Imperial College London

DrPeterWinskill

Faculty of MedicineSchool of Public Health

Research Fellow
 
 
 
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Contact

 

+44 (0)20 7594 3946p.winskill

 
 
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Location

 

UG1247 Praed StreetSt Mary's Campus

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Summary

 

Publications

Publication Type
Year
to

82 results found

Okell L, Kwambai, Dhabangi, Khairallah, Nkosi-Gondwe, Winskill P, Opoka, Mousa A, Kuhl, Lucas, Challenger J, Idro, Weiss, Cairns, O ter Kuile, Phiri, Robberstad, Moriet al., 2023, Projected health impact of post-discharge malaria chemoprevention among children with severe malarial anaemia in Africa, Nature Communications, ISSN: 2041-1723

Journal article

Thompson HA, Hogan AB, Walker PGT, Winskill P, Zongo I, Sagara I, Tinto H, Ouedraogo J-B, Dicko A, Chandramohan D, Greenwood B, Cairns M, Ghani ACet al., 2022, Seasonal use case for the RTS,S/AS01 malaria vaccine: a mathematical modelling study, The Lancet Global Health, Vol: 10, Pages: e1782-e1792, ISSN: 2214-109X

BACKGROUND: A 2021 clinical trial of seasonal RTS,S/AS01E (RTS,S) vaccination showed that vaccination was non-inferior to seasonal malaria chemoprevention (SMC) in preventing clinical malaria. The combination of these two interventions provided significant additional protection against clinical and severe malaria outcomes. Projections of the effect of this novel approach to RTS,S vaccination in seasonal transmission settings for extended timeframes and across a range of epidemiological settings are needed to inform policy recommendations. METHODS: We used a mathematical, individual-based model of malaria transmission that was fitted to data on the relationship between entomological inoculation rate and parasite prevalence, clinical disease, severe disease, and deaths from multiple sites across Africa. The model was validated with results from a phase 3b trial assessing the effect of SV-RTS,S in Mali and Burkina Faso. We developed three intervention efficacy models with varying degrees and durations of protection for our population-level modelling analysis to assess the potential effect of an RTS,S vaccination schedule based on age (doses were delivered to children aged 6 months, 7·5 months, and 9 months for the first three doses, and at 27 months of age for the fourth dose) or season (children aged 5-17 months at the time of first vaccination received the first three doses in the 3 months preceding the transmission season, with any subsequent doses up to five doses delivered annually) in seasonal transmission settings both in the absence and presence of SMC with sulfadoxine-pyrimethamine plus amodiaquine. This is modelled as a full therapeutic course delivered every month for four or five months of the peak in transmission season. Estimates of cases and deaths averted in a population of 100 000 children aged 0-5 years were calculated over a 15-year time period for a range of levels of malaria transmission intensity (Plasmodium falciparum parasite prevalence i

Journal article

Quaife M, Medley GF, Jit M, Drake T, Asaria M, van Baal P, Baltussen R, Bollinger L, Bozzani F, Brady O, Broekhuizen H, Chalkidou K, Chi Y-L, Dowdy DW, Griffin S, Haghparast-Bidgoli H, Hallett T, Hauck K, Hollingsworth TD, McQuaid CF, Menzies NA, Merritt MW, Mirelman A, Morton A, Ruiz FJ, Siapka M, Skordis J, Tediosi F, Walker P, White RG, Winskill P, Vassall A, Gomez GBet al., 2022, Considering equity in priority setting using transmission models: Recommendations and data needs, Epidemics: the journal of infectious disease dynamics, Vol: 41, Pages: 1-8, ISSN: 1755-4365

ObjectivesDisease transmission models are used in impact assessment and economic evaluations of infectious disease prevention and treatment strategies, prominently so in the COVID-19 response. These models rarely consider dimensions of equity relating to the differential health burden between individuals and groups. We describe concepts and approaches which are useful when considering equity in the priority setting process, and outline the technical choices concerning model structure, outputs, and data requirements needed to use transmission models in analyses of health equity.MethodsWe reviewed the literature on equity concepts and approaches to their application in economic evaluation and undertook a technical consultation on how equity can be incorporated in priority setting for infectious disease control. The technical consultation brought together health economists with an interest in equity-informative economic evaluation, ethicists specialising in public health, mathematical modellers from various disease backgrounds, and representatives of global health funding and technical assistance organisations, to formulate key areas of consensus and recommendations.ResultsWe provide a series of recommendations for applying the Reference Case for Economic Evaluation in Global Health to infectious disease interventions, comprising guidance on 1) the specification of equity concepts; 2) choice of evaluation framework; 3) model structure; and 4) data needs. We present available conceptual and analytical choices, for example how correlation between different equity- and disease-relevant strata should be considered dependent on available data, and outline how assumptions and data limitations can be reported transparently by noting key factors for consideration.ConclusionsCurrent developments in economic evaluations in global health provide a wide range of methodologies to incorporate equity into economic evaluations. Those employing infectious disease models need to use the

Journal article

Watson O, Barnsley G, Toor J, Hogan A, Winskill P, Ghani ACet al., 2022, Global impact of the first year of COVID-19 vaccination: a mathematical modelling study, Lancet Infectious Diseases, Vol: 22, Pages: 1293-1302, ISSN: 1473-3099

Background:The first COVID-19 vaccine outside a clinical trial setting was administered on Dec 8, 2020. To ensure global vaccine equity, vaccine targets were set by the COVID-19 Vaccines Global Access (COVAX) Facility and WHO. However, due to vaccine shortfalls, these targets were not achieved by the end of 2021. We aimed to quantify the global impact of the first year of COVID-19 vaccination programmes.Methods:A mathematical model of COVID-19 transmission and vaccination was separately fit to reported COVID-19 mortality and all-cause excess mortality in 185 countries and territories. The impact of COVID-19 vaccination programmes was determined by estimating the additional lives lost if no vaccines had been distributed. We also estimated the additional deaths that would have been averted had the vaccination coverage targets of 20% set by COVAX and 40% set by WHO been achieved by the end of 2021.Findings:Based on official reported COVID-19 deaths, we estimated that vaccinations prevented 14·4 million (95% credible interval [Crl] 13·7–15·9) deaths from COVID-19 in 185 countries and territories between Dec 8, 2020, and Dec 8, 2021. This estimate rose to 19·8 million (95% Crl 19·1–20·4) deaths from COVID-19 averted when we used excess deaths as an estimate of the true extent of the pandemic, representing a global reduction of 63% in total deaths (19·8 million of 31·4 million) during the first year of COVID-19 vaccination. In COVAX Advance Market Commitment countries, we estimated that 41% of excess mortality (7·4 million [95% Crl 6·8–7·7] of 17·9 million deaths) was averted. In low-income countries, we estimated that an additional 45% (95% CrI 42–49) of deaths could have been averted had the 20% vaccination coverage target set by COVAX been met by each country, and that an additional 111% (105–118) of deaths could have been averted had the 40% target set by

Journal article

Dixon-Zegeye M, Winskill P, Harrison W, Whittaker C, Schmidt V, Flórez Sánchez A, Cucunubá Perez ZM, Edia-Asuke A, Walker M, Basanez M-Get al., 2022, Global force-of-infection trends for human taenia solium taeniasis/cysticercosis, eLife, Vol: 11, ISSN: 2050-084X

Infection by Taenia solium poses a major burden across endemic countries. The World Health Organization (WHO) 2021–2030 Neglected Tropical Diseases roadmap has proposed that 30% of endemic countries achieve intensified T. solium control in hyperendemic areas by 2030. Understanding geographical variation in age-prevalence profiles and force-of-infection (FoI) estimates will inform intervention designs across settings. Human taeniasis (HTT) and human cysticercosis (HCC) age-prevalence data from 16 studies in Latin America, Africa and Asia were extracted through a systematic review. Catalytic models, incorporating diagnostic performance uncertainty, were fitted to the data using Bayesian methods, to estimate rates of antibody (Ab)-seroconversion, infection acquisition and Ab-seroreversion or infection loss. HCC FoI and Ab-seroreversion rates were also estimated across 23 departments in Colombia from 28,100 individuals. Across settings, there was extensive variation in all-ages seroprevalence. Evidence for Ab seroreversion or infection loss was found in most settings for both HTT and HCC and for HCC Ab seroreversion in Colombia. The average duration until humans became Ab-seropositive/infected decreased as all-age (sero)prevalence increased. There was no clear relationship between the average duration humans remain Ab-seropositive and all-age seroprevalence. Marked geographical heterogeneity in T. solium transmission rates indicate the need for setting43 specific intervention strategies to achieve the WHO goals.

Journal article

Whittaker C, Watson O, Alvarez-Moreno C, Angkasekwinai N, Boonyasiri A, Triana LC, Chanda D, Charoenpong L, Chayakulkeeree M, Cooke G, Croda J, Cucunubá ZM, Djaafara A, Estofolete CF, Grillet M-E, Faria N, Costa SF, Forero-Peña DA, Gibb DM, Gordon A, Hamers RL, Hamlet A, Irawany V, Jitmuang A, Keurueangkul N, Kimani TN, Lampo M, Levin A, Lopardo G, Mustafa R, Nayagam AS, Ngamprasertchai T, Njeri NIH, Nogueira ML, Ortiz-Prado E, Perroud Jr MW, Phillips AN, Promsin P, Qavi A, Rodger AJ, Sabino EC, Sangkaew S, Sari D, Sirijatuphat R, Sposito AC, Srisangthong P, Thompson H, Udwadia Z, Valderrama-Beltrán S, Winskill P, Ghani A, Walker P, Hallett Tet al., 2022, Understanding the Potential Impact of Different Drug Properties On SARS-CoV-2 Transmission and Disease Burden: A Modelling Analysis, Clinical Infectious Diseases, Vol: 75, Pages: e224-e233, ISSN: 1058-4838

BackgroundThe public health impact of the COVID-19 pandemic has motivated a rapid search for potential therapeutics, with some key successes. However, the potential impact of different treatments, and consequently research and procurement priorities, have not been clear.MethodsUsing a mathematical model of SARS-CoV-2 transmission, COVID-19 disease and clinical care, we explore the public-health impact of different potential therapeutics, under a range of scenarios varying healthcare capacity, epidemic trajectories; and drug efficacy in the absence of supportive care.ResultsThe impact of drugs like dexamethasone (delivered to the most critically-ill in hospital and whose therapeutic benefit is expected to depend on the availability of supportive care such as oxygen and mechanical ventilation) is likely to be limited in settings where healthcare capacity is lowest or where uncontrolled epidemics result in hospitals being overwhelmed. As such, it may avert 22% of deaths in high-income countries but only 8% in low-income countries (assuming R=1.35). Therapeutics for different patient populations (those not in hospital, early in the course of infection) and types of benefit (reducing disease severity or infectiousness, preventing hospitalisation) could have much greater benefits, particularly in resource-poor settings facing large epidemics.ConclusionsAdvances in the treatment of COVID-19 to date have been focussed on hospitalised-patients and predicated on an assumption of adequate access to supportive care. Therapeutics delivered earlier in the course of infection that reduce the need for healthcare or reduce infectiousness could have significant impact, and research into their efficacy and means of delivery should be a priority.

Journal article

Okell L, Brazeau NF, Verity R, Jenks S, Fu H, Whittaker C, Winskill P, Dorigatti I, Walker P, Riley S, Schnekenberg RP, Hoeltgebaum H, Mellan TA, Mishra S, Unwin H, Watson O, Cucunuba Z, Baguelin M, Whittles L, Bhatt S, Ghani A, Ferguson Net al., 2022, Estimating the COVID-19 infection fatality ratio accounting for seroreversion using statistical modelling, Communications Medicine, Vol: 2, Pages: 1-13, ISSN: 2730-664X

Background: The infection fatality ratio (IFR) is a key statistic for estimating the burden of coronavirus disease 2019 (COVID-19) and has been continuously debated throughout the COVID-19 pandemic. The age-specific IFR can be quantified using antibody surveys to estimate total infections, but requires consideration of delay-distributions from time from infection to seroconversion, time to death, and time to seroreversion (i.e. antibody waning) alongside serologic test sensitivity and specificity. Previous IFR estimates have not fully propagated uncertainty or accounted for these potential biases, particularly seroreversion. Methods: We built a Bayesian statistical model that incorporates these factors and applied this model to simulated data and 10 serologic studies from different countries. Results: We demonstrate that seroreversion becomes a crucial factor as time accrues but is less important during first-wave, short-term dynamics. We additionally show that disaggregating surveys by regions with higher versus lower disease burden can inform serologic test specificity estimates. The overall IFR in each setting was estimated at 0.49 -2.53%.Conclusion: We developed a robust statistical framework to account for full uncertainties in the parameters determining IFR. We provide code for others to apply these methods to further datasets and future epidemics.

Journal article

Whittaker C, Winskill P, Sinka M, Pironon S, Massey C, Weiss DJ, Nguyen M, Gething PW, Kumar A, Ghani A, Bhatt Set al., 2022, A novel statistical framework for exploring the population dynamics and seasonality of mosquito populations, Proceedings of the Royal Society B: Biological Sciences, Vol: 289, Pages: 1-10, ISSN: 0962-8452

Understanding the temporal dynamics of mosquito populations underlying vector-borne disease transmission is key to optimizing control strategies. Many questions remain surrounding the drivers of these dynamics and how they vary between species—questions rarely answerable from individual entomological studies (that typically focus on a single location or species). We develop a novel statistical framework enabling identification and classification of time series with similar temporal properties, and use this framework to systematically explore variation in population dynamics and seasonality in anopheline mosquito time series catch data spanning seven species, 40 years and 117 locations across mainland India. Our analyses reveal pronounced variation in dynamics across locations and between species in the extent of seasonality and timing of seasonal peaks. However, we show that these diverse dynamics can be clustered into four ‘dynamical archetypes’, each characterized by distinct temporal properties and associated with a largely unique set of environmental factors. Our results highlight that a range of environmental factors including rainfall, temperature, proximity to static water bodies and patterns of land use (particularly urbanicity) shape the dynamics and seasonality of mosquito populations, and provide a generically applicable framework to better identify and understand patterns of seasonal variation in vectors relevant to public health.

Journal article

Haw D, Forchini G, Doohan P, Christen P, Pianella M, Johnson R, Bajaj S, Hogan A, Winskill P, Miraldo M, White P, Ghani A, Ferguson N, Smith P, Hauck Ket al., 2022, Optimizing social and economic activity while containing SARS-CoV-2 transmission using DAEDALUS, Nature Computational Science, Vol: 2, Pages: 223-233, ISSN: 2662-8457

To study the trade-off between economic, social and health outcomes in the management of a pandemic, DAEDALUS integrates a dynamic epidemiological model of SARS-CoV-2 transmission with a multi-sector economic model, reflecting sectoral heterogeneity in transmission and complex supply chains. The model identifies mitigation strategies that optimize economic production while constraining infections so that hospital capacity is not exceeded but allowing essential services, including much of the education sector, to remain active. The model differentiates closures by economic sector, keeping those sectors open that contribute little to transmission but much to economic output and those that produce essential services as intermediate or final consumption products. In an illustrative application to 63 sectors in the United Kingdom, the model achieves an economic gain of between £161 billion (24%) and £193 billion (29%) compared to a blanket lockdown of non-essential activities over six months. Although it has been designed for SARS-CoV-2, DAEDALUS is sufficiently flexible to be applicable to pandemics with different epidemiological characteristics.

Journal article

Sherrard-Smith E, Winskill P, Hamlet A, 2022, Optimising the deployment of vector control tools against malaria: a data-informed modelling study (vol 6, pg e100, 2022), LANCET PLANETARY HEALTH, Vol: 6, Pages: E191-E191

Journal article

Olivera Mesa D, Hogan A, Watson O, Charles G, Hauck K, Ghani A, Winskill Pet al., 2022, Modelling the impact of vaccine hesitancy in prolonging the need for Non-Pharmaceutical Interventions to control the COVID-19 pandemic, Communications Medicine, Vol: 2, ISSN: 2730-664X

Background: Vaccine hesitancy – a delay in acceptance or refusal of vaccines despite availability – has the potential to threaten the successful roll-out of SARS-CoV-2 vaccines globally. In this study we aim to understand the likely impact of vaccine hesitancy on the control of the COVID-1924pandemic. Methods: We modelled the potential impact of vaccine hesitancy on the control of the pandemic and the relaxation of non-pharmaceutical interventions (NPIs) by combining an epidemiological model of SARS-CoV-2 transmission with data on vaccine hesitancy from population surveys.Results: Our simulations suggest that the mortality over a 2-year period could be up to 7.6 times higher in countries with high vaccine hesitancy compared to an ideal vaccination uptake if NPIs are relaxed. Alternatively, high vaccine hesitancy could prolong the need for NPIs to remain in place.Conclusions: While vaccination is an individual choice, vaccine hesitant individuals have a substantial impact on the pandemic trajectory, which may challenge current efforts to control COVID-19. In order to prevent such outcomes, addressing vaccine hesitancy with behavioural interventions is an important priority in the control of the COVID-19 pandemic.

Journal article

Sherrard-Smith E, Winskill P, Hamlet A, Ngufor C, N'Guessan R, Guelbeogo MW, Sanou A, Nash RK, Hill A, Russell EL, Woodbridge M, Tungu P, Kont MD, McLean T, Fornadel C, Richardson JH, Donnelly MJ, Staedke SG, Gonahasa S, Protopopoff N, Rowland M, Churcher TSet al., 2022, Optimising the deployment of vector control tools against malaria: a data-informed modelling study, The Lancet Planetary Health, Vol: 6, Pages: e100-e109, ISSN: 2542-5196

Background Concern that insecticide resistant mosquitoes are threatening malaria control has driven the development of new types of insecticide treated nets (ITNs) and indoor residual spraying (IRS). Malaria control programmes have a choice of vector control interventions though it is unclear which should be used to combat the disease.MethodsThe entomological impact of ITNs combining a pyrethroid insecticide with the synergist piperonyl butoxide (PBO) is characterised from experimental hut trials and used to parameterise a malaria transmission dynamics model. Model projections are validated for two sites by comparing results to data from pyrethroid-PBO ITN and IRS randomised control trials (RCTs). Models are used to identify optimum intervention packages for scenarios with varying budget, price, entomological and epidemiological factors. Findings Combining entomological data and models can reasonably predict changes in malaria in the Tanzanian and Ugandan RCTs. Models indicate switching from pyrethroid-only to pyrethroid-PBO ITNs could avert up to twice as many cases, though the additional benefit is highly variable and depends upon setting. Annual delivery of long-lasting, non-pyrethroid IRS is projected to prevent substantially more cases over 3-years, but pyrethroid-PBO ITNs tend to be the most cost-effective intervention per case averted. An online tool (MINT) provides users with a method of designing intervention packages given their setting and budget. InterpretationThe most cost-effective vector control package will vary locally. Models able to recreate results of RCTs can be used to extrapolate outcomes elsewhere to support evidence-based decision making for investment in vector control.FundingMedical Research Council, IVCC, Wellcome Trust.

Journal article

Hogan A, Wu SL, Doohan P, Watson OJ, Winskill P, Charles G, Riley EM, Khoury D, Ferguson N, Ghani Aet al., 2021, Report 48: The value of vaccine booster doses to mitigate the global impact of the Omicron SARS-CoV-2 variant

Vaccines have played a central role in mitigating severe disease and death from COVID-19 in the past 12 months. However, efficacy wanes over time and this loss of protection will be compounded by the emergence of the Omicron variant. By fitting an immunological model to population-level vaccine effectiveness data, we estimate that neutralizing antibody titres for Omicron are reduced by 4.5-fold (95% CrI 3.1–7.1) compared to the Delta variant. This is predicted to result in a drop in vaccine efficacy against severe disease (hospitalisation) from 96.5% (95% CrI 96.1%–96.8%) against Delta to 80.1% (95% CrI 76.3%–83.2%) against Omicron for the Pfizer-BioNTech booster by 60 days post boost if NAT decay at the same rate following boosting as following the primary course, and from 97.6% (95% CrI 97.4%-97.9%) against Delta to 85.9% (95% CrI 83.1%-88.3%) against Omicron if NAT decay at half the rate observed after the primary course. Integrating this immunological model within a model of SARS-CoV-2 transmission, we show that booster doses will be critical to mitigate the impact of future Omicron waves in countries with high levels of circulating virus. They will also be needed in “zero-COVID” countries where there is little prior infection-induced immunity in order to open up safely. Where dose supply is limited, targeting boosters to the highest risk groups to ensure continued high protection in the face of waning immunity is of greater benefit than giving these doses as primary vaccination to younger age-groups. In all scenarios it is likely that health systems will be stretched. It may be essential, therefore, to maintain and/or reintroduce NPIs to mitigate the worst impacts of the Omicron variant as it replaces the Delta variant. Ultimately, Omicron variant-specific vaccines are likely to be required.

Report

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

Unwin H, Mwandigha L, Winskill P, Ghani A, Hogan Aet al., 2021, Analysis of the potential for a malaria vaccine to reduce gaps in malaria intervention coverage, Malaria Journal, Vol: 20, Pages: 1-11, ISSN: 1475-2875

BackgroundThe RTS,S/AS01 malaria vaccine is currently being evaluated in a cluster-randomized pilot implementation programme in three African countries. This study seeks to identify whether vaccination could reach additional children who are at risk from malaria but do not currently have access to, or use, core malaria interventions.MethodsUsing data from household surveys, the overlap between malaria intervention coverage and childhood vaccination (diphtheria-tetanus-pertussis dose 3, DTP3) uptake in 20 African countries with at least one first administrative level unit with Plasmodium falciparum parasite prevalence greater than 10% was calculated. Multilevel logistic regression was used to explore patterns of overlap by demographic and socioeconomic variables. The public health impact of delivering RTS,S/AS01 to those children who do not use an insecticide-treated net (ITN), but who received the DTP3 vaccine, was also estimated.ResultsUptake of DTP3 was higher than malaria intervention coverage in most countries. Overall, 34% of children did not use ITNs and received DTP3, while 35% of children used ITNs and received DTP3, although this breakdown varied by country. It was estimated that there are 33 million children in these 20 countries who do not use an ITN. Of these, 23 million (70%) received the DTP3 vaccine. Vaccinating those 23 million children who receive DTP3 but do not use an ITN could avert up to an estimated 9.7 million (range 8.5–10.8 million) clinical malaria cases each year, assuming all children who receive DTP3 are administered all four RTS,S doses. An additional 10.8 million (9.5–12.0 million) cases could be averted by vaccinating those 24 million children who receive the DTP3 vaccine and use an ITN. Children who had access to or used an ITN were 9–13% more likely to reside in rural areas compared to those who had neither intervention regardless of vaccination status. Mothers’ education status was a strong predictor of inte

Journal article

Winskill P, Hogan AB, Thwing J, Mwandigha L, Walker PGT, Lambert Bet al., 2021, Health inequities and clustering of fever, acute respiratory infection, diarrhoea and wasting in children under five in low- and middle-income countries: a Demographic and Health Surveys analysis, BMC Medicine, Vol: 19, ISSN: 1741-7015

BACKGROUND: Pneumonia, diarrhoea and malaria are responsible for over one third of all deaths in children under the age of 5 years in low and middle sociodemographic index countries; many of these deaths are also associated with malnutrition. We explore the co-occurrence and clustering of fever, acute respiratory infection, diarrhoea and wasting and their relationship with equity-relevant variables. METHODS: Multilevel, multivariate Bayesian logistic regression models were fitted to Demographic and Health Survey data from over 380,000 children in 39 countries. The relationship between outcome indicators (fever, acute respiratory infection, diarrhoea and wasting) and equity-relevant variables (wealth, access to health care and rurality) was examined. We quantified the geographical clustering and co-occurrence of conditions and a child's risk of multiple illnesses. RESULTS: The prevalence of outcomes was very heterogeneous within and between countries. There was marked spatial clustering of conditions and co-occurrence within children. For children in the poorest households and those reporting difficulties accessing healthcare, there were significant increases in the probability of at least one of the conditions in 18 of 21 countries, with estimated increases in the probability of up to 0.23 (95% CrI, 0.06-0.40). CONCLUSIONS: The prevalence of fever, acute respiratory infection, diarrhoea and wasting are associated with equity-relevant variables and cluster together. Via pathways of shared aetiology or risk, those children most disadvantaged disproportionately suffer from these conditions. This highlights the need for horizontal approaches, such as integrated community case management, with a focus on equity and targeted to those most at need.

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

Hogan AB, Winskill P, Watson OJ, Walker PGT, Whittaker C, Baguelin M, Brazeau NF, Charles GD, Gaythorpe KAM, Hamlet A, Knock E, Laydon DJ, Lees JA, Løchen A, Verity R, Whittles LK, Muhib F, Hauck K, Ferguson NM, Ghani ACet al., 2021, Within-country age-based prioritisation, global allocation, and public health impact of a vaccine against SARS-CoV-2: a mathematical modelling analysis, Vaccine, Vol: 39, Pages: 2995-3006, ISSN: 0264-410X

The worldwide endeavour to develop safe and effective COVID-19 vaccines has been extraordinary, and vaccination is now underway in many countries. However, the doses available in 2021 are likely to be limited. We extended a mathematical model of SARS-CoV-2 transmission across different country settings to evaluate the public health impact of potential vaccines using WHO-developed target product profiles. We identified optimal vaccine allocation strategies within- and between-countries to maximise averted deaths under constraints on dose supply. We found that the health impact of SARS-CoV-2 vaccination depends on the cumulative population-level infection incidence when vaccination begins, the duration of natural immunity, the trajectory of the epidemic prior to vaccination, and the level of healthcare available to effectively treat those with disease. Within a country we find that for a limited supply (doses for <20% of the population) the optimal strategy is to target the elderly. However, with a larger supply, if vaccination can occur while other interventions are maintained, the optimal strategy switches to targeting key transmitters to indirectly protect the vulnerable. As supply increases, vaccines that reduce or block infection have a greater impact than those that prevent disease alone due to the indirect protection provided to high-risk groups. Given a 2 billion global dose supply in 2021, we find that a strategy in which doses are allocated to countries proportional to population size is close to optimal in averting deaths and aligns with the ethical principles agreed in pandemic preparedness planning.

Journal article

Watson O, Alhaffar M, Mehchy Z, Whittaker C, Akil Z, Brazeau N, Cuomo-Dannenburg G, Hamlet A, Thompson H, Baguelin M, Fitzjohn R, Knock E, Lees J, Whittles L, Mellan T, Winskill P, COVID-19 Response Team IC, Howard N, Clapham H, Checchi F, Ferguson N, Ghani A, Walker P, Beals Eet al., 2021, Leveraging community mortality indicators to infer COVID-19 mortality and transmission dynamics in Damascus, Syria, Nature Communications, Vol: 12, Pages: 1-10, ISSN: 2041-1723

The COVID-19 pandemic has resulted in substantial mortality worldwide. However, to date, countries in the Middle East and Africa have reported considerably lower mortality rates than in Europe and the Americas. Motivated by reports of an overwhelmed health system, we estimate the likely under-ascertainment of COVID-19 mortality in Damascus, Syria. Using all-cause mortality data, we fit a mathematical model of COVID-19 transmission to reported mortality, estimating that 1.25% of COVID-19 deaths (sensitivity range 1.00% – 3.00%) have been reported as of 2 September 2020. By 2 September, we estimate that 4,380 (95% CI: 3,250 – 5,550) COVID-19 deaths in Damascus may have been missed, with 39.0% (95% CI: 32.5% – 45.0%) of the population in Damascus estimated to have been infected. Accounting for under-ascertainment corroborates reports of exceeded hospital bed capacity and is validated by community-uploaded obituary notifications, which confirm extensive unreported mortality in Damascus.

Journal article

Dixon M, Winskill P, Harrison W, Basanez M-Get al., 2021, Taenia solium taeniasis / cysticercosis: from parasite biology and immunology to diagnosis and control, Advances in Parasitology, Vol: 112, Pages: 133-217, ISSN: 0065-308X

Infection with the pork tapeworm (Taenia solium) is responsible for a substantial global burden of disease, not only restricted to its impact on human health, but also resulting in a considerable economic burden to smallholder pig farmers due to pig cysticercosis infection. The life-cycle, parasitology and immunology of T. solium are complex, involving pigs(the intermediate host, harbouring the larval metacestode stage), humans(the definitive host, harbouring the adult tapeworm, in addition to acting as accidental intermediate hosts) and the environment (the source of infection with eggs/proglottids). We review the parasitology, immunology, and epidemiology of the infection associated with each of the T. solium life-cycle stages, including the pre-adult/adult tapeworm responsible for human taeniasis; post-oncosphere and cysticercus associated with porcine and human cysticercosis, and the biological characteristics of eggs in the environment. We discuss the burden associated, in endemic settings, with neurocysticercosis (NCC) in humans, and the broader cross-sectoral economic impact associated both with NCC and porcine cysticercosis, the latter impacting food-value chains. Existing tools for diagnostics and control interventions that target different stages of the T. solium transmission cycle are reviewed and their limitations discussed. Currently, no national T. solium control programmes have been established in endemic areas, with further work required to identify optimal strategies according to epidemiological setting. There is increasing evidence suggesting that cross-sectoral interventions which target the parasite in both the human and pig host provide the most effective approaches for achieving control and ultimately elimination. We discuss future avenues for research on T. soliumto support the attainement of the goals proposed in the revised World Heal

Journal article

Olivera Mesa D, Hogan A, Watson O, Charles G, Hauck K, Ghani A, Winskill Pet al., 2021, Report 43: Quantifying the impact of vaccine hesitancy in prolonging the need for Non-Pharmaceutical Interventions to control the COVID-19 pandemic

Vaccine hesitancy – a delay in acceptance or refusal of vaccines despite availability 1 – has the potential to threaten the successful roll-out of SARS-CoV-2 vaccines globally 2 . Here, we evaluate the potential impact of vaccine hesitancy on the control of the pandemic and the relaxation of non-pharmaceutical interventions (NPIs) by combining an epidemiological model of SARS-CoV-2 transmission 3 with data on vaccine hesitancy from population surveys. Our findings suggest that the mortality over a 2-year period could be up to 8 times higher in countries with high vaccine hesitancy compared to an ideal vaccination uptake if NPIs are relaxed. Alternatively, high vaccine hesitancy could prolong the need for NPIs to remain in place. Addressing vaccine hesitancy with behavioural interventions is therefore an important priority in the control of the COVID-19 pandemic.

Report

Hogan AB, Winskill P, Watson OJ, Walker PGT, Whittaker C, Baguelin M, Brazeau NF, Charles GD, Gaythorpe KAM, Hamlet A, Knock E, Laydon DJ, Lees JA, Løchen A, Verity R, Whittles LK, Muhib F, Hauck K, Ferguson NM, Ghani ACet al., 2021, Within-country age-based prioritisation, global allocation, and public health impact of a vaccine against SARS-CoV-2: a mathematical modelling analysis, Publisher: Cold Spring Harbor Laboratory

The worldwide endeavour to develop safe and effective COVID-19 vaccines has been extraordinary, and vaccination is now underway in many countries. However, the doses available in 2021 are likely to be limited. We extended a mathematical model of SARS-CoV-2 transmission across different country settings to evaluate the public health impact of potential vaccines using WHO-developed target product profiles. We identified optimal vaccine allocation strategies within- and between-countries to maximise averted deaths under constraints on dose supply. We found that the health impact of SARS-CoV-2 vaccination depends on the cumulative population-level infection incidence when vaccination begins, the duration of natural immunity, the trajectory of the epidemic prior to vaccination, and the level of healthcare available to effectively treat those with disease. Within a country we find that for a limited supply (doses for <20% of the population) the optimal strategy is to target the elderly. However, with a larger supply, if vaccination can occur while other interventions are maintained, the optimal strategy switches to targeting key transmitters to indirectly protect the vulnerable. As supply increases, vaccines that reduce or block infection have a greater impact than those that prevent disease alone due to the indirect protection provided to high-risk groups. Given a 2 billion global dose supply in 2021, we find that a strategy in which doses are allocated to countries proportional to population size is close to optimal in averting deaths and aligns with the ethical principles agreed in pandemic preparedness planning.

Working paper

Winskill P, Mousa A, Oresanya O, Counihan H, Okell L, Walker Pet al., 2021, Does integrated community case management (iCCM) target health inequities and treatment delays? Evidence from an analysis of Demographic and Health Surveys data from 21 countries in the period 2010 to 2018, Journal of Global Health, Vol: 11, Pages: 1-10, ISSN: 2047-2978

BackgroundIntegrated community case management (iCCM) is a programme that can, via community health workers (CHWs), increase access to timely and essential treatments for children. As well as improving treatment coverage, iCCM has an additional equity-focus with the aim of targetingunderserved populations. To assess the success of iCCM programmes it is important that we understand the contribution they are making to equitable health coverage.MethodsWe analysed demographic and health survey data from 21 countries over 9 years to assess evidence and evaluate iCCM programmes. We summarise the contribution CHWs are making relative to other healthcare provider groups and what treatment combinations CHWs are commonly prescribing. We assessed the ability of CHWs to target treatment delays and health inequities by evaluating time to treatment following fever onset and relationships between CHWs and wealth, rurality and remoteness.ResultsThere was good evidence that CHWs are being successfully targeted to improve inequities in healthcare coverage. There is a larger contribution of CHWs in areas with higher poverty, rurality and remoteness. In six surveys CHWs were associated with significantly shorter average timebetween fever onset and advice or treatment seeking, whilst in one they were associated with significantly longer times. In areas with active CHW programmes, the contribution of CHWs relative to other healthcare provider groups varied between 11% to 45% of treatment visits. The distribution of types of treatment provided by CHWs was also very variable between countries.ConclusionsThe success of an iCCM programme depends not only on increasing treatment coverage but addressing inequities in access to timely healthcare. Whilst much work is still needed to attain universal healthcare targets, and despite incomplete data, there is evidence that iCCM is successfully addressing treatment delays and targeting underserved populations.

Journal article

Gilmartin C, Nonvignon J, Cairns M, Milligan P, Bocoum F, Winskill P, Moroso D, Collins Det al., 2021, Seasonal malaria chemoprevention in the Sahel subregion of Africa: a cost-effectiveness and cost-savings analysis, LANCET GLOBAL HEALTH, Vol: 9, Pages: E199-E208, ISSN: 2214-109X

Journal article

Verity R, Okell L, Dorigatti I, Winskill P, Whittaker C, Walker P, Donnelly C, Ferguson N, Ghani Aet al., 2021, COVID-19 and the difficulty of inferring epidemiological parameters from clinical data Reply, LANCET INFECTIOUS DISEASES, Vol: 21, Pages: 28-28, ISSN: 1473-3099

Journal article

Fu H, Wang H, Xi X, Boonyasiri A, Wang Y, Hinsley W, Fraser KJ, McCabe R, Olivera Mesa D, Skarp J, Ledda A, Dewé T, Dighe A, Winskill P, van Elsland SL, Ainslie KEC, Baguelin M, Bhatt S, Boyd O, Brazeau NF, Cattarino L, Charles G, Coupland H, Cucunubá ZM, Cuomo-Dannenburg G, Donnelly CA, Dorigatti I, Eales OD, Fitzjohn RG, Flaxman S, Gaythorpe KAM, Ghani AC, Green WD, Hamlet A, Hauck K, Haw DJ, Jeffrey B, Laydon DJ, Lees JA, Mellan T, Mishra S, Nedjati Gilani G, Nouvellet P, Okell L, Parag KV, Ragonnet-Cronin M, Riley S, Schmit N, Thompson HA, Unwin HJT, Verity R, Vollmer MAC, Volz E, Walker PGT, Walters CE, Waston OJ, Whittaker C, Whittles LK, Imai N, Bhatia S, Ferguson NMet al., 2021, A database for the epidemic trends and control measures during the first wave of COVID-19 in mainland China, International Journal of Infectious Diseases, Vol: 102, Pages: 463-471, ISSN: 1201-9712

Objectives: This data collation effort aims to provide a comprehensive database to describe the epidemic trends and responses during the first wave of coronavirus disease 2019 (COVID-19)across main provinces in China. Methods: From mid-January to March 2020, we extracted publicly available data on the spread and control of COVID-19 from 31 provincial health authorities and major media outlets in mainland China. Based on these data, we conducted a descriptive analysis of the epidemics in the six most-affected provinces. Results: School closures, travel restrictions, community-level lockdown, and contact tracing were introduced concurrently around late January but subsequent epidemic trends were different across provinces. Compared to Hubei, the other five most-affected provinces reported a lower crude case fatality ratio and proportion of critical and severe hospitalised cases. From March 2020, as local transmission of COVID-19 declined, switching the focus of measures to testing and quarantine of inbound travellers could help to sustain the control of the epidemic. Conclusions: Aggregated indicators of case notifications and severity distributions are essential for monitoring an epidemic. A publicly available database with these indicators and information on control measures provides useful source for exploring further research and policy planning for response to the COVID-19 epidemic.

Journal article

Thompson H, Imai N, Dighe A, Ainslie K, Baguelin M, Bhatia S, Bhatt S, Boonyasiri A, Boyd O, Brazeau N, Cattarino L, Cooper L, Coupland H, Cucunuba Z, Cuomo-Dannenburg G, Djaafara B, Dorigatti I, van Elsland S, Fitzjohn R, Fu H, Gaythorpe K, Green W, Hallett T, Hamlet A, Haw D, Hayes S, Hinsley W, Jeffrey B, Knock E, Laydon D, Lees J, Mangal T, Mellan T, Mishra S, Mousa A, Nedjati-Gilani G, Nouvellet P, Okell L, Parag K, Ragonnet-Cronin M, Riley S, Unwin H, Verity R, Vollmer M, Volz E, Walker P, Walters C, Wang H, Wang Y, Watson O, Whittaker C, Whittles L, Winskill P, Xi X, Donnelly C, Ferguson Net al., 2020, SARS-CoV-2 infection prevalence on repatriation flights from Wuhan City, China, Journal of Travel Medicine, Vol: 27, Pages: 1-3, ISSN: 1195-1982

We estimated SARS-CoV-2 infection prevalence in cohorts of repatriated citizens from Wuhan to be 0.44% (95% CI: 0.19%–1.03%). Although not representative of the wider population we believe these estimates are helpful in providing a conservative estimate of infection prevalence in Wuhan City, China, in the absence of large-scale population testing early in the epidemic.

Journal article

Hogan A, Winskill P, Ghani A, 2020, Estimated impact of RTS,S/AS01 malaria vaccine allocation strategies in sub-Saharan Africa: a modelling study, PLoS Medicine, Vol: 17, Pages: 1-19, ISSN: 1549-1277

Background: The RTS,S/AS01 vaccine against P. falciparum malaria infection completed phase 3 trials in 2014, and demonstrated efficacy against clinical malaria of approximately 36% over 4 years for a 4-dose schedule in children aged 5–17 months. Pilot vaccine implementation has recently begun in three African countries. If the pilots demonstrate both a positive health impact and resolve remaining safety concerns, wider roll-out could be recommended from 2021 onwards. Vaccine demand may however outstrip initial supply. We sought to identify where vaccine introduction should be prioritised to maximise public health impact under a range of supply constraints using mathematical modelling. Methods and Findings: Using a mathematical model of P. falciparum malaria transmission and RTS,S vaccine impact, we estimated the clinical cases and deaths averted in children aged 0–5 years in sub-Saharan Africa under two scenarios for vaccine coverage (100% and realistic) and two scenarios for other interventions (current coverage and WHO Global Technical Strategy targets). We used a prioritisation algorithm to identify potential allocative efficiency gains fromprioritising vaccine allocation among countries or administrative units to maximise cases or deaths averted. If malaria burden at introduction is similar to current levels, assuming realistic vaccine coverage and country-level prioritisation in areas with parasite prevalence >10%, we estimate 4.3 million (95% credible interval, CrI 2.8–6.8 million) malaria cases and 22,000 (95% CrI 11,000–35,000) deaths in children younger than 5 years could be averted annually at a dose constraint of 30 million. This decreases to 3.0 million (95% CrI 2.0–4.7 million) cases and14,000 (95% CrI 7,000–23,000) deaths at a dose constraint of 20 million,and increases to 6.6 million (95% CrI 4.2–10.8 million) cases and38,000 (95% CrI 18

Journal article

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