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The basic reproduction number, R nought (R0), is defined as the average number of secondary cases of an infectious disease arising from a typical case in a totally susceptible population, and can be estimated in populations if pre-existing immunity can be accounted for in the calculation. R0 determines the herd immunity threshold and therefore the immunisation coverage required to achieve elimination of an infectious disease. As R0 increases, higher immunisation coverage is required to achieve herd immunity. In July, 2010, a panel of experts convened by WHO concluded that measles can and should be eradicated. Despite the existence of an effective vaccine, regions have had varying success in measles control, in part because measles is one of the most contagious infections. For measles, R0 is often cited to be 12–18, which means that each person with measles would, on average, infect 12–18 other people in a totally susceptible population. We did a systematic review to find studies reporting rigorous estimates and determinants of measles R0. Studies were included if they were a primary source of R0, addressed pre-existing immunity, and accounted for pre-existing immunity in their calculation of R0. A search of key databases was done in January, 2015, and repeated in November, 2016, and yielded 10 883 unique citations. After screening for relevancy and quality, 18 studies met inclusion criteria, providing 58 R0 estimates. We calculated median measles R0 values stratified by key covariates. We found that R0 estimates vary more than the often cited range of 12–18. Our results highlight the importance of countries calculating R0 using locally derived data or, if this is not possible, using parameter estimates from similar settings. Additional data and agreed review methods are needed to strengthen the evidence base for measles elimination modelling.

Patients who had a positive laboratory test for influenza were six times as likely to be hospitalized for acute myocardial infarction during the 7 days after specimen collection (the “risk interval”) as during the year before and the year after the risk interval.

Phase 3 randomized-controlled trials have provided promising results of COVID-19 vaccine efficacy, ranging from 50 to 95% against symptomatic disease as the primary endpoints, resulting in emergency use authorization/listing for several vaccines. However, given the short duration of follow-up during the clinical trials, strict eligibility criteria, emerging variants of concern, and the changing epidemiology of the pandemic, many questions still remain unanswered regarding vaccine performance. Post-introduction vaccine effectiveness evaluations can help us to understand the vaccine's effect on reducing infection and disease when used in real-world conditions. They can also address important questions that were either not studied or were incompletely studied in the trials and that will inform evolving vaccine policy, including assessment of the duration of effectiveness; effectiveness in key subpopulations, such as the very old or immunocompromised; against severe disease and death due to COVID-19; against emerging SARS-CoV-2 variants of concern; and with different vaccination schedules, such as number of doses and varying dosing intervals. WHO convened an expert panel to develop interim best practice guidance for COVID-19 vaccine effectiveness evaluations. We present a summary of the interim guidance, including discussion of different study designs, priority outcomes to evaluate, potential biases, existing surveillance platforms that can be used, and recommendations for reporting results.

Background As countries move towards or achieve measles elimination status, serosurveillance is an important public health tool. However, a major challenge of serosurveillance is finding a feasible, accurate, cost-effective, and high throughput assay to measure measles antibody concentrations and estimate susceptibility in a population. We conducted a systematic review to assess, characterize, and – to the extent possible – quantify the performance of measles IgG enzyme-linked assays (EIAs) compared to the gold standard, plaque reduction neutralization tests (PRNT). Methods We followed the PRISMA statement for a systematic literature search and methods for conducting and reporting systematic reviews and meta-analyses recommended by the Cochrane Screening and Diagnostic Tests Methods Group. We identified studies through PubMed and Embase electronic databases and included serologic studies detecting measles virus IgG antibodies among participants of any age from the same source population that reported an index (any EIA or multiple bead-based assays, MBA) and reference test (PRNT) using sera, whole blood, or plasma. Measures of diagnostic accuracy with 95% confidence intervals (CI) were abstracted for each study result, where reported. Results We identified 550 unique publications and identified 36 eligible studies for analysis. We classified studies as high, medium, or low quality; results from high quality studies are reported. Because most high quality studies used the Siemens Enzygnost EIA kit, we generate individual and pooled diagnostic accuracy estimates for this assay separately. Median sensitivity of the Enzygnost EIA was 92.1% [IQR = 82.3, 95.7]; median specificity was 96.9 [93.0, 100.0]. Pooled sensitivity and specificity from studies using the Enzygnost kit were 91.6 (95%CI: 80.7,96.6) and 96.0 (95%CI: 90.9,98.3), respectively. The sensitivity of all other EIA kits across high quality studies ranged from 0% to 98.9% with median (IQR) = 90.6 [86.6, 95.2]; specificity ranged from 58.8% to 100.0% with median (IQR) = 100.0 [88.7, 100.0]. Conclusions Evidence on the diagnostic accuracy of currently available measles IgG EIAs is variable, insufficient, and may not be fit for purpose for serosurveillance goals. Additional studies evaluating the diagnostic accuracy of measles EIAs, including MBAs, should be conducted among diverse populations and settings (e.g., vaccination status, elimination/endemic status, age groups).

Encephalitis has many causes, but for most patients the cause is unknown. We aimed to establish the cause and identify the clinical differences between causes in patients with encephalitis in England. Patients of all ages and with symptoms suggestive of encephalitis were actively recruited for 2 years (staged start between October, 2005, and November, 2006) from 24 hospitals by clinical staff. Systematic laboratory testing included PCR and antibody assays for all commonly recognised causes of infectious encephalitis, investigation for less commonly recognised causes in immunocompromised patients, and testing for travel-related causes if indicated. We also tested for non-infectious causes for acute encephalitis including autoimmunity. A multidisciplinary expert team reviewed clinical presentation and hospital tests and directed further investigations. Patients were followed up for 6 months after discharge from hospital. We identified 203 patients with encephalitis. Median age was 30 years (range 0–87). 86 patients (42%, 95% CI 35–49) had infectious causes, including 38 (19%, 14–25) herpes simplex virus, ten (5%, 2–9) varicella zoster virus, and ten (5%, 2–9) Mycobacterium tuberculosis; 75 (37%, 30–44) had unknown causes. 42 patients (21%, 15–27) had acute immune-mediated encephalitis. 24 patients (12%, 8–17) died, with higher case fatality for infections from M tuberculosis (three patients; 30%, 7–65) and varicella zoster virus (two patients; 20%, 2–56). The 16 patients with antibody-associated encephalitis had the worst outcome of all groups—nine (56%, 30–80) either died or had severe disabilities. Patients who died were more likely to be immunocompromised than were those who survived (OR=3·44). Early diagnosis of encephalitis is crucial to ensure that the right treatment is given on time. Extensive testing substantially reduced the proportion with unknown cause, but the proportion of cases with unknown cause was higher than that for any specific identified cause. The Policy Research Programme, Department of Health, UK.

An underestimation of pertussis burden has impeded understanding of transmission and disallows effective policy and prevention to be prioritized and enacted. Capture-recapture analyses can improve burden estimates; however, uncertainty remains around incorporating health administrative data due to accuracy limitations. The aim of this study is to explore the impact of pertussis case definitions and data accuracy on capture-recapture estimates. We used a dataset from March 7, 2010 to December 31, 2017 comprised of pertussis case report, laboratory, and health administrative data. We compared Chao capture-recapture abundance estimates using prevalence, incidence, and adjusted false positive case definitions. The latter was developed by removing the proportion of false positive physician billing code-only case episodes after validation. We calculated sensitivity by dividing the number of observed cases by abundance. Abundance estimates demonstrated that a high proportion of cases were missed by all sources. Under the primary analysis, the highest sensitivity of 78.5% (95% CI 76.2–80.9%) for those less than one year of age was obtained using all sources after adjusting for false positives, which dropped to 43.1% (95% CI 42.4–43.8%) for those one year of age or older. Most code-only episodes were false positives (91.0%), leading to considerably lower abundance estimates and improvements in laboratory testing and case report sensitivity using this definition. Accuracy limitations can be accounted for in capture-recapture analyses using different case definitions and adjustment. The latter enhanced the validity of estimates, furthering the utility of capture-recapture methods to epidemiological research. Findings demonstrated that all sources consistently fail to detect pertussis cases. This is differential by age, suggesting ascertainment and testing bias. Results demonstrate the value of incorporating real time health administrative data into public health surveillance if accuracy limitations can be addressed.

•Most infants are born immune to measles through maternal antibodies, which decay.•In measles elimination settings, infant immunity wanes earlier.•We conducted a systematic review of infant maternal antibody in elimination settings.•Our findings suggest a proportion of infants are susceptible as early as at birth.•This has implications for infant measles immunization in measles eliminated settings. Most infants are born with immunity to measles through maternal antibodies transferred in pregnancy, which decay over time. However, in measles elimination settings, where measles does not circulate endemically and most immunity is from immunization rather than infection, maternal antibody levels are lower. This results in infant immunity that wanes earlier, and a wider susceptibility gap between maternal antibody decay and infant immunization than in non-eliminated settings. We aimed to systematically quantify the extent and duration of protection from measles in infants in settings that have sustained measles elimination. We conducted a systematic review of studies of measles maternal antibody waning in infants in measles elimination settings. We searched MEDLINE, Embase, CINAHL, Scopus, BIOSIS Previews, and Global Health databases for relevant studies. Studies were included if they were set in countries that had eliminated measles for ≥3 years, and if the study cohort included healthy, full-term, unvaccinated infants ≤12 months, born to healthy mothers, and reported a relevant measure of measles maternal antibody in infants. We assessed study quality using the MetaQAT tool. We identified 4692 unique citations, eight of which met inclusion criteria. One study reported anti-measles antibody in cord blood, six reported antibody in infant sera, and one reported both. Two studies reported that 80 and 100% of infants were protected from measles at birth. One study reported no protection amongst 3–7 month old infants, and another reported limited protection in infants >4 months. The remaining studies reported the proportion of infants with detected antibody, but not the proportion immune. Although limited, these data suggest that in settings that have sustained measles elimination, some infants are susceptible to measles well before the age of routine measles immunization. Setting-specific seroprevalence and vaccine effectiveness studies are required to evaluate this in different jurisdictions.

Reports of measles outbreaks are appearing in the news more frequently as we start to face an unfortunate emerging public health problem with no easy solution. The World Health Organization reported a 300% increase in cases of measles in the first 3 months of 2019, compared with 2018. There have been outbreaks in countries in all regions of the world, associated with many deaths, including 72 in Europe in 2018. Although on the surface the solution--ensuring that all are vaccinated--seems simple, achieving and maintaining universal vaccine coverage is a complex feat. Measles elimination at the local level requires virtually everyone to be vaccinated, which is technically challenging. It has been hard to maintain confidence in immunization. Although those who reject immunization place others at risk of vaccine-preventable diseases, they are not solely to blame. There is a larger systems issue. Sustaining measles elimination requires strong regional public health systems.

To investigate maternal antibody levels to varicella in infants <12 months of age in Ontario, Canada. In this study, we included specimens from infants <12 months of age, born at [greater than or equal to]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. 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. 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.

To evaluate the direct and indirect population impact of rotavirus (RV) immunization on hospitalizations and emergency department (ED) visits for acute gastroenteritis (AGE) in Ontario before and after the publicly-funded RV immunization program. Administrative data was used to identify ED visits and hospitalizations for all Ontarians using ICD-10 codes. We used two outcome definitions: RV-specific AGE (RV-AGE) and codes representing RV-, other viral and cause unspecified AGE (\"overall AGE\"). The pre-program and public program periods were August 1, 2005 to July 31, 2011; and August 1, 2011 to March 31, 2013, respectively. A negative binominal regression model that included the effect of time was used to calculate rates and rate ratios (RRs) and 95% confidence intervals (CIs) for RV-AGE and overall AGE between periods, after adjusting for age, seasonality and secular trends. Analyses were conducted for all ages combined and age stratified. Relative to the pre-program period, the adjusted RRs for RV-AGE and overall AGE hospitalizations in the public program period were 0.29 (95%CI: 0.22-0.39) and 0.68 (95%CI: 0.62-0.75), respectively. Significant reductions in RV-AGE hospitalizations were noted overall and for the following age bands: < 12 months, 12-23 months, 24-35 months, 3-4 years, and 5-19 years. Significant declines in overall AGE hospitalizations were observed across all age bands, including older adults > = 65 years (RR 0.80, 95%CI: 0.72-0.90). The program was associated with adjusted RRs of 0.32 (95% CI: 0.20-0.52) for RV-AGE ED visits and 0.90 (95% CI: 0.85-0.96) for overall AGE ED visits. This large, population-based study provides evidence of the impact of RV vaccine in preventing hospitalizations and ED visits for RV-AGE and overall AGE, including herd effects.