Post-COVID-19 condition and persisting symptoms in English schoolchildren: repeated surveys to March 2022.

BACKGROUND: Both post-COVID-19 condition (long COVID) and the presence of persisting symptoms that do not meet formal definitions of post-COVID-19-condition may adversely affect quality of life and function. However, their prevalence among children and young people in England is unclear. METHODS: We used data from repeated surveys in a large cohort of English schoolchildren from the COVID-19 Schools Infection Survey (SIS) for the school year 2021/22 to describe the weighted prevalence of post-COVID-19-condition and compare persisting symptoms between individuals with a positive SARS-CoV-2 test and those with neither a positive test history nor suspected infection. RESULTS: Among 7797 children from 173 schools, 1.8% of primary school pupils (aged 4 to 11 years), 4.5% of secondary school pupils in years 7-11 (aged 11 to 16 years) and 6.9% of those in years 12-13 (aged 16 to 18 years) met a definition of post-COVID-19 condition in March 2022. Specific persisting symptoms such as anxiety or difficulty concentrating were frequently reported regardless of prior infection status and increased with age: 48.0% of primary school pupils, 52.9% of secondary school pupils in years 7-11 and 79.5% in years 12-13 reporting at least one symptom lasting more than 12 weeks. Persisting loss of smell and taste, cardiovascular and some systemic symptoms were more frequently reported by those with a previous positive test. CONCLUSIONS: We showed that ongoing symptoms were frequently reported by English schoolchildren regardless of SARS-CoV-2 test results and some specific symptoms such as loss of smell and taste were more prevalent in those with a positive test history. Our study emphasises the wide-ranging impacts of the COVID-19 pandemic on the health and wellbeing of children and young people.

From disease- to people-centred pandemic management: organized communities, community-oriented primary care and health information systems.

BACKGROUND: The COVID-19 pandemic exposed the health equity gap between and within countries. Western countries were the first to receive vaccines and mortality was higher among socially deprived, minority and indigenous populations. Surprisingly, many sub-Saharan countries reported low excess mortalities. These countries share experiences with community organization and participation in health. The aim of this article was to analyse if and how this central role of people can promote a successful pandemic response. METHODS: This analysis was partly based on local and national experiences shared during an international and Latin American conference on person-and people-centred care in 2021. Additionally, excess mortality data and pandemic control-relevant data, as well as literature on the pandemic response of countries with an unexpected low excess mortality were consulted. RESULTS: Togo, Mongolia, Thailand and Kenya had a seven times lower mean excess mortality for 2020 and 2021 than the United States of America. More successful pandemic responses were observed in settings with experience in managing epidemics like Ebola and HIV, well-established community networks, a national philosophy of mutual aid, financial government assistance, more human resources for primary care and paid community health workers. DISCUSSION: Since trust in authorities and health needs vary greatly, local strategies are needed to complement national and international pandemic responses. Three key levers were identified to promote locally-tailored pandemic management: well-organized communities, community-oriented primary care, and health information systems. An organized community structure stems from a shared ethical understanding of humanity as being interconnected with each other and the environment. This structure facilitates mutual aid and participation in decision making. Community-oriented primary care includes attention for collective community health and ways to improve health from its roots. A health information system supports collective health and health equity analysis by presenting health needs stratified for social deprivation, ethnicity, and community circumstances. CONCLUSIONS: The difference in excess mortality between countries during the COVID-19 pandemic and various country experiences demonstrate the potential of the levers in promoting a more just and effective health emergency response. These same levers and strategies can promote more inclusive and socially just health systems.

RESUMEN: ANTECEDENTES: La pandemia de COVID-19 expuso la brecha de equidad en salud dentro y entre países. Los países occidentales fueron los primeros en recibir vacunas y la mortalidad fue mayor entre las poblaciones indígenas, minoritarias y socialmente desfavorecidas dentro de los países. Sorprendentemente, muchos países subsaharianos reportaron un exceso de mortalidad bajo. Estos países comparten experiencias de organización y participación comunitaria en salud. El objetivo es analizar si y cómo este papel central de las personas puede promover una respuesta exitosa a la pandemia. MéTODOS: Este análisis se basa en parte en las experiencias locales y nacionales compartidas durante una conferencia internacional y latinoamericana sobre la atención centrada en las personas y comunidades en 2021. Además, se consultó los datos de exceso de mortalidad y los datos relevantes para el control de la pandemia, así como la literatura sobre la respuesta a la pandemia de países con un exceso de mortalidad inesperadamente bajo. RESULTADOS: Togo, Mongolia, Tailandia y Kenia tuvieron un exceso de mortalidad promedio por 2020 y 2021 siete veces menor que los Estados Unidos de América. Se observaron respuestas pandémicas más exitosas en entornos con experiencia en el manejo de epidemias como el ébola y el VIH, redes comunitarias bien establecidas, una filosofía nacional de ayuda mutua, asistencia financiera del gobierno, más recursos humanos para atención primaria y trabajadores de salud comunitarios remunerados. DISCUSIóN: Dado que la confianza en autoridades y las necesidades en salud varían mucho, se necesitan estrategias locales para complementar las respuestas nacionales e internacionales a la pandemia. Se identificaron tres palancas clave para promover la gestión de pandemias adaptada localmente: comunidades bien organizadas, atención primaria orientada a la comunidad y sistemas de información de salud. Una estructura comunitaria organizada surge de una comprensión ética compartida que concibe a la humanidad interconectada entre sí y con el medio ambiente. Esta estructura facilita la ayuda mutua y la participación en la toma de decisiones. La atención primaria orientada a la comunidad incluye la atención a la salud comunitaria colectiva y las formas de mejorar la salud desde sus raíces. Un sistema de información de salud puede apoyar el análisis de la salud colectiva y la equidad en salud al presentar las necesidades de salud estratificadas por privación social, etnicidad y circunstancias de la comunidad. CONCLUSIONES: La diferencia en el exceso de mortalidad entre países durante la pandemia de COVID-19 y las experiencias de varios países, demuestran el potencial de las palancas para promover una respuesta de emergencia sanitaria más justa y eficaz. Estas mismas palancas y estrategias pueden promover sistemas de salud más inclusivos y socialmente justos.

Effectiveness of Influenza Vaccination in Preventing Hospitalization Due to Influenza in Children: A Systematic Review and Meta-analysis.

This systematic review assesses the literature for estimates of influenza vaccine effectiveness (IVE) against laboratory-confirmed influenza-associated hospitalization in children. Studies of any design to June 8, 2020, were included if the outcome was hospitalization, participants were 17 years or younger and influenza infection was laboratory-confirmed. A random-effects meta-analysis of 37 studies that used a test-negative design gave a pooled seasonal IVE against hospitalization of 53.3% (47.2-58.8) for any influenza. IVE was higher against influenza A/H1N1pdm09 (68.7%, 56.9-77.2) and lowest against influenza A/H3N2 (35.8%, 23.4-46.3). Estimates by vaccine type ranged from 44.3% (30.1-55.7) for live-attenuated influenza vaccines to 68.9% (53.6-79.2) for inactivated vaccines. IVE estimates were higher in seasons when the circulating influenza strains were antigenically matched to vaccine strains (59.3%, 48.3-68.0). Influenza vaccination gives moderate overall protection against influenza-associated hospitalization in children supporting annual vaccination. IVE varies by influenza subtype and vaccine type.

Seasonal Influenza Vaccination During Pregnancy and the Risk of Major Congenital Malformations in Live-born Infants: A 2010-2016 Historical Cohort Study.

BACKGROUND: Available evidence indicates that seasonal inactivated influenza vaccination during pregnancy protects both the mother and her newborn and is safe. Nevertheless, ongoing safety assessments are important in sustaining vaccine uptake. Few studies have explored safety in relation to major congenital malformations (MCMs), particularly in the first trimester when most organogenesis occurs. METHODS: Anonymized UK primary care data (the Clinical Practice Research Datalink), including a recently developed Pregnancy Register, were used to identify live-born singletons delivered between 2010 and 2016. Maternal influenza vaccination was determined using primary care records and stratified by trimester. Ascertainment of MCMs from infant primary care records was maximized by linkage to hospitalization data and death certificates. The relationship between vaccination and MCMs recorded in the year after delivery and in early childhood was then assessed using multivariable Cox regression. RESULTS: A total of 78 150 live-birth pregnancies were identified: 6872 (8.8%) were vaccinated in the first trimester, 11 678 (14.9%) in the second, and 12 931 (16.5%) in the third. Overall, 5707 live births resulted in an infant with an MCM recorded in the year after delivery and the adjusted hazard ratio when comparing first-trimester vaccination to no vaccination was 1.06 (99% CI, .94-1.19; P = .2). Results were similar for second- and third-trimester vaccination and for analyses considering MCMs recorded beyond the first birthday. CONCLUSIONS: In this large, population-based historical cohort study there was no evidence to suggest that seasonal influenza vaccine was associated with MCMs when given in the first trimester or subsequently in pregnancy.

Risk Factors for Middle East Respiratory Syndrome Coronavirus Infection among Camel Populations, Southern Jordan, 2014-2018.

After the first detection of Middle East respiratory syndrome coronavirus (MERS-CoV) in camels in Jordan in 2013, we conducted 2 consecutive surveys in 2014-2015 and 2017-2018 investigating risk factors for MERS-CoV infection among camel populations in southern Jordan. Multivariate analysis to control for confounding demonstrated that borrowing of camels, particularly males, for breeding purposes was associated with increased MERS-CoV seroprevalence among receiving herds, suggesting a potential route of viral transmission between herds. Increasing age, herd size, and use of water troughs within herds were also associated with increased seroprevalence. Closed herd management practices were found to be protective. Future vaccination strategies among camel populations in Jordan could potentially prioritize breeding males, which are likely to be shared between herds. In addition, targeted management interventions with the potential to reduce transmission between herds should be considered; voluntary closed herd schemes offer a possible route to achieving disease-free herds.

The identification and validity of congenital malformation diagnoses in UK electronic health records: A systematic review.

PURPOSE: To describe the methods used to identify and validate congenital malformation diagnoses recorded in UK electronic health records, and the results of validation studies. METHODS: Medline and Embase were searched for publications between 1987 and 2019 that involved identifying congenital malformations from UK electronic health records using diagnostic codes. The methods and code-lists used to identify congenital malformations, and the methods and results of validations, were examined. RESULTS: We retrieved 54 eligible studies; 36 identified congenital malformations from primary care data and 18 from secondary care data alone or in combination with birth and/or death records. Identification in secondary care data relied on codes from the 'Q' chapter for congenital malformations in ICD-10. In contrast, studies using primary care data frequently used additional codes outside of the 'P' chapter for congenital malformation diagnoses in Read, although the exact codes used were not always clear. Eight studies validated diagnoses identified in primary care data. The positive predictive value was highest (80%-100%) for congenital malformations overall, major malformations, and heart defects although the validity of the reference standard used was often uncertain. It was lowest for neural tube defects (71%) and developmental hip dysplasia (56%). CONCLUSIONS: Studies identifying congenital malformations from primary care data provided limited details about the methods used. The few validation studies were limited to diagnoses recorded in primary care. Further assessments of all measures of validity in both data sources and of other malformation subgroups are needed, using robust reference standards and adhering to reporting guidelines.

Effectiveness of BCG Vaccination Against Mycobacterium tuberculosis Infection in Adults: A Cross-sectional Analysis of a UK-Based Cohort.

BACKGROUND: BCG appears to reduce acquisition of Mycobacterium tuberculosis infection in children, measured using interferon-gamma release assays (IGRAs). We explored whether BCG vaccination continues to be associated with decreased prevalence of M. tuberculosis infection in adults. METHODS: We conducted a cross-sectional analysis of data from adult contacts of tuberculosis cases participating in a UK cohort study. Vaccine effectiveness (VE) of BCG, ascertained based on presence of a scar or vaccination history, against latent tuberculosis infection (LTBI), measured via IGRA, was assessed using multivariable logistic regression. The effects of age at BCG and time since vaccination were also explored. RESULTS: Of 3453 recent tuberculosis contacts, 27.5% had LTBI. There was strong evidence of an association between BCG and LTBI (adjusted odds ratio = 0.70; 95% confidence interval, .56-.87; P = .0017) yielding a VE of 30%. VE declined with time since vaccination but there was evidence that LTBI prevalence was lower amongst vaccinated individuals even >20 years after vaccination, compared with nonvaccinated participants. CONCLUSIONS: BCG is associated with lower prevalence of LTBI in adult contacts of tuberculosis. These results contribute to growing evidence that suggests BCG may protect against M. tuberculosis infection as well as disease. This has implications for immunization programs, vaccine development, and tuberculosis control efforts worldwide. CLINICAL TRIALS REGISTRATION: NCT01162265.

The association between chronic kidney disease and tuberculosis; a comparative cohort study in England.

BACKGROUND: People with end-stage kidney disease have an increased risk of active tuberculosis (TB). Previous systematic reviews have demonstrated that patients with chronic kidney disease (CKD) have increased risk of severe community-acquired infections. We investigated the association between CKD (prior to renal replacement therapy) and incidence of TB in UK General Practice. METHODS: Using the UK Clinical Practice Research Datalink, 242,349 patients with CKD (stages 3-5) (estimated glomerular filtration rate < 60 mL/min/1.73 m2 for ≥3 months) between April 2004 and March 2014 were identified and individually matched (by age, gender, general practice and calendar time) to a control from the general population without known CKD. The association between CKD (overall and by stage) and incident TB was investigated using a Poisson regression analysis adjusted for age, gender, ethnicity, socio-economic status, chronic obstructive pulmonary disease (COPD) and diabetes. RESULTS: The incidence of TB was higher amongst patients with CKD compared to those without CKD: 14.63 and 9.89 cases per 100,000 person-years. After adjusting for age, gender, ethnicity, socio-economic status, diabetes and COPD, the association between CKD and TB remained (adjusted rate ratio [RR] 1.42, 95% confidence interval [CI] 1.01-1.85). The association may be stronger amongst those from non-white ethnic minorities (adjusted RR 2.83, 95%CI 1.32-6.03, p-value for interaction with ethnicity = 0.061). Amongst those with CKD stages 3-5, there was no evidence of a trend with CKD severity. CONCLUSIONS: CKD is associated with an increased risk of TB diagnosis in a UK General Practice cohort. This group of patients should be considered for testing and treating for latent TB.

The Relationship Between School Holidays and Transmission of Influenza in England and Wales.

School closure is often considered as an influenza control measure, but its effects on transmission are poorly understood. We used 2 approaches to estimate how school holidays affect the contact parameter (the per capita rate of contact sufficient for infection transmission) for influenza using primary care data from England and Wales (1967-2000). Firstly, we fitted an age-structured susceptible-infectious-recovered model to each year's data to estimate the proportional change in the contact parameter during school holidays as compared with termtime. Secondly, we calculated the percentage difference in the contact parameter between holidays and termtime from weekly values of the contact parameter, estimated directly from simple mass-action models. Estimates were combined using random-effects meta-analysis, where appropriate. From fitting to the data, the difference in the contact parameter among children aged 5-14 years during holidays as compared with termtime ranged from a 36% reduction to a 17% increase; estimates were too heterogeneous for meta-analysis. Based on the simple mass-action model, the contact parameter was 17% (95% confidence interval: 10, 25) lower during holidays than during termtime. Results were robust to the assumed proportions of infections that were reported and individuals who were susceptible when the influenza season started. We conclude that school closure may reduce transmission during influenza outbreaks.

Estimating time-varying exposure-outcome associations using case-control data: logistic and case-cohort analyses.

BACKGROUND: Traditional analyses of standard case-control studies using logistic regression do not allow estimation of time-varying associations between exposures and the outcome. We present two approaches which allow this. The motivation is a study of vaccine efficacy as a function of time since vaccination. METHODS: Our first approach is to estimate time-varying exposure-outcome associations by fitting a series of logistic regressions within successive time periods, reusing controls across periods. Our second approach treats the case-control sample as a case-cohort study, with the controls forming the subcohort. In the case-cohort analysis, controls contribute information at all times they are at risk. Extensions allow left truncation, frequency matching and, using the case-cohort analysis, time-varying exposures. Simulations are used to investigate the methods. RESULTS: The simulation results show that both methods give correct estimates of time-varying effects of exposures using standard case-control data. Using the logistic approach there are efficiency gains by reusing controls over time and care should be taken over the definition of controls within time periods. However, using the case-cohort analysis there is no ambiguity over the definition of controls. The performance of the two analyses is very similar when controls are used most efficiently under the logistic approach. CONCLUSIONS: Using our methods, case-control studies can be used to estimate time-varying exposure-outcome associations where they may not previously have been considered. The case-cohort analysis has several advantages, including that it allows estimation of time-varying associations as a continuous function of time, while the logistic regression approach is restricted to assuming a step function form for the time-varying association.

Interventions for avian influenza A (H5N1) risk management in live bird market networks.

Highly pathogenic avian influenza virus subtype H5N1 is endemic in Asia, with live bird trade as a major disease transmission pathway. A cross-sectional survey was undertaken in northern Vietnam to investigate the structure of the live bird market (LBM) contact network and the implications for virus spread. Based on the movements of traders between LBMs, weighted and directed networks were constructed and used for social network analysis and individual-based modeling. Most LBMs were connected to one another, suggesting that the LBM network may support large-scale disease spread. Because of cross-border trade, it also may promote transboundary virus circulation. However, opportunities for disease control do exist. The implementation of thorough, daily disinfection of the market environment as well as of traders' vehicles and equipment in only a small number of hubs can disconnect the network dramatically, preventing disease spread. These targeted interventions would be an effective alternative to the current policy of a complete ban of LBMs in some areas. Some LBMs that have been banned still are very active, and they likely have a substantial impact on disease dynamics, exhibiting the highest levels of susceptibility and infectiousness. The number of trader visits to markets, information that can be collected quickly and easily, may be used to identify LBMs suitable for implementing interventions. This would not require prior knowledge of the force of infection, for which laboratory-confirmed surveillance would be necessary. These findings are of particular relevance for policy development in resource-scarce settings.

Time series regression model for infectious disease and weather.

Time series regression has been developed and long used to evaluate the short-term associations of air pollution and weather with mortality or morbidity of non-infectious diseases. The application of the regression approaches from this tradition to infectious diseases, however, is less well explored and raises some new issues. We discuss and present potential solutions for five issues often arising in such analyses: changes in immune population, strong autocorrelations, a wide range of plausible lag structures and association patterns, seasonality adjustments, and large overdispersion. The potential approaches are illustrated with datasets of cholera cases and rainfall from Bangladesh and influenza and temperature in Tokyo. Though this article focuses on the application of the traditional time series regression to infectious diseases and weather factors, we also briefly introduce alternative approaches, including mathematical modeling, wavelet analysis, and autoregressive integrated moving average (ARIMA) models. Modifications proposed to standard time series regression practice include using sums of past cases as proxies for the immune population, and using the logarithm of lagged disease counts to control autocorrelation due to true contagion, both of which are motivated from "susceptible-infectious-recovered" (SIR) models. The complexity of lag structures and association patterns can often be informed by biological mechanisms and explored by using distributed lag non-linear models. For overdispersed models, alternative distribution models such as quasi-Poisson and negative binomial should be considered. Time series regression can be used to investigate dependence of infectious diseases on weather, but may need modifying to allow for features specific to this context.

Protection by BCG vaccine against tuberculosis: a systematic review of randomized controlled trials.

BACKGROUND: Randomized trials assessing BCG vaccine protection against tuberculosis have widely varying results, for reasons that are not well understood. METHODS: We examined associations of trial setting and design with BCG efficacy against pulmonary and miliary or meningeal tuberculosis by conducting a systematic review, meta-analyses, and meta-regression. RESULTS: We identified 18 trials reporting pulmonary tuberculosis and 6 reporting miliary or meningeal tuberculosis. Univariable meta-regression indicated efficacy against pulmonary tuberculosis varied according to 3 characteristics. Protection appeared greatest in children stringently tuberculin tested, to try to exclude prior infection with Mycobacterium tuberculosis or sensitization to environmental mycobacteria (rate ratio [RR], 0.26; 95% confidence interval [CI], .18-.37), or infants (RR, 0.41; 95% CI, .29-.58). Protection was weaker in children not stringently tested (RR, 0.59; 95% CI, .35-1.01) and older individuals stringently or not stringently tested (RR, 0.88; 95% CI, .59-1.31 and RR, 0.81; 95% CI, .55-1.22, respectively). Protection was higher in trials further from the equator where environmental mycobacteria are less and with lower risk of diagnostic detection bias. These associations were attenuated in a multivariable model, but each had an independent effect. There was no evidence that efficacy was associated with BCG strain. Protection against meningeal and miliary tuberculosis was also high in infants (RR, 0.1; 95% CI, .01-.77) and children stringently tuberculin tested (RR, 0.08; 95% CI, .03-.25). CONCLUSIONS: Absence of prior M. tuberculosis infection or sensitization with environmental mycobacteria is associated with higher efficacy of BCG against pulmonary tuberculosis and possibly against miliary and meningeal tuberculosis. Evaluations of new tuberculosis vaccines should account for the possibility that prior infection may mask or block their effects.

Uptake of neonatal BCG vaccination in England: performance of the current policy recommendations.

BCG uptake among infants in England has not been measured since targeted infant vaccination replaced universal schoolchildren vaccination in 2005, mainly because of the challenges in defining denominators. We estimated uptake between 2006 and 2008 by dividing number of BCG doses administered to infants by number of all live births (where BCG vaccination is universal) or ethnic minority/Eastern Europeans live births (where infant-BCG vaccination is selective). Weighted average uptake was 68% (95% CI 65% to 71%), slightly higher in primary care trusts with universal (72% (95% CI 64% to 80%)) than selective (66% (95% CI 61% to 70%)) policy; and also 13% higher in areas vaccinating in postnatal wards compared with community settings.

COVID-19 infections in English schools and the households of students and staff 2020-21: a self-controlled case-series analysis.

BACKGROUND: The role of children and staff in SARS-CoV-2 transmission outside and within households is still not fully understood when large numbers are in regular, frequent contact in schools. METHODS: We used the self-controlled case-series method during the alpha- and delta-dominant periods to explore the incidence of infection in periods around a household member infection, relative to periods without household infection, in a cohort of primary and secondary English schoolchildren and staff from November 2020 to July 2021. RESULTS: We found the relative incidence of infection in students and staff was highest in the 1-7 days following household infection, remaining high up to 14 days after, with risk also elevated in the 6--12 days before household infection. Younger students had a higher relative incidence following household infection, suggesting household transmission may play a more prominent role compared with older students. The relative incidence was also higher among students in the alpha variant dominant period. CONCLUSIONS: This analysis suggests SARS-CoV2 infection in children, young people and staff at English schools were more likely to be associated with within-household transmission than from outside the household, but that a small increased risk of seeding from outside is observed.

Acute and long-term outcomes of SARS-CoV-2 infection in school-aged children in England: Study protocol for the joint analysis of the COVID-19 schools infection survey (SIS) and the COVID-19 mapping and mitigation in schools (CoMMinS) study.

BACKGROUND: The symptom profiles of acute SARS-CoV-2 infection and long-COVID in children and young people (CYP), risk factors, and associated healthcare needs, are poorly defined. The Schools Infection Survey 1 (SIS-1) was a nationwide study of SARS-CoV-2 infection in primary and secondary schools in England during the 2020/21 school year. The Covid-19 Mapping and Mitigation in Schools (CoMMinS) study was conducted in schools in the Bristol area over a similar period. Both studies conducted testing to identify current and previous SARS-CoV-2 infection, and recorded symptoms and school attendance. These research data have been linked to routine electronic health record (EHR) data. AIMS: To better understand the short- and long-term consequences of SARS-CoV-2 infection, and their risk factors, in CYP. METHODS: Retrospective cohort and nested case-control analyses will be conducted for SIS-1 and CoMMinS data linked to EHR data for the association between (1) acute symptomatic SARS-CoV-2 infection and risk factors; (2) SARS-CoV-2 infection and long-term effects on health: (a) persistent symptoms; (b) any new diagnosis; (c) a new prescription in primary care; (d) health service attendance; (e) a high rate of school absence. RESULTS: Our study will improve understanding of long-COVID in CYP by characterising the trajectory of long-COVID in CYP in terms of things like symptoms and diagnoses of conditions. The research will inform which groups of CYP are more likely to get acute- and long-term outcomes of SARS-CoV-2 infection, and patterns of related healthcare-seeking behaviour, relevant for healthcare service planning. Digested information will be produced for affected families, doctors, schools, and the public, as appropriate. CONCLUSION: Linked SIS-1 and CoMMinS data represent a unique and rich resource for understanding the impact of SARS-CoV-2 infection on children's health, benefiting from enhanced SARS-CoV-2 testing and ability to assess a wide range of outcomes.

MERS-CoV exposure and risk factors for MERS-CoV ELISA seropositivity among members of livestock-owning households in southern Jordan: a population based cross-sectional study.

BACKGROUND: Although dromedary camels (Camelus dromedarius) are known to be the host reservoir for MERS-CoV, the virus causing Middle East respiratory syndrome (MERS), zoonotic transmission pathways and camel subpopulations posing highest transmission risk are poorly understood. Extensively managed herds, ubiquitous across the Arabian Peninsula, present a major potential source of primary infection. In this study we aimed to address key knowledge gaps regarding MERS epidemiology among high-risk communities associated with such herds, which is essential information for effective control strategies. METHODS: We did a cross-sectional study between Sept 27, 2017, and Oct 11, 2018, among members of livestock-owning households in southern Jordan (Aqaba East, Aqaba West, Ma'an East, and Ma'an West regions), with random selection of households (house and tent dwellings) from Ministry of Agriculture lists via computer-generated randomisation lists. Household visits were done, with questionnaires administered to household members regarding potential risk factors for MERS-CoV exposure in the past 6 months and blood samples and nasal and oral swabs collected, alongside physical examination data including blood pressure and blood glucose. Children younger than 5 years and individuals without capacity to provide informed consent were excluded. Serum was tested for IgG antibodies to MERS-CoV spike protein (S1 subunit) and nucleocapsid (N) protein with in-house indirect ELISAs, and viral RNA was detected in nasal and oral samples by RT-PCR. The primary outcome was evidence of MERS-CoV exposure (ascertained by seropositive status on S1 or N ELISAs, or a positive swab sample on RT-PCR); secondary outcomes were potential associations between possible risk factors and seropositive status. RT-PCR data were to be presented descriptively. Seroprevalence estimates were obtained at the individual and household levels, and associations between hypothetical risk factors and seropositive status were assessed with use of mixed-effects logistic regression. FINDINGS: We sampled 879 household members (median age 27 years [IQR 16-44]; 471 [54%] males and 408 [46%] females) from 204 households. 72 (8%) household members were seropositive on S1 ELISA (n=25, 3%) or N ELISA (n=52, 6%). No positive nasal or oral swab samples were identified on RT-PCR. Within-household clustering was identified for seropositivity on S1 ELISA (intraclass correlation coefficient 0·88 [0·35-0·96]) but not N ELISA (0·00 [0·00-0·27]). On multivariable analysis, S1 ELISA seropositivity was associated with frequently (≥weekly) interacting with young (age <1 year) camels (adjusted odds ratio [ORadj] 3·85 [95% CI 1·41-11·61], p=0·011), with frequent kissing and petting (ORadj 4·56 [1·55-15·42], p=0·0074), and frequent feeding and watering (ORadj 4·97 [1·80-15·29], p=0·0027) of young camels identified as risk activities. Attending camel races (ORadj 3·73 [1·11-12·47], p=0·029), frequently feeding and watering camels of any age (ORadj 3·18 [1·12-10·84], p=0·040), and elevated blood glucose (>150 mg/dL; ORadj 4·59 [1·23-18·36], p=0·021) were also associated with S1 ELISA seropositivity. Among individuals without history of camel contact, S1 ELISA seropositivity was associated with sharing a household with an S1 ELISA-positive household member (ORadj 8·92 [1·06-92·99], p=0·044), and with sharing a household with an S1 ELISA-positive household member with history of camel contact (ORadj 24·74 [2·72-306·14], p=0·0050). N ELISA seropositivity was associated with age (categorical, p=0·0069), a household owning a young camel (age <18 months; ORadj 1·98 [1·02-4·09], p=0·043), and frequently feeding and watering camels of any age (ORadj 1·98 [1·09-3·69]; p=0·025). INTERPRETATION: The study findings highlight the importance of effective MERS-CoV surveillance and control strategies among camel-owning communities in Jordan and the Arabian Peninsula. Juvenile dromedaries pose increased risk for zoonotic MERS-CoV transmission and should be prioritised for vaccination once such vaccines become available. Among high-risk communities, vaccination strategies should prioritise camel-owning households, particularly individuals engaged in camel husbandry or racing, and household members who are older or diabetic, with evidence to suggest secondary within-household transmission. FUNDING: UK Medical Research Council and US National Institute of Allergy and Infectious Diseases.

Cancer incidence in South Asian migrants to England, 1986-2004: unraveling ethnic from socioeconomic differentials.

Studies on cancer in migrants are informative about the relative influence of environmental and genetic factors on cancer risk. This study investigates trends in incidence from colorectal, lung, breast and prostate cancer in England among South Asians and examines the influence of deprivation, a key environmental exposure. South Asian ethnicity was assigned to patients recorded in the population-based National Cancer Registry of England during 1986-2004, using the computerized algorithm SANGRA: South Asian Names and Groups Recognition Algorithm. Population denominators were derived from population censuses. Multivariable flexible (splines) Poisson models were used to estimate trends and socioeconomic differentials in incidence in South Asians compared to non-South Asians. Overall, age-adjusted cancer incidence in South Asians was half that in non-South Asians but rose over time. Cancer-specific incidence trends and patterns by age and deprivation differed widely between the two ethnic groups. In contrast to non-South Asians, lung cancer incidence in South Asians did not fall. Colorectal and breast cancer incidence rose in both groups, more steeply in South Asians though remaining less common than in non-South Asians. The deprivation gaps in cancer-specific incidence were much less marked among South Asians, explaining some of the ethnic differences in overall incidence. Although still lower than in non-South Asians, cancer incidence is rising in South Asians, supporting the concept of transition in cancer incidence among South Asians living in England. Although these trends vary by cancer, they have important implications for both prevention and anticipating health-care demand.

Controversies and unresolved issues in tuberculosis prevention and control: a low-burden-country perspective.

Despite declining incidence in most high-income countries, tuberculosis shows no signs of disappearing in the near future. Although surveillance data from most Western European countries show relatively stable declines in the rate of tuberculosis over the past several decades, some have reported either an increasing rate or a decelerating pace of reduction in recent years. The burden of disease now disproportionately affects high-risk groups such as migrants, homeless persons, and prisoners. In view of the concentration of cases in urban areas and high-risk deprived groups, interventions that may not be efficient when applied to the general population may be highly cost effective when targeted at high-risk groups. In this article, we examine some controversial elements of tuberculosis prevention and control in low-burden countries and recommend issues for further research. In particular, we assess current evidence on the duration of protection by BCG vaccine, the screening of migrants and hard-to-reach groups, and the use of preventive therapy for contacts of cases of infectious multidrug-resistant tuberculosis. This analysis is presented from the perspective of low-tuberculosis-burden, high-income countries attempting to eliminate tuberculosis.

A cross-sectional study of Q fever in Camels: Risk factors for infection, the role of small ruminants and public health implications for desert-dwelling pastoral communities.

Q fever represents an important 'neglected zoonosis', with high prevalences recorded across the Middle East region. Among rural desert-dwelling communities in the region, camel milk is largely consumed raw, due to perceptions of dromedaries as a uniquely clean livestock species mentioned in the Qur'an and Islamic hadith, while milk from other livestock species is usually boiled. As a result, camels present a unique public health threat among such communities from milk-borne pathogens, including Coxiella burnetii. In view of this, a cross-sectional study was conducted among dromedary herds in southern Jordan between September 2017 and October 2018, including 404 camels from 121 randomly selected herds. In addition, 510 household members associated with these herds were interviewed regarding potential high-risk practices for zoonotic transmission. Weight adjusted camel population seroprevalence for C. burnetii was 49.6% (95% CI: 44.7-54.5), with evidence of maternally derived immunity in calves ≤6 months old. Adjusted herd-level prevalence was 76.0% (95% CI 72.7-80.2). It was estimated 30.4% (144/477) of individuals consumed raw milk from infected herds monthly or more. Following multivariable logistic regression analysis, seropositive status in camels was found to be associated with increasing age, high herd tick burdens, keeping the herd together throughout the year including when calving, and owning larger (>50) sheep and goat flocks, with goats presenting a higher risk than sheep. Racing camel status was found to be protective. Socioculturally appropriate interventions aimed at raising awareness of potential risks associated with drinking raw camel milk, alongside appropriate livestock management interventions, should be considered.