Maternal varicella antibodies in children aged less than one year: Assessment of antibody decay.

OBJECTIVES: To investigate maternal antibody levels to varicella in infants <12 months of age in Ontario, Canada. STUDY DESIGN: In this study, we included specimens from infants <12 months of age, born at ≥37 weeks gestational age, who had sera collected at The Hospital for Sick Children (Toronto, Canada) between 2014-2016. We tested sera using a glycoprotein-based enzyme-linked immunosorbent assay (gpELISA). We measured varicella susceptibility (antibody concentration <150mIU/mL) and mean varicella antibody concentration, and assessed the probability of susceptibility and concentration between one and 11 months of age using multivariable logistic regression and Poisson regression. RESULTS: We found that 32% of 196 included specimens represented infants susceptible to varicella at one month of age, increasing to nearly 80% at three months of age. At six months of age, all infants were susceptible to varicella and the predicted mean varicella antibody concentration declined to 62 mIU/mL (95% confidence interval 40, 84), well below the threshold of protection. CONCLUSIONS: We found that varicella maternal antibody levels wane rapidly in infants, leaving most infants susceptible by four months of age. Our findings have implications for the timing of first dose of varicella-containing vaccine, infection control measures, and infant post-exposure prophylaxis recommendations.

Protocol for a longitudinal cohort study of Lyme disease with physical, mental and immunological assessment.

INTRODUCTION: There are limited data on the longitudinal impact of Lyme disease. Predictors of recovery have not been fully established using validated data collection instruments. There are sparse data on the immunological response to infection over time. METHODS AND ANALYSIS: This study is a longitudinal cohort study that will recruit 120 participants with Lyme disease in Ontario and Nova Scotia, Canada, with follow-up for up to 24 months. Data will be collected using the Short-Form 36 physical and mental component summaries, Depression and Anxiety Severity Scale Questionnaire, Fatigue Severity Scale and a battery of neuropsychological tests. Mononuclear cells, gene expression and cytokine profiling from blood samples will be used to assess immunological response. Analyses will include the use of non-linear mixed-effects modelling and proportional hazards models. ETHICS AND DISSEMINATION: Ethics approval has been obtained from ethics boards at McMaster University (Hamilton Integrated Research Ethics Board) (7564), Queens University (EMD 315-20) and Nova Scotia Health Research Ethics Board (1027173), and the study is enrolling participants. Written informed consent is obtained from all participants. The results will be disseminated by publication in a peer-reviewed journal and presented at a relevant conference. A brief report will be provided to decision-makers and patient groups.

Age-stratified burden of pneumococcal community acquired pneumonia in hospitalised Canadian adults from 2010 to 2015.

BACKGROUND: In Canada, 13-valent pneumococcal conjugate vaccine (PCV13) is recommended in childhood, in individuals at high risk of invasive pneumococcal disease (IPD) and in healthy adults aged ≥65 years for protection against vaccine-type IPD and pneumococcal community-acquired pneumonia (pCAP). Since vaccine recommendations in Canada include both age-based and risk-based guidance, this study aimed to describe the burden of vaccine-preventable pCAP in hospitalised adults by age. METHODS: Surveillance for community-acquired pneumonia (CAP) in hospitalised adults was performed prospectively from 2010 to 2015. CAP was radiologically confirmed, and pCAP was identified using blood and sputum culture and urine antigen testing. Patient demographics and outcomes were stratified by age (16-49, 50-64, ≥65 and ≥50 years). RESULTS: Of 6666/8802 CAP cases tested, 830 (12.5%) had pCAP, and 418 (6.3%) were attributed to a PCV13 serotype. Of PCV13 pCAP, 41% and 74% were in adults aged ≥65 and ≥50 years, respectively. Compared with non-pCAP controls, pCAP cases aged ≥50 years were more likely to be admitted to intensive care units (ICUs) and to require mechanical ventilation. Older adults with pCAP were less likely to be admitted to ICU or required mechanical ventilation, given their higher mortality and goals of care. Of pCAP deaths, 67% and 90% were in the ≥65 and ≥50 age cohorts, respectively. CONCLUSIONS: Adults hospitalised with pCAP in the age cohort of 50-64 years contribute significantly to the burden of illness, suggesting that an age-based recommendation for adults aged ≥50 years should be considered in order to optimise the impact of pneumococcal vaccination programmes in Canada.

Increase in Gonorrhea Incidence Associated With Enhanced Partner Notification Strategy.

OBJECTIVES: Partner notification services for reportable sexually transmitted infections vary based on jurisdiction, resources, type of infection, and whether an outbreak has been reported. The objective of this study was to determine whether case finding increased after implementation of enhanced notification and follow-up activities for contacts of cases of Neisseria gonorrhoeae in Central Zone, the largest health authority in Nova Scotia, Canada. METHODS: Enhanced contact tracing by public health professionals was implemented in May 2015. N. gonorrhoeae multiantigen sequence typing (NG-MAST) was conducted on all positive specimens. Epidemiologic and NG-MAST information for reported gonorrhea cases were captured and analyzed. Case numbers, rates, and NG-MAST results in the preintervention and postintervention periods were compared. Laboratory testing data were extracted and analyzed for association with reported incidence. RESULTS: There was a significant increase in the number of reported gonorrhea cases per month when comparing the preintervention and postintervention periods. The reported gonorrhea rate in 2016 was 2.9 times that in 2014. This increase was not associated with changes in testing rates and was more pronounced among women than men. Larger groups of cases sharing the same NG-MAST profiles were detected postintervention. CONCLUSIONS: The implementation of an enhanced contact tracing program for N. gonorrhoeae resulted in increased case finding and a notable increase in the reported rate of cases per 100,000 population. Owing to these findings, the practice of enhanced partner notification was continued as standard public health practice in Central Zone. An understanding of case finding efforts is required when interpreting observed trends in rates of N. gonorrhoeae, as early infection is highly asymptomatic in women and can be asymptomatic in men.

Assessment of population immunity to measles in Ontario, Canada: a Canadian Immunization Research Network (CIRN) study.

Canada eliminated measles in 1998. We conducted a sero-epidemiology study to estimate population immunity to measles in the province of Ontario, Canada and to identify groups at higher risk of outbreaks. We used a previously developed modified enzyme immunoassay to test 1,199 residual sera from patients aged 1-39 years. We re-tested negative and equivocal sera using a plaque reduction neutralization assay. We interpreted our results in the context of Ontario's immunization program and vaccine coverage data. Of 1,199 sera, 1035 (86.3%, 95% confidence interval (CI) 84.4, 88.2) were above the measles threshold for protection, 70 (5.8%, 95% CI 4.5, 7.2) were equivocal and 94 (7.8%, 95% CI 6.3, 9.4) were negative. The proportion of positive sera was highest for those 1-5 years, with 180/199 (90.5%, 95% CI 86.4, 94.5) positive sera, and lowest for those age 12-19 years, at 158/199 (79.4%, 95% CI 73.8, 85.0). Adjusted for age, females were more likely than males to have antibody titers above the threshold of protection (odds ratio = 1.60, 95% CI 1.14, 2.24). Most of the study cohort were eligible for two measles vaccine doses, and vaccine uptake in Ontario is >90% for school-aged cohorts. We observed a higher than expected proportion of sera with antibody levels below the threshold of protection, suggesting that immunity in some Ontario age-groups may be waning, despite high vaccine coverage. Alternatively, the traditional measles correlates of protection may not be an appropriate measure of population protection in measles-eliminated settings.

Resource utilization and cost of influenza requiring hospitalization in Canadian adults: A study from the serious outcomes surveillance network of the Canadian Immunization Research Network.

BACKGROUND: Consideration of cost determinants is crucial to inform delivery of public vaccination programs. OBJECTIVES: To estimate the average total cost of laboratory-confirmed influenza requiring hospitalization in Canadians prior to, during, and 30 days following discharge. To analyze effects of patient/disease characteristics, treatment, and regional differences in costs. METHODS: Study utilized previously recorded clinical characteristics, resource use, and outcomes of laboratory-confirmed influenza patients admitted to hospitals in the Serious Outcomes Surveillance (SOS), Canadian Immunization Research Network (CIRN), from 2010/11 to 2012/13. Unit costs including hospital overheads were linked to inpatient/outpatient resource utilization before and after admissions. RESULTS: Dataset included 2943 adult admissions to 17 SOS Network hospitals and 24 Toronto Invasive Bacterial Disease Network hospitals. Mean age was 69.5 years. Average hospital stay was 10.8 days (95% CI: 10.3, 11.3), general ward stays were 9.4 days (95% CI: 9.0, 9.8), and ICU stays were 9.8 days (95% CI: 8.6, 11.1) for the 14% of patients admitted to the ICU. Average cost per case was $14 612 CAD (95% CI: $13 852, $15 372) including $133 (95% CI: $116, $150) for medical care prior to admission, $14 031 (95% CI: $13 295, $14 768) during initial hospital stay, $447 (95% CI: $271, $624) post-discharge, including readmission within 30 days. CONCLUSION: The cost of laboratory-confirmed influenza was higher than previous estimates, driven mostly by length of stay and analyzing only laboratory-confirmed influenza cases. The true per-patient cost of influenza-related hospitalization has been underestimated, and prevention programs should be evaluated in this context.

The Importance of Frailty in the Assessment of Influenza Vaccine Effectiveness Against Influenza-Related Hospitalization in Elderly People.

Background: Influenza is an important cause of morbidity and mortality among older adults. Even so, effectiveness of influenza vaccine for older adults has been reported to be lower than for younger adults, and the impact of frailty on vaccine effectiveness (VE) and outcomes is uncertain. We aimed to study VE against influenza hospitalization in older adults, focusing on the impact of frailty. Methods: We report VE of trivalent influenza vaccine (TIV) in people ≥65 years of age hospitalized during the 2011-2012 influenza season using a multicenter, prospective, test-negative case-control design. A validated frailty index (FI) was used to measure frailty. Results: Three hundred twenty cases and 564 controls (mean age, 80.6 and 78.7 years, respectively) were enrolled. Cases had higher baseline frailty than controls (P = .006). In the fully adjusted model, VE against influenza hospitalization was 58.0% (95% confidence interval [CI], 34.2%-73.2%). The contribution of frailty was important; adjusting for frailty alone yielded a VE estimate of 58.7% (95% CI, 36.2%-73.2%). VE was 77.6% among nonfrail older adults and declined as frailty increased. Conclusions: Despite commonly held views that VE is poor in older adults, we found that TIV provided good protection against influenza hospitalization in older adults who were not frail, though VE diminished as frailty increased. Clinical Trials Registration: NCT01517191.

Molecular detection of varicella zoster virus while keeping an eye on the budget.

Varicella zoster virus (VZV) PCR is highly sensitive compared to traditional detection methods like culture and direct fluorescent antibody testing (DFA); however, the high cost of commercial assays prohibits their use in many clinical laboratories. Major contributors to cost are the nucleic acid extraction and the PCR reagents. This study evaluated an "in-house" qualitative real-time PCR where the nucleic acid extraction was replaced by a crude extraction, homogenization and heat treatment. Three methods were compared: virus culture and DFA and real-time PCR following each extraction methods. The real-time PCR was highly specific for VZV, and the analytical sensitivity was equivalent following both extraction methods. In contrast, virus culture and DFA was approximately 10,000-fold less sensitive. Using 200 clinical specimens, the sensitivity for the real-time PCR following nucleic acid extraction or homogenization and heat treatment was essentially equivalent at 100% and 97.2%, respectively; whereas, virus culture and DFA was significantly less sensitive at 54.8%. Overall, homogenization and heat treatment combined with a qualitative in-house real-time PCR is a rapid, accurate and cost effective method for the detection of VZV.

A cost effective real-time PCR for the detection of adenovirus from viral swabs.

Compared to traditional testing strategies, nucleic acid amplification tests such as real-time PCR offer many advantages for the detection of human adenoviruses. However, commercial assays are expensive and cost prohibitive for many clinical laboratories. To overcome fiscal challenges, a cost effective strategy was developed using a combination of homogenization and heat treatment with an "in-house" real-time PCR. In 196 swabs submitted for adenovirus detection, this crude extraction method showed performance characteristics equivalent to viral DNA obtained from a commercial nucleic acid extraction. In addition, the in-house real-time PCR outperformed traditional testing strategies using virus culture, with sensitivities of 100% and 69.2%, respectively. Overall, the combination of homogenization and heat treatment with a sensitive in-house real-time PCR provides accurate results at a cost comparable to viral culture.

Homogenization with heat treatment: A cost effective alternative to nucleic acid extraction for herpes simplex virus real-time PCR from viral swabs.

Most laboratories use expensive commercial kits to purify nucleic acids and remove PCR inhibitors that may be present in clinical specimens. In this study a simple homogenization with heat treatment of herpes simplex virus types 1 and 2 (HSV-1/2) was shown to be equivalent to commercial kit-based nucleic acid extraction methods. With a cost of less than $1 USD per extraction, this method provides an economical, rapid, and effective method to recover HSV-1/2 DNA from swabs suitable for real-time HSV PCR.

Yield increases in intact influenza vaccine virus from chicken allantoic fluid through isolation from insoluble allantoic debris.

A yield enhancement technology for use in influenza vaccine manufacturing has been developed to maximize the recovery of influenza virus from allantoic fluid of virus-infected chick embryos; the standard raw material for influenza vaccine. Virus associated with amorphous debris in the allantoic fluid can be dissociated from the debris and recovered, thereby increasing viral yield. Dissociation can be achieved by subjecting the virus-debris complex to conditions of increased ionic strength at defined pH. Multifold increases in viral yield per ml of allantoic fluid were observed. The degree of yield enhancement is strain-specific, however, increases were observed in all type A and type B influenza strains tested. The heightened influenza virus recoveries can facilitate rapid vaccine manufacture, with increased numbers of doses produced, and may become essential at a time of influenza pandemic.