Factors associated with return of home oral fluid kits by suspected cases of measles, cohort study, London and South East of England, 2016-2018.

A testing rate for measles above 80% is required by the WHO European Region Measles Elimination strategy to verify elimination. To comply with this rate, we explored factors associated with the return of oral fluid kits (OFK) by suspected measles cases. We described the cases and conducted a mixed-effects analysis to assess the relationship between socio-demographic and public health management characteristics and the likelihood of returning an OFK to the reference laboratory. Of 3,929 cases who were sent a postal OFK, 2,513 (67%) returned the kit. Adjusting for confounding, registration with a general practitioner (GP) (aOR:1.48, 95%CI:1.23-1.76) and living in a less deprived area (aOR:1.35, 95%CI:1.04-1.74) were associated with an increased likelihood of returning the OFK. The odds of returning the OFK also increased if the HPT contacted the parents/guardians of all cases prior to sending the kit and confirmed their address (aOR:2.01, 95%CI:1.17-3.42). Cases notified by a hospital (aOR:1.94, 95%CI:1.31-2.87) or GP (aOR:1.52; 95%CI:1.06-2.16) also had higher odds of returning the OFK. HPTs may want to consider these factors when managing suspected cases of measles since this may help in increasing the testing rates to the WHO-recommended level.

Protective effect of a first SARS-CoV-2 infection from reinfection: a matched retrospective cohort study using PCR testing data in England.

The duration of immunity after first severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and the extent to which prior immunity prevents reinfection is uncertain and remains an important question within the context of new variants. This is a retrospective population-based matched observational study where we identified the first polymerase chain reaction (PCR) positive of primary SARS-CoV-2 infection case tests between 1 March 2020 and 30 September 2020. Each case was matched by age, sex, upper tier local authority of residence and testing route to one individual testing negative in the same week (controls) by PCR. After a 90-day pre-follow-up period for cases and controls, any subsequent positive tests up to 31 December 2020 and deaths within 28 days of testing positive were identified, this encompassed an essentially vaccine-free period. We used a conditional logistic regression to analyse the results. There were 517 870 individuals in the matched cohort with 2815 reinfection cases and 12 098 first infections. The protective effect of a prior SARS-CoV-2 PCR-positive episode was 78% (odds ratio (OR) 0.22, 0.21-0.23). Protection rose to 82% (OR 0.18, 0.17-0.19) after a sensitivity analysis excluded 933 individuals with a first test between March and May and a subsequent positive test between June and September 2020. Amongst individuals testing positive by PCR during follow-up, reinfection cases had 77% lower odds of symptoms at the second episode (adjusted OR 0.23, 0.20-0.26) and 45% lower odds of dying in the 28 days after reinfection (adjusted OR 0.55, 0.42-0.71). Prior SARS-CoV-2 infection offered protection against reinfection in this population. There was some evidence that reinfections increased with the alpha variant compared to the wild-type SARS-CoV-2 variant highlighting the importance of continued monitoring as new variants emerge.

Triangulation of measles vaccination data in the United Kingdom of Great Britain and Northern Ireland.

OBJECTIVE: To illustrate how data triangulation involving routine data sources can optimize data usage and provide insights into vaccine programme effectiveness by considering measles vaccination and disease incidence data in England. METHODS: We obtained data on measles, mumps and rubella (MMR) vaccine coverage in birth cohorts from 1985 to 2016 from child health records and adjusted for under-ascertainment and catch-up campaigns. We assumed that the population had no natural immunity and that vaccine effectiveness was 95% for one dose and 99.75% for two doses. Vaccinations done outside the routine schedule and in people who entered England after the age of immunization were identified from primary care records. Measles susceptibility was defined as the percentage of individuals who were not immune despite all vaccination activities. We triangulated measles susceptibility and incidence data. FINDINGS: Median susceptibility was 4.6% (range: 1.2-9.2). Among cohorts eligible for two MMR vaccine doses, those born between 1998 and 2004 were most susceptible. Measles incidence was highest in these cohorts. Data from primary care and child health records were comparable for cohorts after 2000, suggesting that little supplementary vaccination took place. For cohorts before 2000, primary care data quality was insufficient for accurately estimating coverage. CONCLUSION: Triangulating routine data on measles vaccination coverage and disease surveillance provided new insights into population immunity and helped identify vulnerable groups, which was useful for prioritizing public health actions to close gaps in immunity. This approach could be applied in any country that routinely records vaccine coverage and disease incidence.

Rubella infection in pregnancy and congenital rubella in United Kingdom, 2003 to 2016.

Rubella vaccination has been included in the United Kingdom's (UK) routine childhood schedule for nearly 30 years. The UK achieved World Health Organization (WHO) elimination status in 2016 and acute rubella infections are rare. In the period 2003-16, 31 rubella infections in pregnancy (0.23 per 100,000 pregnancies) were identified through routine surveillance, of which 26 were in women who were born abroad. Five of the 31 rubella infections led to congenital rubella syndrome in the infant and three had confirmed congenital rubella infection without congenital rubella syndrome. An additional seven babies were identified with congenital rubella syndrome, although rubella infection in pregnancy had not been reported. Place of birth was known for six of these seven mothers, all of whom were born outside the UK, and in five cases maternal infection was acquired abroad. WHO Europe has set targets for measles and rubella elimination and prevention of congenital rubella syndrome by 2015. Vaccination uptake and rubella immunity is high in the UK population and most infections in pregnancy since 2003 were acquired abroad and in unvaccinated women. Every contact with a health professional should be used to check that women are fully immunised according to UK schedule.

Summer music and arts festivals as hot spots for measles transmission: experience from England and Wales, June to October 2016.

We report 52 cases of measles linked to music and arts festivals in England and Wales, between mid-June and mid-October 2016. Nearly half were aged 15 to 19 years. Several individuals who acquired measles at one festival subsequently attended another festival while infectious, resulting in multiple interlinked outbreaks. Transmission within festivals resulted in a geographical spread of cases nationally as well as internationally, which presents particular challenges for measles control.

A Re-emergence of Subacute Sclerosing Panencephalitis in the United Kingdom.

New pediatric and adult subacute sclerosing panencephalitis cases between 1996 and 2020 were reported based on an established UK registry with no evidence of under-ascertainment using a separate pediatric surveillance system. After 15 years with no pediatric UK-acquired cases, 3 cases arose from 2017 after increased measles. Modeling suggested this was in line with measles notifications, underreporting of laboratory-confirmed measles or increased subacute sclerosing panencephalitis risk.

Monitoring the safety of COVID-19 vaccination in pregnancy in the UK: A national study using the UK Obstetric Surveillance System (UKOSS), UK Teratology Information Service (UKTIS) and Vaccination in Pregnancy (VIP) safety monitoring systems.

Background: COVID-19 vaccines are protective against disease. Pregnant women benefit from vaccination as they are at higher risk of poor maternal and neonatal outcomes following infection. Methods: Following regulatory approval of two COVID-19 vaccines in the United Kingdom, a rapid national study of vaccination in pregnancy was instituted using three existing safety surveillance platforms: UKOSS, UKTIS and VIP. This preliminary report describes the data collected up to the 15th June 2021. Results: There were 971 reports of COVID-19 vaccination in the UKOSS/UKTIS (n = 493) and VIP (n = 478) monitoring systems describing 908 individual pregnancies. Pfizer-BioNTech mRNA vaccination was most common (n = 501, 55.2%), most women were vaccinated in their second or third trimester (n = 566, 62.3%), and were mainly vaccinated due to occupational infection risk (n = 577, 63.5%). Conclusion: Obstetric outcome data will be obtained by December 2021. However, women should not delay vaccination whilst awaiting further safety data to emerge.

Risk of SARS-CoV-2 reinfections in children: a prospective national surveillance study between January, 2020, and July, 2021, in England.

BACKGROUND: Reinfection after primary SARS-CoV-2 infection is uncommon in adults, but little is known about the risks, characteristics, severity, or outcomes of reinfection in children. We aimed to assess the risk of SARS-CoV-2 reinfection in children and compare this with the risk in adults, by analysis of national testing data for England. METHODS: In our prospective, national surveillance study to assess reinfection of SARS-CoV-2 in children in England, we used national SARS-CoV-2 testing data to estimate the risk of reinfection at least 90 days after primary infection from Jan 27, 2020, to July, 31, 2021, which encompassed the alpha (B.1.1.7) and delta (B.1.617.2) variant waves in England. Data from children up to age 16 years who met the criteria for reinfection were included. Disease severity was assessed by linking reinfection cases to national hospital admission data, intensive care admission, and death registration datasets. FINDINGS: Reinfection rates closely followed community infection rates, with a small peak during the alpha wave and a larger peak during the delta wave. In children aged 16 years and younger, 688 418 primary infections and 2343 reinfections were identified. The overall reinfection rate was 66·88 per 100 000 population, which was higher in adults (72·53 per 100 000) than children (21·53 per 100 000). The reinfection rate after primary infection was 0·68% overall, 0·73% in adults compared with 0·18% in children age younger than 5 years, 0·24% in those aged 5-11 years, and 0·49% in those aged 12-16 years. Of the 109 children admitted to hospital with reinfection, 78 (72%) had comorbidities. Hospital admission rates were similar for the first (64 [2·7%] of 2343) and second episode (57 [2·4%] of 2343) and intensive care admissions were rare (seven children for the first episode and four for reinfections). There were 44 deaths within 28 days after primary infection (0·01%) and none after reinfection. INTERPRETATION: The risk of SARS-CoV-2 reinfection is strongly related to exposure due to community infection rates, especially during the delta variant wave. Children had a lower risk of reinfection than did adults, but reinfections were not associated with more severe disease or fatal outcomes. FUNDING: UK Health Security Agency.

Disease severity during SARS-COV-2 reinfection: a nationwide study.

OBJECTIVE: We aimed to look at the burden of disease caused by SARS-COV-2 reinfections and identified potential risk factors for disease severity. METHODS: We used national surveillance data to collect information on all SARS-CoV-2 primary infection and suspected reinfection cases between January 2020 until early May 2021. Reinfection cases were positive COVID-19 PCR or antigen test, 90 days after their first COVID-19 positive test. We collected information on case demographics, hospital and ICU admission, immunisation status and if individuals were at risk of complication for COVID-19. RESULTS: Deaths reported within 28 days of testing positive were 61% (95% confidence interval: 56% to 65%) lower in suspected COVID-19 reinfection than primary infection cases. In the unvaccinated cohort, reinfections were associated with 49% (37% to 58%) lower odds of hospital admission in cases aged 50 to 65 years in the population not identified at risk of complication for COVID-19, and 34% (17% to 48%) in those at risk. ICU admission at reinfection compared to primary infection decreased 76% (55% to 87%). Individuals at risk and those aged below 50 years, who received at least 1 dose of vaccine against COVID-19, were 62% (39% to 74%) and 58% (24% to 77%) less likely to get admitted to hospital at reinfection, respectively. CONCLUSION: Prior SARS-CoV-2 infection was associated with lower odds of dying, and both prior infection and immunisation showed a protective effect against severe disease in selected populations. Older age, sex and underlying comorbidities appeared as principal risk factors for illness severity at reinfection. FUNDING: PHE/UKHSA.

Mumps complications and effects of mumps vaccination, England and Wales, 2002-2006.

We analyzed data from hospital admissions and enhanced mumps surveillance to assess mumps complications during the largest mumps outbreak in England and Wales, 2004-2005, and their association with mumps vaccination. When compared with nonoutbreak periods, the outbreak was associated with a clear increase in hospitalized patients with orchitis, meningitis, and pancreatitis. Routine mumps surveillance and hospital data showed that 6.1% of estimated mumps patients were hospitalized, 4.4% had orchitis, 0.35% meningitis, and 0.33% pancreatitis. Enhanced surveillance data showed 2.9% of mumps patients were hospitalized, 6.1% had orchitis, 0.3% had meningitis, and 0.25% had pancreatitis. Risk was reduced for hospitalization (odds ratio [OR] 0.54, 95% confidence interval [CI] 0.43-0.68), mumps orchitis (OR 0.72, 95% CI 0.56-0.93) and mumps meningitis (OR 0.28, 95% CI 0.14-0.56) when patient had received 1 dose of measles, mumps, and rubella vaccine. The protective effect of vaccination on disease severity is critical in assessing the total effects of current and future mumps control strategies.

Oral fluid testing during 10 years of rubella elimination, England and Wales.

Surveillance of rubella in England and Wales has included immunoglobulin M testing of oral (crevicular) fluid from reported case-patients since 1994. The need for laboratory confirmation to monitor rubella elimination is emphasized by poor sensitivity (51%, 95% confidence interval 48.9%-54.0%) and specificity (55%, 95% confidence interval 53.7%-55.6%) of the clinical case definition. During 1999-2008, oral fluid from 11,709 (84%) of 13,952 reported case-patients was tested; 143 (1.0%) cases were confirmed and 11,566 (99%) were discarded (annual investigation and discard rate of clinically suspected rubella cases was 2,208/100,000 population). Incidence of confirmed rubella increased from 0.50 to 0.77/1 million population when oral fluid testing was included. Oral fluid tests confirmed that cases were more likely to be in older, unvaccinated men. Testing of oral fluid has improved ascertainment of confirmed rubella in children and men and provided additional information for assessing UK progress toward the World Health Organization elimination goal.

A national quality assessment scheme for counting residual leucocytes in unfixed leucodepleted products: the effect of standardisation and 48 hour storage.

BACKGROUND: WBC counting, an essential part of quality monitoring of WBC-reduced blood components, is carried out logistically within 48-72 h of collection. The between-laboratory variability and effects of 24-48 h storage were investigated using three major counting technologies. STUDY DESIGN AND METHODS: Samples of RBC and platelets with WBC in the range 0-50/microl were transported by courier. WBC counting was performed on days 1 and 2, by IMAGN 2000, flow cytometry and Nageotte, initially using local protocols and then using a national flow protocol. Up to 15 laboratories participated in each exercise. RESULTS: For "real failed leucodepleted" red cell products, higher levels of variability were observed for flow and Nageotte, as compared to IMAGN. For spiked RBC samples at critical decision making point (3-20 WBC/microl), between-laboratory the coefficients of variation (CVs) were low for IMAGN and were the highest for Nageotte. Flow cytometry CVs were generally high but improved subsequent to standardisation of sampling and the gating strategy. A similar pattern in the variability of results was observed for platelet concentrates. Sign tests using all samples (carried out for each method in each exercise; 25 in total) demonstrated no overall tendency for larger WBC counts to be recorded on day 1 when compared to day 2, although this difference was significant (p < 0.001) in certain cases depending on the nature of the spiked product. CONCLUSIONS: We conclude that while a good performance is achieved using validated automated technologies for low residual leucocyte counting, the unification of reagents and standardisation of sampling and gating strategies are essential in obtaining interchangeable results. Unfixed RBC and platelet samples can generally be stored for 48 h before WBC counting.

A platelet quality assessment scheme for comparing the performance of quality monitoring laboratories in the UK National Blood Service.

This exercise focused on performance of NBS quality monitoring establishments with respect to enumeration of low leucocyte and other quality indexes of platelet concentration. Paired identical leucodepleted platelet samples, spiked with WBC (20 cells/microl) in 'vacuette' or 'pouch' were assessed by participants (n = 20) on days 1, 2 and 5. For low WBC counting, all laboratories gave estimates within acceptable range (+/-25%) and good agreement between storage and assay methods was observed on days 1 and 2. Day 5 results showed greater variability. Under improved performance criteria (+/-15%), only one laboratory under-estimated at days 1 and 2. Similarly, other parameters demonstrated good agreement between storage methods on days 1 and 2. At day 5, mean results were often significantly different to previous days. Improved performance target (+/-15%) will allow identification of non-conformers.

The effect of measles on health-related quality of life: a patient-based survey.

BACKGROUND: Measles is a highly contagious and potentially fatal illness preventable through vaccination. Outbreaks in the UK and many other European countries have been increasing over recent years, with over 3,207 laboratory-confirmed cases reported by Public Health England from January 2012 to the end of June 2013. To aid rational decision making regarding measles control versus other use of healthcare resources, it is important to measure the severity of measles in units that are comparable to other diseases. The standard metric for this in the UK is the quality-adjust life year (QALY). To our knowledge, the impact of measles on health-related quality of life (HRQoL) in terms of QALYs has not been quantified. METHODS AND FINDINGS: Individuals with confirmed measles were sent questionnaires requesting information on the short-term impact of the illness on their HRQoL using the EuroQol EQ-5D-3L questionnaire. HRQoL was reported for the day the questionnaire was received, the worst day of infection and at follow-up three weeks later. 507 questionnaires were sent to individuals with confirmed measles with 203 returned (40%). The majority of respondents were not vaccinated. The mean time off work or school was 9.6 days. The mean duration of perceived illness was 13.8 days. The mean number of QALYs lost was 0.019 (equivalent to 6.9 days). The overall burden of disease in terms of QALYs lost in England based on the total number of confirmed cases in the twelve month period from 1st June 2012 was estimated to be 44.2 QALYs. CONCLUSION: The short-term impact of measles infection on HRQoL is substantial, both at the level of the individual patient and in terms of the overall disease burden. This is the first attempt to quantify QALY-loss due to measles at a population level, and provides important parameters to guide future intervention and control measures.