Imperial College London

DrOliverRatmann

Faculty of Natural SciencesDepartment of Mathematics

Reader in Statistics and Machine Learning for Public Good
 
 
 
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oliver.ratmann05 Website

 
 
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525Huxley BuildingSouth Kensington Campus

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Summary

 

Publications

Publication Type
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79 results found

Bogers SJ, Schim van der Loeff MF, Boyd A, Davidovich U, van der Valk M, Brinkman K, Sigaloff K, Branger J, Bokhizzou N, de Bree GJ, Reiss P, van Bergen JEAM, Geerlings SE, HIV Transmission Elimination AMsterdam H-TEAM Initiativeet al., 2022, Improving indicator-condition guided testing for HIV in the hospital setting (PROTEST 2·0): A multicenter, interrupted time-series analysis., Lancet Reg Health Eur, Vol: 23

Background: Indicator-condition (IC) guided HIV testing is a feasible and cost-effective strategy to identify undiagnosed people living with HIV (PLHIV), but remains insufficiently implemented. We aimed to promote IC-guided HIV testing in seven ICs. Methods: Relevant departments in five hospitals of the Amsterdam region participated. HIV testing among adult patients without known HIV infection but with an IC was assessed using electronic health records during pre-intervention (January 2015-June 2020) and intervention (July 2020-June 2021) periods. The multifaceted intervention included audit and feedback. The primary endpoint was HIV testing ≤3 months before or after IC diagnosis and the effect of the intervention was evaluated using segmented Poisson regression. Findings: Data from 7986 patients were included, of whom 6730 (84·3%) were diagnosed with an IC in the pre-intervention period and 1256 (15·7%) in the intervention period. The proportion HIV tested ≤3 months before or after IC diagnosis increased from 36.8% to 47.0% (adjusted risk ratio [RR]= 1.16, 95% CI=1.03-1.30, p=0.02). For individual ICs, we observed significant increases in HIV testing among patients with cervical cancer or intraepithelial neoplasia grade 3 (adjusted RR=3.62, 95% CI=1.93-6.79) and peripheral neuropathy (adjusted RR=2.27 95% CI=1.48-3.49), but not the other ICs. Eighteen of 3068 tested patients were HIV positive (0.6%). Interpretation: Overall IC-guided testing improved after the intervention, but not for all ICs. Variations in effect by IC may have been due to variations in implemented developments, but the effect of separate elements could not be assessed. Funding: HIV Transmission Elimination Amsterdam (H-TEAM) initiative, Aidsfonds (grant number: P-42702).

Journal article

Prete CA, Buss LF, Whittaker C, Salomon T, Oikawa MK, Pereira RHM, Moura ICG, Delerino L, Barral-Netto M, Tavares NM, Franca RFO, Boaventura VS, Miyajima F, Mendrone-Junior A, de Almeida-Neto C, Salles NA, Ferreira SC, Fladzinski KA, de Souza LM, Schier LK, Inoue PM, Xabregas LA, Crispim MAE, Fraiji N, Araujo FLV, Carlos LMB, Pessoa V, Ribeiro MA, de Souza RE, da Silva SMN, Cavalcante AF, Valença MIB, da Silva MV, Lopes E, Filho LA, Mateos SOG, Nunes GT, Silva-Junior AL, Busch MP, Castro MC, Dye C, Ratmann O, Faria NR, Nascimento VH, Sabino ECet 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

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

Journal article

Monod M, Blenkinsop A, Brizzi A, Chen Y, Cardoso Correia Perello C, Jogarah V, Wang Y, Flaxman S, Bhatt S, Ratmann Oet al., 2022, Regularised B-splines projected Gaussian Process priors to estimate time-trends in age-specific COVID-19 deaths, Bayesian Analysis, 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.

Journal article

Brizzi A, Whittaker C, Servo LMS, Hawryluk I, Prete CA, de Souza WM, Aguiar RS, Araujo LJT, Bastos LS, Blenkinsop A, Buss LF, Candido D, Castro MC, Costa SF, Croda J, de Souza Santos AA, Dye C, Flaxman S, Fonseca PLC, Geddes VEV, Gutierrez B, Lemey P, Levin AS, Mellan T, Bonfim DM, Miscouridou X, Mishra S, Monod M, Moreira FRR, Nelson B, Pereira RHM, Ranzani O, Schnekenberg RP, Semenova E, Sonnabend R, Souza RP, Xi X, Sabino EC, Faria NR, Bhatt S, Ratmann Oet 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.

Working paper

Blenkinsop A, Monod M, van Sighem A, Pantazis N, Bezemer D, Op de Coul E, van de Laar T, Fraser C, Prins M, Reiss P, de Bree GJ, Ratmann O, HIV Transmission Elimination AMsterdam H-TEAM collaborationet al., 2022, Estimating the potential to prevent locally acquired HIV infections in a UNAIDS Fast-Track City, Amsterdam.

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 birth. Of the locally acquired infections, a

Working paper

Blenkinsop A, Monod M, van Sighem A, Pantazis N, Bezemer D, Op de Coul E, van de Laar T, Fraser C, Prins M, Reiss P, de Bree G, Ratmann Oet al., 2022, Estimating the potential to prevent locally acquired HIV infections in a UNAIDS Fast-Track City, Amsterdam, eLife, ISSN: 2050-084X

BackgroundMore than 300 cities including the city of Amsterdam in the Netherlands have joined theUNAIDS Fast-Track Cities initiative, committing to accelerate their HIV response and end theAIDS epidemic in cities by 2030. To support this commitment, we aimed to estimate thenumber and proportion of Amsterdam HIV infections that originated within the city, fromAmsterdam residents. We also aimed to estimate the proportion of recent HIV infectionsduring the 5-year period 2014-2018 in Amsterdam that remained undiagnosed.MethodsWe located diagnosed HIV infections in Amsterdam using postcode data (PC4) at time ofregistration in the ATHENA observational HIV cohort, and used HIV sequence data toreconstruct phylogeographically distinct, partially observed Amsterdam transmission chains.Individual-level infection times were estimated from biomarker data, and used to date thephylogenetically observed transmission chains as well as to estimate undiagnosedproportions among recent infections. A Bayesian Negative Binomial branching process2model was used to estimate the number, size and growth of the unobserved Amsterdamtransmission chains from the partially observed phylogenetic data.ResultsBetween January 1 2014 and May 1 2019, there were 846 HIV diagnoses in Amsterdamresidents, of whom 516 (61%) were estimated to have been infected in 2014-2018. The rateof new Amsterdam diagnoses since 2014 (104 per 100,000) remained higher than thenational rates excluding Amsterdam (24 per 100,000), and in this sense Amsterdamremained a HIV hotspot in the Netherlands. An estimated 14% [12-16%] of infections inAmsterdan MSM in 2014-2018 remained undiagnosed by May 1 2019, and 41% [35-48%] inAmsterdam heterosexuals, with variation by region of birth. An estimated 68% [61-74%] ofAmsterdam MSM infections in 2014-2018 had an Amsterdam resident as source, and 57%[41-71%] in Amsterdam heterosexuals, with heterogeneity by region of birth. Of the locallyacquired infections, an estimated 43% [37-49%] were

Journal article

Brizzi A, Whittaker C, Servo LMS, Hawryluk I, Prete CA, de Souza WM, Aguiar RS, Araujo LJT, Bastos LS, Blenkinsop A, Buss LF, Candido D, Castro MC, Costa SF, Croda J, de Souza Santos AA, Dye C, Flaxman S, Fonseca PLC, Geddes VEV, Gutierrez B, Lemey P, Levin AS, Mellan T, Bonfim DM, Miscouridou X, Mishra S, Monod M, Moreira FRR, Nelson B, Pereira RHM, Ranzani O, Schnekenberg RP, Semenova E, Sonabend R, Souza RP, Xi X, Sabino EC, Faria NR, Bhatt S, Ratmann Oet al., 2022, Spatial and temporal fluctuations in COVID-19 fatality rates in Brazilian hospitals (May, 10.1038/s41591-022-01807-1, 2022), NATURE MEDICINE, Vol: 28, Pages: 1509-1509, ISSN: 1078-8956

Journal article

Xi X, Spencer SEF, Hall M, Grabowski MK, Kagaayi J, Ratmann Oet 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.

Journal article

Flaxman S, Whittaker C, Semenova E, Rashid T, Parks RM, Blenkinsop A, Unwin HJT, Mishra S, Bhatt S, Gurdasani D, Ratmann Oet 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>

Journal article

Brizzi A, Whittaker C, Servo LMS, Hawryluk I, Prete Jr CA, de Souza WM, Aguiar RS, Araujo LJT, Bastos LS, Blenkinsop A, Buss LF, Candido D, Castro M, Costa S, Croda J, de Souza Santos AA, Dye C, Flaxman S, Fonseca PLC, Geddes VEV, Gutierrez B, Lemey P, Levin AS, Mellan T, Bonfim D, Miscoridou X, Mishra S, Monod M, Moreira FRR, Ranzani O, Schnekenberg R, Semenova E, Sonnabend R, Souza RP, Xi X, Sabino E, Faria NR, Bhatt S, Ratmann Oet 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.

Journal article

Unwin HJT, Hillis S, Cluver L, Flaxman S, Goldman PS, Butchart A, Bachman G, Rawlings L, Donnelly CA, Ratmann O, Green P, Nelson CA, Blenkinsop A, Bhatt S, Desmond C, Villaveces A, Sherr Let 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

Journal article

Bareng OT, Moyo S, Zahralban-Steele M, Maruapula D, Ditlhako T, Mokaleng B, Mokgethi P, Choga WT, Moraka NO, Pretorius-Holme M, Mine MO, Raizes E, Molebatsi K, Motswaledi MS, Gobe I, Mohammed T, Gaolathe T, Shapiro R, Mmalane M, Makhema JM, Lockman S, Essex M, Novitsky V, Gaseitsiwe Set 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

Journal article

Hillis S, Blenkinsop A, Villaveces A, Annor F, Liburd L, Massetti G, Demissie Z, Mercy J, Nelson C, Cluver L, Flaxman S, Sherr L, Donnelly C, Ratmann O, Unwin Jet 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.

Journal article

Mousa A, Winskill P, Watson OJ, Ratmann O, Monod M, Ajelli M, Diallo A, Dodd PJ, Grijalva CG, Kiti MC, Krishnan A, Kumar R, Kumar S, Kwok KO, Lanata CF, de Waroux OLP, Leung K, Mahikul W, Melegaro A, Morrow CD, Mossong J, Neal EFG, Nokes DJ, Pan-ngum W, Potter GE, Russell FM, Saha S, Sugimoto JD, Wei WI, Wood RR, Wu JT, Zhang J, Walker PGT, Whittaker Cet 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

Journal article

Mousa A, Winskill P, Watson OJ, Ratmann O, Monod M, Ajelli M, Diallo A, Dodd P, Grijalva CG, Kiti MC, Krishnan A, Kumar R, Kumar S, Kwok KO, Lanata C, Le Polain de Waroux O, Leung K, Mahikul W, Melegaro A, Morrow CD, Mossong J, Neal EFG, Nokes DJ, Pan-ngum W, Potter GE, Russel FM, Saha S, Sugimoto JD, Wei WI, Wood RR, Wu JT, Zhang J, Walker PGT, Whittaker Cet 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.

Journal article

Gurdasani D, Bhatt S, Costello A, Denaxas S, Flaxman S, Greenhalgh T, Griffin S, Hyde Z, Katzourakis A, McKee M, Michie S, Ratmann O, Reicher S, Scally G, Tomlinson C, Yates C, Ziauddeen H, Pagel Cet 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.

Journal article

Hall M, Golubchik T, Bonsall D, Abeler-Dörner L, Limbada M, Kosloff B, Schaap A, de Cesare M, MacIntyre-Cockett G, Probert W, Ratmann O, Cruz AB, Piwowar-Manning E, Burns DN, Cohen MS, Donnell DJ, Eshleman SH, Simwinga M, Hayes R, Fidler S, Ayles H, Fraser Cet al., 2021, Demographic characteristics of sources of HIV-1 transmission in the era of test and treat

<jats:title>Abstract</jats:title><jats:p>In recent years, universally available antiretroviral therapy has reduced HIV infection rates in sub-Saharan Africa. We used phylogenetics to understand the demographic characteristics of transmission in the HPTN 071-02 (PopART) study in Zambia. After estimating that 59.4% of transmissions were from a male source to a female recipient, we further found that 43.1% (95% CI: 36.6%-49.5%) were from men aged 25-40. Overall, men infected 2.09-fold more women per capita than vice versa, a ratio peaking at 5.98 (3.14-13.6) amongst those aged 35-39. 25.6% (19.9%-31.3%) of sources were recently infected, 16.8% (12%-21.7%) transmitted drug-resistant virus and 13% lived in a different community than the recipient; these characteristics played no outsize role in transmission. Men aged 25-40 should be a focus of treatment for prevention interventions.</jats:p><jats:sec><jats:title>One sentence summary</jats:title><jats:p>Men aged 25-40 are the source of 43% of HIV transmissions in Zambia and HIV prevention activities should be more inclusive of this demographic group</jats:p></jats:sec>

Journal article

Brizzi A, Whittaker C, Servo LMS, Hawryluk I, Prete Jr CA, de Souza WM, Aguiar RS, Araujo LJT, Bastos LS, Blenkinsop A, Buss LF, Candido D, Castro MC, Costa SF, Croda J, de Souza Santos A, Dye C, Flaxman S, Fonseca PLC, Geddes VEV, Gutierrez B, Lemey P, Levin AS, Mellan T, Bonfim DM, Miscouridou X, Mishra S, Monod M, Moreira FRR, Nelson B, Pereira RHM, Ranzani O, Schnekenberg RP, Semenova E, Sonnabend R, Souza RP, Xi X, Sabino EC, Faria NR, Bhatt S, Ratmann Oet 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.

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Bezemer D, Blenkinsop A, Hall M, Van Sighem A, Cornelissen M, Wessels E, van Kampen J, van de Laar T, Reiss P, Fraser C, Ratmann Oet 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.

Journal article

Whittaker C, Ratmann O, Dye C, Sabino EC, Faria NRet 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

Journal article

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

Journal article

Mishra S, Scott JA, Laydon DJ, Flaxman S, Gandy A, Mellan TA, Unwin HJT, Vollmer M, Coupland H, Ratmann O, Monod M, Zhu HH, Cori A, Gaythorpe KAM, Whittles LK, Whittaker C, Donnelly CA, Ferguson NM, Bhatt Set 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.

Journal article

Hillis S, Unwin H, Chen Y, Cluver L, Sherr L, Goldman P, Ratmann O, Donnelly C, Bhatt S, Villaveces A, Butchart A, Bachman G, Rawlings L, Green P, Nelson C, Flaxman Set 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.

Journal article

Mishra S, Mindermann S, Sharma M, Whittaker C, Mellan TA, Wilton T, Klapsa D, Mate R, Fritzsche M, Zambon M, Ahuja J, Howes A, Miscouridou X, Nason GP, Ratmann O, Semenova E, Leech G, Sandkuehler JF, Rogers-Smith C, Vollmer M, Unwin HJT, Gal Y, Chand M, Gandy A, Martin J, Volz E, Ferguson NM, Bhatt S, Brauner JM, Flaxman Set al., 2021, Changing composition of SARS-CoV-2 lineages and rise of Delta variant in England, ECLINICALMEDICINE, Vol: 39

Journal article

Meyerowitz-Katz G, Bhatt S, Ratmann O, Brauner JM, Flaxman S, Mishra S, Sharma M, Mindermann S, Bradley V, Vollmer M, Merone L, Yamey Get al., 2021, Is the cure really worse than the disease? The health impacts of lockdowns during COVID-19, BMJ Global Health, Vol: 6, Pages: 1-6, ISSN: 2059-7908

Journal article

Mousa A, Winskill P, Watson OJ, Ratmann O, Monod M, Ajelli M, Diallo A, Dodd PJ, Grijalva CG, Kiti MC, Krishnan A, Kumar R, Kumar S, Kwok KO, Lanata CF, Le Polain de Waroux O, Leung K, Mahikul W, Melegaro A, Morrow CD, Mossong J, Neal EF, Nokes DJ, Pan-Ngum W, Potter GE, Russell FM, Saha S, Sugimoto JD, Wei WI, Wood RR, Wu JT, Zhang J, Walker PG, Whittaker Cet al., 2021, Social Contact Patterns and Implications for Infectious Disease Transmission: A Systematic Review and Meta-Analysis of Contact Surveys., medRxiv

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, but low-income settings were 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. FUNDING: This work is primarily being funded by joint Centre funding from the UK Medical Research Council and DFID (MR/R015600/1).

Journal article

Bogers SJ, Schim van der Loeff MF, Davidovich U, Boyd A, van der Valk M, Brinkman K, de Bree GJ, Reiss P, van Bergen JEAM, Geerlings SE, HIV Transmission Elimination AMsterdam H-TEAM Consortiumet al., 2021, Promoting HIV indicator condition-guided testing in hospital settings (PROTEST 2.0): study protocol for a multicentre interventional study, BMC Infectious Diseases, Vol: 21, ISSN: 1471-2334

BACKGROUND: Late presentation remains a key barrier towards controlling the HIV epidemic. Indicator conditions (ICs) are those that are AIDS-defining, associated with a prevalence of undiagnosed HIV > 0.1%, or whose clinical management would be impeded if an HIV infection were undiagnosed. IC-guided HIV testing is an effective strategy in identifying undiagnosed HIV, but opportunities for earlier HIV diagnosis through IC-guided testing are being missed. We present a protocol for an interventional study to improve awareness of IC-guided testing and increase HIV testing in patients presenting with ICs in a hospital setting. METHODS: We designed a multicentre interventional study to be implemented at five hospitals in the region of Amsterdam, the Netherlands. Seven ICs were selected for which HIV test ratios (proportion of patients with an IC tested for HIV) will be measured: tuberculosis, cervical/vulvar cancer or high-grade cervical/vulvar dysplasia, malignant lymphoma, hepatitis B and C, and peripheral neuropathy. Prior to the intervention, a baseline assessment of HIV test ratios across ICs will be performed in eligible patients (IC diagnosed January 2015 through May 2020, ≥18 years, not known HIV positive) and an assessment of barriers and facilitators for HIV testing amongst relevant specialties will be conducted using qualitative (interviews) and quantitative methods (questionnaires). The intervention phase will consist of an educational intervention, including presentation of baseline results as competitive graphical audit and feedback combined with discussion on implementation and opportunities for improvement. The effect of the intervention will be assessed by comparing HIV test ratios of the pre-intervention and post-intervention periods. The primary endpoint is the HIV test ratio within ±3 months of IC diagnosis. Secondary endpoints are the HIV test ratio within ±6 months of diagnosis, ratio ever tested f

Journal article

Dijkstra M, van Rooijen MS, Hillebregt MM, van Sighem A, Smit C, Hogewoning A, Davidovich U, Heijman T, Hoornenborg E, Reiss P, van der Valk M, Prins M, Prins JM, van der Loeff MFS, de Bree GJet al., 2021, Decreased Time to Viral Suppression After Implementation of Targeted Testing and Immediate Initiation of Treatment of Acute Human Immunodeficiency Virus Infection Among Men Who Have Sex With Men in Amsterdam, CLINICAL INFECTIOUS DISEASES, Vol: 72, Pages: 1952-1960, ISSN: 1058-4838

Journal article

Faria NR, Mellan TA, Whittaker C, Claro IM, Candido DDS, Mishra S, Crispim MAE, Sales FC, Hawryluk I, McCrone JT, Hulswit RJG, Franco LAM, Ramundo MS, de Jesus JG, Andrade PS, Coletti TM, Ferreira GM, Silva CAM, Manuli ER, Pereira RHM, Peixoto PS, Kraemer MU, Gaburo N, Camilo CDC, Hoeltgebaum H, Souza WM, Rocha EC, de Souza LM, de Pinho MC, Araujo LJT, Malta FS, de Lima AB, Silva JDP, Zauli DAG, Ferreira ACDS, Schnekenberg RP, Laydon DJ, Walker PGT, Schlueter HM, dos Santos ALP, Vidal MS, Del Caro VS, Filho RMF, dos Santos HM, Aguiar RS, Proenca-Modena JLP, Nelson B, Hay JA, Monod M, Miscouridou X, Coupland H, Sonabend R, Vollmer M, Gandy A, Prete CA, Nascimento VH, Suchard MA, Bowden TA, Pond SLK, Wu C-H, Ratmann O, Ferguson NM, Dye C, Loman NJ, Lemey P, Rambaut A, Fraiji NA, Carvalho MDPSS, Pybus OG, Flaxman S, Bhatt S, Sabino ECet al., 2021, Genomics and epidemiology of the P.1 SARS-CoV-2 lineage in Manaus, Brazil, Science, Vol: 372, Pages: 815-821, ISSN: 0036-8075

Cases of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in Manaus, Brazil, resurged in late 2020 despite previously high levels of infection. Genome sequencing of viruses sampled in Manaus between November 2020 and January 2021 revealed the emergence and circulation of a novel SARS-CoV-2 variant of concern. Lineage P.1 acquired 17 mutations, including a trio in the spike protein (K417T, E484K, and N501Y) associated with increased binding to the human ACE2 (angiotensin-converting enzyme 2) receptor. Molecular clock analysis shows that P.1 emergence occurred around mid-November 2020 and was preceded by a period of faster molecular evolution. Using a two-category dynamical model that integrates genomic and mortality data, we estimate that P.1 may be 1.7- to 2.4-fold more transmissible and that previous (non-P.1) infection provides 54 to 79% of the protection against infection with P.1 that it provides against non-P.1 lineages. Enhanced global genomic surveillance of variants of concern, which may exhibit increased transmissibility and/or immune evasion, is critical to accelerate pandemic responsiveness.

Journal article

Mishra S, Mindermann S, Sharma M, Whittaker C, Mellan T, Wilton T, Klapsa D, Mate R, Fritzsche M, Zambon M, Ahuja J, Howes A, Miscouridou X, Nason G, Ratmann O, Leech G, Fabienne Sandkühler J, Rogers-Smith C, Vollmer M, Unwin H, Gal Y, Chand M, Gandy A, Martin J, Volz E, Ferguson N, Bhatt S, Brauner J, Flaxman Set al., 2021, Report 44: Recent trends in SARS-CoV-2 variants of concern in England, Report 44: Recent trends in SARS-CoV-2 variants of concern in England, Publisher: Imperial College London, 44

Since its emergence in Autumn 2020, the SARS-CoV-2 Variant of Concern (VOC) B.1.1.7 rapidly became the dominant lineage across much of Europe. Simultaneously, several other VOCs were identified globally. Unlike B.1.1.7, some of these VOCs possess mutations thought to confer partial immune escape. Understanding when, whether, and how these additional VOCs pose a threat in settings where B.1.1.7 is currently dominant is vital. This is particularly true for England, which has high coverage from vaccines that are likely more protective against B.1.1.7 than some other VOCs. We examine trends in B.1.1.7’s prevalence in London and other English regions using passive-case detection PCR data, cross-sectional community infection surveys, genomic surveillance, and wastewater monitoring. Our results suggest shifts in the composition of SARS-CoV-2 lineages driving transmission in England between March and April 2021. Local transmission of non-B.1.1.7 VOCs may be increasing; this warrants urgent further investigation.

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