Adverse events following 12 and 18 month vaccinations: a population-based, self-controlled case series analysis

Background

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.

Methods

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.

Results

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.

Conclusions

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.     

Post-pandemic seroprevalence of pandemic influenza A (H1N1) 2009 infection (swine flu) among children <18 years in Germany

Background

We determined antibodies to the pandemic influenza A (H1N1) 2009 virus in children to assess: the incidence of (H1N1) 2009 infections in the 2009/2010 season in Germany, the proportion of subclinical infections and to compare titers in vaccinated and infected children.

Methodology/Principal Findings

Eight pediatric hospitals distributed over Germany prospectively provided sera from in- or outpatients aged 1 to 17 years from April 1^st to July 31^st 2010. Vaccination history, recall of infections and sociodemographic factors were ascertained. Antibody titers were measured with a sensitive and specific in-house hemagglutination inhibition test (HIT) and compared to age-matched sera collected during 6 months before the onset of the pandemic in Germany. We analyzed 1420 post-pandemic and 300 pre-pandemic sera. Among unvaccinated children aged 1–4 and 5–17 years the prevalence of HI titers (≥1∶10) was 27.1% (95% CI: 23.5–31.3) and 53.5% (95% CI: 50.9–56.2) compared to 1.7% and 5.5%, respectively, for pre-pandemic sera, accounting for a serologically determined incidence of influenza A (H1N1) 2009 during the season 2009/2010 of 25,4% (95% CI : 19.3–30.5) in children aged 1–4 years and 48.0% (95% CI: 42.6–52.0) in 5–17 year old children. Of children with HI titers ≥1∶10, 25.5% (95% CI: 22.5–28.8) reported no history of any infectious disease since June 2009. Among vaccinated children, 92% (95%-CI: 87.0–96.6) of the 5–17 year old but only 47.8% (95%-CI: 33.5–66.5) of the 1–4 year old children exhibited HI titers against influenza A virus (H1N1) 2009.

Conclusion

Serologically determined incidence of influenza A (H1N1) 2009 infections in children indicates high infection rates with older children (5–17 years) infected twice as often as younger children. In about a quarter of the children with HI titers after the season 2009/2010 subclinical infections must be assumed. Low HI titers in young children after vaccination with the AS03_B-adjuvanted split virion vaccine need further scrutiny.     

Stevens-Johnson Syndrome Associated with Drugs and Vaccines in Children: A Case-Control Study

Objective

Stevens-Johnson Syndrome (SJS) is one of the most severe muco-cutaneous diseases and its occurrence is often attributed to drug use. The aim of the present study is to quantify the risk of SJS in association with drug and vaccine use in children.

Methods

A multicenter surveillance of children hospitalized through the emergency departments for acute conditions of interest is currently ongoing in Italy. Cases with a diagnosis of SJS were retrieved from all admissions. Parents were interviewed on child’s use of drugs and vaccines preceding the onset of symptoms that led to the hospitalization. We compared the use of drugs and vaccines in cases with the corresponding use in a control group of children hospitalized for acute neurological conditions.

Results

Twenty-nine children with a diagnosis of SJS and 1,362 with neurological disorders were hospitalized between 1^st November 1999 and 31^st October 2012. Cases were more frequently exposed to drugs (79% vs 58% in the control group; adjusted OR 2.4; 95% CI 1.0–6.1). Anticonvulsants presented the highest adjusted OR: 26.8 (95% CI 8.4–86.0). Significantly elevated risks were also estimated for antibiotics use (adjusted OR 3.3; 95% CI 1.5–7.2), corticosteroids (adjusted OR 4.2; 95% CI 1.8–9.9) and paracetamol (adjusted OR 3.2; 95% CI 1.5–6.9). No increased risk was estimated for vaccines (adjusted OR: 0.9; 95% CI 0.3–2.8).

Discussion

Our study provides additional evidence on the etiologic role of drugs and vaccines in the occurrence of SJS in children.     

Influenza Vaccination Uptake among the Working Age Population of Japan: Results from a National Cross-Sectional Survey

Background

Influenza vaccination rates among Japanese people of working age (20–69 years) is currently suboptimal, and the reasons for this have not been clearly elucidated. This study examined factors associated with vaccination intention among the working age population in Japan during September 2011, one-month prior to influenza vaccination becoming available.

Methodology/Principal Findings

A web-based survey of intention to be vaccinated against influenza in the coming season was undertaken among 3,129 Japanese aged 20 to 69 years. Multinomial logistic regression analysis was used to explore the associations between vaccination intent and other variables. Influenza vaccination intent was associated with having been vaccinated in the previous year (Odds Ratio (OR): 3.81; 95% Confidence Interval (CI): 3.75–3.86), the number of children per household (one compared with zero; OR: 1.37; 95%CI: 1.11–1.65), and household income ($50,000 to <$100,000 compared with $0 to <$50,000; OR: 1.30; 95%CI: 1.07–1.54). Smoking was inversely associated with influenza vaccine uptake (current smokers compared with non-smokers; OR: 0.79; 95%CI: 0.61–0.98). A history of either the survey respondent or a household member having being medically diagnosed with influenza in the previous year was not statistically associated with future influenza vaccination intent.

Conclusions/Significance

Overall, this suggests that intention to be vaccinated among working age Japanese is associated with a past history of influenza vaccination, having children, and the household''s income. As such, consideration of these factors should now form the cornerstone of strategies to encourage increased uptake of vaccination against influenza in future years.     

The Impact of Influenza Vaccinations on the Adverse Effects and Hospitalization Rate in the Elderly: A National Based Study in an Asian Country

Objectives

To examine the risk of adverse effects of special interest in persons vaccinated against seasonal influenza compared with unvaccinated persons aged 65 and above.

Methods

We retrospectively observed 41,986 vaccinated elderly persons and 50,973 unvaccinated elderly persons in Taiwan from October 1, 2008, through September 30, 2009, using the National Health Insurance database. Neurological and autoimmune disorders and one-year hospitalization rates and in-hospital mortality rates were analyzed according to the vaccination status. Propensity score analysis was used to assess the relationship between adverse outcomes, hospitalization rates, and vaccination status.

Results

45% of the elderly received influenza vaccination. Multiple logistic regression showed that the probability of being vaccinated was related to more patients visiting for URI symptoms (odds ratio (OR), 1.03; 95% CI, 1.02–1.03), men (OR, 1.15; 95% CI, 1.12–1.17), increased age (OR, 1.02; 95% CI, 1.02–1.03), and more comorbidities (OR, 1.2; 95% CI, 1.17–1.23). There were no statistical differences in neurological and autoimmune diseases between the vaccinated and unvaccinated individuals using propensity score analysis, but vaccinated persons had a reduced hospitalization rate of 19% (odds ratio [OR], 0.81; 95% CI, 0.77–0.84) for the first six-months and 13% for one-year of follow-up (OR, 0.87; 95% CI, 0.85–0.9).

Conclusions

Based on data from the one-year follow-ups among 93,049 elderly persons in Taiwan, reassuring results for selected neurological and autoimmune diseases were found among the vaccinated individuals after adjusting other factors. Influenza vaccination decreased the risk for hospitalization. Public health strategies must continue to improve the influenza vaccination rate among the elderly with information based upon tangible evidence.     

Early Life Disease Programming during the Preconception and Prenatal Period: Making the Link between Stressful Life Events and Type-1 Diabetes

Background

To assess the risk of developing Type-1 diabetes among children who were exposed to maternal bereavement during the prenatal or 1-year preconception period.

Methods

We identified N = 1,548,746 singleton births born in Denmark between January 1^st 1979 through December 31^st 2004, and their next of kin. Altogether, 39,857 children were exposed to bereavement during their prenatal life. The main outcome of interest was hospitalization for type-1 diabetes (ICD 8: 249; ICD 10: E10).

Results

We found the strongest association for type-1 diabetes among children exposed to traumatic father or sibling deaths (aIRR: 2.03, 1.22–3.38); the association was mainly seen for girls (aIRR: 2.91, 1.61–5.26).

Conclusions

We found evidence to suggest that female fetuses exposed to severe prenatal stress are at increased risk for developing type-1 diabetes.     

Population Dynamics of Owned,Free-Roaming Dogs: Implications for Rabies Control

Background

Rabies is a serious yet neglected public health threat in resource-limited communities in Africa, where the virus is maintained in populations of owned, free-roaming domestic dogs. Rabies elimination can be achieved through the mass vaccination of dogs, but maintaining the critical threshold of vaccination coverage for herd immunity in these populations is hampered by their rapid turnover. Knowledge of the population dynamics of free-roaming dog populations can inform effective planning and implementation of mass dog vaccination campaigns to control rabies.

Methodology/Principal Findings

We implemented a health and demographic surveillance system in dogs that monitored the entire owned dog population within a defined geographic area in a community in Mpumalanga Province, South Africa. We quantified demographic rates over a 24-month period, from 1^st January 2012 through 1^st January 2014, and assessed their implications for rabies control by simulating the decline in vaccination coverage over time. During this period, the population declined by 10%. Annual population growth rates were +18.6% in 2012 and -24.5% in 2013. Crude annual birth rates (per 1,000 dog-years of observation) were 451 in 2012 and 313 in 2013. Crude annual death rates were 406 in 2012 and 568 in 2013. Females suffered a significantly higher mortality rate in 2013 than males (mortality rate ratio [MRR] = 1.54, 95% CI = 1.28–1.85). In the age class 0–3 months, the mortality rate of dogs vaccinated against rabies was significantly lower than that of unvaccinated dogs (2012: MRR = 0.11, 95% CI = 0.05–0.21; 2013: MRR = 0.31, 95% CI = 0.11–0.69). The results of the simulation showed that achieving a 70% vaccination coverage during annual campaigns would maintain coverage above the critical threshold for at least 12 months.

Conclusions and Significance

Our findings provide an evidence base for the World Health Organization’s empirically-derived target of 70% vaccination coverage during annual campaigns. Achieving this will be effective even in highly dynamic populations with extremely high growth rates and rapid turnover. This increases confidence in the feasibility of dog rabies elimination in Africa through mass vaccination.     

Incidence of and Risk Factors Associated with Pulmonary and Extra-Pulmonary Tuberculosis in Saudi Arabia (2010–2011)

Setting

National Tuberculosis Program, Department of Public Health, Ministry of Health, Kingdom of Saudi Arabia (KSA).

Objective

To summarize data on the incidence of tuberculosis and associated risk factors for cases reported during 2010–2011.

Design

Retrospective analysis of routinely collected data through an established national disease notification system of the Ministry of Health in KSA.

Results

The estimated incidence of all forms of tuberculosis fell from 15.8/100000 (95% CI: 15.3/100,000–16.3/100,000) in 2010 to 13.8/100,000 (95% CI: 13.4/100,000–14.2/100,000) in 2011. Saudis experienced a decrease from 11.8/100,000 (95% CI: 11.3/100,000 to 12.3/100,000) in 2010 to 9.9/100,000 (95% CI: 9.5/100,000–10.4/100,000) in 2011 while the incidence in non-Saudis declined from 24.7/100,000 (95% CI: 23.6/100,000 to 25.7/100,000) in 2010 to 22.5/100,000 (95% CI: 21.5/100,000 to 23.4/100,000) in 2011. The proportion of Extra Pulmonary TB (EPTB) which increased minimally from 30% in 2010 to 32% in 2011 was higher than global figures and strongly associated with age, sex, nationality and occupation.

Conclusion

The current estimated incidence of about 14/100,000 in 2011 is less than half its estimated value of 44/100000 in 1990. Without prejudice to any under-reporting, the KSA appeared to be on the course for TB elimination by 2050 having reached the first milestone set by WHO. The proportion of EPTB remains higher than global figure and age, sex, nationality and occupation were significant independent predictors of EPTB.     

The population impact of a large school-based influenza vaccination campaign

Background

The optimal vaccination strategy to mitigate the impact of influenza epidemics is unclear. In 2005, a countywide school-based influenza vaccination campaign was launched in Knox County, Tennessee (population 385,899). Approximately 41% and 48% of eligible county children aged 5–17 years were immunized with live attenuated influenza vaccine before the 2005–2006 and 2006–2007 influenza seasons, respectively. We sought to determine the population impact of this campaign.

Methods

Laboratory-confirmed influenza data defined influenza seasons. We calculated the incidence of medically attended acute respiratory illness attributable to influenza in Knox and Knox-surrounding counties (concurrent controls) during consecutive seasons (5 precampaign and 2 campaign seasons) using negative binomial regression and rate difference methods. Age-stratified analyses compared the incidence of emergency department (ED) visits and hospitalizations attributable to influenza.

Results

During precampaign seasons, estimated ED visit rates attributable to influenza were 12.39 (95% CI: 10.34–14.44) per 1000 Knox children aged 5–17 years and similar in Knox-surrounding counties. During the campaign seasons, annual Knox influenza-associated ED visit rates declined relative to rates in Knox-surrounding counties: rate ratios 0.55 (95% CI: 0.27–0.83) and 0.70 (95% CI: 0.56–0.84) for the first and second campaign seasons, respectively. Overall, there were about 35% or 4.86 per 1000 fewer influenza-associated ED visits among Knox County children aged 5–17 years attributable to the campaign. No significant declines in Knox compared to surrounding counties were detected for influenza associated ED visits in children aged <5 years, all adults combined or selected adult age subgroups, although power for these analyses was limited. Alternate rate-difference analyses yielded consistent results.

Conclusion

Vaccination of approximately 45% of Knox school-aged children with influenza vaccine was associated with a 35% annual reduction (4.86 per 1000) in ED visit rates attributable to influenza. Higher vaccination coverage and/or larger studies would be needed to determine whether similar interventions have indirect benefits in other age groups.     

Risk of Narcolepsy Associated with Inactivated Adjuvanted (AS03) A/H1N1 (2009) Pandemic Influenza Vaccine in Quebec

Context

An association between an adjuvanted (AS03) A/H1N1 pandemic vaccine and narcolepsy has been reported in Europe.

Objective

To assess narcolepsy risk following administration of a similar vaccine in Quebec.

Design

Retrospective population-based study.

Setting

Neurologists and lung specialists in the province were invited to report narcolepsy cases to a single reference centre.

Population

Patients were interviewed by two sleep experts and standard diagnostic tests were performed. Immunization status was verified in the provincial pandemic influenza vaccination registry.

Main Outcome Measures

Confirmed narcolepsy with or without cataplexy with onset of excessive daytime sleepiness between January 1^st, 2009, and December 31^st, 2010. Relative risks (RRs) were calculated using a Poisson model in a cohort analysis, by a self-controlled case series (SCCS) and a case-control method.

Results

A total of 24 cases were included and overall incidence rate was 1.5 per million person-years. A cluster of 7 cases was observed among vaccinated persons in the winter 2009–2010. In the primary cohort analysis, 16-week post-vaccination RR was 4.32 (95% CI: 1.50–11.12). RR was 2.07 (0.70–6.17) in the SCCS, and 1.48 (0.37–7.03) using the case-control method. Estimates were lower when observation was restricted to the period of pandemic influenza circulation, and tended to be higher in persons <20 years old and for cataplexy cases.

Conclusions

Results are compatible with an excess risk of approximately one case per million vaccine doses, mainly in persons less than 20 years of age. However, a confounding effect of the influenza infection cannot be ruled out.     

Attitudes toward and uptake of H1N1 vaccine among health care workers during the 2009 H1N1 pandemic

Background

Though recommended by many and mandated by some, influenza vaccination rates among health care workers, even in pandemics, remain below optimal levels. The objective of this study was to assess vaccination uptake, attitudes, and distinguishing characteristics (including doctor-nurse differences) of health care workers who did and did not receive the pandemic H1N1 influenza vaccine in late 2009.

Methodology/Principal Findings

In early 2010 we mailed a self-administered survey to 800 physicians and 800 nurses currently licensed and practicing in Minnesota. 1,073 individuals responded (cooperation rate: 69%). 85% and 62% of Minnesota physicians and nurses, respectively, reported being vaccinated. Accurately estimating the risk of vaccine side effects (OR 2.0; 95% CI 1.5–2.7), agreeing with a professional obligation to be vaccinated (OR 10.1; 95% CI 7.1–14.2), an ethical obligation to follow public health authorities'' recommendations (OR 9.9; 95% CI 6.6–14.9), and laws mandating pandemic vaccination (OR 3.1; 95% CI 2.3–4.1) were all independently associated with receiving the H1N1 influenza vaccine.

Conclusions/Significance

While a majority of health care workers in one midwestern state reported receiving the pandemic H1N1 vaccine, physicians and nurses differed significantly in vaccination uptake. Several key attitudes and perceptions may influence health care workers'' decisions regarding vaccination. These data inform how states might optimally enlist health care workers'' support in achieving vaccination goals during a pandemic.     

Public Health Impact of Complete and Incomplete Rotavirus Vaccination among Commercially and Medicaid Insured Children in the United States

Background

This study ({"type":"clinical-trial","attrs":{"text":"NCT01682005","term_id":"NCT01682005"}}NCT01682005) aims to assess clinical and cost impacts of complete and incomplete rotavirus (RV) vaccination.

Methods

Beneficiaries who continuously received medical and pharmacy benefits since birth were identified separately in Truven Commercial Claims and Encounters (2000–2011) and Truven Medicaid Claims (2002–2010) and observed until the first of end of insurance eligibility or five years. Infants with ≥1 RV vaccine within the vaccination window (6 weeks-8 months) were divided into completely and incompletely vaccinated cohorts. Historically unvaccinated (before 2007) and contemporarily unvaccinated (2007 and after) cohorts included children without RV vaccine. Claims with International Classification of Disease 9^th edition (ICD-9) codes for diarrhea and RV were identified. First RV episode incidence, RV-related and diarrhea-related healthcare resource utilization after 8 months old were calculated and compared across groups. Poisson regressions were used to generate incidence rates with 95% confidence intervals (CIs). Mean total, inpatient, outpatient and emergency room costs for first RV and diarrhea episodes were calculated; bootstrapping was used to construct 95% CIs to evaluate cost differences.

Results

1,069,485 Commercial and 515,557 Medicaid patients met inclusion criteria. Among commercially insured, RV incidence per 10,000 person-years was 3.3 (95% CI 2.8–3.9) for completely, 4.0 (95% CI 3.3–5.0) for incompletely vaccinated, and 20.9 (95% CI 19.5–22.4) for contemporarily and 40.3 (95% CI 38.6–42.1) for historically unvaccinated. Rates in Medicaid were 7.5 (95% CI 4.8–11.8) for completely, 9.0 (95% CI 6.5–12.3) for incompletely vaccinated, and 14.6 (95% CI 12.8–16.7) for contemporarily and 52.0 (95% CI 50.2–53.8) for historically unvaccinated. Mean cost for first RV episode per cohort member was $15.33 (95% CI $12.99-$18.03) and $4.26 ($95% CI $2.34-$6.35) lower for completely vaccinated versus contemporarily unvaccinated in Commercial and Medicaid, respectively.

Conclusions

RV vaccination results in significant reduction in RV infection. There is evidence of indirect benefit to unvaccinated individuals.     

Good glycemic control is associated with better survival in diabetic patients on peritoneal dialysis: a prospective observational study

Background

The effect of glycemic control after starting peritoneal dialysis (PD) on the survival of diabetic PD patients has largely been unexplored, especially in Asian population.

Methods

We conducted a prospective observational study, in which 140 incident PD patients with diabetes were recruited. Patients were divided into tertiles according to the means of quarterly HbA1C levels measured during the first year after starting PD. We examined the association between HbA1C and all-cause mortality using Cox proportional hazards models.

Results

The mean age was 58.7 years, 59.3% were male, and the mean follow-up duration was 3.5 years (range 0.4–9.5 years). The mean HbA1C levels were 6.3%, 7.1%, and 8.5% in the 1^st, 2^nd, and 3^rd tertiles, respectively. Compared to the 1^st tertile, the all-cause mortality rates were higher in the 2^nd [hazard ratio (HR), 4.16; 95% confidence interval (CI), 0.91–18.94; p = 0.065] and significantly higher in the 3^rd (HR, 13.16; 95% CI, 2.67–64.92; p = 0.002) tertiles (p for trend = 0.005), after adjusting for confounding factors. Cardiovascular mortality, however, did not differ significantly among the tertiles (p for trend = 0.682). In contrast, non-cardiovascular deaths, most of which were caused by infection, were more frequent in the 2^nd (HR, 7.67; 95% CI, 0.68–86.37; p = 0.099) and the 3^rd (HR, 51.24; 95% CI, 3.85–681.35; p = 0.003) tertiles than the 1^st tertile (p for trend = 0.007).

Conclusions

Poor glycemic control is associated with high mortality rates in diabetic PD patients, suggesting that better glycemic control may improve the outcomes of these patients.     

Effects of community-wide vaccination with PCV-7 on pneumococcal nasopharyngeal carriage in the Gambia: a cluster-randomized trial

Background

Introduction of pneumococcal conjugate vaccines (PCVs) of limited valency is justified in Africa by the high burden of pneumococcal disease. Long-term beneficial effects of PCVs may be countered by serotype replacement. We aimed to determine the impact of PCV-7 vaccination on pneumococcal carriage in rural Gambia.

Methods and Findings

A cluster-randomized (by village) trial of the impact of PCV-7 on pneumococcal nasopharyngeal carriage was conducted in 21 Gambian villages between December 2003 to June 2008 (5,441 inhabitants in 2006). Analysis was complemented with data obtained before vaccination. Because efficacy of PCV-9 in young Gambian children had been shown, it was considered unethical not to give PCV-7 to young children in all of the study villages. PCV-7 was given to children below 30 mo of age and to those born during the trial in all study villages. Villages were randomized (older children and adults) to receive one dose of PCV-7 (11 vaccinated villages) or meningococcal serogroup C conjugate vaccine (10 control villages). Cross-sectional surveys (CSSs) to collect nasopharyngeal swabs were conducted before vaccination (2,094 samples in the baseline CSS), and 4–6, 12, and 22 mo after vaccination (1,168, 1,210, and 446 samples in CSS-1, -2, and -3, respectively).A time trend analysis showed a marked fall in the prevalence of vaccine-type pneumococcal carriage in all age groups following vaccination (from 23.7% and 26.8% in the baseline CSS to 7.1% and 8.5% in CSS-1, in vaccinated and control villages, respectively). The prevalence of vaccine-type pneumococcal carriage was lower in vaccinated than in control villages among older children (5 y to <15 y of age) and adults (≥15 y of age) at CSS-2 (odds ratio [OR] = 0.15 [95% CI 0.04–0.57] and OR = 0.32 [95% CI 0.10–0.98], respectively) and at CSS-3 (OR = 0.37 [95% CI 0.15–0.90] for older children, and 0% versus 7.6% for adults in vaccinated and control villages, respectively). Differences in the prevalence of non-vaccine-type pneumococcal carriage between vaccinated and control villages were small.

Conclusions

Vaccination of Gambian children reduced vaccine-type pneumococcal carriage across all age groups, indicating a “herd effect” in non-vaccinated older children and adults. No significant serotype replacement was detected. Please see later in the article for the Editors'' Summary     

Encephalitis Hospitalization Rates and Inpatient Mortality in the United States, 2000-2010

Background

Encephalitis rates by etiology and acute-phase outcomes for encephalitis in the 21^st century are largely unknown. We sought to evaluate cause-specific rates of encephalitis hospitalizations and predictors of inpatient mortality in the United States.

Methods

Using the Nationwide Inpatient Sample (NIS) from 2000 to 2010, a retrospective observational study of 238,567 patients (mean [SD] age, 44.8 [24.0] years) hospitalized within non-federal, acute care hospitals in the U.S. with a diagnosis of encephalitis was conducted. Hospitalization rates were calculated using population-level estimates of disease from the NIS and population estimates from the United States Census Bureau. Adjusted odds of mortality were calculated for patients included in the study.

Results

In the U.S. from 2000–2010, there were 7.3±0.2 encephalitis hospitalizations per 100,000 population (95% CI: 7.1–7.6). Encephalitis hospitalization rates were highest among females (7.6±0.2 per 100,000) and those <1 year and >65 years of age with rates of 13.5±0.9 and 14.1±0.4 per 100,000, respectively. Etiology was unknown for approximately 50% of cases. Among patients with identified etiology, viral causes were most common (48.2%), followed by Other Specified causes (32.5%), which included predominantly autoimmune conditions. The most common infectious agents were herpes simplex virus, toxoplasma, and West Nile virus. Comorbid HIV infection was present in 7.7% of hospitalizations. Average length of stay was 11.2 days with mortality of 5.6%. In regression analysis, patients with comorbid HIV/AIDS or cancer had increased odds of mortality (odds ratio [OR]  = 1.70; 95% CI: 1.30–2.22 and OR = 2.26; 95% CI: 1.88–2.71, respectively). Enteroviral, postinfectious, toxic, and Other Specified causes were associated with lower odds vs. herpes simplex encephalitis.

Conclusions

While encephalitis and encephalitis-related mortality impose a considerable burden in the U.S. in the 21^st Century, the reported demographics of hospitalized encephalitis patients may be changing.     

Parental intention to have daughters receive the human papillomavirus vaccine

Background

Concerns have been raised that parents may be reluctant to have their daughters receive the human papillomavirus (HPV) vaccine, because of a belief that doing so might be interpreted as condoning earlier and more frequent sexual activity. We determined intentions regarding vaccination among Canadian parents and factors that predicted parental intention to have their daughters vaccinated against HPV.

Methods

Parents of children 8–18 years of age, recruited from across Canada, were asked to respond to questions in the context of a grade 6, publicly funded, school-based HPV vaccine program. We performed backward logistic regression analysis to identify factors predictive of parents'' intention to have their daughters vaccinated against HPV.

Results

Of the 1350 respondents with female children, more than 70% (73.8%; 95% confidence interval [CI] 71.5%– 76.1%) intended to have their daughters undergo vaccination against HPV. In multivariable modelling, parents who had positive attitudes toward vaccines (odds ratio [OR] 9.9, 95% CI 4.7–21.1), those who were influenced by subjective norms (OR 9.2, 95% CI 6.6–12.9), those who felt that the vaccine had limited influence on sexual behaviour (OR 3.2, 95% CI 2.2–4.6) and those who thought someone they knew was likely to get cervical cancer (OR 1.5, 95% CI 1.1–2.1) were more likely to intend that their daughters receive the HPV vaccine. Parents who were older (v. younger) (OR 0.6, 95% CI 0.4–0.8) and those who resided in British Columbia or Yukon Territory (v. Atlantic Canada) (OR 0.5, 95% CI 0.3–0.9) were less likely to intend that their daughters receive the HPV vaccine.

Interpretation

Most of the parents surveyed intended that their daughters would receive vaccination against HPV. Overall attitudes toward vaccines in general and toward the HPV vaccine in particular constituted the most significant predictor of parental intention with regard to vaccination.The vaccine against the human papillomavirus (HPV) represents a major step toward the prevention of cervical cancer.^1,2 HPV is a sexually acquired virus, and mathematical modelling and economic analyses have demonstrated that the vaccine''s maximum benefit in terms of preventing cervical cancer is achieved when vaccination programs target female and possibly male adolescents before their sexual debut, likely before the age of 12 years.³ The clinical efficacy and safety of the currently available HPV vaccine have been established,⁴ but concerns have been raised that parents may be reluctant to have their children undergo vaccination at this age, because of a belief that doing so might be interpreted to mean that they are condoning or even promoting earlier and more frequent sexual activity. Since parental attitudes play a crucial role in vaccination uptake and can provide direction for messaging and education in support of vaccination uptake,⁵ we sought to determine parental intentions to have daughters vaccinated against HPV and the factors that predict those intentions.     

A School-Based Human Papillomavirus Vaccination Program in Barretos,Brazil: Final Results of a Demonstrative Study

Introduction

The implementation of a public HPV vaccination program in several developing countries, especially in Latin America, is a great challenge for health care specialists.

Aim

To evaluate the uptake and the three-dose completion rates of a school-based HPV vaccination program in Barretos (Brazil).

Methods

The study included girls who were enrolled in public and private schools and who regularly attended the sixth and seventh grades of elementary school (mean age: 11.9 years). A meeting with the parents or guardians occurred approximately one week before the vaccination in order to explain the project and clarify the doubts. The quadrivalent vaccine was administered using the same schedule as in the product package (0–2–6 months). The school visits for regular vaccination occurred on previously scheduled dates. The vaccine was also made available at Barretos Cancer Hospital for the girls who could not be vaccinated on the day when the team visited the school.

Results

Among the potential candidates for vaccination (n = 1,574), the parents or guardians of 1,513 girls (96.1%) responded to the invitation to participate in the study. A total of 1,389 parents or guardians agreed to participate in the program (acceptance rate = 91.8%). The main reason for refusing to participate in the vaccination program was fear of adverse events. The vaccine uptake rates for the first, second, and third doses were 87.5%, 86.3% and 85.0%, respectively. The three-dose completion rate was 97.2%.

Conclusions

This demonstrative study achieved high rates of vaccination uptake and completion of three vaccine doses in children 10–16 years old from Brazil. The feasibility and success of an HPV vaccination program for adolescents in a developing country may depend on the integration between the public health and schooling systems.     

Elderly subjects have a delayed antibody response and prolonged viraemia following yellow fever vaccination: a prospective controlled cohort study

Background

Yellow fever vaccination (YF-17D) can cause serious adverse events (SAEs). The mechanism of these SAEs is poorly understood. Older age has been identified as a risk factor. We tested the hypothesis that the humoral immune response to yellow fever vaccine develops more slowly in elderly than in younger subjects.

Method

We vaccinated young volunteers (18–28 yrs, N = 30) and elderly travelers (60–81 yrs, N = 28) with YF-17D and measured their neutralizing antibody titers and plasma YF-17D RNA copy numbers before vaccination and 3, 5, 10, 14 and 28 days after vaccination.

Results

Ten days after vaccination seroprotection was attained by 77% (23/30) of the young participants and by 50% (14/28) of the elderly participants (p = 0.03). Accordingly, the Geometric Mean Titer of younger participants was higher than the GMT of the elderly participants. At day 10 the difference was +2.9 IU/ml (95% CI 1.8–4.7, p = 0.00004) and at day 14 +1.8 IU/ml (95% CI 1.1–2.9, p = 0.02, using a mixed linear model. Viraemia was more common in the elderly (86%, 24/28) than in the younger participants (60%, 14/30) (p = 0.03) with higher YF-17D RNA copy numbers in the elderly participants.

Conclusions

We found that elderly subjects had a delayed antibody response and higher viraemia levels after yellow fever primovaccination. We postulate that with older age, a weaker immune response to yellow fever vaccine allows the attenuated virus to cause higher viraemia levels which may increase the risk of developing SAEs. This may be one piece in the puzzle of the pathophysiology of YEL-AVD.

Trial Registration

Trialregitser.nl NTR1040     

Low Birth Weight,Small for Gestational Age and Preterm Births before and after the Economic Collapse in Iceland: A Population Based Cohort Study

Objective

Infants born small for gestational age (SGA) or preterm have increased rates of perinatal morbidity and mortality. Stressful events have been suggested as potential contributors to preterm birth (PB) and low birth weight (LBW). We studied the effect of the 2008 economic collapse in Iceland on the risks of adverse birth outcomes.

Study design

The study population constituted all Icelandic women giving birth to live-born singletons from January 1^st 2006 to December 31^st 2009. LBW infants were defined as those weighing <2500 grams at birth, PB infants as those born before 37 weeks of gestation and SGA as those with a birth weight for gestational age more than 2 standard deviations (SD''s) below the mean according to the Swedish fetal growth curve. We used logistic regression analysis to estimate odds ratios [OR] and corresponding 95 percent confidence intervals [95% CI] of adverse birth outcomes by exposure to calendar time of the economic collapse, i.e. after October 6^th 2008.

Results

Compared to the preceding period, we observed an increased adjusted odds in LBW-deliveries following the collapse (aOR = 1.24, 95% CI [1.02, 1.52]), particularly among infants born to mothers younger than 25 years (aOR = 1.85, 95% CI [1.25, 2.72]) and not working mothers (aOR = 1.61, 95% CI [1.10, 2.35]). Similarly, we found a tendency towards higher incidence of SGA-births (aOR = 1.14, 95% CI [0.86, 1.51]) particularly among children born to mothers younger than 25 years (aOR = 1.87, 95% CI [1.09, 3.23]) and not working mothers (aOR = 1.86, 95% CI [1.09, 3.17]). No change in risk of PB was observed. The increase of LBW was most distinct 6–9 months after the collapse.

Conclusion

The results suggest an increase in risk of LBW shortly after the collapse of the Icelandic national economy. The increase in LBW seems to be driven by reduced fetal growth rate rather than shorter gestation.