Kimberley Simmonds

Shingles in Alberta: before and after publicly funded varicella vaccination.

PURPOSE A universal publicly funded chickenpox vaccination program was implemented in Alberta in 2002. We examine the epidemiology of medically attended shingles in Alberta from 1994 to 2010. METHODS Incident shingles cases (earliest health service utilizations for ICD-9 053 or ICD-10-CA B02) and their co-morbid conditions for the 12 months prior to shingles diagnosis were identified from the records of Albertas universal, publicly funded health-care insurance system for 1994-2010. Shingles diagnostic codes at least 180 days after the first were classified as recurrent episodes. Denominators for rates were estimated using mid-year population estimates from the Alberta Health Care Insurance Plan Registry. Annual age- and sex-specific rates were estimated. We estimated the proportion of all cases that were hospitalized. We explored the pattern of rates for sex, age-group co-morbidity and year effects and their interactions. RESULTS Crude rates of shingles increased over the interval 1994-2010. Most persons had only a single episode of shingles; 4% of cases were hospitalized. Shingles rates were higher among females than males. While only 2% of shingles cases had one or more co-morbidities, this proportion was also higher for females than males. Prior to 2002, all age groups of both sexes experienced increasing annual rates of shingles. However, there was a sharp decline in the rate of shingles for both females and males under the age of 10 years for 2002-2010, the period in which there was publicly funded chickenpox vaccination. CONCLUSION The declining rates of shingles among persons under the age of 10 years are consistent with an impact of the chickenpox vaccination program. The trend of increasing rates of shingles among older persons began prior to implementation of vaccination.

Characterization of Enterovirus Activity, Including That of Enterovirus D68, in Pediatric Patients in Alberta, Canada, in 2014

In the late summer and fall of 2014, the province of Alberta, Canada (4.1 million people), was in the midst of peak entero-rhinovirus (ERV) activity, as descriptions of enterovirus D68 (EV-D68) activity were being publicized ([1][1], [2][2]). This analysis was undertaken with several goals: (i) to

Risk of febrile seizures after first dose of measles–mumps–rubella–varicella vaccine: a population-based cohort study

Background: The combination measles–mumps–rubella–varicella (MMRV) vaccine currently used in Canada (Priorix-Tetra) may increase the risk of febrile seizures relative to the separate vaccines (MMR and varicella) previously administered. We determined the risk of febrile seizure after the first dose of MMRV, as well as any additional risk for children at high risk for seizures because of pre-existing medical conditions. Methods: In this retrospective, population-based cohort study, we compared the risk of seizures after the first dose of MMRV with the risk after same-day administration of separate MMR and varicella vaccines (MMR+V) in children 12 to 23 months of age in the province of Alberta. We deterministically linked vaccination data to health service utilization data for seizures. We used Poisson regression, with adjustment for age and calendar year, to determine the risk for the full cohort and for high-risk children. Results: The risk of seizures 7 to 10 days after vaccination was twice as high with MMRV as with MMR+V (relative risk [RR] 1.99, 95% confidence interval [CI] 1.30–3.05). The excess absolute risk of seizures was 3.52 seizures per 10 000 doses of MMRV relative to MMR+V. In high-risk children, the risk was not differentially higher for MMRV (RR 1.30, 95% CI 0.60–2.79). Interpretation: Despite an increased risk of febrile seizures following MMRV (compared with MMR+V), the absolute level of risk was small. Policy-makers need to balance these findings with the potential benefits of administering the combination vaccine or determine whether the choice of vaccine rests with clinicians and/or parents.

Molecular Profiling of Escherichia coli O157:H7 and Non-O157 Strains Isolated from Humans and Cattle in Alberta, Canada

ABSTRACT Virulence markers in Shiga toxin-producing Escherichia coli (STEC) and their association with diseases remain largely unknown. This study determines the importance of 44 genetic markers for STEC (O157 and non-O157) from human clinical cases and their correlation to disease outcome. STEC isolated from a cattle surveillance program were also included. The virulence genes tested were present in almost all O157:H7 isolates but highly variable in non-O157 STEC isolates. Patient age was a significant determinant of clinical outcome.

Adverse events following HPV vaccination, Alberta 2006-2014.

BACKGROUND In Canada, private purchase of human papilloma virus (HPV) vaccines has been possible since 2006. In Alberta, Canada, a publicly funded quadrivalent HPV vaccine program began in the 2008/2009 school year. There have been concerns about adverse events, including venous thromboembolism (VTE) associated with HPV vaccines. We describe the frequencies of adverse events following HPV vaccination among Alberta females aged 9 years or older and look at VTE following HPV vaccination. METHODS We used the Alberta Immunization and Adverse Reaction to Immunization (Imm/ARI) repository (publicly funded vaccine), the population-based Pharmaceutical Information Network (PIN) information system (dispensing of a vaccine), and the Alberta Morbidity and Ambulatory Care Abstract reporting system (MACAR) for June 1, 2006-November 19, 2014. Deterministic data linkage used unique personal identifiers. We identified all reported adverse events following immunization (AEFI) and all emergency department (ED) utilization or hospitalizations within 42 days of immunization. We calculated the frequency of AEFI by type, rates per 100,000 doses of HPV vaccine administered and the frequencies of ICD-10-CA codes for hospitalizations and emergency department visits. RESULTS Over the period 195,270 females received 528,913 doses of HPV vaccine. Of those receiving at least one dose, 192 reported one or more AEFI events (198 AEFI events), i.e., 37.4/100,000 doses administered (95% CI 32.5-43.0). None were consistent with VTE. Of the women who received HPV vaccine 958 were hospitalized and 19,351 had an ED visit within 42 days of immunization. Four women who had an ED visit and hospitalization event were diagnosed with VTE. Three of these had other diagnoses known to be associated with VTE; the fourth woman had VTE among ED diagnoses but not among those for the hospitalization. CONCLUSIONS Rates of AEFI after HPV immunization in Alberta are low and consistent with types of events seen elsewhere.

Exploring the heterogeneity among partially vaccinated children in a population-based cohort.

INTRODUCTION Vaccination status is often categorized as complete or not-complete. This ignores the potentially important heterogeneity in children whose vaccinations are not-complete. We sought to subcategorize not-completely vaccinated children and determine whether characteristics differed among these subgroups. METHODS This retrospective cohort study assessed vaccination status at 2 years of age for 43,965 children in the 2008 Alberta (Canada) birth cohort who were registered with provincial vital statistics records. Children were categorized (based on the five routinely scheduled childhood vaccines) as complete, incomplete, selective, or non-vaccination status. Characteristics derived from administrative health databases were used to determine factors associated with vaccination status. RESULTS Population-level vaccination status at 2 years of age was found to be: 71.1% complete and 28.9% not complete (21.9% incomplete, 2.0% selective, and 5.1% non-vaccinated). Midwife delivery at home, compared to physician delivery in hospital, was strongly associated with non-vaccination status (adjusted odds ratio [aOR] 51.70, 95% CI 37.10-72.10). Factors that might pose barriers to vaccination, such as single marital status (aOR 1.58, 95% CI 1.49-1.67), large number of household children (≥4 vs. 1) (aOR 3.24, 95% CI 2.95-3.54), and multiple household moves (≥3 vs. 0) (aOR 1.69, 95% CI 1.35-2.10), were all strongly associated with incomplete vaccination status. CONCLUSIONS Of the children who were not completely vaccinated at age 2, the vast majority had started but not completed the vaccination series, while a smaller number were selectively vaccinated or not vaccinated at all. Distinct differences are present among these groups that require attention when addressing vaccine coverage.

Enteropathogen detection in children with diarrhoea, or vomiting, or both, comparing rectal flocked swabs with stool specimens: an outpatient cohort study

BACKGROUND Enteropathogen detection traditionally relies on diarrhoeal stool samples, but these are inconvenient to collect if they are not immediately available, leading to suboptimum return rates of samples and delayed or missed diagnostic opportunities. We sought to compare the enteropathogen yields of rectal swabs and stool specimens in children with diarrhoea or vomiting, or both. METHODS The Alberta Provincial Pediatric EnTeric Infection TEam (APPETITE) did a study in three outpatient cohorts in Calgary and Edmonton (AB, Canada)-children enrolled in the Pediatric Emergency Research Canada emergency departments, children receiving routine vaccinations at a Calgary health clinic, and symptomatic children who met criteria for treatment at home. Eligible participants were children younger than 18 years, with at least three episodes of vomiting or diarrhoea in the preceding 24 h and fewer than 7 days of symptoms. After excluding those enrolled within the previous fortnight, unable to follow-up, or having psychiatric illness, neutropenia, or requiring emergent care, we attempted to collect rectal swabs and stool from all participants. Specimens were tested with the multianalyte assay Luminex xTAG Gastrointestinal Pathogen Panel, an in-house five-virus panel and bacterial culture. Primary outcomes were comparative yield (calculated as the proportion of submitted paired specimens only in which at least one pathogen was identified) and overall yield (which calculated the proportion of study participants in whom at least one pathogen was identified in all specimens, where unsubmitted specimens were analysed as negative). We used McNemars test to do pathogen-specific analyses, and generalised estimating equations (GEE) for the global (ie, any) pathogen analyses, with adjustments made for the presence of diarrhoea, location, and their interactions with specimen type. FINDINGS Between Dec 12, 2014, and Aug 31, 2016, we studied 1519 eligible participants, 1147 (76%) of whom provided stool specimens and 1514 (>99%) provided swab specimens. 871 (76%) of 1147 stool specimens and 1024 (68%) of 1514 swabs were positive for any pathogen (p<0·0001). Comparative yield adjusted odds ratios (ORs) for stool specimens relative to swabs were 1·24 (95% CI 1·11-1·38) in children with diarrhoea at presentation and 1·76 (1·47-2·11) in children without diarrhoea. GEE analysis identified an interaction between the presence of diarrhoea and specimen type (p=0·0011) and collection location (p=0·0078). In an overall yield analysis, pathogen yield was 57% (871 of 1519 children) for stool specimens and 67% (1024 of 1519 children) for rectal swabs, with an unadjusted OR of 0·65 (95% CI 0·59-0·72) for stool relative to swab. INTERPRETATION Rectal swabs should be done when enteropathogen identification and rapid detection are needed, appropriate molecular diagnostic technology is available, and a stool specimen is not immediately available. In view of their high yield, we urge that the recommendation against the use of rectal swabs as diagnostic specimens be reconsidered. FUNDING Alberta Innovates-Health Solutions Team Collaborative Research Innovation Opportunity.

Hepatitis B Virus (HBV) Variants in Untreated and Tenofovir Treated Chronic Hepatitis B (CHB) Patients during Pregnancy and Post-Partum Follow-Up

Background Chronic hepatitis B (CHB) is a dynamic disease that may be affected by immune changes in pregnancy. Guidelines suggest consideration of nucleos/tide analogs (NA), i.e., tenofovir, (TDF) in highly viremic mothers to reduce vertical transmission risk. HBV variability affects CHB outcome, but little is known about HBV genetic changes in pregnancy due to immune or NA selection. Objectives To evaluate HBV diversity in NA treated or untreated pregnant vs. post-partum CHB carriers. Study Design In plasma collected from 21 mothers (7 matching pre/post-partum), HBV serological tests, genotype and viral load were assayed. The HBV pre-surface (S) /S overlapping polymerase (P) (N = 20), pre-core (C) /C (N = 11) and/or full genome PCR amplicons (N = 3) underwent clonal sequence analysis. Results The median age was 31 y, 71% Asian, 68% genotype B or C, 33% HBV eAg+, 5 received TDF (median HBV DNA 8.5 log IU/ml). In untreated mothers, median antepartum vs. post-partum ALT was 21 vs. 24 U/L and HBV DNA was 2.7 vs. 2.4 log(10) IU/ml. ALT and/or HBV DNA flares occurred during pregnant and/or post-partum period in 47% (10/21). Clonal sequencing antepartum showed the presence of minor “a determinant” and/or vaccine escape mutants (VEM) but drug resistant variants were infrequent. Analysis of pregnant vs. post-partum samples showed different HBV variants and viral diversity. Conclusions Differences in immune and/or by NA selective pressures during pregnancy may affect HBV evolution during pregnancy. The presence of minor VEM warrant infant follow-up.

Emergence of New CMRSA7/USA400 Methicillin-Resistant Staphylococcus aureus spa Types in Alberta, Canada, from 2005 to 2012

ABSTRACT Methicillin-resistant Staphylococcus aureus (MRSA) has become one of the most significant pathogens affecting global public health and health care systems. In Canada and the United States, the spread of MRSA is primarily attributed to a single dominant epidemic clone: CMRSA10/USA300. Despite this, the CMRSA7/USA400 epidemic clone has been reported to be the predominate epidemic clone in several Canadian provinces and some parts of the United States. This study examined the epidemiology of CMRSA7/USA400 MRSA in Alberta, Canada, from June 2005 to December 2012. Molecular characterization of CMRSA7/USA400 isolates was done using spa, SCCmec, PVL, and PFGE typing and identified two predominant spa types in Alberta: t128 and t1787. Although closely related, these spa types have distinct geographic distributions. From 2010 to 2012, the number of t128 infections has remained stable while there has been a nearly 3-fold increase in the number of provincial t1787 infections, accompanied by 10-fold increases in t1787 infection rates in some communities. Most t128 and t1787 patients were First Nations or Inuit people, and isolates were usually from skin and soft tissue infections in outpatients. t128 patients were significantly older than t1787 patients. Antimicrobial susceptibility testing showed higher mupirocin resistance in t1787 than in t128 MRSA. Improved strategies to reduce or stabilize t1787 infections in Alberta are needed.

The effectiveness of shingles vaccine among Albertans aged 50 years or older: A retrospective cohort study

PURPOSE We assessed the effectiveness of shingles vaccine in preventing incident shingles among Alberta residents aged 50 years or older over the period 2009 - 2015, using administrative health data. METHODS The cohort comprised of Albertans from the Alberta Health Care Insurance Plan Registry (AHCIP) as of June 30, 2009 and aged 50 years or older. Those who received shingles vaccine were identified from the provincial pharmaceutical information network. The occurrence of incident shingles was identified through both inpatient and outpatients/community care data. Incident shingles was defined as the earliest dated record of ICD 9-CM 053 or ICD-10-CA B02. Starting on November 1, 2009, individuals with no history of shingles or shingles vaccination were followed until Nov 1, 2015 (6 years), or until shingles incidence, death, or AHCIP cancellation (including leaving Alberta). Vaccine effectiveness (VE) was estimated as the inverse of the relative risk of developing incident shingles in each year following vaccination compared to time at risk without vaccination, while adjusting for age, sex, income quintile, and immune compromising conditions (identified from physician claims, inpatient, and cancer registry data). RESULTS There were 1,094,236 individuals in the cohort, with 85,439 (7.80%) vaccinated individuals. The shingles incidence rate was 9.03 [95% CI: 8.95, 9.11] cases per 1,000 person years (49,243 cases). Adjusted VE in the first year following immunization was 50.02% [95% CI: 44.71%, 54.83%] against incident shingles, decreasing to no effect by the fifth year (VE = 14.00% [95% CI: -20.99%, 38.88%]). CONCLUSIONS Our findings are consistent with observations from other population based studies and provide population level data for policy-makers to review when making decisions related to public funding of shingles vaccine.