several factors that influenced the time between the availability of a Hib conjugate vaccine in a country and a decision being made to introduce routine Hib vaccination. The receipt of GAVI support speeded the decision to adopt vaccination by 63%, for example, and sharing borders with two or more countries that had adopted the vaccine speeded the decision by 50%. By contrast, for each 1% increase in vaccine costs, the time to decision to adopt vaccination was delayed by 2%. The 1998 and 2006 World Health Organization recommendations on routine Hib vaccination and the existence of local studies on Hib disease had no influence on the time to decision.
What Do These Findings Mean?
These findings confirm previous studies that showed that increases in the price of Hib vaccine increase the time to adoption. In addition, they suggest that GAVI eligibility accelerates decisions to adopt this vaccine and show that the decisions made by neighboring countries are important, which suggests that policy diffusion may occur. Thus, in the case of adoption of the Hib vaccine, both supply-side and demand-side factors seem to be important. Its is relevant to note that during writing of the article, JCS, MLS, MRR, APB, and RAH were employed by the Hib Initiative, which was funded by the GAVI Alliance. The findings do not necessarily represent the views, policies or decisions of the Hib Initiative or the GAVI Alliance. Importantly, these findings are explanatory, not predictive, so they cannot be applied directly to new vaccines to improve their rate of adoption. Nevertheless, these findings highlight the potential importance of setting up formal and informal networks to facilitate policy diffusion and suggest that long-term price and supply certainty might be factors that could help to accelerate national decisions to adopt new and/or underutilized vaccines and other public-health technologies.
Additional Information
Please access these Web sites via the online version of this summary at
The World Health Organization provides information on immunization and on Haemophilus influenza type b (in several languages)
The GAVI Alliance Web site describes the work of this public–private partnership and provides details of developing countries eligible for Hib vaccination support
The Hib Initiative aims to reduce the risk of childhood death and disability through sustained use of Hib vaccine
MedlinePlus provides links to further resources on immunization and information on the Haemophilus influenzae type b vaccine (in English and Spanish)
PMCID: PMC2838745  PMID: 20305714
24.  Differences in HIV vaccine acceptability between genders 
AIDS care  2008;20(5):542-546.
The development of safe and efficacious preventive HIV vaccines offers the best long-term hope of controlling the AIDS pandemic. Nevertheless, suboptimal uptake of safe and efficacious vaccines that already exist suggest that HIV vaccine acceptability cannot be assumed, particularly among communities most vulnerable to HIV. The present study aimed to identify barriers and motivators to future HIV vaccine acceptability among low socioeconomic, ethnically diverse men and women in Los Angeles County. Participants completed a cross-sectional survey assessing their attitudes and beliefs regarding future HIV vaccines. Hypothetical HIV vaccine scenarios were administered to determine HIV vaccine acceptability. Two-sided t-tests were performed, stratified by gender, to examine the association between vaccine acceptability and potential barriers and motivators. Barriers to HIV vaccine acceptability differed between men and women. For women, barriers to HIV vaccine acceptability were related to their intimate relationships (p <0.05), negative experiences with health care providers (p <0.05) and anticipated difficulties procuring insurance (p <0.01). Men were concerned that the vaccine would weaken the immune system (p <0.005) or would affect their HIV test results (p <0.05). Motivators for women included the ability to conceive a child without worrying about contracting HIV (p <0.10) and support from their spouse/significant other for being vaccinated (p <0.10). Motivators for men included feeling safer with sex partners (p <0.05) and social influence from friends to get vaccinated (p <0.005). Family support for HIV immunization was a motivator for both men and women (p <0.10). Gender-specific interventions may increase vaccine acceptability among men and women at elevated risk for HIV infection. Among women, interventions need to focus on addressing barriers due to gendered power dynamics in relationships and discrimination in health care. Among men, education that addresses fears and misconceptions about adverse effects of HIV vaccination on health and the importance of vaccination as one component of integrated HIV prevention may increase vaccine acceptability.
PMCID: PMC2836013  PMID: 18484322
HIV vaccine; barriers; gender; motivators; acceptability
25.  Predictive factors associated with the acceptance of pandemic and seasonal influenza vaccination in health care workers and students in Tuscany, Central Italy 
Human Vaccines & Immunotherapeutics  2013;9(12):2603-2612.
Assessing the beliefs and attitudes of Health Care Workers (HCW) to influenza and influenza vaccination can be useful in overcoming low compliance rates. The purpose of our study is to evaluate the opinion of HCW and students regarding influenza, influenza vaccine and the factors associated with vaccination compliance. A survey was conducted between October 2010 and April 2011 in the Florence metropolitan area. A questionnaire was administered to HCW in three local healthcare units and at Careggi University Teaching Hospital. Students matriculating in health degree programs at Florence University were also surveyed.
The coverage with vaccination against seasonal and pandemic influenza is generally low, and it is lower in students than in HCW (12.5% vs 15% for the seasonal vaccination, 8.5% vs 18% for the pandemic vaccination). Individuals comply with vaccination offer mainly to protect themselves and their contacts. Individuals not receiving vaccination did not consider themselves at risk, had never been vaccinated before or believed that pandemic influenza was not a public health concern. Physicians had the highest compliance to vaccination and women were less frequently vaccinated than men. HCW do not appear to perceive their possible influenza infections as a risk for patients: HCW receive vaccination mainly as a form of personal protection.
Low compliance to vaccination is determined by various factors and therefore requires a multi-faceted strategy of response. This should include short-term actions to overcome organizational barriers, in addition to long-term interventions to raise HCW’s level of knowledge about influenza and influenza vaccination.
PMCID: PMC4162047  PMID: 23954990
attitudes towards vaccine; vaccine policy; health care workers; influenza; H1N1; pandemic

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