OBJECTIVES:Measles is a highly infectious virus with potentially serious complications. Infants too young to be vaccinated depend on maternally-derived, transplacentally-transferred antibodies for early protection. We aimed to identify factors influencing maternal measles immunity, and determine predictors of maternal susceptibility and infant immunity during the first year of life. METHODS:Using a prospective cross-sectional study design, we collected data and samples from infant-mother pairs admitted to the Hospital for Sick Children between 2018 and 2020. Measles antibody titres were measured using the gold-standard plaque reduction neutralisation test. RESULTS:We recruited 258 mothers aged 16-45 years, of whom 80.6% (95% CI: 75.8,85.4) had protective antibody levels. The proportion with protective antibodies was lowest among mothers <25 years at 67.9% (95% CI: 50.6,85.2), increasing to 100% (95% CI: 100.0,100.0) in those >40 years. Among the 233 individuals reporting vaccination status, 97.0% received at least one measles-containing vaccine. CONCLUSIONS:Nearly one-fifth of mothers in our study were seronegative to measles, increasing to nearly one-third of mothers under 30 years. The higher susceptibility observed in younger individuals within a highly-vaccinated cohort may suggest waning humoral immunity. Further research is needed to understand the significance of the high proportion of seronegative individuals in younger age groups.

INTRODUCTION:We reviewed evidence on whether vaccinated individuals can transmit measles and conducted a meta-analysis to understand transmission characteristics. METHODS:We searched and extracted data from peer-reviewed and gray literature and included studies reporting measles transmission events from vaccinated individuals. We meta-analyzed the data to calculate the median number of transmissions from vaccinated cases by measles burden, number of doses, and time since first and last dose. RESULTS:We identified 11,911 peer-reviewed and 22 gray literature records and included 33 articles in our review. Seventy individuals who had received 1 or more doses of measles-containing vaccine transmitted measles virus, resulting in 237 secondary cases. Vaccinated transmitters in eliminated areas were older (median age of 19 years (IQR: 3, 21)) than those in non-eliminated areas (median age 16 years; IQR 13, 18) (p = 0.12). Additionally, 91% (30/33) of studies provided data on subsequent transmission generations, leading to 812 measles cases traced back to vaccinated individuals, with a median of 4 (IQR: 1, 10) cases per vaccinated transmitter. CONCLUSION:Measles transmissions from vaccinated cases, although relatively uncommon, must be considered in public health investigations, as such transmissions can contribute to outbreaks.

BACKGROUND:Prior to receiving their first dose of measles-containing vaccine, infants may be protected against infection either via antibodies obtained transplacentally from their mothers or by herd immunity. However, there is evidence that transplacental protection may wane well-before the age of first measles vaccination. METHODS:We conducted a cross-sectional study of infants <12 months of age at The Hospital for Sick Children (SickKids) in Toronto, Ontario, and their mothers. We calculated the probability of measles susceptibility in infants and predicted the mean antibody titre by age. RESULTS:Measles seroprevalence decreased with age, starting at 70.4 % (38/54) in the first month of life and declining to 0.0 % (0/18) by four months of age. Regression models adjusted for maternal place of birth and measles immunity status indicated that the odds of susceptibility approximately tripled with every increasing month of age. INTERPRETATION:Infants in our study are likely susceptible to measles for the majority of their first year of life. All measles-exposed infants should be presumed susceptible, regardless of age. High population-level measles vaccine coverage is essential to protect this susceptible population.

Late-onset sepsis (LOS) in the neonatal intensive care unit (NICU) causes significant morbidity and mortality, yet guidance on empiric management is limited. We surveyed NICUs across Canada and the United States regarding their empiric antimicrobial regimens for LOS, thereby identifying large practice variations and high rates of empiric vancomycin use.

INTRODUCTION:The incidence of varicella in Canada has decreased by almost 99% since vaccination was introduced. However, variation in the timing and eligibility of vaccination programs across the country has resulted in some cohorts being under-vaccinated and therefore potentially susceptible to infection. METHODS:We used nationally representative specimens from the Biobank of Statistics Canada's Canadian Health Measures Survey (CHMS) as well as residual specimens from Ontario collected between 2009-2014 to estimate population immunity across age-groups and geography, and identify any groups at increased risk of varicella infection. RESULTS:The weighted proportion of specimens with antibody levels above the threshold of protection was 93.6% (95% CI: 92.4, 95.0). Protection was lowest among those aged 3-5 years (54.3%; 95% CI: 47.3, 61.4), but increased with age. Individuals born outside Canada had more than twice the odds of varicella susceptibility than those born in Canada (aOR: 2.7; 95% CI: 1.4, 5.0; p = 0.004). There were no differences by sex or geography within Canada, and there were no statistically significant differences when Ontario CHMS sera were compared to Ontario residual sera, apart from in participants aged 12-19 year age-group, for whom the CHMS estimate (91.2%; 95% CI: 86.7, 95.7) was significantly higher (p = 0.03) than that from residual specimens (85.9%, 95% CI: 81.1, 90.8). DISCUSSION:Varicella immunity in Canada is changing. Children appear to have low population immunity, placing them at greater risk of infection and at increased risk of severe disease as they age. Our results underscore the importance of performing periodic serosurveys to monitor further population immunity changes as the proportion of vaccine-eligible birth-cohorts increases, and to continually assess the risk of outbreaks.

SARS-CoV-2 seroprevalence reflects the efficacy of pandemic infection prevention and control measures. We performed anti-spike IgG serological testing on residual sera of children 1-11 years old at a tertiary care referral center between October and November 2021. Immunocompromised patients had the highest SARS-CoV-2 seroprevalence, at 40.5%, compared to 19.3% in non-immunocompromised patients. Targeted infection prevention and public health interventions are warranted for pediatric immunocompromised patients in future pandemics.

Introduction: Pertussis causes significant morbidity and mortality in infants aged <6 months. Maternal pertussis vaccination during pregnancy has been recommended in Canada since 2018 to reduce these negative outcomes. In the absence of routine immunization coverage data, our objective was to evaluate uptake in Toronto, Canada.Methods: We recruited mother-infant pairs at The Hospital for Sick Children, Toronto, between 2018 and 2020. We performed logistic regression to examine associations between demographics and self-reported pertussis vaccination.Results: 76/243 mothers (31.3 %) reported receiving pertussis vaccination during their most recent pregnancy. Odds of receiving vaccination more than doubled with each 1-year increase in year of pregnancy (aOR: 2.2; 95 % CI: 1.3, 3.6; p < 0.01) and among those born in Canada as compared to those not (aOR: 2.0; 95 % CI: 1.1, 3.6; p = 0.02)Conclusion: Uptake of pertussis vaccination during pregnancy in Ontario has increased in recent years, however coverage remains lower than desirable.

We aimed to determine population immunity to measles in Canada, and to assess the risk of future out -breaks. We tested 11,176 sera from Cycles 2 (2009-2011) and 3 (2011-2013) cohorts from the biobank of Statistics Canada's Canadian Health Measures Survey (CHMS) using the BioPlex 2220 MMRV IgG assay. We then tested all BioPlex negative and equivocal samples using a more sensitive Plaque Reduction Neutralization Test (PRNT). We determined the weighted proportion of positive, equivocal, and negative samples by age, sex, region and whether individuals were born in Canada. We found that 90.0% (95% con-fidence interval (CI): 88.2, 91.9) of samples were positive, 4.5% (95% CI: 3.4, 5.5) were equivocal and 5.5% (95% CI: 4.3, 6.7) were negative. Individuals in the 12-19 year age band had the lowest proportion pos-itive at 78.7% (95% CI: 74.2, 83.2) and the highest proportion of positive samples was found in those 60- 79 years (99.6%, 95% CI: 99.3, 99.9). Seropositivity was consistently <90% across a broad range of pediatric and adult age bands (6-39 years). We found that a slightly higher proportion of females were positive (91.9%, 95% CI: 90.1, 93.6) compared to males (88.3%, 95% CI: 85.8, 90.7). When taking into account inter -action between age and born in Canada status, we found individuals born in Canada aged 19 and under were less susceptible (OR = 0.6 (95% CI: 0.4, 0.95)) compared to those born outside Canada whereas, those aged 20 and over were more susceptible (OR = 1.7 (95% CI: 1.1, 2.8)). Our findings indicate that measles immunity in Canada is below the 95% immunity threshold required to sustain measles elimination, underscoring the importance of maintaining high vaccine coverage to prevent future measles outbreaks and sustain Canada's elimination status.(c) 2022 Published by Elsevier Ltd.

Background A correlate of protection (CoP) is an immunological marker associated with protection against infection. Despite an urgent need, a CoP for SARS-CoV-2 is currently undefined. Objectives Our objective was to review the evidence for a humoral correlate of protection for SARS-CoV-2, including variants of concern. Methods We searched OVID MEDLINE, EMBASE, Global Health, Biosis Previews and Scopus to January 4, 2022 and pre-prints (using NIH iSearch COVID-19 portfolio) to December 31, 2021, for studies describing SARS-CoV-2 re-infection or breakthrough infection with associated antibody measures. Two reviewers independently extracted study data and performed quality assessment. Results Twenty-five studies were included in our systematic review. Two studies examined the correlation of antibody levels to VE, and reported values from 48.5% to 94.2%. Similarly, several studies found an inverse relationship between antibody levels and infection incidence, risk, or viral load, suggesting that both humoral immunity and other immune components contribute to protection. However, individual level data suggest infection can still occur in the presence of high levels of antibodies. Two studies estimated a quantitative CoP: for Ancestral SARS-CoV-2, these included 154 (95% confidence interval (CI) 42, 559) anti-S binding antibody units/mL (BAU/mL), and 28.6% (95% CI 19.2, 29.2%) of the mean convalescent antibody level following infection. One study reported a CoP for the Alpha (B.1.1.7) variant of concern of 171 (95% CI 57, 519) BAU/mL. No studies have yet reported an Omicron-specific CoP. Conclusions Our review suggests that a SARS-CoV-2 CoP is likely relative, where higher antibody levels decrease the risk of infection, but do not eliminate it completely. More work is urgently needed in this area to establish a SARS-CoV-2 CoP and guide policy as the pandemic continues.

The COVID-19 pandemic has demonstrated the need for real-time, open-access epidemiological information to inform public health decision-making and outbreak control efforts. In Canada, authority for healthcare delivery primarily lies at the provincial and territorial level; however, at the outset of the pandemic no definitive pan-Canadian COVID-19 datasets were available. The COVID-19 Canada Open Data Working Group was created to fill this crucial data gap. As a team of volunteer contributors, we collect daily COVID-19 data from a variety of governmental and non-governmental sources and curate a line-list of cases and mortality for all provinces and territories of Canada, including information on location, age, sex, travel history, and exposure, where available. We also curate time series of COVID-19 recoveries, testing, and vaccine doses administered and distributed. Data are recorded systematically at a fine sub-national scale, which can be used to support robust understanding of COVID-19 hotspots. We continue to maintain this dataset, and an accompanying online dashboard, to provide a reliable pan-Canadian COVID-19 resource to researchers, journalists, and the general public.

BACKGROUND:Kyrgyzstan has made considerable progress in reducing child mortality compared with other countries in the region, despite a comparatively low economic standing. However, maternal mortality is still high. Given the availability of an established birth registration system, we aimed to comprehensively assess the trends and determinants of reproductive, maternal, newborn, and child health in Kyrgyzstan.METHODS:For this Countdown to 2030 country case study, we used publicly available data repositories and the national birth registry of Kyrgyzstan to examine trends and inequalities of reproductive, maternal, and newborn health and mortality between 1990 and 2018, at a national and subnational level. Coverage of newborn and maternal health interventions was assessed and disaggregated by equity dimensions. We did Oaxaca-Blinder decomposition to determine the contextual factors associated with the observed decline in newborn mortality rates. We also undertook a comprehensive review of national policies and programmes, as well as a prospective Lives Saved Tool analysis, to highlight interventions that have the potential to avert the most maternal, neonatal, and child deaths.FINDINGS:Over the past two decades, Kyrgyzstan reduced newborn mortality rates by 46% and mortality rates of children younger than 5 years by 69%, whereas maternal mortality rates were reduced by 7% and stillbirth rates by 29%. The leading causes of neonatal deaths were prematurity and asphyxia or hypoxia, and preterm small-for-gestational-age infants were more than 80 times more likely to die in their first month of life compared with those born appropriate-for-gestational age at term. Except for contraceptive use, coverage of essential interventions has increased and is generally high, with limited sociodemographic inequities. With scale-up of a few essential neonatal and maternal interventions, 39% of neonatal deaths, 11% of stillbirths, and 19% of maternal deaths could be prevented by 2030.INTERPRETATION:Kyrgyzstan has reduced newborn mortality rates considerably, with the potential for further reduction. To achieve and exceed the Sustainable Development Goal 3 targets for newborn survival and reducing stillbirths, Kyrgyzstan needs to scale up packages of interventions for the care of small and sick babies, assure quality of care in all health-care facilities with regionalised perinatal care, and create a linked national registry for mothers and neonates with rapid feedback and accountability.FUNDING:US Fund for UNICEF under the Countdown to 2015, UNICEF Kyrgyzstan Office.

Background: The Kyrgyz Republic has made great progress in reducing neonatal mortality rate (NMR), compared to the region, despite its regional comparatively low GDP per capita. Given the availability of an established civil registration and vital statistics system, the country is uniquely positioned to undertake a comprehensive assessment of trends and determinants of newborn mortality. Methods: We used publicly available data repositories and the national birth registry data to examine trends and inequalities of reproductive, maternal and newborn health and mortality between 1990 and 2018 at a national and subnational level. Coverage of newborn and maternal health interventions were assessed and disaggregating by equity dimensions. Oaxaca-Blinder decomposition was done to determine the contextual factors associated with the observed decline in NMR. We undertook a comprehensive review of national policies and programs, as well as a prospective Lives Saved Tool (LiST) analysis to highlight interventions that will save the most lives. Findings: In the past two decades, with the help of investments and appropriate policies, the Kyrgyz Republic has reduced NMR by 54%, with the leading causes of death attributable to prematurity and asphyxia. Neonates born pre-term small-for-gestational age are over 80 times more likely to die in their first month of life, compared to those born full term, appropriate-for-gestational age. With the exception of contraceptive use, coverage of essential interventions is increasing and exceptionally high with limited sociodemographic inequities. By 2030, improved case management of premature babies will save the most neonatal lives. Interpretation: The Kyrgyz Republic has reduced NMR considerably, with the potential for further reduction given its remarkably high coverage and low inequities of preventative maternal and newborn health interventions. A particular focus is needed on scaling-up packages of interventions to care for small and sick babies, assuring quality of care in all healthcare facilities, and creating a linked national registry system for mothers and newborns.Funding Statement: US Fund for UNICEF under the Countdown to 2015 and UNICEF KyrgyzstanDeclaration of Interests: All authors declare no competing interests.

BACKGROUND:Soil-transmitted helminths (STH) are intestinal parasites estimated to infect over 1.5 billion people. Current treatment programmes are aimed at morbidity control through school-based deworming programmes (targeting school-aged children, SAC) and treating women of reproductive age (WRA), as these two groups are believed to record the highest morbidity. More recently, however, the potential for interrupting transmission by treating entire communities has been receiving greater emphasis and the feasibility of such programmes are now under investigation in randomised clinical trials through the Bill & Melinda Gates Foundation funded DeWorm3 studies. Helminth parasites are known to be highly aggregated within human populations, with a small minority of individuals harbouring most worms. Empirical evidence from the TUMIKIA project in Kenya suggests that aggregation may increase significantly after anthelminthic treatment. METHODS:A stochastic, age-structured, individual-based simulation model of parasite transmission is employed to better understand the factors that might induce this pattern. A simple probabilistic model based on compounded negative binomial distributions caused by age-dependencies in both treatment coverage and exposure to infection is also employed to further this understanding. RESULTS:Both approaches confirm helminth aggregation is likely to increase post-mass drug administration as measured by a decrease in the value of the negative binomial aggregation parameter, k. Simple analytical models of distribution compounding describe the observed patterns well. CONCLUSIONS:The helminth aggregation that was observed in the field was replicated with our stochastic individual-based model. Further work is required to generalise the probabilistic model to take account of the respective sensitivities of different diagnostics on the presence or absence of infection.

Termed by the Lancet, as “potentially the most important medical advance of the twentieth century,” therapy with oral rehydration solutions (ORSs) has been essential to reducing mortality in children less than 5 years (under five) with infectious gastroenteritis and diarrhea. The target of the diarrhea-control programs in the 1990s was to achieve ORS use in 80% of diarrhea cases by the year 2000. Nevertheless, nearly 20 years later, global uptake remains limited to only a third of the cases. Our analysis shows that from 1990 to 2017, mean ORS coverage in Countdown countries [the 81 Countdown-to-2030 priority countries, which together account for 95% of maternal deaths and 90% of under-five deaths] increased from ~ 30% to nearly 40%. Flawed government policies, inadequate supplies, and lack of awareness among health workers and communities all contributed to this shortfall in coverage. Moreover, imperfect measurement methodology is implicated in questionable coverage data. A multipronged approach focusing on the manufacture, supply, training, and behavioral change is essential to ensure that ORS is used in all epidemic diarrhea cases globally, especially in the under-five population.