Reconstructed influenza A/H3N2 infection histories reveal variation in incidence and antibody dynamics over the life course.

Humans experience many influenza infections over their lives, resulting in complex and varied immunological histories. Although experimental and quantitative analyses have improved our understanding of the immunological processes defining an individual's antibody repertoire, how these within-host processes are linked to population-level influenza epidemiology remains unclear. Here, we used a multi-level mathematical model to jointly infer antibody dynamics and individual-level lifetime influenza A/H3N2 infection histories for 1,130 individuals in Guangzhou, China, using 67,683 haemagglutination inhibition (HI) assay measurements against 20 A/H3N2 strains from repeat serum samples collected between 2009 and 2015. These estimated infection histories allowed us to reconstruct historical seasonal influenza patterns and to investigate how influenza incidence varies over time, space and age in this population. We estimated median annual influenza infection rates to be approximately 18% from 1968 to 2015, but with substantial variation between years. 88% of individuals were estimated to have been infected at least once during the study period (2009-2015), and 20% were estimated to have three or more infections in that time. We inferred decreasing infection rates with increasing age, and found that annual attack rates were highly correlated across all locations, regardless of their distance, suggesting that age has a stronger impact than fine-scale spatial effects in determining an individual's antibody profile. Finally, we reconstructed each individual's expected antibody profile over their lifetime and inferred an age-stratified relationship between probability of infection and HI titre. Our analyses show how multi-strain serological panels provide rich information on long term, epidemiological trends, within-host processes and immunity when analyzed using appropriate inference methods, and adds to our understanding of the life course epidemiology of influenza A/H3N2.

The national distribution of lymphatic filariasis cases in Malawi using patient mapping and geostatistical modelling.

BACKGROUND: In 2020 the World Health Organization (WHO) declared that Malawi had successfully eliminated lymphatic filariasis (LF) as a public health problem. Understanding clinical case distributions at a national and sub-national level is important, so essential care packages can be provided to individuals living with LF symptoms. This study aimed to develop a national database and map of LF clinical cases across Malawi using geostatistical modelling approaches, programme-identified clinical cases, antigenaemia prevalence and climate information. METHODOLOGY: LF clinical cases identified through programme house-to-house surveys across 90 sub-district administrative boundaries (Traditional Authority (TA)) and antigenaemia prevalence from 57 sampled villages in Malawi were used in a two-step geostatistical modelling process to predict LF clinical cases across all TAs of the country. First, we modelled antigenaemia prevalence in relation to climate covariates to predict nationwide antigenaemia prevalence. Second, we modelled clinical cases for unmapped TAs based on our antigenaemia prevalence spatial estimates. PRINCIPLE FINDINGS: The models estimated 20,938 (95% CrI 18,091 to 24,071) clinical cases in unmapped TAs (70.3%) in addition to the 8,856 (29.7%), programme-identified cases in mapped TAs. In total, the overall national number of LF clinical cases was estimated to be 29,794 (95% CrI 26,957 to 32,927). The antigenaemia prevalence and clinical case mapping and modelling found the highest burden of disease in Chikwawa and Nsanje districts in the Southern Region and Karonga district in the Northern Region of the country. CONCLUSIONS: The models presented in this study have facilitated the development of the first national LF clinical case database and map in Malawi, the first endemic country in sub-Saharan Africa. It highlights the value of using existing LF antigenaemia prevalence and clinical case data together with modelling approaches to produce estimates that may be used for the WHO dossier requirements, to help target limited resources and implement long-term health strategies.

A Bayesian approach to identifying the role of hospital structure and staff interactions in nosocomial transmission of SARS-CoV-2.

Nosocomial infections threaten patient safety, and were widely reported during the COVID-19 pandemic. Effective hospital infection control requires a detailed understanding of the role of different transmission pathways, yet these are poorly quantified. Using patient and staff data from a large UK hospital, we demonstrate a method to infer unobserved epidemiological event times efficiently and disentangle the infectious pressure dynamics by ward. A stochastic individual-level, continuous-time state-transition model was constructed to model transmission of SARS-CoV-2, incorporating a dynamic staff-patient contact network as time-varying parameters. A Metropolis-Hastings Markov chain Monte Carlo (MCMC) algorithm was used to estimate transmission rate parameters associated with each possible source of infection, and the unobserved infection and recovery times. We found that the total infectious pressure exerted on an individual in a ward varied over time, as did the primary source of transmission. There was marked heterogeneity between wards; each ward experienced unique infectious pressure over time. Hospital infection control should consider the role of between-ward movement of staff as a key infectious source of nosocomial infection for SARS-CoV-2. With further development, this method could be implemented routinely for real-time monitoring of nosocomial transmission and to evaluate interventions.

Determining the distance patterns in the movements of future doctors in UK between 2002 and 2015: a retrospective cohort study.

OBJECTIVE: To determine and identify distance patterns in the movements of medical students and junior doctors between their training locations. DESIGN: A retrospective cohort study of UK medical students from 2002 to 2015 (UKMED data). SETTING: All UK medical schools, foundations and specialty training organisation. PARTICIPANTS: All UK medical students from 2002 to 2015, for a total of 97 932 participants. OUTCOME MEASURES: Individual movements and number of movements by county of students from family home to medical school training, from medical school to foundation training and from foundation to specialty training. METHODS: Leslie matrix, principal components analysis, Gini coefficient, χ2 test, generalised linear models and variable selection methods were employed to explore the different facets of students' and junior doctors' movements from the family home to medical school and for the full pathway (from family home to specialty training). RESULTS: The majority of the movements between the different stages of the full pathway were restricted to a distance of up to 50 km; although the proportion of movements changed from year-to-year, with longer movements during 2007-2008. At the individual level, ethnicity, socioeconomic class of the parent(s) and the deprivation score of the family home region were found to be the most important factors associated with the length of the movements from the family home to medical school. Similar results were found when movements were aggregated at the county level, with the addition of factors such as gender and qualification at entry (to medical school) being statistically associated with the number of new entrant students moving between counties. CONCLUSION: Our findings show that while future doctors do not move far from their family home or training location, this pattern is not homogeneous over time. Distances are influenced by demographics, socioeconomic status and deprivation. These results may contribute in designing interventions aimed at solving the chronic problems of maldistribution and underdoctoring in the UK.

Epidemiology of Human Seasonal Coronaviruses Among People With Mild and Severe Acute Respiratory Illness in Blantyre, Malawi, 2011-2017.

BACKGROUND: The aim of this study was to characterize the epidemiology of human seasonal coronaviruses (HCoVs) in southern Malawi. METHODS: We tested for HCoVs 229E, OC43, NL63, and HKU1 using real-time polymerase chain reaction (PCR) on upper respiratory specimens from asymptomatic controls and individuals of all ages recruited through severe acute respiratory illness (SARI) surveillance at Queen Elizabeth Central Hospital, Blantyre, and a prospective influenza-like illness (ILI) observational study between 2011 and 2017. We modeled the probability of having a positive PCR for each HCoV using negative binomial models, and calculated pathogen-attributable fractions (PAFs). RESULTS: Overall, 8.8% (539/6107) of specimens were positive for ≥1 HCoV. OC43 was the most frequently detected HCoV (3.1% [191/6107]). NL63 was more frequently detected in ILI patients (adjusted incidence rate ratio [aIRR], 9.60 [95% confidence interval {CI}, 3.25-28.30]), while 229E (aIRR, 8.99 [95% CI, 1.81-44.70]) was more frequent in SARI patients than asymptomatic controls. In adults, 229E and OC43 were associated with SARI (PAF, 86.5% and 89.4%, respectively), while NL63 was associated with ILI (PAF, 85.1%). The prevalence of HCoVs was similar between children with SARI and controls. All HCoVs had bimodal peaks but distinct seasonality. CONCLUSIONS: OC43 was the most prevalent HCoV in acute respiratory illness of all ages. Individual HCoVs had distinct seasonality that differed from temperate settings.

Prevalence of Endemic Respiratory Viruses During the COVID-19 Pandemic in Urban and Rural Malawi.

Background: We investigated endemic respiratory virus circulation patterns in Malawi, where no lockdown was imposed, during the COVID-19 pandemic. Methods: Within a prospective household cohort in urban and rural Malawi, adult participants provided upper respiratory tract (URT) samples at 4 time points between February 2021 and April 2022. Polymerase chain reaction (PCR) was performed for SARS-CoV-2, influenza, and other endemic respiratory viruses. Results: 1626 URT samples from 945 participants in 542 households were included. Overall, 7.6% (n = 123) samples were PCR- positive for >1 respiratory virus; SARS-CoV-2 (4.4%) and rhinovirus (2.0%) were most common. No influenza A virus was detected. Influenza B and respiratory syncytial virus (RSV) were rare. Higher virus positivity were detected in the rural setting and at earlier time points. Coinfections were infrequent. Conclusions: Endemic respiratory viruses circulated in the community in Malawi during the pandemic, though influenza and RSV were rarely detected. Distinct differences in virus positivity and demographics were observed between urban and rural cohorts.

Mental health conditions in people affected by filarial lymphoedema in Malawi: prevalence, associated risk factors and the impact of an enhanced self-care intervention.

BACKGROUND: This study aimed to determine the key mental health indicators affecting people affected by lymphatic filariasis (LF) lymphoedema by assessing the prevalence of depressive symptoms and quality of life (QOL), identifying associated sociodemographic and clinical risk factors, and evaluating the impact of an enhanced self-care intervention for lymphoedema management. METHODS: A prospective cohort study of adults with filarial lymphoedema from two regions of Malawi was conducted over six months in 2021. Depressive symptoms and QOL were assessed using Patient Health Questionnaire (PHQ-9) and LF Specific QOL Questionnaire, respectively, at baseline (pre-intervention), 3- and 6-months (postintervention). Beta regression analysis identified risk factors, and assessed the impact of the intervention. RESULTS: Three hundred eleven affected individuals were surveyed with 23% (95% CI 18%-29%) reporting mild/moderate depressive symptoms and 31% (95% CI 26%-37%) reporting moderately low/low QOL. Higher depressive symptom scores were associated with high frequency of acute filarial attack episodes. Individuals with higher depressive symptoms (Adjusted Odds Ratios (AOR) 0.93, 95% CI 0.93-0.93) and lower QOL (AOR 0.98, 0.98-0.98) showed greatest improvement in mental health indicators over 3-months but was not sustained to the same level at 6-months. CONCLUSIONS: Sustained morbidity management and psychological support is recommended for affected persons to ensure long-term positive mental health and clinical outcomes. CONTEXTE: Cette étude vise à déterminer les principaux indicateurs de santé mentale affectant les personnes atteintes de lymphœdème dû à la filariose lymphatique (FL) en évaluant la prévalence des symptômes dépressifs et la qualité de vie (QV), en identifiant les facteurs de risque sociodémographiques et cliniques associés, et en évaluant l'impact d'une intervention améliorée d'autosoins pour la gestion du lymphœdème. MÉTHODES: Une étude de cohorte prospective d'adultes atteints de lymphoedème filaire dans deux régions du Malawi a été menée pendant six mois en 2021. Les symptômes dépressifs et la qualité de vie ont été évalués à l'aide du questionnaire sur la santé des patients (PHQ-9) et du questionnaire sur la qualité de vie spécifique au lymphœdème, respectivement, au début de l'étude (avant l'intervention), et à 3 puis 6 mois après l'intervention. Une analyse de régression beta a permis d'identifier les facteurs de risque et d'évaluer l'impact de l'intervention. RÉSULTATS: Trois cent onze personnes affectées ont été interrogées, dont 23% (95% CI 18%-29%) ont déclaré des symptômes dépressifs légers/modérés et 31% (95% CI 26%-37%) ont déclaré une qualité de vie modérément faible/faible. Des scores élevés de symptômes dépressifs ont été associés à une fréquence élevée d'épisodes de crises filariennes aiguës. Les personnes présentant des symptômes dépressifs plus élevés (rapport de cotes ajusté (RCA) 0.93, IC à 95 % 0.93-0.93) et une qualité de vie plus faible (RCA 0.98, 0.98-0.98) ont montré la plus grande amélioration des indicateurs de santé mentale au cours des trois mois, mais cette amélioration ne s'est pas maintenue au même niveau au cours des six mois suivants. CONCLUSION: Gestion de la morbidité et soutien psychologique sont des éléments clés pour garantir une santé mentale et des résultats cliniques satisfaisants de personnes atteintes sur le long terme. ANTECEDENTES: Este estudio tuvo como objetivo determinar los indicadores clave de salud mental que afectan a las personas afectadas por linfedema por filariasis linfática (FL) mediante la evaluación de la prevalencia de síntomas depresivos y calidad de vida (CdV), la identificación de factores de riesgo sociodemográficos y clínicos asociados, y la evaluación del impacto de una intervención de autocuidado mejorada para el manejo del linfedema. MÉTODOS: Se realizó un estudio prospectivo de cohortes de adultos con linfedema filarial de dos regiones de Malawi durante seis meses en 2021. Los síntomas depresivos y la calidad de vida se evaluaron mediante el Cuestionario de Salud del Paciente (PHQ-9) y el Cuestionario de Calidad de Vida específico para el LF Cuestionario, respectivamente, al inicio (preintervención) y a los 3 y 6 meses (posintervención). El análisis de regresión beta identificó los factores de riesgo y evaluó el impacto de la intervención. RESULTADOS: Se encuestó a 311 afectados, de los cuales el 23% (IC 95%, 18%-29%) presentaba síntomas depresivos leves/moderados y el 31% (IC 95%, 26%-37%) una CdV moderadamente baja/baja CdV. Las puntuaciones más altas de síntomas depresivos se asociaron con una alta frecuencia de episodios de ataques agudos de filarias. Los individuos con mayores síntomas depresivos (Odds Ratios Ajustados [ORA] 0.93; IC 95%: 0.93-0.93) y menor CdV (ORA 0.98; 0.98-0.98) mostraron la mayor mejoría en los indicadores de salud mental a los 3 meses, pero no se mantuvo al mismo nivel a los 6 meses. CONCLUSIONES: Se recomienda el manejo sostenido de la morbilidad y el apoyo psicológico a las personas afectadas para garantizar resultados clínicos y de salud mental positivos a largo plazo.

Participant perceptions and experiences of a novel community-based respiratory longitudinal sampling method in Liverpool, UK: A mixed methods feasibility study.

Longitudinal, community-based sampling is important for understanding prevalence and transmission of respiratory pathogens. Using a minimally invasive sampling method, the FAMILY Micro study monitored the oral, nasal and hand microbiota of families for 6 months. Here, we explore participant experiences and opinions. A mixed methods approach was utilised. A quantitative questionnaire was completed after every sampling timepoint to report levels of discomfort and pain, as well as time taken to collect samples. Participants were also invited to discuss their experiences in a qualitative structured exit interview. We received questionnaires from 36 families. Most adults and children >5y experienced no pain (94% and 70%) and little discomfort (73% and 47% no discomfort) regardless of sample type, whereas children ≤5y experienced variable levels of pain and discomfort (48% no pain but 14% hurts even more, whole lot or worst; 38% no discomfort but 33% moderate, severe, or extreme discomfort). The time taken for saliva and hand sampling decreased over the study. We conducted interviews with 24 families. Families found the sampling method straightforward, and adults and children >5y preferred nasal sampling using a synthetic absorptive matrix over nasopharyngeal swabs. It remained challenging for families to fit sampling into their busy schedules. Adequate fridge/freezer space and regular sample pick-ups were found to be important factors for feasibility. Messaging apps proved extremely effective for engaging with participants. Our findings provide key information to inform the design of future studies, specifically that self-sampling at home using minimally invasive procedures is feasible in a family context.

The burden and dynamics of hospital-acquired SARS-CoV-2 in England.

Hospital-based transmission had a dominant role in Middle East respiratory syndrome coronavirus (MERS-CoV) and severe acute respiratory syndrome coronavirus (SARS-CoV) epidemics1,2, but large-scale studies of its role in the SARS-CoV-2 pandemic are lacking. Such transmission risks spreading the virus to the most vulnerable individuals and can have wider-scale impacts through hospital-community interactions. Using data from acute hospitals in England, we quantify within-hospital transmission, evaluate likely pathways of spread and factors associated with heightened transmission risk, and explore the wider dynamical consequences. We estimate that between June 2020 and March 2021 between 95,000 and 167,000 inpatients acquired SARS-CoV-2 in hospitals (1% to 2% of all hospital admissions in this period). Analysis of time series data provided evidence that patients who themselves acquired SARS-CoV-2 infection in hospital were the main sources of transmission to other patients. Increased transmission to inpatients was associated with hospitals having fewer single rooms and lower heated volume per bed. Moreover, we show that reducing hospital transmission could substantially enhance the efficiency of punctuated lockdown measures in suppressing community transmission. These findings reveal the previously unrecognized scale of hospital transmission, have direct implications for targeting of hospital control measures and highlight the need to design hospitals better equipped to limit the transmission of future high-consequence pathogens.

Strengthening quality in sexual, reproductive, maternal, and newborn health systems in low- and middle-income countries through midwives and facility mentoring: an integrative review.

BACKGROUND: There is an urgent global call for health systems to strengthen access to quality sexual, reproductive, maternal, newborn and adolescent health, particularly for the most vulnerable. Professional midwives with enabling environments are identified as an important solution. However, a multitude of barriers prevent midwives from fully realizing their potential. Effective interventions to address known barriers and enable midwives and quality sexual, reproductive, maternal, newborn and adolescent health are less well known. This review intends to evaluate the literature on (1) introducing midwives in low- and middle-income countries, and (2) on mentoring as a facilitator to enable midwives and those in midwifery roles to improve sexual, reproductive, maternal, newborn and adolescent health service quality within health systems. METHODS: An integrative systematic literature review was conducted, guided by the Population, Intervention, Comparison, Outcome framework. Articles were reviewed for quality and relevance using the Gough weight-of-evidence framework and themes were identified. A master table categorized articles by Gough score, methodology, country of focus, topic areas, themes, classification of midwives, and mentorship model. The World Health Organization health systems building block framework was applied for data extraction and analysis. RESULTS: Fifty-three articles were included: 13 were rated as high, 36 as medium, and four as low according to the Gough criteria. Studies that focused on midwives primarily highlighted human resources, governance, and service delivery while those focused on mentoring were more likely to highlight quality services, lifesaving commodities, and health information systems. Midwives whose pre-service education met global standards were found to have more efficacy. The most effective mentoring packages were comprehensive, integrated into existing systems, and involved managers. CONCLUSIONS: Effectively changing sexual, reproductive, maternal, newborn and adolescent health systems is complex. Globally standard midwives and a comprehensive mentoring package show effectiveness in improving service quality and utilization. TRIAL REGISTRATION: The protocol is registered in PROSPERO (CRD42022367657).

Contact patterns of UK home delivery drivers and their use of protective measures during the COVID-19 pandemic: a cross-sectional study.

OBJECTIVES: To quantify contact patterns of UK home delivery drivers and identify protective measures adopted during the pandemic. METHODS: We conducted a cross-sectional online survey to measure the interactions of 170 UK delivery drivers during a working shift between 7 December 2020 and 31 March 2021. RESULTS: Delivery drivers had a mean number of 71.6 (95% CI 61.0 to 84.1) customer contacts per shift and 15.0 (95% CI 11.2 to 19.2) depot contacts per shift. Maintaining physical distancing with customers was more common than at delivery depots. Prolonged contact (more than 5 min) with customers was reported by 5.4% of drivers on their last shift. We found 3.0% of drivers had tested positive for SARS-CoV-2 since the start of the pandemic and 16.8% of drivers had self-isolated due to a suspected or confirmed case of COVID-19. In addition, 5.3% (95% CI 2.3% to 10.2%) of participants reported having worked while ill with COVID-19 symptoms, or with a member of their household having a suspected or confirmed case of COVID-19. CONCLUSION: Delivery drivers had a large number of face-to-face customer and depot contacts per shift compared with other working adults during this time. However, transmission risk may be curtailed as contact with customers was of short duration. Most drivers were unable to maintain physical distance with customers and at depots at all times. Usage of protective items such as face masks and hand sanitiser was widespread.

Coughs, colds and "freshers' flu" survey in the University of Cambridge, 2007-2008.

Universities provide many opportunities for the spread of infectious respiratory illnesses. Students are brought together into close proximity from all across the world and interact with one another in their accommodation, through lectures and small group teaching and in social settings. The COVID-19 global pandemic has highlighted the need for sufficient data to help determine which of these factors are important for infectious disease transmission in universities and hence control university morbidity as well as community spillover. We describe the data from a previously unpublished self-reported university survey of coughs, colds and influenza-like symptoms collected in Cambridge, UK, during winter 2007-2008. The online survey collected information on symptoms and socio-demographic, academic and lifestyle factors. There were 1076 responses, 97% from University of Cambridge students (5.7% of the total university student population), 3% from staff and <1% from other participants, reporting onset of symptoms between September 2007 and March 2008. Undergraduates are seen to report symptoms earlier in the term than postgraduates; differences in reported date of symptoms are also seen between subjects and accommodation types, although these descriptive results could be confounded by survey biases. Despite the historical and exploratory nature of the study, this is one of few recent detailed datasets of influenza-like infection in a university context and is especially valuable to share now to improve understanding of potential transmission dynamics in universities during the current COVID-19 pandemic.

Household Transmission Dynamics of Seasonal Human Coronaviruses.

BACKGROUND: Household transmission studies inform how viruses spread among close contacts, but few characterize household transmission of endemic coronaviruses. METHODS: We used data collected from 223 households with school-age children participating in weekly disease surveillance over 2 respiratory virus seasons (December 2015 to May 2017), to describe clinical characteristics of endemic human coronaviruses (HCoV-229E, HcoV-HKU1, HcoV-NL63, HcoV-OC43) infections, and community and household transmission probabilities using a chain-binomial model correcting for missing data from untested households. RESULTS: Among 947 participants in 223 households, we observed 121 infections during the study, most commonly subtype HCoV-OC43. Higher proportions of infected children (<19 years) displayed influenza-like illness symptoms than infected adults (relative risk, 3.0; 95% credible interval [CrI], 1.5-6.9). The estimated weekly household transmission probability was 9% (95% CrI, 6-13) and weekly community acquisition probability was 7% (95% CrI, 5-10). We found no evidence for differences in community or household transmission probabilities by age or symptom status. Simulations suggest that our study was underpowered to detect such differences. CONCLUSIONS: Our study highlights the need for large household studies to inform household transmission, the challenges in estimating household transmission probabilities from asymptomatic individuals, and implications for controlling endemic CoVs.

Characterizing the evolving SARS-CoV-2 seroprevalence in urban and rural Malawi between February 2021 and April 2022: A population-based cohort study.

OBJECTIVES: This study aimed to investigate the changing SARS-CoV-2 seroprevalence and associated health and sociodemographic factors in Malawi between February 2021 and April 2022. METHODS: In total, four 3-monthly serosurveys were conducted within a longitudinal population-based cohort in rural Karonga District and urban Lilongwe, testing for SARS-CoV-2 S1 immunoglobulin (Ig)G antibodies using an enzyme-linked immunosorbent assay. Population seroprevalence was estimated in all and unvaccinated participants. Bayesian mixed-effects logistic models estimated the odds of seropositivity in the first survey, and of seroconversion between surveys, adjusting for age, sex, occupation, location, and assay sensitivity/specificity. RESULTS: Of the 2005 participants (Karonga, n = 1005; Lilongwe, n = 1000), 55.8% were female and median age was 22.7 years. Between Surveys (SVY) 1 and 4, population-weighted SARS-CoV-2 seroprevalence increased from 26.3% to 89.2% and 46.4% to 93.9% in Karonga and Lilongwe, respectively. At SVY4, seroprevalence did not differ by COVID-19 vaccination status in adults, except for those aged 30+ years in Karonga (unvaccinated: 87.4%, 95% credible interval 79.3-93.0%; two doses: 98.1%, 94.8-99.5%). Location and age were associated with seroconversion risk. Individuals with hybrid immunity had higher SARS-CoV-2 seropositivity and antibody titers, than those infected. CONCLUSION: High SARS-CoV-2 seroprevalence combined with low morbidity and mortality indicate that universal vaccination is unnecessary at this stage of the pandemic, supporting change in national policy to target at-risk groups.

Social mixing patterns in the UK following the relaxation of COVID-19 pandemic restrictions, July-August 2020: a cross-sectional online survey.

OBJECTIVES: To quantify and characterise non-household contact and to identify the effect of shielding and isolating on contact patterns. DESIGN: Cross-sectional study. SETTING AND PARTICIPANTS: Anyone living in the UK was eligible to take part in the study. We recorded 5143 responses to the online questionnaire between 28 July 2020 and 14 August 2020. OUTCOME MEASURES: Our primary outcome was the daily non-household contact rate of participants. Secondary outcomes were propensity to leave home over a 7 day period, whether contacts had occurred indoors or outdoors locations visited, the furthest distance travelled from home, ability to socially distance and membership of support bubble. RESULTS: The mean rate of non-household contacts per person was 2.9 d-1. Participants attending a workplace (adjusted incidence rate ratio (aIRR) 3.33, 95% CI 3.02 to 3.66), self-employed (aIRR 1.63, 95% CI 1.43 to 1.87) or working in healthcare (aIRR 5.10, 95% CI 4.29 to 6.10) reported significantly higher non-household contact rates than those working from home. Participants self-isolating as a precaution or following Test and Trace instructions had a lower non-household contact rate than those not self-isolating (aIRR 0.58, 95% CI 0.43 to 0.79). We found limited evidence that those shielding had reduced non-household contacts compared with non-shielders. CONCLUSION: The daily rate of non-household interactions remained lower than prepandemic levels measured by other studies, suggesting continued adherence to social distancing guidelines. Individuals attending a workplace in-person or employed as healthcare professionals were less likely to maintain social distance and had a higher non-household contact rate, possibly increasing their infection risk. Shielding and self-isolating individuals required greater support to enable them to follow the government guidelines and reduce non-household contact and therefore their risk of infection.

Long term intrinsic cycling in human life course antibody responses to influenza A(H3N2): an observational and modeling study.

Background: Over a life course, human adaptive immunity to antigenically mutable pathogens exhibits competitive and facilitative interactions. We hypothesize that such interactions may lead to cyclic dynamics in immune responses over a lifetime. Methods: To investigate the cyclic behavior, we analyzed hemagglutination inhibition titers against 21 historical influenza A(H3N2) strains spanning 47 years from a cohort in Guangzhou, China, and applied Fourier spectrum analysis. To investigate possible biological mechanisms, we simulated individual antibody profiles encompassing known feedbacks and interactions due to generally recognized immunological mechanisms. Results: We demonstrated a long-term periodicity (about 24 years) in individual antibody responses. The reported cycles were robust to analytic and sampling approaches. Simulations suggested that individual-level cross-reaction between antigenically similar strains likely explains the reported cycle. We showed that the reported cycles are predictable at both individual and birth cohort level and that cohorts show a diversity of phases of these cycles. Phase of cycle was associated with the risk of seroconversion to circulating strains, after accounting for age and pre-existing titers of the circulating strains. Conclusions: Our findings reveal the existence of long-term periodicities in individual antibody responses to A(H3N2). We hypothesize that these cycles are driven by preexisting antibody responses blunting responses to antigenically similar pathogens (by preventing infection and/or robust antibody responses upon infection), leading to reductions in antigen-specific responses over time until individual's increasing risk leads to an infection with an antigenically distant enough virus to generate a robust immune response. These findings could help disentangle cohort effects from individual-level exposure histories, improve our understanding of observed heterogeneous antibody responses to immunizations, and inform targeted vaccine strategy. Funding: This study was supported by grants from the NIH R56AG048075 (DATC, JL), NIH R01AI114703 (DATC, BY), the Wellcome Trust 200861/Z/16/Z (SR), and 200187/Z/15/Z (SR). This work was also supported by research grants from Guangdong Government HZQB-KCZYZ-2021014 and 2019B121205009 (YG and HZ). DATC, JMR and SR acknowledge support from the National Institutes of Health Fogarty Institute (R01TW0008246). JMR acknowledges support from the Medical Research Council (MR/S004793/1) and the Engineering and Physical Sciences Research Council (EP/N014499/1). The funders had no role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript.

The impact of professional midwives and mentoring on the quality and availability of maternity care in government sub-district hospitals in Bangladesh: a mixed-methods observational study.

BACKGROUND: This study compared government sub-district hospitals in Bangladesh without globally standard midwives, with those with recently introduced midwives, both with and without facility mentoring, to see if the introduction of midwives was associated with improved quality and availability of maternity care. In addition, it analysed the experiences of the newly deployed midwives and the maternity staff and managers that they joined. METHODS: This was a mixed-methods observational study. The six busiest hospitals from three pre-existing groups of government sub-district hospitals were studied; those with no midwives, those with midwives, and those with midwives and mentoring. For the quantitative component, observations of facility readiness (n = 18), and eight quality maternity care practices (n = 641) were carried out using three separate tools. Willing maternity staff (n = 237) also completed a survey on their knowledge, perceptions, and use of the maternity care interventions. Descriptive statistics and logistic regression were used to identify differences between the hospital types. The qualitative component comprised six focus groups and 18 interviews involving midwives, other maternity staff, and managers from the three hospital types. Data were analysed using an inductive cyclical process of immersion and iteration to draw out themes. The quantitative and qualitative methods complemented each other and were used synergistically to identify the study's insights. RESULTS: Quantitative analysis found that, of the eight quality practices, hospitals with midwives but no mentors were significantly more likely than hospitals without midwives to use three: upright labour (94% vs. 63%; OR = 22.57, p = 0.001), delayed cord clamping (88% vs. 11%; OR = 140.67, p < 0.001), skin-to-skin (94% vs. 13%; OR = 91.21, p < 0.001). Hospitals with mentors were significantly more likely to use five: ANC card (84% vs. 52%; OR = 3.29, p = 0.002), partograph (97% vs. 14%; OR = 309.42, p = 0.002), upright positioning for labour (95% vs. 63%; OR = 1850, p < 0.001), delayed cord clamping (98% vs. 11%; OR = 3400, p = 0.003), and skin-to-skin contact following birth (93% vs. 13%; OR = 70.89, p < 0.001) Qualitative analysis identified overall acceptance of midwives and the transition to improved quality care; this was stronger with facility mentoring. The most resistance to quality care was expressed in facilities without midwives. In facilities with midwives and mentoring, midwives felt proud, and maternity staff conveyed the greatest acceptance of midwives. CONCLUSION: Facilities with professional midwives had better availability and quality of maternity care across multiple components of the health system. Care quality further improved with facility mentors who created enabling environments, and facilitated supportive relationships between existing maternity staff and managers and the newly deployed midwives.

The contribution of hospital-acquired infections to the COVID-19 epidemic in England in the first half of 2020.

BACKGROUND: SARS-CoV-2 is known to transmit in hospital settings, but the contribution of infections acquired in hospitals to the epidemic at a national scale is unknown. METHODS: We used comprehensive national English datasets to determine the number of COVID-19 patients with identified hospital-acquired infections (with symptom onset > 7 days after admission and before discharge) in acute English hospitals up to August 2020. As patients may leave the hospital prior to detection of infection or have rapid symptom onset, we combined measures of the length of stay and the incubation period distribution to estimate how many hospital-acquired infections may have been missed. We used simulations to estimate the total number (identified and unidentified) of symptomatic hospital-acquired infections, as well as infections due to onward community transmission from missed hospital-acquired infections, to 31st July 2020. RESULTS: In our dataset of hospitalised COVID-19 patients in acute English hospitals with a recorded symptom onset date (n = 65,028), 7% were classified as hospital-acquired. We estimated that only 30% (range across weeks and 200 simulations: 20-41%) of symptomatic hospital-acquired infections would be identified, with up to 15% (mean, 95% range over 200 simulations: 14.1-15.8%) of cases currently classified as community-acquired COVID-19 potentially linked to hospital transmission. We estimated that 26,600 (25,900 to 27,700) individuals acquired a symptomatic SARS-CoV-2 infection in an acute Trust in England before 31st July 2020, resulting in 15,900 (15,200-16,400) or 20.1% (19.2-20.7%) of all identified hospitalised COVID-19 cases. CONCLUSIONS: Transmission of SARS-CoV-2 to hospitalised patients likely caused approximately a fifth of identified cases of hospitalised COVID-19 in the "first wave" in England, but less than 1% of all infections in England. Using time to symptom onset from admission for inpatients as a detection method likely misses a substantial proportion (> 60%) of hospital-acquired infections.

Rainfall anomalies and typhoid fever in Blantyre, Malawi.

Typhoid fever is a major cause of illness and mortality in low- and middle-income settings. We investigated the association of typhoid fever and rainfall in Blantyre, Malawi, where multi-drug-resistant typhoid has been transmitting since 2011. Peak rainfall preceded the peak in typhoid fever by approximately 15 weeks [95% confidence interval (CI) 13.3, 17.7], indicating no direct biological link. A quasi-Poisson generalised linear modelling framework was used to explore the relationship between rainfall and typhoid incidence at biologically plausible lags of 1-4 weeks. We found a protective effect of rainfall anomalies on typhoid fever, at a two-week lag (P = 0.006), where a 10 mm lower-than-expected rainfall anomaly was associated with up to a 16% reduction in cases (95% CI 7.6, 26.5). Extreme flooding events may cleanse the environment of S. Typhi, while unusually low rainfall may reduce exposure from sewage overflow. These results add to evidence that rainfall anomalies may play a role in the transmission of enteric pathogens, and can help direct future water and sanitation intervention strategies for the control of typhoid fever.

The contribution of hospital-acquired infections to the COVID-19 epidemic in England in the first half of 2020.

Background SARS-CoV-2 is known to transmit in hospital settings, but the contribution of infections acquired in hospitals to the epidemic at a national scale is unknown. Methods We used comprehensive national English datasets to determine the number of COVID-19 patients with identified hospital-acquired infections (with symptom onset >7 days after admission and before discharge) in acute English hospitals up to August 2020. As patients may leave the hospital prior to detection of infection or have rapid symptom onset, we combined measures of the length of stay and the incubation period distribution to estimate how many hospital-acquired infections may have been missed. We used simulations to estimate the total number (identified and unidentified) of symptomatic hospital-acquired infections, as well as infections due to onward community transmission from missed hospital-acquired infections, to 31 st July 2020. Results In our dataset of hospitalised COVID-19 patients in acute English hospitals with a recorded symptom onset date (n = 65,028), 7% were classified as hospital-acquired. We estimated that only 30% (range across weeks and 200 simulations: 20-41%) of symptomatic hospital-acquired infections would be identified, with up to 15% (mean, 95% range over 200 simulations: 14.1%-15.8%) of cases currently classified as community-acquired COVID-19 potentially linked to hospital transmission. We estimated that 26,600 (25,900 to 27,700) individuals acquired a symptomatic SARS-CoV-2 infection in an acute Trust in England before 31st July 2020, resulting in 15,900 (15,200-16,400) or 20.1% (19.2%-20.7%) of all identified hospitalised COVID-19 cases. Conclusions Transmission of SARS-CoV-2 to hospitalised patients likely caused approximately a fifth of identified cases of hospitalised COVID-19 in the "first wave" in England, but less than 1% of all infections in England. Using time to symptom onset from admission for inpatients as a detection method likely misses a substantial proportion (>60%) of hospital-acquired infections.