Publications
21 results found
Brizzi A, Kagaayi J, Ssekubugu R, et al., 2024, Age and gender profiles of HIV infection burden and viraemia: novel metrics for HIV epidemic control in African populations with high antiretroviral therapy coverage., medRxiv
INTRODUCTION: To prioritize and tailor interventions for ending AIDS by 2030 in Africa, it is important to characterize the population groups in which HIV viraemia is concentrating. METHODS: We analysed HIV testing and viral load data collected between 2013-2019 from the open, population-based Rakai Community Cohort Study (RCCS) in Uganda, to estimate HIV seroprevalence and population viral suppression over time by gender, one-year age bands and residence in inland and fishing communities. All estimates were standardized to the underlying source population using census data. We then assessed 95-95-95 targets in their ability to identify the populations in which viraemia concentrates. RESULTS: Following the implementation of Universal Test and Treat, the proportion of individuals with viraemia decreased from 4.9% (4.6%-5.3%) in 2013 to 1.9% (1.7%-2.2%) in 2019 in inland communities and from 19.1% (18.0%-20.4%) in 2013 to 4.7% (4.0%-5.5%) in 2019 in fishing communities. Viraemia did not concentrate in the age and gender groups furthest from achieving 95-95-95 targets. Instead, in both inland and fishing communities, women aged 25-29 and men aged 30-34 were the 5-year age groups that contributed most to population-level viraemia in 2019, despite these groups being close to or had already achieved 95-95-95 targets. CONCLUSIONS: The 95-95-95 targets provide a useful benchmark for monitoring progress towards HIV epidemic control, but do not contextualize underlying population structures and so may direct interventions towards groups that represent a marginal fraction of the population with viraemia.
Monod M, Brizzi A, Galiwango RM, et al., 2024, Longitudinal population-level HIV epidemiologic and genomic surveillance highlights growing gender disparity of HIV transmission in Uganda, Nature Microbiology, Vol: 9, Pages: 35-54, ISSN: 2058-5276
HIV incidence in eastern and southern Africa has historically been concentrated among girls and women aged 15-24 years. As new cases decline with HIV interventions, population-level infection dynamics may shift by age and gender. Here, we integrated population-based surveillance of 38,749 participants in the Rakai Community Cohort Study and longitudinal deep-sequence viral phylogenetics to assess how HIV incidence and population groups driving transmission have changed from 2003 to 2018 in Uganda. We observed 1,117 individuals in the incidence cohort and 1,978 individuals in the transmission cohort. HIV viral suppression increased more rapidly in women than men, however incidence declined more slowly in women than men. We found that age-specific transmission flows shifted: whereas HIV transmission to girls and women (aged 15-24 years) from older men declined by about one-third, transmission to women (aged 25-34 years) from men that were 0-6 years older increased by half in 2003 to 2018. Based on changes in transmission flows, we estimated that closing the gender gap in viral suppression could have reduced HIV incidence in women by half in 2018. This study suggests that HIV programmes to increase HIV suppression in men are critical to reduce incidence in women, close gender gaps in infection burden and improve men's health in Africa.
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.
Flaxman S, Kasonka L, Cluver L, et al., 2023, List child dependents on death certificates, SCIENCE, Vol: 380, ISSN: 0036-8075
Choodari-Oskooei B, Thwin SS, Blenkinsop A, et al., 2023, Treatment selection in multi-arm multi-stage designs: With application to a postpartum haemorrhage trial, CLINICAL TRIALS, Vol: 20, Pages: 71-80, ISSN: 1740-7745
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
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
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
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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.
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
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.
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.
Monod M, Blenkinsop A, Xi X, et al., 2020, Report 32: Age groups that sustain resurging COVID-19 epidemics in the United States
<jats:title>Summary</jats:title><jats:p>Following initial declines, in mid 2020, a resurgence in transmission of novel coronavirus disease (COVID-19) has occurred in the United States and parts of Europe. Despite the wide implementation of non-pharmaceutical interventions, it is still not known how they are impacted by changing contact patterns, age and other demographics. As COVID-19 disease control becomes more localised, understanding the age demographics driving transmission and how these impacts the loosening of interventions such as school reopening is crucial. Considering dynamics for the United States, we analyse aggregated, age-specific mobility trends from more than 10 million individuals and link these mechanistically to age-specific COVID-19 mortality data. In contrast to previous approaches, we link mobility to mortality via age specific contact patterns and use this rich relationship to reconstruct accurate transmission dynamics. Contrary to anecdotal evidence, we find little support for age-shifts in contact and transmission dynamics over time. We estimate that, until August, 63.4% [60.9%-65.5%] of SARS-CoV-2 infections in the United States originated from adults aged 20-49, while 1.2% [0.8%-1.8%] originated from children aged 0-9. In areas with continued, community-wide transmission, our transmission model predicts that re-opening kindergartens and elementary schools could facilitate spread and lead to additional COVID-19 attributable deaths over a 90-day period. These findings indicate that targeting interventions to adults aged 20-49 are an important consideration in halting resurgent epidemics and preventing COVID-19-attributable deaths when kindergartens and elementary schools reopen.</jats:p><jats:sec><jats:title>One sentence summary</jats:title><jats:p>Adults aged 20-49 are a main driver of the COVID-19 epidemic in the United States; yet, in areas with resurging epidemics, opening schools will lea
Monod M, Blenkinsop A, Xi X, et al., 2020, Report 32: Targeting interventions to age groups that sustain COVID-19 transmission in the United States, Pages: 1-32
Following inial declines, in mid 2020, a resurgence in transmission of novel coronavirus disease (COVID-19) has occurred in the United States and parts of Europe. Despite the wide implementaon of non-pharmaceucal inter-venons, it is sll not known how they are impacted by changing contact paerns, age and other demographics. As COVID-19 disease control becomes more localised, understanding the age demographics driving transmission and how these impact the loosening of intervenons such as school reopening is crucial. Considering dynamics for the United States, we analyse aggregated, age-specific mobility trends from more than 10 million individuals and link these mechaniscally to age-specific COVID-19 mortality data. In contrast to previous approaches, we link mobility to mortality via age specific contact paerns and use this rich relaonship to reconstruct accurate trans-mission dynamics. Contrary to anecdotal evidence, we find lile support for age-shis in contact and transmission dynamics over me. We esmate that, unl August, 63.4% [60.9%-65.5%] of SARS-CoV-2 infecons in the United States originated from adults aged 20-49, while 1.2% [0.8%-1.8%] originated from children aged 0-9. In areas with connued, community-wide transmission, our transmission model predicts that re-opening kindergartens and el-ementary schools could facilitate spread and lead to considerable excess COVID-19 aributable deaths over a 90-day period. These findings indicate that targeng intervenons to adults aged 20-49 are an important con-sideraon in halng resurgent epidemics, and prevenng COVID-19-aributable deaths when kindergartens and elementary schools reopen.
Blenkinsop A, van der Flier WM, Wolk D, et al., 2020, Non-memory cognitive symptom development in Alzheimer's disease, EUROPEAN JOURNAL OF NEUROLOGY, Vol: 27, Pages: 995-1002, ISSN: 1351-5101
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Lensen S, Macnair A, Love SB, et al., 2020, Access to routinely collected health data for clinical trials - review of successful data requests to UK registries, TRIALS, Vol: 21
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- Citations: 11
Blenkinsop A, Choodari-Oskooei B, 2019, Multiarm, multistage randomized controlled trials with stopping boundaries for efficacy and lack of benefit: An update to nstage, STATA JOURNAL, Vol: 19, Pages: 782-802, ISSN: 1536-867X
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Blenkinsop A, Parmar MKB, Choodari-Oskooei B, 2019, Assessing the impact of efficacy stopping rules on the error rates under the multi-arm multi-stage framework, CLINICAL TRIALS, Vol: 16, Pages: 132-141, ISSN: 1740-7745
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