85 results found
Penn MJ, Laydon DJ, Penn J, et al., 2023, Intrinsic randomness in epidemic modelling beyond statistical uncertainty, Communications Physics, Vol: 6
Uncertainty can be classified as either aleatoric (intrinsic randomness) or epistemic (imperfect knowledge of parameters). The majority of frameworks assessing infectious disease risk consider only epistemic uncertainty. We only ever observe a single epidemic, and therefore cannot empirically determine aleatoric uncertainty. Here, we characterise both epistemic and aleatoric uncertainty using a time-varying general branching process. Our framework explicitly decomposes aleatoric variance into mechanistic components, quantifying the contribution to uncertainty produced by each factor in the epidemic process, and how these contributions vary over time. The aleatoric variance of an outbreak is itself a renewal equation where past variance affects future variance. We find that, superspreading is not necessary for substantial uncertainty, and profound variation in outbreak size can occur even without overdispersion in the offspring distribution (i.e. the distribution of the number of secondary infections an infected person produces). Aleatoric forecasting uncertainty grows dynamically and rapidly, and so forecasting using only epistemic uncertainty is a significant underestimate. Therefore, failure to account for aleatoric uncertainty will ensure that policymakers are misled about the substantially higher true extent of potential risk. We demonstrate our method, and the extent to which potential risk is underestimated, using two historical examples.
Monod M, Blenkinsop A, Brizzi A, et al., 2023, Regularised B-splines projected Gaussian Process priors to estimate time-trends in age-specific COVID-19 deaths, Bayesian Analysis, Vol: 18, Pages: 957-987, ISSN: 1931-6690
The COVID-19 pandemic has caused severe public health consequences in the United States. In this study, we use a hierarchical Bayesian model to estimate the age-specific COVID-19 attributable deaths over time in the United States. The model is specified by a novel non-parametric spatial approach over time and age, a low-rank Gaussian Process (GP) projected by regularised B-splines. We show that this projection defines a new GP with attractive smoothness and computational efficiency properties, derive its kernel function, and discuss the penalty terms induced by the projected GP. Simulation analyses and benchmark results show that the B-splines projected GP may perform better than standard B-splines and Bayesian P-splines, and equivalently well as a standard GP at considerably lowerruntimes. We apply the model to weekly, age-stratified COVID-19 attributabledeaths reported by the US Centers for Disease Control, which are subject to censoring and reporting biases. Using the B-splines projected GP, we can estimate longitudinal trends in COVID-19 associated deaths across the US by 1-year age bands. These estimates are instrumental to calculate age-specific mortality rates, describe variation in age-specific deaths across the US, and for fitting epidemic models. Here, we couple the model with age-specific vaccination rates to show that vaccination rates were significantly associated with the magnitude of resurgences in COVID-19 deaths during the summer 2021. With counterfactual analyses, we quantify the avoided COVID-19 deaths under lower vaccination rates and avoidable COVID-19 deaths under higher vaccination rates. The B-splines projected GP priors that we develop are likely an appealing addition to the arsenal of Bayesianregularising priors.
Rosen JG, Reynolds SJ, Galiwango RM, et al., 2023, A moving target: impacts of lowering viral load suppression cutpoints on progress towards HIV epidemic control goals., AIDS, Vol: 37, Pages: 1486-1489
Redefining viral load suppression (VLS) using lower cutpoints could impact progress towards the United Nations Programme on HIV/AIDS 95-95-95 targets. We assessed impacts of lowering the VLS cutpoint on achieving the 'third 95' in the Rakai Community Cohort Study. Population VLS would fall from 86% to 84% and 76%, respectively, after lowering VLS cutpoints from <1000 to <200 and <50 copies/ml. The fraction of viremic persons increased by 17% after lowering the VLS cutpoint from <1000 to <200 copies/ml.
Rosen JG, Ssekubugu R, Chang LW, et al., 2023, Temporal dynamics and drivers of durable HIV viral load suppression and persistent high- and low-level viremia during Universal Test and Treat scale-up in Uganda: a population-based study., medRxiv
INTRODUCTION: Population-level data on durable HIV viral load suppression (VLS) following implementation of Universal Test and Treat (UTT) in Africa are limited. We assessed trends in durable VLS and viremia among persons living with HIV in 40 Ugandan communities during UTT scale-up. METHODS: In 2015-2020, we measured VLS (defined as <200 RNA copies/mL) among participants in the Rakai Community Cohort Study, a longitudinal population-based HIV surveillance cohort in southern Uganda. Persons with unsuppressed viral loads were characterized as having low-level (200-999 copies/mL) or high-level (≥1,000 copies/mL) viremia. Individual virologic outcomes were assessed over two consecutive RCCS survey visits (i.e., visit-pairs; ∼18 month visit intervals) and classified as durable VLS (<200 copies/mL at both visits), new/renewed VLS (<200 copies/mL at follow-up only), viral rebound (<200 copies/mL at initial visit only), or persistent viremia (<200 copies/mL at neither visit). Population prevalence of each outcome was assessed over calendar time. Community-level prevalence and individual-level predictors of persistent high-level viremia were also assessed using multivariable Poisson regression with generalized estimating equations. RESULTS: Overall, 3,080 participants contributed 4,604 visit-pairs over three survey rounds. Most visit-pairs (72.4%) exhibited durable VLS, with few (2.5%) experiencing viral rebound. Among those with viremia at the initial visit ( n =1,083), 46.9% maintained viremia through follow-up, 91.3% of which was high-level viremia. One-fifth (20.8%) of visit-pairs exhibiting persistent high-level viremia self-reported antiretroviral therapy (ART) use for ≥12 months. Prevalence of persistent high-level viremia varied substantially across communities and was significantly elevated among young persons aged 15-29 years (versus 40-49-year-olds; adjusted risk ratio [adjRR]=2.96; 95% confidence interval [95%CI]:2.21-3.96), men (versus
Dan S, Chen Y, Chen Y, et al., 2023, Estimating fine age structure and time trends in human contact patterns from coarse contact data: The Bayesian rate consistency model., PLoS Comput Biol, Vol: 19
Since the emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), large-scale social contact surveys are now longitudinally measuring the fundamental changes in human interactions in the face of the pandemic and non-pharmaceutical interventions. Here, we present a model-based Bayesian approach that can reconstruct contact patterns at 1-year resolution even when the age of the contacts is reported coarsely by 5 or 10-year age bands. This innovation is rooted in population-level consistency constraints in how contacts between groups must add up, which prompts us to call the approach presented here the Bayesian rate consistency model. The model can also quantify time trends and adjust for reporting fatigue emerging in longitudinal surveys through the use of computationally efficient Hilbert Space Gaussian process priors. We illustrate estimation accuracy on simulated data as well as social contact data from Europe and Africa for which the exact age of contacts is reported, and then apply the model to social contact data with coarse information on the age of contacts that were collected in Germany during the COVID-19 pandemic from April to June 2020 across five longitudinal survey waves. We estimate the fine age structure in social contacts during the early stages of the pandemic and demonstrate that social contact intensities rebounded in an age-structured, non-homogeneous manner. The Bayesian rate consistency model provides a model-based, non-parametric, computationally tractable approach for estimating the fine structure and longitudinal trends in social contacts and is applicable to contemporary survey data with coarsely reported age of contacts as long as the exact age of survey participants is reported.
Penn M, Laydon D, penn J, et al., 2023, The uncertainty of infectious disease outbreaks is underestimated
<jats:title>Abstract</jats:title> <jats:p>Uncertainty can be classified as either aleatoric (intrinsic randomness) or epistemic (imperfect knowledge of parameters). The majority of frameworks assessing infectious disease risk consider only epistemic uncertainty. We only ever observe a single epidemic, and therefore cannot empirically determine aleatoric uncertainty. Here, for the first time, we characterise both epistemic and aleatoric uncertainty using a time-varying general branching processes. Our framework explicitly decomposes aleatoric variance into mechanistic components, quantifying the contribution to uncertainty produced by each factor in the epidemic process, and how these contributions vary over time. The aleatoric variance of an outbreak is itself a renewal equation where past variance affects future variance. Perhaps surprisingly, superspreading is not necessary for substantial uncertainty, and profound variation in outbreak size can occur even without overdispersion in the offspring distribution (i.e. the distribution of the number of secondary infections an infected person produces). Crucially, aleatoric forecasting uncertainty grows dynamically and rapidly, and so forecasting using only epistemic uncertainty is a significant underestimate. Therefore, failure to account for aleatoric uncertainty will ensure that policymakers are misled about the substantially higher true extent of potential risk. We demonstrate our method, and the extent to which potential risk is underestimated, using two historical examples: firstly the 2003 Hong Kong severe acute respiratory syndrome (SARS) outbreak, and secondly the early 2020 UK COVID-19 epidemic. Our framework provides analytical tools to estimate epidemic uncertainty with limited data, to provide reasonable worst-case scenarios and assess both epistemic and aleatoric uncertainty in forecasting, and to retrospectively assess an epidemic and thereby provide a baseline risk estimate for f
Flaxman S, Whittaker C, Semenova E, et al., 2023, Assessment of COVID-19 as the underlying cause of death among children and young people aged 0 to 19 years in the US., Jama Network Open, Vol: 6, Pages: 1-9, ISSN: 2574-3805
IMPORTANCE: COVID-19 was the underlying cause of death for more than 940 000 individuals in the US, including at least 1289 children and young people (CYP) aged 0 to 19 years, with at least 821 CYP deaths occurring in the 1-year period from August 1, 2021, to July 31, 2022. Because deaths among US CYP are rare, the mortality burden of COVID-19 in CYP is best understood in the context of all other causes of CYP death. OBJECTIVE: To determine whether COVID-19 is a leading (top 10) cause of death in CYP in the US. DESIGN, SETTING, AND PARTICIPANTS: This national population-level cross-sectional epidemiological analysis for the years 2019 to 2022 used data from the US Centers for Disease Control and Prevention Wide-Ranging Online Data for Epidemiologic Research (WONDER) database on underlying cause of death in the US to identify the ranking of COVID-19 relative to other causes of death among individuals aged 0 to 19 years. COVID-19 deaths were considered in 12-month periods between April 1, 2020, and August 31, 2022, compared with deaths from leading non-COVID-19 causes in 2019, 2020, and 2021. MAIN OUTCOMES AND MEASURES: Cause of death rankings by total number of deaths, crude rates per 100 000 population, and percentage of all causes of death, using the National Center for Health Statistics 113 Selected Causes of Death, for ages 0 to 19 and by age groupings (<1 year, 1-4 years, 5-9 years, 10-14 years, 15-19 years). RESULTS: There were 821 COVID-19 deaths among individuals aged 0 to 19 years during the study period, resulting in a crude death rate of 1.0 per 100 000 population overall; 4.3 per 100 000 for those younger than 1 year; 0.6 per 100 000 for those aged 1 to 4 years; 0.4 per 100 000 for those aged 5 to 9 years; 0.5 per 100 000 for those aged 10 to 14 years; and 1.8 per 100 000 for those aged 15 to 19 years. COVID-19 mortality in the time period of August 1, 2021, to July 31, 2022, was among the 10 leading causes of death in CYP aged 0 to 19 years in the US
Bogers S, Zimmermann H, Ndong A, et al., 2023, Mapping hematologists' HIV testing behavior among lymphoma patients-A mixed-methods study., PLoS One, Vol: 18
BACKGROUND: HIV testing among patients with malignant lymphoma (PWML) is variably implemented. We evaluated HIV testing among PWML, and mapped factors influencing hematologists' testing behavior. MATERIALS: We conducted a mixed-methods study assessing HIV testing among PWML, factors influencing HIV testing and opportunities for improvement in five hospitals in the region of Amsterdam, the Netherlands. The proportion of PWML tested for HIV within 3 months before or after lymphoma diagnosis and percentage positive were assessed from January 2015 through June 2020. Questionnaires on intention, behavior and psychosocial determinants for HIV testing were conducted among hematologists. Through twelve semi-structured interviews among hematologists and authors of hematology guidelines, we further explored influencing factors and opportunities for improvement. FINDINGS: Overall, 1,612 PWML were included for analysis, including 976 patients newly diagnosed and 636 patients who were referred or with progressive/relapsed lymphoma. Seventy percent (678/976) of patients newly diagnosed and 54% (343/636) of patients with known lymphoma were tested for HIV. Overall, 7/1,021 (0.7%) PWML tested HIV positive, exceeding the 0.1% cost-effectiveness threshold. Questionnaires were completed by 40/77 invited hematologists, and 85% reported intention to test PWML for HIV. In the interviews, hematologists reported varying HIV testing strategies, including testing all PWML or only when lymphoma treatment is required. Recommendations for improved HIV testing included guideline adaptations, providing electronic reminders and monitoring and increasing awareness. CONCLUSIONS: Missed opportunities for HIV testing among PWML occurred and HIV test strategies varied among hematologists. Efforts to improve HIV testing among PWML should include a combination of approaches.
Bogers SJ, van der Loeff MFS, Boyd A, et al., 2022, Improving indicator-condition guided testing for HIV in the hospital setting (PROTEST 2.0): A multicenter, interrupted time-series analysis, LANCET REGIONAL HEALTH-EUROPE, Vol: 23, ISSN: 2666-7762
Blenkinsop A, Monod M, van Sighem A, et al., 2022, Estimating the potential to prevent locally acquired HIV infections in a UNAIDS Fast-Track City, Amsterdam, eLife, Vol: 11, ISSN: 2050-084X
Background:More than 300 cities including the city of Amsterdam in the Netherlands have joined the UNAIDS Fast-Track Cities initiative, committing to accelerate their HIV response and end the AIDS epidemic in cities by 2030. To support this commitment, we aimed to estimate the number and proportion of Amsterdam HIV infections that originated within the city, from Amsterdam residents. We also aimed to estimate the proportion of recent HIV infections during the 5-year period 2014–2018 in Amsterdam that remained undiagnosed.Methods:We located diagnosed HIV infections in Amsterdam using postcode data (PC4) at time of registration in the ATHENA observational HIV cohort, and used HIV sequence data to reconstruct phylogeographically distinct, partially observed Amsterdam transmission chains. Individual-level infection times were estimated from biomarker data, and used to date the phylogenetically observed transmission chains as well as to estimate undiagnosed proportions among recent infections. A Bayesian Negative Binomial branching process model was used to estimate the number, size, and growth of the unobserved Amsterdam transmission chains from the partially observed phylogenetic data.Results:Between 1 January 2014 and 1 May 2019, there were 846 HIV diagnoses in Amsterdam residents, of whom 516 (61%) were estimated to have been infected in 2014–2018. The rate of new Amsterdam diagnoses since 2014 (104 per 100,000) remained higher than the national rates excluding Amsterdam (24 per 100,000), and in this sense Amsterdam remained a HIV hotspot in the Netherlands. An estimated 14% [12–16%] of infections in Amsterdan MSM in 2014–2018 remained undiagnosed by 1 May 2019, and 41% [35–48%] in Amsterdam heterosexuals, with variation by region of birth. An estimated 67% [60–74%] of Amsterdam MSM infections in 2014–2018 had an Amsterdam resident as source, and 56% [41–70%] in Amsterdam heterosexuals, with heterogeneity by region of b
Prete CA, Buss LF, Whittaker C, et al., 2022, SARS-CoV-2 antibody dynamics in blood donors and COVID-19 epidemiology in eight Brazilian state capitals: A serial cross-sectional study, eLife, Vol: 11, ISSN: 2050-084X
BACKGROUND: The COVID-19 situation in Brazil is complex due to large differences in the shape and size of regional epidemics. Understanding these patterns is crucial to understand future outbreaks of SARS-CoV-2 or other respiratory pathogens in the country. METHODS: We tested 97,950 blood donation samples for IgG antibodies from March 2020 to March 2021 in 8 of Brazil's most populous cities. Residential postal codes were used to obtain representative samples. Weekly age- and sex-specific seroprevalence were estimated by correcting the crude seroprevalence by test sensitivity, specificity, and antibody waning. RESULTS: The inferred attack rate of SARS-CoV-2 in December 2020, before the Gamma variant of concern (VOC) was dominant, ranged from 19.3% (95% credible interval [CrI] 17.5-21.2%) in Curitiba to 75.0% (95% CrI 70.8-80.3%) in Manaus. Seroprevalence was consistently smaller in women and donors older than 55 years. The age-specific infection fatality rate (IFR) differed between cities and consistently increased with age. The infection hospitalisation rate increased significantly during the Gamma-dominated second wave in Manaus, suggesting increased morbidity of the Gamma VOC compared to previous variants circulating in Manaus. The higher disease penetrance associated with the health system's collapse increased the overall IFR by a minimum factor of 2.91 (95% CrI 2.43-3.53). CONCLUSIONS: These results highlight the utility of blood donor serosurveillance to track epidemic maturity and demonstrate demographic and spatial heterogeneity in SARS-CoV-2 spread. FUNDING: This work was supported by Itaú Unibanco 'Todos pela Saude' program; FAPESP (grants 18/14389-0, 2019/21585-0); Wellcome Trust and Royal Society Sir Henry Dale Fellowship 204311/Z/16/Z; the Gates Foundation (INV- 034540 and INV-034652); REDS-IV-P (grant HHSN268201100007I); the UK Medical Research Council (MR/S0195/1, MR/V038109/1); CAPES; CNPq (304714/2018-6); Fundação Faculdade de Me
Brizzi A, Whittaker C, Servo LMS, et al., 2022, Report 46: Factors driving extensive spatial and temporal fluctuations in COVID-19 fatality rates in Brazilian hospitals., Publisher: MedrXiv
The SARS-CoV-2 Gamma variant spread rapidly across Brazil, causing substantial infection and death waves. We use individual-level patient records following hospitalisation with suspected or confirmed COVID-19 to document the extensive shocks in hospital fatality rates that followed Gamma's spread across 14 state capitals, and in which more than half of hospitalised patients died over sustained time periods. We show that extensive fluctuations in COVID-19 in-hospital fatality rates also existed prior to Gamma's detection, and were largely transient after Gamma's detection, subsiding with hospital demand. Using a Bayesian fatality rate model, we find that the geographic and temporal fluctuations in Brazil's COVID-19 in-hospital fatality rates are primarily associated with geographic inequities and shortages in healthcare capacity. We project that approximately half of Brazil's COVID-19 deaths in hospitals could have been avoided without pre-pandemic geographic inequities and without pandemic healthcare pressure. Our results suggest that investments in healthcare resources, healthcare optimization, and pandemic preparedness are critical to minimize population wide mortality and morbidity caused by highly transmissible and deadly pathogens such as SARS-CoV-2, especially in low- and middle-income countries. NOTE: The following manuscript has appeared as 'Report 46 - Factors driving extensive spatial and temporal fluctuations in COVID-19 fatality rates in Brazilian hospitals' at https://spiral.imperial.ac.uk:8443/handle/10044/1/91875 . ONE SENTENCE SUMMARY: COVID-19 in-hospital fatality rates fluctuate dramatically in Brazil, and these fluctuations are primarily associated with geographic inequities and shortages in healthcare capacity.
Blenkinsop A, Monod M, van Sighem A, et al., 2022, Estimating the potential to prevent locally acquired HIV infections in a UNAIDS Fast-Track City, Amsterdam, Publisher: eLIFE SCIENCES PUBL LTD
Brizzi A, Whittaker C, Servo LMS, et al., 2022, Author correction: spatial and temporal fluctuations in COVID-19 fatality rates in Brazilian hospitals, Nature Medicine, Vol: 28, Pages: 1509-1509, ISSN: 1078-8956
Correction to: Nature Medicine https://doi.org/10.1038/s41591-022-01807-1, published online 10 May 2022.
Xi X, Spencer SEF, Hall M, et al., 2022, Inferring the sources of HIV infection in Africa from deep-sequence data with semi-parametric Bayesian Poisson flow models, Journal of the Royal Statistical Society Series C: Applied Statistics, Vol: 71, Pages: 517-540, ISSN: 0035-9254
Pathogen deep-sequencing is an increasingly routinely used technology in infectious disease surveillance. We present a semi-parametric Bayesian Poisson model to exploit these emerging data for inferring infectious disease transmission flows and the sources of infection at the population level. The framework is computationally scalable in high-dimensional flow spaces thanks to Hilbert Space Gaussian process approximations, al-lows for sampling bias adjustments, and estimation of gender- and age-specific transmis-sion flows at finer resolution than previously possible. We apply the approach to densely sampled, population-based HIV deep-sequence data from Rakai, Uganda, and find sub-stantive evidence that adolescent and young women are predominantly infected through age-disparate relationships.
Flaxman S, Whittaker C, Semenova E, et al., 2022, Covid-19 is a leading cause of death in children and young people ages 0-19 years in the United States
<jats:title>Abstract</jats:title><jats:p>Covid-19 has caused more than 1 million deaths in the US, including at least 1,204 deaths among children and young people (CYP) aged 0-19 years, with 796 occurring in the one year period April 1, 2021 - March 31, 2022. Deaths among US CYP are rare in general, and so we argue here that the mortality burden of Covid-19 in CYP is best understood in the context of all other causes of CYP death. Using publicly available data from CDC WONDER on NCHS’s 113 Selected Causes of Death, and comparing to mortality in 2019, the immediate pre-pandemic period, we find that Covid-19 mortality is among the 10 leading causes of death in CYP aged 0-19 years in the US, ranking 8th among all causes of deaths, 5th in disease-related causes of deaths (excluding accidents, assault and suicide), and 1st in deaths caused by infectious or respiratory diseases. Covid-19 deaths constitute 2.3% of the 10 leading causes of death in this age group. Covid-19 caused substantially more deaths in CYP than major vaccine-preventable diseases did historically in the period before vaccines became available. Various factors including underreporting and Covid-19’s role as a contributing cause of death from other diseases mean that our estimates may understate the true mortality burden of Covid-19. Our findings underscore the public health relevance of Covid-19 to CYP. In the likely future context of sustained SARS-CoV-2 circulation, pharmaceutical and non-pharmaceutical interventions will continue to play an important role in limiting transmission of the virus in CYP and mitigating severe disease.</jats:p>
Brizzi A, Whittaker C, Servo LMS, et al., 2022, Spatial and temporal fluctuations in COVID-19 fatality rates in Brazilian hospitals, Nature Medicine, Vol: 28, ISSN: 1078-8956
The SARS-CoV-2 Gamma variant of concern spread rapidly across Brazil since late 2020, causing substantial infection and death waves. We use individual-level patient records following hospitalisation with suspected or confirmed COVID-19 between 20 January 2020 and 26 July 2021 to document temporary, sweeping shocks in hospital fatality rates that followed Gamma’s spread across 14 state capitals, during which typically more than half of hospitalised patients aged 70 and over died. We show that such extensive shocks in COVID-19 in-hospital fatality rates also existed prior to detection of Gamma. Using a Bayesian fatality rate model, we find that the geographic and temporal fluctuations in Brazil’s COVID-19 in-hospital fatality rates were primarily associated with geographic inequities and shortages in healthcare capacity. We estimate that approximately half of the COVID-19 deaths in hospitals in the 14 cities could have been avoided without pre-pandemic geographic inequities and without pandemic healthcare pressure. Our results suggest that investments in healthcare resources, healthcare optimization, and pandemic preparedness are critical to minimize population wide mortality and morbidity caused by highly transmissible and deadly pathogens such as SARS-CoV-2, especially in low- and middle-income countries.
Unwin HJT, Hillis S, Cluver L, et al., 2022, Global, regional, and national minimum estimates of children affected by COVID-19-associated orphanhood and caregiver death, by age and family circumstance up to Oct 31, 2021: an updated modelling study, The Lancet Child & Adolescent Health, Vol: 6, Pages: 249-259, ISSN: 2352-4642
BACKGROUND: In the 6 months following our estimates from March 1, 2020, to April 30, 2021, the proliferation of new coronavirus variants, updated mortality data, and disparities in vaccine access increased the amount of children experiencing COVID-19-associated orphanhood. To inform responses, we aimed to model the increases in numbers of children affected by COVID-19-associated orphanhood and caregiver death, as well as the cumulative orphanhood age-group distribution and circumstance (maternal or paternal orphanhood). METHODS: We used updated excess mortality and fertility data to model increases in minimum estimates of COVID-19-associated orphanhood and caregiver deaths from our original study period of March 1, 2020-April 30, 2021, to include the new period of May 1-Oct 31, 2021, for 21 countries. Orphanhood was defined as the death of one or both parents; primary caregiver loss included parental death or the death of one or both custodial grandparents; and secondary caregiver loss included co-residing grandparents or kin. We used logistic regression and further incorporated a fixed effect for western European countries into our previous model to avoid over-predicting caregiver loss in that region. For the entire 20-month period, we grouped children by age (0-4 years, 5-9 years, and 10-17 years) and maternal or paternal orphanhood, using fertility contributions, and we modelled global and regional extrapolations of numbers of orphans. 95% credible intervals (CrIs) are given for all estimates. FINDINGS: The number of children affected by COVID-19-associated orphanhood and caregiver death is estimated to have increased by 90·0% (95% CrI 89·7-90·4) from April 30 to Oct 31, 2021, from 2 737 300 (95% CrI 1 976 100-2 987 000) to 5 200 300 (3 619 400-5 731 400). Between March 1, 2020, and Oct 31, 2021, 491 300 (95% CrI 485 100-497 900) children
Bareng OT, Moyo S, Zahralban-Steele M, et al., 2022, HIV-1 drug resistance mutations among individuals with low-level viraemia while taking combination ART in Botswana, JOURNAL OF ANTIMICROBIAL CHEMOTHERAPY, Vol: 77, Pages: 1385-1395, ISSN: 0305-7453
Hillis S, Blenkinsop A, Villaveces A, et al., 2021, COVID-19-associated orphanhood and caregiver death in the United States, Pediatrics, Vol: 148, Pages: 1-13, ISSN: 0031-4005
Background: Most COVID-19 deaths occur among adults, not children, and attention has focused on mitigating COVID-19 burden among adults. However, a tragic consequence of adult deaths is that high numbers of children might lose their parents and caregivers to COVID-19-associated deaths.Methods: We quantified COVID-19-associated caregiver loss and orphanhood in the US and for each state using fertility and excess and COVID-19 mortality data. We assessed burden and rates of COVID-19-associated orphanhood and deaths of custodial and co-residing grandparents, overall and by race/ethnicity. We further examined variations in COVID-19-associated orphanhood by race/ethnicity for each state. Results: We found that from April 1, 2020 through June 30, 2021, over 140,000 children in the US experienced the death of a parent or grandparent caregiver. The risk of such loss was 1.1 to 4.5 times higher among children of racial and ethnic minorities, compared to Non-Hispanic White children. The highest burden of COVID-19-associated death of parents and caregivers occurred in Southern border states for Hispanic children, Southeastern states for Black children, and in states with tribal areas for American Indian/Alaska Native populations.Conclusions: We found substantial disparities in distributions of COVID-19-associated death of parents and caregivers across racial and ethnic groups. Children losing caregivers to COVID-19 need care and safe, stable, and nurturing families with economic support, quality childcare and evidence-based parenting support programs. There is an urgent need to mount an evidence-based comprehensive response focused on those children at greatest risk, in the states most affected.
Mousa A, Winskill P, Watson OJ, et al., 2021, Social contact patterns and implications for infectious disease transmission: a systematic review and meta-analysis of contact surveys, eLife, Vol: 10, ISSN: 2050-084X
Background: Transmission of respiratory pathogens such as SARS-CoV-2 depends on patterns of contact and mixing across populations. Understanding this is crucial to predict pathogen spread and the effectiveness of control efforts. Most analyses of contact patterns to date have focussed on high-income settings.Methods: Here, we conduct a systematic review and individual-participant meta-analysis of surveys carried out in low- and middle-income countries and compare patterns of contact in these settings to surveys previously carried out in high-income countries. Using individual-level data from 28,503 participants and 413,069 contacts across 27 surveys we explored how contact characteristics (number, location, duration and whether physical) vary across income settings.Results: Contact rates declined with age in high- and upper-middle-income settings, but not in low-income settings, where adults aged 65+ made similar numbers of contacts as younger individuals and mixed with all age-groups. Across all settings, increasing household size was a key determinant of contact frequency and characteristics, with low-income settings characterised by the largest, most intergenerational households. A higher proportion of contacts were made at home in low-income settings, and work/school contacts were more frequent in high-income strata. We also observed contrasting effects of gender across income-strata on the frequency, duration and type of contacts individuals made.Conclusions: These differences in contact patterns between settings have material consequences for both spread of respiratory pathogens, as well as the effectiveness of different non-pharmaceutical interventions.
Mousa A, Winskill P, Watson OJ, et al., 2021, Social contact patterns and implications for infectious disease transmission - a systematic review and meta-analysis of contact surveys, ELIFE, Vol: 10, ISSN: 2050-084X
Gurdasani D, Bhatt S, Costello A, et al., 2021, Vaccinating adolescents against SARS-CoV-2 in England: a risk-benefit analysis., Journal of the Royal Society of Medicine, Vol: 114, Pages: 513-524, ISSN: 0141-0768
OBJECTIVE: To offer a quantitative risk-benefit analysis of two doses of SARS-CoV-2 vaccination among adolescents in England. SETTING: England. DESIGN: Following the risk-benefit analysis methodology carried out by the US Centers for Disease Control, we calculated historical rates of hospital admission, Intensive Care Unit admission and death for ascertained SARS-CoV-2 cases in children aged 12-17 in England. We then used these rates alongside a range of estimates for incidence of long COVID, vaccine efficacy and vaccine-induced myocarditis, to estimate hospital and Intensive Care Unit admissions, deaths and cases of long COVID over a period of 16 weeks under assumptions of high and low case incidence. PARTICIPANTS: All 12-17 year olds with a record of confirmed SARS-CoV-2 infection in England between 1 July 2020 and 31 March 2021 using national linked electronic health records, accessed through the British Heart Foundation Data Science Centre. MAIN OUTCOME MEASURES: Hospitalisations, Intensive Care Unit admissions, deaths and cases of long COVID averted by vaccinating all 12-17 year olds in England over a 16-week period under different estimates of future case incidence. RESULTS: At high future case incidence of 1000/100,000 population/week over 16 weeks, vaccination could avert 4430 hospital admissions and 36 deaths over 16 weeks. At the low incidence of 50/100,000/week, vaccination could avert 70 hospital admissions and two deaths over 16 weeks. The benefit of vaccination in terms of hospitalisations in adolescents outweighs risks unless case rates are sustainably very low (below 30/100,000 teenagers/week). Benefit of vaccination exists at any case rate for the outcomes of death and long COVID, since neither have been associated with vaccination to date. CONCLUSIONS: Given the current (as at 15 September 2021) high case rates (680/100,000 population/week in 10-19 year olds) in England, our findings support vaccination of adolescents against SARS-CoV2.
Hall M, Golubchik T, Bonsall D, et al., 2021, Demographics of people who transmit HIV-1 in Zambia: a molecular epidemiology analysis in the HPTN-071 PopART study
<jats:title>Abstract</jats:title><jats:sec><jats:title>Background</jats:title><jats:p>In the last decade, universally available antiretroviral therapy (ART) has led to greatly improved health and survival of people living with HIV in sub-Saharan Africa, and appears to have contributed to reduced rates of new infections. Individuals acting as sources of infection need to be characterised to design effective prevention strategies.</jats:p></jats:sec><jats:sec><jats:title>Methods</jats:title><jats:p>We used viral genomes to investigate the demographic characteristics of sources of HIV-1 infection. Between 2014 and 2018, the HPTN 071 PopART study was conducted to quantify the public health benefits of ART. Viral samples from 7,124 study participants in Zambia were deep-sequenced as part of HPTN 071-02 PopART Phylogenetics, an ancillary study. We identified 300 likely HIV-1 transmission pairs and investigated the source individuals in those pairs to better understand transmission in the general population.</jats:p></jats:sec><jats:sec><jats:title>Findings</jats:title><jats:p>After demographic weighting, 59.4% of transmissions were male to female, with 43·2% (95% CI: 36·8%-49·7%) of transmissions being from males aged 25-40. Overall, men transmitted 2.09-fold (2·06-2·29) more infections per capita than women, a ratio peaking, when stratified by source age, at 5.88 (2·78-15·8) in the 35-39 age group. 17·4% of sources (12·5%-22·4%) carried viruses resistant to first-line ART. 12·9% (8·5%-17·3%) of transmissions linked individuals from different communities in the trial.</jats:p></jats:sec><jats:sec><jats:title>Interpretation</jats:title><jats:p>HIV-1 transmission in the HPTN 071 study communities comes from a wide range of age and sex groups
Brizzi A, Whittaker C, Servo LMS, et al., 2021, Factors driving extensive spatial and temporal fluctuations in COVID-19 fatality rates in Brazilian hospitals
The SARS‐CoV‐2 Gamma variant spread rapidly across Brazil, causing substantial infection and death wa ves. We use individual‐level patient records following hospitalisation with suspected or confirmed COVID‐19 to document the extensive shocks in hospital fatality rates that followed Gamma’s spread across 14 state capitals, and in which more than half of hospitalised patients died over sustained time pe riods. We show that extensive fluctuations in COVID‐19 in‐hospital fatality rates also existed prior to Gamma’s detection, and were largely transient after Gamma’s detection, subsiding with hospital d emand. Using a Bayesian fatality rate model, we find that the geo‐graphic and temporal fluctuations in Brazil’s COVID‐19 in‐hospital fatality rates are primarily associated with geo‐graphic inequities and shortages in healthcare c apacity. We project that approximately half of Brazil’s COVID‐19 deaths in hospitals could have been avoided without pre‐pandemic geographic inequities and without pandemic healthcare pressure. Our results suggest that investments in healthcare resources, healthcare optimization, and pandemic preparedness are critical to minimize population wide mortality and morbidity caused by highly trans‐missible and deadly pathogens such as SARS‐CoV‐2, especially in low‐ and middle‐income countries.
Bezemer D, Blenkinsop A, Hall M, et al., 2021, Many but small HIV-1 non-B transmission chains in the Netherlands, AIDS, Vol: 36, Pages: 83-94, ISSN: 0269-9370
Objective To investigate introductions and spread of different HIV-1 subtypes in the Netherlands. Design We identified distinct HIV-1 transmission chains in the Netherlands within the global epidemic context through viral phylogenetic analysis of partial HIV-1 polymerase sequences from individuals enrolled in the ATHENA national HIV cohort of all persons in care since 1996, and publicly available international background sequences. Methods Viral lineages circulating in the Netherlands were identified through maximum parsimony phylogeographic analysis. The proportion of HIV-1 infections acquired in-country among heterosexuals and men having sex with men (MSM) was estimated from phylogenetically observed, national transmission chains using a branching process model that accounts for incomplete sampling. Results As of January 1st 2019, 2,589 (24%) of 10,971 (41%) HIV-1 sequenced individuals in ATHENA had non-B subtypes (A1, C, D, F, G) or circulating recombinant forms (CRF01AE, CRF02AG, CRF06-cpx). The 1,588 heterosexuals were in 1,224, and 536 MSM in 270 phylogenetically observed transmission chains. After adjustments for incomplete sampling, most heterosexual (75%) and MSM (76%) transmission chains were estimated to include only the individual introducing the virus (size=1). Onward transmission occurred mostly in chains size 2-5 amongst heterosexuals (62%) and in chains size ≥10 amongst MSM (64%). Considering some chains originated in-country from other risk-groups, 40% (95%CI: 36-44%) of non-B-infected heterosexuals and 62% (95%CI: 49%-73%) of MSM acquired infection in-country. Conclusions Whilst most HIV-1 non-B introductions showed no or very little onward transmission, a considerable proportion of non-B infections amongst both heterosexuals and MSM in the Netherlands have been acquired in-country.
Whittaker C, Ratmann O, Dye C, et al., 2021, Altered demographic profile of hospitalizations during the second COVID-19 wave in Amazonas, Brazil, The Lancet Regional Health - Americas, Vol: 2, ISSN: 2667-193X
Ratmann O, Bhatt S, Flaxman S, 2021, Implications of a highly transmissible variant of SARS-CoV-2 for children, Archives of Disease in Childhood, Vol: 106, Pages: 1-1, ISSN: 0003-9888
Mishra S, Scott JA, Laydon DJ, et al., 2021, Comparing the responses of the UK, Sweden and Denmark to COVID-19 using counterfactual modelling, SCIENTIFIC REPORTS, Vol: 11, Pages: 1-9, ISSN: 2045-2322
The UK and Sweden have among the worst per-capita COVID-19 mortality in Europe. Sweden stands out for its greater reliance on voluntary, rather than mandatory, control measures. We explore how the timing and effectiveness of control measures in the UK, Sweden and Denmark shaped COVID-19 mortality in each country, using a counterfactual assessment: what would the impact have been, had each country adopted the others’ policies? Using a Bayesian semi-mechanistic model without prior assumptions on the mechanism or effectiveness of interventions, we estimate the time-varying reproduction number for the UK, Sweden and Denmark from daily mortality data. We use two approaches to evaluate counterfactuals which transpose the transmission profile from one country onto another, in each country’s first wave from 13th March (when stringent interventions began) until 1st July 2020. UK mortality would have approximately doubled had Swedish policy been adopted, while Swedish mortality would have more than halved had Sweden adopted UK or Danish strategies. Danish policies were most effective, although differences between the UK and Denmark were significant for one counterfactual approach only. Our analysis shows that small changes in the timing or effectiveness of interventions have disproportionately large effects on total mortality within a rapidly growing epidemic.
Hillis S, Unwin H, Chen Y, et al., 2021, Global minimum estimates of children affected by COVID-19-associated orphanhood and deaths of caregivers: a modelling study, The Lancet, Vol: 398, Pages: 391-402, ISSN: 0140-6736
Background: The COVID-19 pandemic response has focused on prevention, detection, and response. Beyond morbidity and mortality, pandemics carry secondary impacts, such as children orphaned or bereft of their caregivers. Such children often face adverse consequences, including poverty, abuse, and institutionalization. We provide estimates for the magnitude of this problem resulting from COVID-19 and describe the need for resource allocation.Methods: We use mortality and fertility data to model minimum estimates and rates of COVID-19-associated orphanhood (death of 1 or both parents) and deaths of custodial and co-residing grandparents for 21 countries. We use these estimates to model global extrapolations for the number of children experiencing COVID-19-associated deaths of parents and grandparents ages 60-84.Results: Globally, from March 1, 2020-March 31, 2021, we estimate 974,000 children experienced death of primary caregivers, including parents or custodial grandparents; >1.3 million experienced death of primary caregivers and co-residing grandparents (or kin). Countries with rates of primary caregiver deaths >1/1000 children included Peru, South Africa, Mexico, Colombia, Brazil, I.R. Iran, U.S.A., and Russia (range, 1.0-8.5/1000). Numbers of children orphaned exceeded numbers of deaths among those aged 15 – 44; 2 – 5 times more children had deceased fathers than deceased mothers. Conclusions: Orphanhood and caregiver deaths are a hidden pandemic resulting from COVID-19-associated deaths. Accelerating equitable vaccine delivery is key to prevention. Psychosocial and economic support can help families nurture children bereft of caregivers and help ensure institutionalization is avoided. These data demonstrate the need for an additional pillar of our response: prevent, detect, respond, and care for children.
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