Preventable neonatal mortality due to tetanus infection remains common. We aimed to examine antenatal vaccination impact in a context of continuing high neonatal mortality in rural northern India.
Methods and Findings
Using the third round of the Indian National Family Health Survey (NFHS) 2005–06, mortality of most recent singleton births was analysed in discrete-time logistic model with maternal tetanus vaccination, together with antenatal care utilisation and supplementation with iron and folic acid. 59% of mothers reported receiving antenatal care, 48% reported receiving iron and folic acid supplementation and 68% reported receiving two or more doses of tetanus toxoid (TT) vaccination. The odds of all-cause neonatal death were reduced following one or more antenatal dose of TT with odds ratios (OR) of 0.46 (95% CI 0.26 to 0.78) after one dose and 0.45 (95% CI 0.31 to 0.66) after two or more doses. Reported utilisation of antenatal care and iron-folic acid supplementation did not influence neonatal mortality. In the statistical model, 16% (95% CI 5% to 27%) of neonatal deaths could be attributed to a lack of at least two doses of TT vaccination during pregnancy, representing an estimated 78,632 neonatal deaths in absolute terms.
Substantial gains in newborn survival could be achieved in rural North India through increased coverage of antenatal TT vaccination. The apparent substantial protective effect of a single antenatal dose of TT requires further study. It may reflect greater population vaccination coverage and indicates that health programming should prioritise universal antenatal coverage with at least one dose.
The global and within-country epidemiology of cervical cancer exemplifies health inequity. Public health programs may reduce absolute risk but increase inequity; inequity may be further compounded by screening programs. In this context, we aimed to explore what the impact of human papillomavirus (HPV) vaccine might have on health equity allowing for uncertainty surrounding the long-term effect of HPV vaccination programs.
A simple static multi-way sensitivity analysis was carried out to compare the relative risk, comparing after to before implementation of a vaccination program, of infections which would cause invasive cervical cancer if neither prevented nor detected, using plausible ranges of vaccine effectiveness, vaccination coverage, screening sensitivity, screening uptake and changes in uptake.
We considered a total number of 3,793,902 scenarios. In 63.9% of scenarios considered, vaccination would lead to a better outcome for a population or subgroup with that combination of parameters. Regardless of vaccine effectiveness and coverage, most simulations led to lower rates of disease.
If vaccination coverage and screening uptake are high, then communities are always better off with a vaccination program. The findings highlight the importance of achieving and maintaining high immunization coverage and screening uptake in high risk groups in the interest of health equity.
Although an increasing number of studies are documenting uses of syndromic surveillance by front line public health, few detail the value added from linking syndromic data to public health decision-making. This study seeks to understand how syndromic data informed specific public health actions during the 2009 H1N1 pandemic.
Semi-structured telephone interviews were conducted with participants from Ontario’s public health departments, the provincial ministry of health and federal public health agency to gather information about syndromic surveillance systems used and the role of syndromic data in informing specific public health actions taken during the pandemic. Responses were compared with how the same decisions were made by non-syndromic surveillance users.
Findings from 56 interviews (82% response) show that syndromic data were most used for monitoring virus activity, measuring impact on the health care system and informing the opening of influenza assessment centres in several jurisdictions, and supporting communications and messaging, rather than its intended purpose of early outbreak detection. Syndromic data had limited impact on decisions that involved the operation of immunization clinics, school closures, sending information letters home with school children or providing recommendations to health care providers. Both syndromic surveillance users and non-users reported that guidance from the provincial ministry of health, communications with stakeholders and vaccine availability were driving factors in these public health decisions.
Syndromic surveillance had limited use in decision-making during the 2009 H1N1 pandemic in Ontario. This study provides insights into the reasons why this occurred. Despite this, syndromic data were valued for providing situational awareness and confidence to support public communications and recommendations. Developing an understanding of how syndromic data are utilized during public health events provides valuable evidence to support future investments in public health surveillance.
Decision making; Pandemic influenza; Public health; Surveillance; Syndromic surveillance
Factor H Binding protein (fHbp) is an important meningococcal virulence factor, enabling the meningococcus to evade the complement system, and a main target for vaccination. Recently, the structure of fHBP complexed with factor H (fH) was published. Two fHbp glutamic acids, E283 and E304, form salt bridges with fH, influencing interaction between fHbp and fH. Fifteen amino acids were identified forming hydrogen bonds with fH. We sequenced fHbp of 254 meningococcal isolates from adults with meningococcal meningitis included in a prospective clinical cohort to study the effect of fHbp variants on meningococcal disease severity and outcome. All fHbp of subfamily A had E304 substituted with T304. Of the 15 amino acids in fHbp making hydrogen bonds to fH, 3 were conserved, 11 show a similar distribution between the two fHbp subfamilies as the polymorphism at position 304. The proportion of patients infected with meningococci with fHbp of subfamily A with unfavorable outcome was 2.5-fold lower than that of patients infected with meningococci with fHbp of subfamily B (2 of 40 (5%) vs. 27 of 213 (13%) (P = 0.28). The charge of 2 of 15 amino acids (at position 184 and 306) forming hydrogen bonds was either basic or acidic. The affinity of fHbpK184 and of fHbpD184 for recombinant purified human fH was assessed by Surface Plasmon Resonance and showed average KD of 2.60×10−8 and 1.74×10−8, respectively (ns). Patients infected with meningococci with fHbpD184 were more likely to develop septic shock during admission (11 of 42 [26%] vs. 19 of 211 [9%]; P = 0.002) resulting in more frequent unfavorable outcome (9 of 42 [21%] vs. 20 of 211 [10%]; P = 0.026). In conclusion, we dentified fHBPD184 to be associated with septic shock in patients with meningococcal meningitis.
The success of influenza vaccination campaigns may be suboptimal if subgroups of the population face unique barriers or have misconceptions about vaccination. We conducted a national study to estimate influenza vaccine coverage across 12 ethnic groups in Canada to assess the presence of ethnic disparities.
We pooled responses to the Canadian Community Health Survey between 2003 and 2009 (n = 437 488). We estimated ethnicity-specific self-reported influenza vaccine coverage for the overall population, for people aged 65 years and older, and for people aged 12–64 years with and without chronic conditions. We used weighted logistic regression models to examine the association between ethnicity and influenza vaccination, adjusting for sociodemographic factors and health status.
Influenza vaccination coverage ranged from 25% to 41% across ethnic groups. After adjusting for sociodemographic factors and health status for people aged 12 years and older, all ethnic groups were more likely to have received a vaccination against influenza than people who self-identified as white, with the exception of those who self-identified as black (odds ratio [OR] 1.01, 95% confidence interval [CI] 0.88–1.15). Compared with white Canadians, Canadians of Filipino (OR 2.00, 95% CI 1.67–2.40) and Southeast Asian (OR 1.66, 95% CI 1.36–2.03) descent had the greatest likelihood of having received vaccination against influenza.
Influenza vaccine coverage in Canada varies by ethnicity. Black and white Canadians have the lowest uptake of influenza vaccine of the ethnic groups represented in our study. Further research is needed to understand the facilitators, barriers and misconceptions relating to vaccination that exist across ethnic groups, and to identify promotional strategies that may improve uptake among black and white Canadians.
Climate and weather influence the occurrence, distribution, and incidence of infectious diseases, particularly those caused by vector-borne or zoonotic pathogens. Thus, models based on meteorological data have helped predict when and where human cases are most likely to occur. Such knowledge aids in targeting limited prevention and control resources and may ultimately reduce the burden of diseases. Paradoxically, localities where such models could yield the greatest benefits, such as tropical regions where morbidity and mortality caused by vector-borne diseases is greatest, often lack high-quality in situ local meteorological data. Satellite- and model-based gridded climate datasets can be used to approximate local meteorological conditions in data-sparse regions, however their accuracy varies. Here we investigate how the selection of a particular dataset can influence the outcomes of disease forecasting models. Our model system focuses on plague (Yersinia pestis infection) in the West Nile region of Uganda. The majority of recent human cases have been reported from East Africa and Madagascar, where meteorological observations are sparse and topography yields complex weather patterns. Using an ensemble of meteorological datasets and model-averaging techniques we find that the number of suspected cases in the West Nile region was negatively associated with dry season rainfall (December-February) and positively with rainfall prior to the plague season. We demonstrate that ensembles of available meteorological datasets can be used to quantify climatic uncertainty and minimize its impacts on infectious disease models. These methods are particularly valuable in regions with sparse observational networks and high morbidity and mortality from vector-borne diseases.
Evidence-based priority setting is increasingly important for rationally distributing scarce health resources and for guiding future health research. We sought to quantify the contribution of a wide range of infectious diseases to the overall infectious disease burden in a high-income setting.
We used health-adjusted life years (HALYs), a composite measure comprising premature mortality and reduced functioning due to disease, to estimate the burden of 51 infectious diseases and associated syndromes in Ontario using 2005–2007 data. Deaths were estimated from vital statistics data and disease incidence was estimated from reportable disease, healthcare utilization, and cancer registry data, supplemented by local modeling studies and national and international epidemiologic studies. The 51 infectious agents and associated syndromes accounted for 729 lost HALYs, 44.2 deaths, and 58,987 incident cases per 100,000 population annually. The most burdensome infectious agents were: hepatitis C virus, Streptococcus pneumoniae, Escherichia coli, human papillomavirus, hepatitis B virus, human immunodeficiency virus, Staphylococcus aureus, influenza virus, Clostridium difficile, and rhinovirus. The top five, ten, and 20 pathogens accounted for 46%, 67%, and 75% of the total infectious disease burden, respectively. Marked sex-specific differences in disease burden were observed for some pathogens. The main limitations of this study were the exclusion of certain infectious diseases due to data availability issues, not considering the impact of co-infections and co-morbidity, and the inability to assess the burden of milder infections that do not result in healthcare utilization.
Infectious diseases continue to cause a substantial health burden in high-income settings such as Ontario. Most of this burden is attributable to a relatively small number of infectious agents, for which many effective interventions have been previously identified. Therefore, these findings should be used to guide public health policy, planning, and research.
Invasive meningococcal disease (IMD) caused by serogroup B is the last major serogroup in Canada to become vaccine-preventable. The anticipated availability of vaccines targeting this serogroup prompted an assessment of the epidemiology of serogroup B disease in Ontario, Canada.
We retrieved information on confirmed IMD cases reported to Ontario’s reportable disease database between January 1, 2000 and December 31, 2010 and probabilistically-linked these cases to Public Health Ontario Laboratory records. Rates were calculated with denominator data obtained from Statistics Canada. We calculated a crude number needed to vaccinate using the inverse of the infant (<1 year) age-specific incidence multiplied by expected vaccine efficacies between 70% and 80%, and assuming only direct protection (no herd effects).
A total of 259 serogroup B IMD cases were identified in Ontario over the 11-year period. Serogroup B was the most common cause of IMD. Incidence ranged from 0.11 to 0.27/100,000/year, and fluctuated over time. Cases ranged in age from 13 days to 101 years; 21.4% occurred in infants, of which 72.7% were <6 months. Infants had the highest incidence (3.70/100,000). Case-fatality ratio was 10.7% overall. If we assume that all infant cases would be preventable by vaccination, we would need to vaccinate between 33,784 and 38,610 infants to prevent one case of disease.
Although rare, the proportion of IMD caused by serogroup B has increased and currently causes most IMD in Ontario, with infants having the highest risk of disease. Although serogroup B meningococcal vaccines are highly anticipated, our findings suggest that decisions regarding publicly funding serogroup B meningococcal vaccines will be difficult and may not be based on disease burden alone.
Invasive meningococcal disease; Neisseria meningitidis; Serogroup B; Epidemiology; Surveillance; Ontario; Canada
Five observational studies from Canada found an association between seasonal influenza vaccine receipt and increased risk of pandemic influenza H1N1 2009 infection. This association remains unexplained. Although uncontrolled confounding has been suggested as a possible explanation, the nature of such confounding has not been identified. Observational studies of influenza vaccination can be affected by confounding due to healthy users and the influence of social determinants on health. The purpose of this study was to investigate the influence that these two potential confounders may have in combination with temporary immunity, using stratified tables. The hypothesis is that respiratory virus infections may activate a temporary immunity that provides short-term non-specific protection against influenza and that the relationship with being a healthy user or having a social determinant may result in confounding.
We simulated the effect of confounding on vaccine effectiveness assuming that this could result from both social determinants and healthy user effects as they both influence the risk of seasonal influenza and non-influenza respiratory virus infections as well as the likelihood of being vaccinated. We then examined what impact this may have had on measurement of seasonal influenza vaccine effectiveness against pandemic influenza.
In this simulation, failure to adjust for healthy users and social determinants would result in an erroneously increased risk of pandemic influenza infection associated with seasonal influenza vaccination. The effect sizes were not however large.
We found that unmeasured healthy user effects and social determinants could result in an apparent association between seasonal influenza vaccine and pandemic influenza infection by virtue of being related to temporary immunity. Adjustment for social determinants of health and the healthy user effects are required in order to improve the quality of observational studies of influenza vaccine effectiveness.
Influenza; Influenza vaccination; Confounding; Epidemiology
Increases in the number of salmonellosis cases due to Salmonella Enteritidis (SE) in 2010 and 2011 prompted a public health investigation in Ontario, Canada. In this report, we describe the current epidemiology of travel-related (TR) SE, compare demographics, symptoms and phage types (PTs) of TR and domestically-acquired (DA) cases, and estimate the odds of acquiring SE by region of the world visited.
All incident cases of culture confirmed SE in Ontario obtained from isolates and specimens submitted to public health laboratories were included in this study. Demographic and illness characteristics of TR and DA cases were compared. A national travel survey was used to provide estimates for the number of travellers to various destinations to approximate rates of SE in travellers. Multivariate logistic regression was used to estimate the odds of acquiring SE when travelling to various world regions.
Overall, 51.9% of SE cases were TR during the study period. This ranged from 35.7% TR cases in the summer travel period to 65.1% TR cases in the winter travel period. Compared to DA cases, TR cases were older and were less likely to seek hospital care. For Ontario travellers, the adjusted odds of acquiring SE was the highest for the Caribbean (OR 37.29, 95% CI 17.87-77.82) when compared to Europe. Certain PTs were more commonly associated with travel (e.g., 1, 4, 5b, 7a, Atypical) than with domestic infection. Of the TR cases, 88.9% were associated with travel to the Caribbean and Mexico region, of whom 90.1% reported staying on a resort. Within this region, there were distinct associations between PTs and countries.
There is a large burden of TR illness from SE in Ontario. Accurate classification of cases by travel history is important to better understand the source of infections. The findings emphasize the need to make travellers, especially to the Caribbean, and health professionals who provide advice to travellers, aware of this risk. The findings may be generalized to other jurisdictions with travel behaviours in their residents similar to Ontario residents.
To determine accuracy of measures of deaths attributable to Clostridium difficile infection, we compared 3 measures for 2007–2008 in Ontario, Canada: death certificate; death within 30 days of infection; and panel review. Data on death within 30 days were more feasible than panel review and more accurate than death certificate data.
Clostridium difficile; mortality; mortality rates; deaths; death certificates; panel review; Ontario; Canada
Efforts must be made to maintain high vaccination coverage.
Diphtheria incidence has decreased in Europe since its resurgence in the 1990s, but circulation continues in some countries in eastern Europe, and sporadic cases have been reported elsewhere. Surveillance data from Diphtheria Surveillance Network countries and the World Health Organization European Region for 2000–2009 were analyzed. Latvia reported the highest annual incidence in Europe each year, but the Russian Federation and Ukraine accounted for 83% of all cases. Over the past 10 years, diphtheria incidence has decreased by >95% across the region. Although most deaths occurred in disease-endemic countries, case-fatality rates were highest in countries to which diphtheria is not endemic, where unfamiliarity can lead to delays in diagnosis and treatment. In western Europe, toxigenic Corynebacterium ulcerans has increasingly been identified as the etiologic agent. Reduction in diphtheria incidence over the past 10 years is encouraging, but maintaining high vaccination coverage is essential to prevent indigenous C. ulcerans and reemergence of C. diphtheriae infections.
diphtheria; Corynebacterium diphtheriae; Corynebacterium ulcerans; bacteria; toxin; surveillance; immunization; vaccination; pseudomembrane; antitoxin; epidemiology; Europe
Live vaccines have distinct safety profiles, potentially causing systemic reactions one to 2 weeks after administration. In the province of Ontario, Canada, live MMR vaccine is currently recommended at age 12 months and 18 months.
Using the self-controlled case series design we examined 271,495 12 month vaccinations and 184,312 18 month vaccinations to examine the relative incidence of the composite endpoint of emergency room visits or hospital admissions in consecutive one day intervals following vaccination. These were compared to a control period 20 to 28 days later. In a post-hoc analysis we examined the reasons for emergency room visits and the average acuity score at presentation for children during the at-risk period following the 12 month vaccine.
Four to 12 days post 12 month vaccination, children had a 1.33 (1.29–1.38) increased relative incidence of the combined endpoint compared to the control period, or at least one event during the risk interval for every 168 children vaccinated. Ten to 12 days post 18 month vaccination, the relative incidence was 1.25 (95%, 1.17–1.33) which represented at least one excess event for every 730 children vaccinated. The primary reason for increased events was statistically significant elevations in emergency room visits following all vaccinations. There were non-significant increases in hospital admissions. There were an additional 20 febrile seizures for every 100,000 vaccinated at 12 months.
There are significantly elevated risks of primarily emergency room visits approximately one to two weeks following 12 and 18 month vaccination. Future studies should examine whether these events could be predicted or prevented.
We evaluated a cohort of Canadian donors for T cell and antibody responses against influenza A/California/7/2009 (pH1N1) at 8-10 months after the 2nd pandemic wave by flow cytometry and microneutralization assays. Memory CD8 T cell responses to pH1N1 were detectable in 58% (61/105) of donors. These responses were largely due to cross-reactive CD8 T cell epitopes as, for those donors tested, similar recall responses were obtained to A/California 2009 and A/PR8 1934 H1N1 Hviruses. Longitudinal analysis of a single infected individual showed only a small and transient increase in neutralizing antibody levels, but a robust CD8 T cell response that rose rapidly post symptom onset, peaking at 3 weeks, followed by a gradual decline to the baseline levels seen in a seroprevalence cohort post-pandemic. The magnitude of the influenza-specific CD8 T cell memory response at one year post-pandemic was similar in cases and controls as well as in vaccinated and unvaccinated donors, suggesting that any T cell boosting from infection was transient. Pandemic H1-specific antibodies were only detectable in approximately half of vaccinated donors. However, those who were vaccinated within a few months following infection had the highest persisting antibody titers, suggesting that vaccination shortly after influenza infection can boost or sustain antibody levels. For the most part the circulating influenza-specific T cell and serum antibody levels in the population at one year post-pandemic were not different between cases and controls, suggesting that natural infection does not lead to higher long term T cell and antibody responses in donors with pre-existing immunity to influenza. However, based on the responses of one longitudinal donor, it is possible for a small population of pre-existing cross-reactive memory CD8 T cells to expand rapidly following infection and this response may aid in viral clearance and contribute to a lessening of disease severity.
We designed a seroprevalence study using multiple testing assays and population sources to estimate the community seroprevalence of pH1N1/09 and risk factors for infection before the outbreak was recognized and throughout the pandemic to the end of 2009/10 influenza season.
Residual serum specimens from five time points (between 01/2009 and 05/2010) and samples from two time points from a prospectively recruited cohort were included. The distribution of risk factors was explored in multivariate adjusted analyses using logistic regression among the cohort. Antibody levels were measured by hemagglutination inhibition (HAI) and microneutralization (MN) assays.
Residual sera from 3375 patients and 1024 prospectively recruited cohort participants were analyzed. Pre-pandemic seroprevalence ranged from 2%–12% across age groups. Overall seropositivity ranged from 10%–19% post-first wave and 32%–41% by the end of the 2009/10 influenza season. Seroprevalence and risk factors differed between MN and HAI assays, particularly in older age groups and between waves. Following the H1N1 vaccination program, higher GMT were noted among vaccinated individuals. Overall, 20–30% of the population was estimated to be infected.
Combining population sources of sera across five time points with prospectively collected epidemiological information yielded a complete description of the evolution of pH1N1 infection.
Infection of the CNS is considered to be the major cause of encephalitis and more than 100 different pathogens have been recognized as causative agents. Despite being identified worldwide as an important public health concern, studies on encephalitis are very few and often focus on particular types (with respect to causative agents) of encephalitis (e.g. West Nile, Japanese, etc.). Moreover, a number of other infectious and non-infectious conditions present with similar symptoms, and distinguishing encephalitis from other disguising conditions continues to a challenging task.
We used canonical correlation analysis (CCA) to assess associations between set of exposure variable and set of symptom and diagnostic variables in human encephalitis. Data consists of 208 confirmed cases of encephalitis from a prospective multicenter study conducted in the United Kingdom. We used a covariance matrix based on Gini's measure of similarity and used permutation based approaches to test significance of canonical variates.
Results show that weak pair-wise correlation exists between the risk factor (exposure and demographic) and symptom/laboratory variables. However, the first canonical variate from CCA revealed strong multivariate correlation (ρ = 0.71, se = 0.03, p = 0.013) between the two sets. We found a moderate correlation (ρ = 0.54, se = 0.02) between the variables in the second canonical variate, however, the value is not statistically significant (p = 0.68). Our results also show that a very small amount of the variation in the symptom sets is explained by the exposure variables. This indicates that host factors, rather than environmental factors might be important towards understanding the etiology of encephalitis and facilitate early diagnosis and treatment of encephalitis patients.
There is no standard laboratory diagnostic strategy for investigation of encephalitis and even experienced physicians are often uncertain about the cause, appropriate therapy and prognosis of encephalitis. Exploration of human encephalitis data using advanced multivariate statistical modelling approaches that can capture the inherent complexity in the data is, therefore, crucial in understanding the causes of human encephalitis. Moreover, application of multivariate exploratory techniques will generate clinically important hypotheses and offer useful insight into the number and nature of variables worthy of further consideration in a confirmatory statistical analysis.
This investigation was done to assess vaccine effectiveness of one and two doses of the measles, mumps and rubella (MMR) vaccine during an outbreak of mumps in Ontario. The level of coverage required to reach herd immunity and interrupt community transmission of mumps was also estimated.
Information on confirmed cases of mumps was retrieved from Ontario’s integrated Public Health Information System. Cases that occurred between Sept. 1, 2009, and June 10, 2010, were included. Selected health units supplied coverage data from the Ontario Immunization Record Information System. Vaccine effectiveness by dose was calculated using the screening method. The basic reproductive number (R0) represents the average number of new infections per case in a fully susceptile population, and R0 values of between 4 and 10 were considered for varying levels of vaccine effectiveness.
A total of 134 confirmed cases of mumps were identified. Information on receipt of MMR vaccine was available for 114 (85.1%) cases, of whom 63 (55.3%) reported having received only one dose of vaccine; 32 (28.1%) reported having received two doses. Vaccine effectiveness of one dose of the MMR vaccine ranged from 49.2% to 81.6%, whereas vaccine effectiveness of two doses ranged from 66.3% to 88.0%. If we assume vaccine effectiveness of 85% for two doses of the vaccine, vaccine coverage of 88.2% and 98.0% would be needed to interrupt community transmission of mumps if the corresponding reproductive values were four and six.
Our estimates of vaccine effectiveness of one and two doses of mumps-containing vaccine were consistent with the estimates that have been reported in other outbreaks. Outbreaks occurring in Ontario and elsewhere serve as a warning against complacency over vaccination programs.
The province of Ontario, Canada initiated mass immunization clinics with adjuvanted pandemic H1N1 influenza vaccine in October 2009. Due to the scale of the campaign, temporal associations with Guillain-Barré syndrome (GBS) and vaccination were expected. The objectives of this analysis were to estimate the number of background GBS cases expected to occur in the projected vaccinated population and to estimate the number of additional GBS cases which would be expected if an association with vaccination existed. The number of influenza-associated GBS cases was also determined.
Baseline incidence rates of GBS were determined from published Canadian studies and applied to projected vaccine coverage data to estimate the expected number of GBS cases in the vaccinated population. Assuming an association with vaccine existed, the number of additional cases of GBS expected was determined by applying the rates observed during the 1976 Swine Flu and 1992/1994 seasonal influenza campaigns in the United States. The number of influenza-associated GBS cases expected to occur during the vaccination campaign was determined based on risk estimates of GBS after influenza infection and provincial influenza infection rates using a combination of laboratory-confirmed cases and data from a seroprevalence study.
The overall provincial vaccine coverage was estimated to be between 32% and 38%. Assuming 38% coverage, between 6 and 13 background cases of GBS were expected within this projected vaccinated cohort (assuming 32% coverage yielded between 5-11 background cases). An additional 6 or 42 cases would be expected if an association between GBS and influenza vaccine was observed (assuming 32% coverage yielded 5 or 35 additional cases); while up to 31 influenza-associated GBS cases could be expected to occur. In comparison, during the same period, only 7 cases of GBS were reported among vaccinated persons.
Our analyses do not suggest an increased number of GBS cases due to the vaccine. Awareness of expected rates of GBS is crucial when assessing adverse events following influenza immunization. Furthermore, since individuals with influenza infection are also at risk of developing GBS, they must be considered in such analyses, particularly if the vaccine campaign and disease are occurring concurrently.
Understanding transmission dynamics of the pandemic influenza A (H1N1) virus in various exposure settings and determining whether transmissibility differed from seasonal influenza viruses was a priority for decision making on mitigation strategies at the beginning of the pandemic. The objective of this study was to estimate household secondary attack rates for pandemic influenza in a susceptible population where control measures had yet to be implemented.
All Ontario local health units were invited to participate; seven health units volunteered. For all laboratory-confirmed cases reported between April 24 and June 18, 2009, participating health units performed contact tracing to detect secondary cases among household contacts. In total, 87 cases and 266 household contacts were included in this study. Secondary cases were defined as any household member with new onset of acute respiratory illness (fever or two or more respiratory symptoms) or influenza-like illness (fever plus one additional respiratory symptom). Attack rates were estimated using both case definitions.
Secondary attack rates were estimated at 10.3% (95% CI 6.8-14.7) for secondary cases with influenza-like illness and 20.2% (95% CI 15.4-25.6) for secondary cases with acute respiratory illness. For both case definitions, attack rates were significantly higher in children under 16 years than adults (25.4% and 42.4% compared to 7.6% and 17.2%). The median time between symptom onset in the primary case and the secondary case was estimated at 3.0 days.
Secondary attack rates for pandemic influenza A (H1N1) were comparable to seasonal influenza estimates suggesting similarities in transmission. High secondary attack rates in children provide additional support for increased susceptibility to infection.
Objective To assess the effectiveness of the pandemic influenza A/H1N1 vaccine used in Canada during autumn 2009.
Design Test negative incident case-control study based on sentinel physician surveillance system.
Setting Community based clinics contributing to sentinel networks in British Columbia, Alberta, Ontario, and Quebec, Canada.
Participants 552 patients who presented to a sentinel site within seven days of onset of influenza-like illness during the primary analysis period between 8 November and 5 December 2009; participants were mostly (>80%) children and adults under 50 years old.
Interventions Monovalent AS03 adjuvanted pandemic influenza A/H1N1 vaccine as the predominant formulation (>95%) distributed in Canada.
Main outcome measures Vaccine effectiveness calculated as 1−(odds ratio for influenza in vaccinated (received pandemic H1N1 vaccine at least two weeks before onset of influenza-like illness) versus unvaccinated participants), with adjustment for age, comorbidity, province, timeliness of specimen collection, and week of illness onset. Sensitivity analyses explored the influence of varying analysis periods between 1 November and 31 December, receipt of trivalent seasonal influenza vaccine, and restriction to participants without comorbidity.
Results During the primary analysis period, pandemic H1N1 was detected by reverse transcription polymerase chain reaction in 209/552 (38%) participants; rates were highest in children and young adults (40%) and lowest in people aged 65 or over (9%). Among the 209 cases, 35 (17%) reported comorbidity compared with 80/343 (23%) controls. Two (1%) cases had received pandemic H1N1 vaccine at least two weeks before the onset of illness, compared with 58/343 (17%) controls, all single dose. Adjusted vaccine effectiveness overall was 93% (95% confidence interval 69% to 98%). High estimates of vaccine protection—generally at least 90%—were maintained across most sensitivity analyses.
Conclusions Although limited by a small number of vaccine failures, this study suggests that the monovalent AS03 adjuvanted vaccine used in Canada during autumn 2009 was highly effective in preventing medically attended, laboratory confirmed pandemic H1N1 illness, with reference in particular to a single dose in children and young adults.
Encephalitis is an acute clinical syndrome of the central nervous system (CNS), often associated with fatal outcome or permanent damage, including cognitive and behavioural impairment, affective disorders and epileptic seizures. Infection of the central nervous system is considered to be a major cause of encephalitis and more than 100 different pathogens have been recognized as causative agents. However, a large proportion of cases have unknown disease etiology.
We perform hierarchical cluster analysis on a multicenter England encephalitis data set with the aim of identifying sub-groups in human encephalitis. We use the simple matching similarity measure which is appropriate for binary data sets and performed variable selection using cluster heatmaps. We also use heatmaps to visually assess underlying patterns in the data, identify the main clinical and laboratory features and identify potential risk factors associated with encephalitis.
Our results identified fever, personality and behavioural change, headache and lethargy as the main characteristics of encephalitis. Diagnostic variables such as brain scan and measurements from cerebrospinal fluids are also identified as main indicators of encephalitis. Our analysis revealed six major clusters in the England encephalitis data set. However, marked within-cluster heterogeneity is observed in some of the big clusters indicating possible sub-groups. Overall, the results show that patients are clustered according to symptom and diagnostic variables rather than causal agents. Exposure variables such as recent infection, sick person contact and animal contact have been identified as potential risk factors.
It is in general assumed and is a common practice to group encephalitis cases according to disease etiology. However, our results indicate that patients are clustered with respect to mainly symptom and diagnostic variables rather than causal agents. These similarities and/or differences with respect to symptom and diagnostic measurements might be attributed to host factors. The idea that characteristics of the host may be more important than the pathogen is also consistent with the observation that for some causes, such as herpes simplex virus (HSV), encephalitis is a rare outcome of a common infection.
To obtain information on the use of single antigen measles, mumps and rubella vaccines to improve estimates of population immunity and help predict outbreaks.
We requested information from providers of single antigen vaccines and from the Medicine and Healthcare products Regulatory Agency on requests for importation of single antigen measles and mumps vaccines.
England and Wales.
Main outcome measures
Number of doses of single measles, mumps and rubella vaccine, by age of child (in months), year given and area of residence, and number of children who have received all three single vaccinations.
Of 27 providers identified, 13 held single site clinics: nine were individual general practitioners and five held clinics at multiple sites. Data were received from 9/27 (33%) providers operating 40/74 (54%) clinic sites. We received information on 60 768 vaccinations administered by single vaccine providers and 269 917 doses requested for importation. For children born in 2001/2002, the minimum estimates for the proportion who received single measles vaccine are 1.7% in 2001 and 2.1% in 2002, with a reasonable maximum estimate of 5.6% over the 2 years. For single mumps vaccine, the minimum estimates are 0.3% in 2001 and 0.02% in 2002, with a maximum estimate of 4.0%.
The contribution of single vaccines to immunity is small in comparison to that of the combined measles, mumps and rubella vaccine (MMR). For recent birth cohorts this contribution could increase routine coverage for measles‐containing vaccines by around 2%, still below the level of immunity required to sustain elimination.
measles vaccine; mumps vaccine; rubella vaccine; MMR vaccine; vaccination coverage
Immunization information systems (IISs) are electronic registries used to monitor individual vaccination status and assess vaccine coverage. IISs are currently not widely used across Canada, where health jurisdictions employ a range of approaches to capture influenza immunization information. Conducted in advance of the 2009 H1N1 vaccination campaign, the objectives of this study were to understand the perceived value of individual-level data and IISs for influenza control, identify ideal system functions, and explore barriers to implementation.
In July and August 2009, semi-structured interviews were conducted with key informants engaged in vaccine delivery and/or pandemic planning at regional, provincial/territorial and federal levels across Canada. Key informants were recruited using a combination of convenience and snowball sampling methodologies. Qualitative analysis was used to extract themes from interview content.
Patient management, assessment of vaccine coverage, and evaluation of safety and effectiveness were identified as public health priorities that would be achieved in a more timely manner, and with greater accuracy, through the use of an IIS. Features described as ideal included system flexibility, rapid data entry, and universality. Financial and human resource constraints as well as coordination between immunization providers were expressed as barriers to implementation.
IISs were perceived as valuable by key informants for strengthening management capacity and improving evaluation of both seasonal and pandemic influenza vaccination campaigns. However, certain implementation restrictions may need to be overcome for these benefits to be achieved.
To assess the knowledge and current tetanus prevention practices of various staff members in accident and emergency (A&E) departments.
Design, setting and participants
A structured questionnaire containing 16 questions on tetanus guidance, anti‐tetanus practice, vaccination preparations and information on the population served by the department was sent to medical and nursing staff in A&E departments across England.
366 completed questionnaires from 67 hospitals were returned. 48.9% of the questionnaires were completed by the medical staff and 39.9% by the nursing staff at various grades. 75% of respondents said that their department had a local tetanus guideline, but only 29% stated that the tetanus guidelines were always followed. 31.4% of respondents said that injecting drug users were managed as a high‐risk group in their department. Many respondents did not follow the national policy; they tended to err on the side of caution when it came to defining and treating tetanus‐prone wounds, with 22.1% stating that they would consider any wound tetanus prone. Contrary to current Department of Health guidelines, 46.2% of respondents said that they would give a booster dose if the fifth dose had been given >10 years ago.
There are clear differences between the recommended guidelines for tetanus prevention and current practice in A&E departments. The changes announced in 2002 do not seem to have been widely implemented. As a result, the apparent success of the national tetanus vaccination programme may be the result of more cautious clinical practice than would be expected from the UK policy. If national recommendations for tetanus are implemented in clinical practice, then the impact on control of the disease should be monitored closely.