In Elimination Settings, Measles Antibodies Wane After Vaccination but Not After Infection: A Systematic Review and Meta-Analysis.

BACKGROUND: We conducted a systematic review to assess whether measles humoral immunity wanes in previously infected or vaccinated populations in measles elimination settings. METHODS: After screening 16 822 citations, we identified 9 articles from populations exposed to wild-type measles and 16 articles from vaccinated populations that met our inclusion criteria. RESULTS: Using linear regression, we found that geometric mean titers (GMTs) decreased significantly in individuals who received 2 doses of measles-containing vaccine (MCV) by 121.8 mIU/mL (95% confidence interval [CI], -212.4 to -31.1) per year since vaccination over 1 to 5 years, 53.7 mIU/mL (95% CI, -95.3 to -12.2) 5 to 10 years, 33.2 mIU/mL (95% CI, -62.6 to -3.9), 10 to 15 years, and 24.1 mIU/mL (95% CI, -51.5 to 3.3) 15 to 20 years since vaccination. Decreases in GMT over time were not significant after 1 dose of MCV or after infection. Decreases in the proportion of seropositive individuals over time were not significant after 1 or 2 doses of MCV or after infection. CONCLUSIONS: Measles antibody waning in vaccinated populations should be considered in planning for measles elimination.

What Is the Evidence to Support a Correlate of Protection for Measles? A Systematic Review.

BACKGROUND: Many studies assume that the serologic correlate of protection from measles disease is 120 mIU/mL. We systematically reviewed the literature to examine the evidence supporting this correlate of protection. METHODS: We searched peer-reviewed and gray literature for articles reporting a measles correlate of protection. We excluded studies focusing on special populations, infants aged <9 months, and those using animal models or nonstandard vaccines or administration routes. We extracted and synthesized data from full-text articles that met inclusion criteria. RESULTS: We screened 14 778 articles and included 5 studies in our review. The studies reported either preexposure antibody concentrations of individuals along with a description of symptoms postexposure, or the proportion of measles cases that had preexposure antibody concentrations above a threshold of immunity specified by the authors. Some studies also described secondary antibody responses upon exposure. The variation in laboratory methods between studies made comparisons difficult. Some of the studies that assumed 120 mIU/mL as a correlate of protection identified symptomatic individuals with preexposure titers exceeding this threshold. CONCLUSIONS: Our findings underscore the scant data upon which the commonly used 120 mIU/mL measles threshold of protection is based, suggesting that further work is required to characterize the measles immunity threshold.

An Exploration of How Individuals with an Ostomy Communicatively Manage Uncertainty.

Individuals with an ostomy (a surgical diversion of part of the digestive tract through the abdomen) face a variety of uncertainties, due to the chronic and anatomy-altering nature of living with an ostomy, as well as the perceived stigma attached to having one. However, little is known about how these individuals negotiate uncertainty, and more specifically, how they manage the information they receive and disclose in the uncertainty management process. Thus, through 21 semi-structured interviews of individuals with an ostomy and the use of Uncertainty Management Theory as a theoretical framework, the current study found individuals with an ostomy attempted to negotiate uncertainty by managing information received and disclosed and by adapting to chronic uncertainty. This investigation recommends practical applications for medical professionals, supportive others, patients with an ostomy, as well as future surgical candidates to help manage uncertainty.

The importance of size and disorder in the cryoprotective effects of dehydrins.

Dehydrins protect plant proteins and membranes from damage during drought and cold. Vitis riparia K2 is a 48-residue protein that can protect lactate dehydrogenase from freeze-thaw damage by preventing the aggregation and denaturation of the enzyme. To further elucidate its mechanism, we used a series of V. riparia K2 concatemers (K4, K6, K8, and K10) and natural dehydrins (V. riparia YSK2, 60 kilodalton peach dehydrin [PCA60], barley dehydrin5 [Dhn5], Thellungiella salsuginea dehydrin2 [TsDHN-2], and Opuntia streptacantha dehydrin1 [OpsDHN-1]) to test the effect of the number of K-segments and dehydrin size on their ability to protect lactate dehydrogenase from freeze-thaw damage. The results show that the larger the hydrodynamic radius of the dehydrin, the more effective the cryoprotection. A similar trend is observed with polyethylene glycol, which would suggest that the protection is simply a nonspecific volume exclusion effect that can be manifested by any protein. However, structured proteins of a similar range of sizes did not show the same pattern and level of cryoprotection. Our results suggest that with respect to enzyme protection, dehydrins function primarily as molecular shields and that their intrinsic disorder is required for them to be an effective cryoprotectant. Lastly, we show that the cryoprotection by a dehydrin is not due to any antifreeze protein-like activity, as has been reported previously.

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.

Exploring the reasons for low pertussis vaccine effectiveness in Ontario, Canada, 2006-2008: a Canadian Immunization Research Network study.

OBJECTIVES: Although pertussis vaccines have been widely used for many decades, a burden of illness persists. Resurgences in Ontario, Canada, have not been substantial in the past decade, but an outbreak of pertussis occurred in Toronto between 1 October 2005 and 31 March 2006. Previous Ontario studies found high vaccine effectiveness (VE) in the initial years post-immunization. In order to explore the impact of outbreaks and external factors on VE, we investigated pertussis VE during the period 2006-2008. METHODS: We assessed pertussis VE using a frequency-matched case-control study for the period 1 March 2006 to 31 December 2008. We used logistic regression to estimate VE by age, time since last vaccination, and vaccination status according to the Ontario recommended schedule. We compared analyses including and excluding cases from Toronto, and to two recent Ontario pertussis VE studies. RESULTS: We included 1797 confirmed cases and 7188 matched controls. Most cases were under 4 years of age during the study period. Pertussis VE was 3.8% (95% CI: - 21.0, 24.0) in the period 15-364 days following the last pertussis vaccine dose, and increased with increasing time since vaccination. Pertussis VE in the first 15-364 days excluding Toronto increased to 57.1% (95% CI: 26.0, 75.1), but the trend of increasing VE with time since vaccination persisted. Although VE was higher in older (6-11 years) than younger (0-5 years) children, it was lower at 12-13 years than after 14 years. CONCLUSION: VE was lower in comparison with other studies conducted in Ontario, particularly in younger children. Various factors occurring during the study period may have influenced the results, including clinical testing of asymptomatic contacts, laboratory testing and methods and reporting practice, and a sensitive case definition. Further studies are needed to optimize methods for measuring VE to inform pertussis vaccine policy.

RéSUMé: OBJECTIFS: Bien que les vaccins anticoquelucheux soient couramment utilisés depuis des dizaines d'années, la charge de morbidité de la coqueluche persiste. Sa réapparition en Ontario, au Canada, a été modérée au cours des 10 dernières années, mais une éclosion de coqueluche s'est produite à Toronto entre le 1er octobre 2005 et le 31 mars 2006. Des études antérieures menées en Ontario ont fait état d'une efficacité vaccinale (EV) élevée dans les premières années qui suivent l'immunisation. Pour explorer l'impact des éclosions et des facteurs externes sur l'EV, nous avons étudié l'efficacité des vaccins anticoquelucheux pour la période 2006-2008. MéTHODE: Nous avons évalué l'efficacité des vaccins anticoquelucheux à l'aide d'une étude cas-témoins assortie par fréquence pour la période du 1er mars 2006 au 31 décembre 2008. Nous avons procédé par régression logistique pour estimer l'EV selon l'âge, le temps écoulé depuis la dernière vaccination et le statut vaccinal d'après le calendrier recommandé en Ontario. Nous avons comparé les analyses en incluant et en excluant les cas de Toronto et par rapport à deux récentes études ontariennes sur l'efficacité des vaccins anticoquelucheux. RéSULTATS: Nous avons inclus 1 797 cas confirmés et 7 188 témoins assortis. La plupart des cas avaient moins de 4 ans durant la période de l'étude. L'efficacité des vaccins anticoquelucheux était de 3,8 % (IC de 95 % : -21,0, 24,0) au cours des 15 à 364 jours suivant la dernière dose de vaccin anticoquelucheux et augmentait avec le temps après la vaccination. En excluant Toronto, l'efficacité des vaccins anticoquelucheux au cours des 15 à 364 premiers jours passait à 57,1 % (IC de 95 % : 26,0, 75,1), mais la tendance d'augmentation de l'EV avec le temps après la vaccination était toujours présente. Bien que l'EV ait été supérieure chez les enfants plus vieux (6 à 11 ans) que chez les plus jeunes (0 à 5 ans), elle était plus faible chez les 12-13 ans qu'après 14 ans. CONCLUSION: Nous avons observé une EV plus faible que dans d'autres études menées en Ontario, surtout chez les jeunes enfants. Divers facteurs survenus durant la période de l'étude pourraient en avoir influencé les résultats, dont les tests cliniques menés sur les contacts asymptomatiques, les épreuves et les méthodes de laboratoire, les pratiques de déclaration et l'usage d'une définition de cas sensible. D'autres études sont nécessaires pour optimiser la méthode de mesure de l'EV afin d'éclairer la politique vaccinale contre la coqueluche.

Epidemiology of norovirus and viral gastroenteritis in Ontario, Canada, 2009-2014.

BACKGROUND: Norovirus is the most common cause of acute gastroenteritis in Canada. The illness causes great morbidity and high societal costs. The objective of this article is to describe the epidemiology of norovirus in the province of Ontario, Canada from 2009 to 2014. METHODS: To assess activity of norovirus and viral gastroenteritis (VGE) in Ontario, three datasets were acquired from the provincial government: two traditional surveillance datasets (outbreak and laboratory) and syndromic surveillance data (telehealth), all spanning 2009-2014. All outbreaks, laboratory submissions and telehealth calls were first assessed for total VGE. Norovirus and norovirus-like illness totals were calculated as a proportion of VGE to estimate agent-specific activity levels. Affected institution types, sexes and age groups were also analyzed. RESULTS: Between 2009 and 2014, 41.5% of VGE outbreaks, 63.4% of VGE laboratory submissions and 36.6% of all acute gastroenteritis-related (not restricted to viral causes) telehealth calls were attributed to norovirus and norovirus-like illness in Ontario. The most commonly affected institution type was long-term care homes and the most commonly affected age groups were younger (younger than five years) and older (older than 65 years) individuals. Females were slightly more frequently affected than males. CONCLUSION: Norovirus and norovirus-like illnesses were the leading cause of VGE in Ontario between 2009 and 2014. They comprised the greatest percentage of VGE when compared with all other VGE-associated viruses. Additional work is needed to determine all component costs and necessary public health actions to reduce the burden of disease.

The effect of time since measles vaccination and age at first dose on measles vaccine effectiveness - A systematic review.

BACKGROUND: In settings where measles has been eliminated, vaccine-derived immunity may in theory wane more rapidly due to a lack of immune boosting by circulating measles virus. We aimed to assess whether measles vaccine effectiveness (VE) waned over time, and if so, whether differentially in measles-eliminated and measles-endemic settings. METHODS: We performed a systematic literature review of studies that reported VE and time since vaccination with measles-containing vaccine (MCV). We extracted information on case definition (clinical symptoms and/or laboratory diagnosis), method of vaccination status ascertainment (medical record or vaccine registry), as well as any biases which may have arisen from cold chain issues and a lack of an age at first dose of MCV. We then used linear regression to evaluate VE as a function of age at first dose of MCV and time since MCV. RESULTS: After screening 14,782 citations, we identified three full-text articles from measles-eliminated settings and 33 articles from measles-endemic settings. In elimination settings, two-dose VE estimates increased as age at first dose of MCV increased and decreased as time since MCV increased; however, the small number of studies available limited interpretation. In measles-endemic settings, one-dose VE increased by 1.5% (95% CI 0.5, 2.5) for every month increase in age at first dose of MCV. We found no evidence of waning VE in endemic settings. CONCLUSIONS: The paucity of data from measles-eliminated settings indicates that additional studies and approaches (such as studies using proxies including laboratory correlates of protection) are needed to answer the question of whether VE in measles-eliminated settings wanes. Age at first dose of MCV was the most important factor in determining VE. More VE studies need to be conducted in elimination settings, and standards should be developed for information collected and reported in such studies.

Measles Antibody Levels in Young Infants.

BACKGROUND: Infants are often assumed to be immune to measles through maternal antibodies transferred during pregnancy and, in many countries, receive their first measles-containing vaccine at 12 to 15 months. Immunity may wane before this time in measles-eliminated settings, placing infants at risk for measles and complications. We investigated humoral immunity to measles in infants <12 months of age in Ontario, Canada. METHODS: We selected sera collected at a tertiary pediatric hospital from infants <12 months who were born at ≥37 weeks' gestational age. We excluded infants with conditions that affect antibody levels. We selected ≤25 sera from 8 predetermined age bands and tested them for measles-neutralizing antibody using the plaque-reduction neutralization test. We calculated the proportion immune at each age band, and predictors of infant susceptibility were assessed by using multivariable logistic regression and Poisson regression. RESULTS: Of 196 infant sera, 56% (110 of 196) were from boys, and 35% (69 of 196) were from infants with underlying medical conditions. In the first month, 20% (5 of 25) of infants had antibodies below the protective threshold, which increased to 92% (22 of 24) by 3 months. By 6 months, all infants had titers below the protective threshold. In a multivariable analysis, infant age was the strongest predictor of susceptibility (odds ratio = 2.13 for each additional month increase; 95% confidence interval: 1.52-2.97). CONCLUSIONS: Most infants were susceptible to measles by 3 months of age in this elimination setting. Our findings inform important policy discussions relating to the timing of the first dose of measles-containing vaccine and infant postexposure prophylaxis recommendations.

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.