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1.  Parental perceptions of school-based influenza immunisation in Ontario, Canada: a qualitative study 
BMJ Open  2014;4(6):e005189.
To understand the perspectives of Ontario parents regarding the advantages and disadvantages of adding influenza immunisation to the currently existing Ontario school-based immunisation programmes.
Descriptive qualitative study.
Parents of school-age children in Ontario, Canada, who were recruited using a variety of electronic strategies (social media, emails and media releases), and identified as eligible (Ontario resident, parent of one or more school-age children, able to read/write English) on the basis of a screening questionnaire. We used stratified purposeful sampling to obtain maximum variation in two groups: parents who had ever immunised at least one child against influenza or who had never done so. We conducted focus groups (teleconference or internet forum) and individual interviews to collect data. Thematic analysis was used to analyse the data.
Ontario, Canada.
Of the 55 participants, 16 took part in four teleconference focus groups, 35 in 6 internet forum focus groups and four in individual interviews conducted between October 2012 and February 2013. Participants who stated that a school-based influenza immunisation programme would be worthwhile for their child valued its convenience and its potential to reduce influenza transmission without interfering with the family routine. However, most thought that for a programme to be acceptable, it would need to be well designed and voluntary, with adequate parental control and transparent communication between the key stakeholder groups of public health, schools and parents.
These results will benefit decision-makers in the public health and education sectors as they consider the advantages and disadvantages of immunising children in schools as part of a system-wide influenza prevention approach. Further research is needed to assess the perceptions of school board and public health stakeholders.
PMCID: PMC4054656  PMID: 24902736
2.  Oral Fluid Testing for Pertussis, England and Wales, June 2007–August 2009  
Emerging Infectious Diseases  2014;20(6):968-975.
Existing pertussis surveillance systems tend to underidentify less severe cases among older children and adults. For routine follow-up of notified, nonconfirmed, clinically diagnosed pertussis cases, use of an oral fluid test was pilot tested in England and Wales during June 2007–August 2009. During that period, 1,852 cases of pertussis were confirmed by established laboratory methods and another 591 by oral fluid testing only. Although introduction of serologic testing in 2002 led to the greatest increase in ascertainment of pertussis, oral fluid testing increased laboratory ascertainment by 32% overall; maximal increase (124%) occurred among children 5–9 years of age. Patients whose pertussis was confirmed by oral fluid testing were least likely to be hospitalized, suggesting that milder community cases were being confirmed by this method. Oral fluid testing is an easily administered, noninvasive surveillance tool that could further our understanding of pertussis epidemiology and thereby contribute to decisions on vaccination strategies.
PMCID: PMC4036755  PMID: 24856627
3.  Ethnic disparities in acquiring 2009 pandemic H1N1 influenza: a case–control study 
BMC Public Health  2014;14:214.
Novel risk factors were associated with the 2009 pandemic A/H1N1 virus (pH1N1). Ethnicity was among these risk factors. Ethnic disparities in hospitalization and death due to pH1N1 were noted. The purpose of this study is to determine whether there are ethnic disparities in acquiring the 2009 pandemic H1N1.
We conducted a test-negative case–control study of the risk of pH1N1 infection using data from Ontario, Canada. Cases were laboratory confirmed to have influenza using reverse-transcriptase polymerase chain reaction (RT-PCR), and controls were obtained from the same population and were RT-PCR negative. Multivariate logistic regression was used to determine the association between ethnicity and pH1N1 infection, while adjusting for demographic, clinical and ecological covariates.
Adult cases were more likely than controls to be self-classified as East/Southeast Asian (OR = 2.59, 95% CI 1.02-6.57), South Asian (OR = 6.22, 95% CI 2.01-19.24) and Black (OR = 9.72, 95% CI 2.29-41.27). Pediatric cases were more likely to be self-identified as Black (OR = 6.43, 95% CI 1.83-22.59). However, pediatric cases without risk factors for severe influenza infection were more likely to be South Asian (OR 2.92, 95% CI 1.11-7.68), Black (OR 16.02, 95% CI 2.85-89.92), and West Asian/Arab, Latin American or Multi-racial groups (OR 3.09 95% CI 1.06-9.00).
pH1N1 cases were more likely to come from certain ethnic groups compared to test-negative controls. Insights into whether these disparities arise due to social or biological factors are needed in order to understand what approaches can be taken to reduce the burden of a future influenza pandemic.
PMCID: PMC3942768  PMID: 24580862
Influenza; Ethnicity; Epidemiology
4.  Low Prevalence of Liver Disease but Regional Differences in HBV Treatment Characteristics Mark HIV/HBV Co-Infection in a South African HIV Clinical Trial 
PLoS ONE  2013;8(12):e74900.
Hepatitis B virus (HBV) infection is endemic in South Africa however, there is limited data on the degree of liver disease and geographic variation in HIV/HBV coinfected individuals. In this study, we analysed data from the CIPRA-SA ‘Safeguard the household study’ in order to assess baseline HBV characteristics in HIV/HBV co-infection participants prior to antiretroviral therapy (ART) initiation.
812 participants from two South African townships Soweto and Masiphumelele were enrolled in a randomized trial of ART (CIPRA-SA). Participants were tested for hepatitis B surface antigen (HBsAg), hepatitis B e antigen (HBeAg), and HBV DNA. FIB-4 scores were calculated at baseline.
Forty-eight (5.9%) were HBsAg positive, of whom 28 (58.3%) were HBeAg positive. Of those with HBV, 29.8% had an HBV DNA<2000 IU/ml and ALT<40 IU/ml ; 83.0% had a FIB-4 score <1.45, consistent with absent or minimal liver disease. HBV prevalence was 8.5% in Masiphumelele compared to 3.8% in Soweto (relative risk 2.3; 95% CI: 1.3–4.0). More participants in Masiphumelele had HBeAg-negative disease (58% vs. 12%, p = 0.002) and HBV DNA levels ≤2000 IU/ml, (43% vs. 6% p<0.007).
One third of HIV/HBV co-infected subjects had low HBV DNA levels and ALT while the majority had indicators of only mild liver disease. There were substantial regional differences in HBsAg and HbeAg prevalence in HIV/HBV co-infection between two regions in South Africa. This study highlights the absence of severe liver disease and the marked regional differences in HIV/HBV co-infection in South Africa and will inform treatment decisions in these populations.
PMCID: PMC3855615  PMID: 24324573
5.  Association between Birth Order and Emergency Room Visits and Acute Hospital Admissions following Pediatric Vaccination: A Self-Controlled Study 
PLoS ONE  2013;8(12):e81070.
We investigated the association between a child's birth order and emergency room (ER) visits and hospital admissions following 2-,4-,6- and 12-month pediatric vaccinations.
We included all children born in Ontario between April 1st, 2006 and March 31st, 2009 who received a qualifying vaccination. We identified vaccinations, ER visits and admissions using health administrative data housed at the Institute for Clinical Evaluative Sciences. We used the self-controlled case series design to compare the relative incidence (RI) of events among 1st-born and later-born children using relative incidence ratios (RIR).
For the 2-month vaccination, the RIR for 1st-borns versus later-born children was 1.37 (95% CI: 1.19–1.57), which translates to 112 additional events/100,000 vaccinated. For the 4-month vaccination, the RIR for 1st-borns vs. later-borns was 1.70 (95% CI: 1.45–1.99), representing 157 additional events/100,000 vaccinated. At 6 months, the RIR for 1st vs. later-borns was 1.27 (95% CI: 1.09–1.48), or 77 excess events/100,000 vaccinated. At the 12-month vaccination, the RIR was 1.11 (95% CI: 1.02–1.21), or 249 excess events/100,000 vaccinated.
Birth order is associated with increased incidence of ER visits and hospitalizations following vaccination in infancy. 1st-born children had significantly higher relative incidence of events compared to later-born children.
PMCID: PMC3852020  PMID: 24324662
6.  New Estimates of Incidence of Encephalitis in England 
Emerging Infectious Diseases  2013;19(9):1455-1462.
Encephalitis causes high rates of illness and death, yet its epidemiology remains poorly understood. To improve incidence estimates in England and inform priority setting and treatment and prevention strategies, we used hospitalization data to estimate incidence of infectious and noninfectious encephalitis during 2005–2009. Hospitalization data were linked to a dataset of extensively investigated cases of encephalitis from a prospective study, and capture–recapture models were applied. Incidence was estimated from unlinked hospitalization data as 4.32 cases/100,000 population/year. Capture–recapture models gave a best estimate of encephalitis incidence of 5.23 cases/100,000/year, although the models’ indicated incidence could be as high as 8.66 cases/100,000/year. This analysis indicates that the incidence of encephalitis in England is considerably higher than previously estimated. Therefore, encephalitis should be a greater priority for clinicians, researchers, and public health officials.
PMCID: PMC3810913  PMID: 23969035
encephalitis; incidence studies; viral infections; autoimmune diseases; acute disseminated encephalomyelitis; neurological; viruses
7.  Get the News Out Loudly and Quickly: The Influence of the Media on Limiting Emerging Infectious Disease Outbreaks 
PLoS ONE  2013;8(8):e71692.
During outbreaks of infectious diseases with high morbidity and mortality, individuals closely follow media reports of the outbreak. Many will attempt to minimize contacts with other individuals in order to protect themselves from infection and possibly death. This process is called social distancing. Social distancing strategies include restricting socializing and travel, and using barrier protections. We use modeling to show that for short-term outbreaks, social distancing can have a large influence on reducing outbreak morbidity and mortality. In particular, public health agencies working together with the media can significantly reduce the severity of an outbreak by providing timely accounts of new infections and deaths. Our models show that the most effective strategy to reduce infections is to provide this information as early as possible, though providing it well into the course of the outbreak can still have a significant effect. However, our models for long-term outbreaks indicate that reporting historic infection data can result in more infections than with no reporting at all. We examine three types of media influence and we illustrate the media influence with a simulated outbreak of a generic emerging infectious disease in a small city. Social distancing can never be complete; however, for a spectrum of outbreaks, we show that leaving isolation (stopping applying social distancing measures) for up to 4 hours each day has modest effect on the overall morbidity and mortality.
PMCID: PMC3753329  PMID: 23990974
8.  The Expected Number of Background Disease Events during Mass Immunization in China 
PLoS ONE  2013;8(8):e71818.
It is critical to distinguish events that are temporarily associated with, but not caused by, vaccination from those caused by vaccination during mass immunization. We performed a literature search in China National Knowledge Infrastructure and Pubmed databases. The number of coincident events was calculated based on its incidence rate and periods after receipt of a dose of hypothesized vaccine. We included background incidences of Guillain-Barré syndrome, anaphylaxis, seizure, sudden adult death syndrome, sudden cardiac death, spontaneous abortion, and preterm labour or delivery. In a cohort of 10 million individuals, 7.71 cases of Guillain-Barré syndrome would be expected to occur within six weeks of vaccination as coincident background cases. Even for rare events, a large number of events can be expected in a short period because of the large population targeted for immunization. These findings may encourage health authorities to screen the safety of vaccines against unpredictable pathogens.
PMCID: PMC3748117  PMID: 23977153
9.  Rubella immunity among prenatal women in Ontario, 2006–2010 
BMC Infectious Diseases  2013;13:362.
Countries of the Americas have been working towards rubella elimination since 2003 and endemic rubella virus transmission appears to have been interrupted since 2009. To contribute towards monitoring of rubella elimination, we assessed rubella seroprevalence among prenatal screening tests performed in Ontario.
Specimens received for prenatal rubella serologic testing at the Public Health Ontario Laboratory, the provincial reference laboratory, between 2006 and 2010 were analyzed. A patient-based dataset was created using all tests occurring among 15–49 year-old females, where prenatal screening was indicated. Multiple tests were assigned to the same patient on the basis of health card number, name and date of birth. Only unique tests performed at least nine months apart were included. SAS version 9.2 was used for analysis.
Between 2006 and 2010, we identified 459,963 women who underwent 551,160 unique prenatal screening tests for rubella. Of these, 81.6%, 17.1% and 1.4% had one, two and three or more tests respectively.
Rubella immunity remained stable at approximately 90% overall; the proportion of susceptible women was 4.4%. Additionally, 0.6% of women were initially susceptible and subsequently developed immunity. Across the province, susceptibility was highest in the north and declined with increasing age (p < 0.0001). Among women with multiple tests, the proportion who remained susceptible declined as the number of years between tests increased (p < .0001). Based on age at first test, younger women had the highest susceptibility (4.2% among 15–19 year-olds) and were significantly more likely to develop immunity if previously susceptible (p < .0001).
Rubella susceptibility among prenatal women in Ontario supports elimination goals as population immunity in this group is relatively high. Higher susceptibility among young women and women living in the north highlights an opportunity for greater focus on identification and immunization of susceptible women in these groups.
PMCID: PMC3735453  PMID: 23914729
Rubella; Seroprevalence study; Prenatal screening; Rubella elimination goals; Ontario; Canada
10.  Vaccine Effectiveness Against Laboratory-Confirmed Influenza Hospitalizations Among Elderly Adults During the 2010–2011 Season 
Although the benefits of influenza vaccines for preventing serious influenza outcomes in elderly adults are uncertain, the results of this study suggest that the 2010–2011 influenza vaccine was 42% effective in reducing laboratory-confirmed influenza hospitalizations in this high-risk population.
Background. Although annual influenza immunization is recommended for adults aged ≥65 years due to the substantial burden of illness, the evidence base for this recommendation is weak. Prior observational studies that examined influenza vaccine effectiveness against nonspecific serious outcomes suffered from selection bias and the lack of laboratory confirmation for influenza infection. The objective of this study was to determine the effectiveness of the 2010–2011 seasonal influenza vaccine against laboratory-confirmed influenza hospitalizations among community-dwelling elderly adults, a serious and highly specific outcome.
Methods. We conducted a test-negative study of community-dwelling adults aged >65 years in Ontario, Canada. Respiratory specimens collected between 1 December 2010 and 30 April 2011 from patients admitted to acute care hospitals were tested for influenza using nucleic acid amplification techniques. Influenza vaccination was ascertained from physician billing claims through linkage to health administrative datasets.
Results. Receipt of the 2010–2011 seasonal influenza vaccine was associated with a 42% (95% confidence interval, 29%–53%) reduction in laboratory-confirmed influenza hospitalizations. Vaccine effectiveness estimates were consistent across age groups, by sex, and regardless of outcome severity, timing of testing, and when considering individuals vaccinated <7 or <14 days prior to admission as unvaccinated.
Conclusions. Results of this study will better inform decision making regarding influenza vaccination of elderly adults. Similar analyses are needed annually due to antigenic drift and frequent changes in influenza vaccine composition. The linkage of routinely collected laboratory testing and health administrative data represents an efficient method for estimating influenza vaccine effectiveness that complements prospective studies.
PMCID: PMC3749748  PMID: 23788243
influenza vaccine; hospitalization; vaccine effectiveness; elderly adults
11.  Contagious Comments: What Was the Online Buzz About the 2011 Quebec Measles Outbreak? 
PLoS ONE  2013;8(5):e64072.
Although interruption of endemic measles was achieved in the Americas in 2002, Quebec experienced an outbreak in 2011 of 776 reported cases; 80% of these individuals had not been fully vaccinated. We analyzed readers’ online responses to Canadian news articles regarding the outbreak to better understand public perceptions of measles and vaccination.
We searched Canadian online English and French news sites for articles posted between April 2011 and March 2012 containing the words “measles” and “Quebec”. We included articles that i) concerned the outbreak or related vaccination strategies; and ii) generated at least ten comments. Two English and two bilingual researchers coded the unedited comments, categorizing codes to allow themes to emerge.
We analyzed 448 comments from 188 individuals, in response to three French articles and six English articles; 112 individuals expressed positive perceptions of measles vaccination (2.2 comments/person), 38 were negative (4.2 comments/person), 11 had mixed feelings (1.5 comments/person), and 27 expressed no opinion (1.1 comments/person). Vaccine-supportive themes involved the success of vaccination in preventing disease spread, societal responsibility to vaccinate for herd immunity, and refutation of the autism link. Those against measles vaccination felt it was a personal rather than societal choice, and conveyed a distrust of vaccine manufacturers, believing that measles infection is not only safe but safer than vaccination. Commenters with mixed feelings expressed uncertainty of the infection’s severity, and varied in support of all vaccines based on perceived risk/benefit ratios.
The anti-vaccine minority’s volume of comments translates to a disproportionately high representation on online boards. Public health messages should address concerns by emphasizing that immunization is always a personal choice in Canada, and that the pharmaceutical industry is strictly controlled. Illustrating the dangers of measles through personal stories, rather than scientific data only, may also serve to strengthen messaging.
PMCID: PMC3654905  PMID: 23691152
13.  Maternal Tetanus Toxoid Vaccination and Neonatal Mortality in Rural North India 
PLoS ONE  2012;7(11):e48891.
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.
PMCID: PMC3494717  PMID: 23152814
14.  Human papilloma virus vaccination programs reduce health inequity in most scenarios: a simulation study 
BMC Public Health  2012;12:935.
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.
PMCID: PMC3529110  PMID: 23113881
15.  The use of syndromic surveillance for decision-making during the H1N1 pandemic: A qualitative study 
BMC Public Health  2012;12:929.
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.
PMCID: PMC3539916  PMID: 23110473
Decision making; Pandemic influenza; Public health; Surveillance; Syndromic surveillance
16.  Meningococcal Factor H Binding Protein fHbpd184 Polymorphism Influences Clinical Course of Meningococcal Meningitis 
PLoS ONE  2012;7(10):e47973.
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.
PMCID: PMC3479137  PMID: 23110143
17.  Influenza vaccination coverage across ethnic groups in Canada 
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.
PMCID: PMC3478352  PMID: 22966054
18.  Improvement of Disease Prediction and Modeling through the Use of Meteorological Ensembles: Human Plague in Uganda 
PLoS ONE  2012;7(9):e44431.
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.
PMCID: PMC3443104  PMID: 23024750
19.  The Impact of Infection on Population Health: Results of the Ontario Burden of Infectious Diseases Study 
PLoS ONE  2012;7(9):e44103.
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.
Methodology/Principal Findings
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.
PMCID: PMC3433488  PMID: 22962601
20.  Epidemiology of serogroup B invasive meningococcal disease in Ontario, Canada, 2000 to 2010 
BMC Infectious Diseases  2012;12:202.
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.
PMCID: PMC3472197  PMID: 22928839
Invasive meningococcal disease; Neisseria meningitidis; Serogroup B; Epidemiology; Surveillance; Ontario; Canada
21.  The potential effect of temporary immunity as a result of bias associated with healthy users and social determinants on observations of influenza vaccine effectiveness; could unmeasured confounding explain observed links between seasonal influenza vaccine and pandemic H1N1 infection? 
BMC Public Health  2012;12:458.
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.
PMCID: PMC3490826  PMID: 22716096
Influenza; Influenza vaccination; Confounding; Epidemiology
22.  The epidemiology of travel-related Salmonella Enteritidis in Ontario, Canada, 2010–2011 
BMC Public Health  2012;12:310.
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.
PMCID: PMC3356229  PMID: 22537320
23.  Determining Mortality Rates Attributable to Clostridium difficile Infection 
Emerging Infectious Diseases  2012;18(2):305-307.
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.
PMCID: PMC3310441  PMID: 22305427
Clostridium difficile; mortality; mortality rates; deaths; death certificates; panel review; Ontario; Canada
24.  Diphtheria in the Postepidemic Period, Europe, 2000–2009 
Emerging Infectious Diseases  2012;18(2):217-225.
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.
PMCID: PMC3310452  PMID: 22304732
diphtheria; Corynebacterium diphtheriae; Corynebacterium ulcerans; bacteria; toxin; surveillance; immunization; vaccination; pseudomembrane; antitoxin; epidemiology; Europe
25.  Adverse Events following 12 and 18 Month Vaccinations: a Population-Based, Self-Controlled Case Series Analysis 
PLoS ONE  2011;6(12):e27897.
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.
PMCID: PMC3236196  PMID: 22174753

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