Imperial College London


Faculty of MedicineSchool of Public Health

Chair in Infectious Disease Epidemiology



+44 (0)20 7594 5764a.ghani Website




Norfolk PlaceSt Mary's Campus





Publication Type

358 results found

Hogan A, Doohan P, Wu S, Olivera Mesa D, Turner J, Watson O, Winskill P, Charles G, Barnsley G, Riley E, Khoury D, Ferguson N, Ghani Aet al., 2023, Estimating long-term vaccine effectiveness against SARS-CoV-2 variants: a model-based approach, Nature Communications, Vol: 14, Pages: 1-10, ISSN: 2041-1723

With the ongoing evolution of the SARS-CoV-2 virus updated vaccines may be needed. We fitted a model linking immunity levels and protection to vaccine effectiveness data from England for three vaccines (Oxford/AstraZeneca AZD1222, Pfizer-BioNTech BNT162b2, Moderna mRNA-1273) and two variants (Delta, Omicron). Our model reproduces the observed sustained protection against hospitalisation and death from the Omicron variant over the first six months following dose 3 with the monovalent vaccines but projects a gradual waning to moderate protection after 1 year. Switching the fourth dose to a variant-matched vaccine against Omicron BA.1/2 is projected to prevent nearly twice as many hospitalisations and deaths over a 1-year period compared to administering the ancestral vaccine. This result is sensitive to the degree to which immunogenicity data can be used to predict vaccine effectiveness and uncertainty regarding the impact that infection-induced immunity (not captured here) may play in modifying future vaccine effectiveness.

Journal article

Sheppard R, Watson OJ, Pieciak R, Lungu J, Kwenda G, Moyo C, Longa Chanda S, Barnsley G, Brazeau NF, Gerard-Ursin ICG, Olivera Mesa D, Whittaker C, Gregson S, Okell LC, Ghani AC, MacLeod WB, Del Fava E, Melegaro A, Hines JZ, Mulenga LB, Walker P, Mwananyanda L, Gill CJet al., 2023, Using mortuary and burial data to place COVID-19 in Lusaka, Zambia within a global context, Nature Communications, Vol: 14, Pages: 1-15, ISSN: 2041-1723

Reported COVID-19 cases and associated mortality remain low in many sub-Saharan countries relative to global averages, but true impact is difficult to estimate given limitations around surveillance and mortality registration. In Lusaka, Zambia, burial registration and SARS-CoV-2prevalence data during 2020 allow estimation of excess mortality and transmission. Relative to pre-pandemic patterns, we estimate age-dependent mortality increases, totalling 3,212 excess deaths (95% CrI: 2,104-4,591), representing an 18.5% (95% CrI: 13.0-25.2%) increase relative to pre-pandemic levels. Using a dynamical model-based inferential framework, we find that these mortalitypatterns and SARS-CoV-2 prevalence data are in agreement with established COVID-19 severity estimates. Our results support hypotheses that COVID-19 impact in Lusaka during 2020 was consistent with COVID-19 epidemics elsewhere, without requiring exceptional explanations for low reported figures. For more equitable decision-making during future pandemics, barriers to ascertaining attributable mortality in low-income settings must be addressed and factored into discourse around reported impact differences.

Journal article

Olivera Mesa D, Winskill P, Ghani AC, Hauck Ket al., 2023, The societal cost of vaccine refusal: A modelling study using measles vaccination as a case study., Vaccine, Vol: 41, Pages: 4129-4137

BACKGROUND: Increasing vaccine hesitancy and refusal poses a challenge to public health as even small reductions in vaccine uptake can result in large outbreaks of infectious diseases. Here we estimate the societal costs of vaccine refusal using measles as a case study. METHODS: We developed a compartmental metapopulation model of measles transmission to explore how the changes in the size and level of social mixing between populations that are "pro-vaccination", and "anti-vaccination" impacts the burden of measles. Using the projected cases and deaths, we calculated the health, healthcare, direct medical costs, and productivity loss associated with vaccine refusal. Using measles in England as a case study, we quantified the societal costs that each vaccine refusal imposes on society. FINDINGS: When there is a high level of mixing between the pro- and anti-vaccination populations, those that refuse to be vaccinated benefit from the herd immunity afforded by the pro-vaccination population. At the same time, their refusal to be vaccinated increases the burden in those that are vaccinated due to imperfect vaccines, and in those that are not able to be vaccinated due to other underlying health conditions. Using England as a case study, we estimate that this translates to a societal loss of GBP 292 million and disease burden of 17 630 quality-adjusted-life-years (sensitivity range 10 594-50 379) over a 20-year time horizon. Of these costs, 26 % are attributable to healthcare costs and 74 % to productivity losses for patients and their carers. This translates to a societal loss per vaccine refusal of GBP 162.21 and 0.01 (0.006-0.03) quality-adjusted-life-years. INTERPRETATION: Our findings demonstrate that even low levels of vaccine refusal can have a substantial and measurable societal burden on the population. These estimates can support the value of investment in interventions that address vaccine hesitancy and vaccine refusal, providing not only im

Journal article

Fornace KM, Topazian HM, Routledge I, Asyraf S, Jelip J, Lindblade KA, Jeffree MS, Ruiz Cuenca P, Bhatt S, Ahmed K, Ghani AC, Drakeley Cet al., 2023, No evidence of sustained nonzoonotic Plasmodium knowlesi transmission in Malaysia from modelling malaria case data., Nat Commun, Vol: 14

Reported incidence of the zoonotic malaria Plasmodium knowlesi has markedly increased across Southeast Asia and threatens malaria elimination. Nonzoonotic transmission of P. knowlesi has been experimentally demonstrated, but it remains unknown whether nonzoonotic transmission is contributing to increases in P. knowlesi cases. Here, we adapt model-based inference methods to estimate RC, individual case reproductive numbers, for P. knowlesi, P. falciparum and P. vivax human cases in Malaysia from 2012-2020 (n = 32,635). Best fitting models for P. knowlesi showed subcritical transmission (RC < 1) consistent with a large reservoir of unobserved infection sources, indicating P. knowlesi remains a primarily zoonotic infection. In contrast, sustained transmission (RC > 1) was estimated historically for P. falciparum and P. vivax, with declines in RC estimates observed over time consistent with local elimination. Together, this suggests sustained nonzoonotic P. knowlesi transmission is highly unlikely and that new approaches are urgently needed to control spillover risks.

Journal article

McCabe R, Sheppard R, Abdelmagid N, Ahmed A, Alabdeen IZ, Brazeau N, Abd Elhameed AEA, Bin-Ghouth AS, Hamlet A, AbuKoura R, Barnsley G, Hay J, Alhaffar M, Besson EK, Saje SM, Sisay BG, Gebreyesus SH, Sikamo AP, Worku A, Ahmed YS, Mariam DH, Sisay MM, Checchi F, Dahab M, Endris BS, Ghani A, Walker P, Donnelly C, Watson Oet al., 2023, Alternative epidemic indicators for COVID-19 in three settings with incomplete death registration systems, Science Advances, Vol: 23, Pages: 1-10, ISSN: 2375-2548

Not all COVID-19 deaths are officially reported, and particularly in low-income and humanitarian settings, the magnitude of reporting gaps remains sparsely characterized. Alternative data sources, including burial site worker reports, satellite imagery of cemeteries, and social media–conducted surveys of infection may offer solutions. By merging these data with independently conducted, representative serological studies within a mathematical modeling framework, we aim to better understand the range of underreporting using examples from three major cities: Addis Ababa (Ethiopia), Aden (Yemen), and Khartoum (Sudan) during 2020. We estimate that 69 to 100%, 0.8 to 8.0%, and 3.0 to 6.0% of COVID-19 deaths were reported in each setting, respectively. In future epidemics, and in settings where vital registration systems are limited, using multiple alternative data sources could provide critically needed, improved estimates of epidemic impact. However, ultimately, these systems are needed to ensure that, in contrast to COVID-19, the impact of future pandemics or other drivers of mortality is reported and understood worldwide.

Journal article

Topazian HM, Schmit N, Gerard-Ursin I, Charles GD, Thompson H, Ghani AC, Winskill Pet al., 2023, Modelling the relative cost-effectiveness of the RTS,S/AS01 malaria vaccine compared to investment in vector control or chemoprophylaxis., Vaccine, Vol: 41, Pages: 3215-3223

BACKGROUND: The World Health Organization has recommended a 4-dose schedule of the RTS,S/AS01 (RTS,S) vaccine for children in regions of moderate to high P. falciparum transmission. Faced with limited supply and finite resources, global funders and domestic malaria control programs will need to examine the relative cost-effectiveness of RTS,S and identify target areas for vaccine implementation relative to scale-up of existing interventions. METHODS: Using an individual-based mathematical model of P. falciparum, we modelled the cost-effectiveness of RTS,S across a range of settings in sub-Saharan Africa, incorporating various rainfall patterns, insecticide-treated net (ITN) use, treatment coverage, and parasite prevalence bands. We compare age-based and seasonal RTS,S administration to increasing ITN usage, switching to next generation ITNs in settings experiencing insecticide-resistance, and introduction of seasonal malaria chemoprevention (SMC) in areas of seasonal transmission. RESULTS: For RTS,S to be the most cost-effective intervention option considered, the maximum cost per dose was less than $9.30 USD in 90.9% of scenarios. Nearly all (89.8%) values at or above $9.30 USD per dose were in settings with 60% established bed net use and / or with established SMC, and 76.3% were in the highest PfPR2-10 band modelled (40%). Addition of RTS,S to strategies involving 60% ITN use, increased ITN usage or a switch to PBO nets, and SMC, if eligible, still led to significant marginal case reductions, with a median of 2,653 (IQR: 1,741 to 3,966) cases averted per 100,000 people annually, and 82,270 (IQR: 54,034 to 123,105) cases averted per 100,000 fully vaccinated children (receiving at least three doses). CONCLUSIONS: Use of RTS,S results in reductions in malaria cases and deaths even when layered upon existing interventions. When comparing relative cost-effectiveness, scale up of ITNs, introduction of SMC, and switching to new technology nets should be prioritized in e

Journal article

Schmit N, Topazian H, Pianella M, Charles G, Winskill P, White M, Hauck K, Ghani Aet al., 2023, Resource allocation strategies to achieve malaria eradication, eLife, ISSN: 2050-084X

Background: Large reductions in the global malaria burden have been achieved in the last decades, but plateauing funding poses a challenge for progressing towards the ultimate goal of malaria eradication. We aimed to determine the optimal strategy to allocate global resources to achieve this goal.Methods: Using previously published mathematical models of Plasmodium falciparum and Plasmodium vivax transmission incorporating insecticide-treated nets (ITNs) as an illustrative intervention, we sought to identify the global funding allocation that maximized impact under defined objectives and across a range of global funding budgets.Results: We found that the optimal strategy for case reduction closely mirrored an allocation framework that prioritizes funding for high-transmission settings, resulting in total case reductions of 76% (optimal strategy) and 66% (prioritizing high-transmission settings) at intermediate budget levels. Allocation strategies that had the greatest impact on case reductions were associated with lesser near-term impacts on the global population at risk, highlighting a trade-off between reducing burden and “shrinking the map” through a focus on near-elimination settings. The optimal funding distribution prioritized high ITN coverage in high-transmission settings endemic for P. falciparum only, while maintaining lower levels in low-transmission settings. However, at high budgets, 62% of funding was targeted to low-transmission settings co-endemic for P. falciparum and P. vivax.Conclusions: These results support current global strategies to prioritize funding to high-burden P. falciparum-endemic settings in sub-Saharan Africa to minimize clinical malaria burden and progress towards elimination but highlight competing goals of reducing the global population at risk and addressing the burden of P. vivax.

Journal article

Imai N, Rawson T, Knock E, Sonabend R, Elmaci Y, Perez-Guzman P, Whittles L, Thekke Kanapram D, Gaythorpe K, Hinsley W, Djaafara B, Wang H, Fraser K, Fitzjohn R, Hogan A, Doohan P, Ghani A, Ferguson N, Baguelin M, Cori Aet al., 2023, Quantifying the impact of delaying the second COVID-19 vaccine dose in England: a mathematical modelling study, The Lancet Public Health, Vol: 8, Pages: e174-e183, ISSN: 2468-2667

Background: The UK was the first country to start national COVID-19 vaccination programmes, initially administering doses 3-weeks apart. However, early evidence of high vaccine effectiveness after the first dose and the emergence of the Alpha variant prompted the UK to extend the interval between doses to 12-weeks. In this study, we aim to quantify the impact of delaying the second vaccine dose on the epidemic in England.Methods: We used a previously described model of SARS-CoV-2 transmission, calibrated to English COVID-19 surveillance data including hospital admissions, hospital occupancy, seroprevalence data, and population-level PCR testing data using a Bayesian evidence synthesis framework. We modelled and compared the epidemic trajectory assuming that vaccine doses were administered 3-weeks apart against the real reported vaccine roll-out schedule. We estimated and compared the resulting number of daily infections, hospital admissions, and deaths. Scenarios spanning a range of vaccine effectiveness and waning assumptions were investigated.Findings: We estimate that delaying the interval between the first and second COVID-19 vaccine doses from 3- to 12-weeks prevented an average 58,000 COVID-19 hospital admissions and 10,100 deaths between 8th December 2020 and 13th September 2021. Similarly, we estimate that the 3-week strategy would have resulted in more infections and deaths compared to the 12-week strategy. Across all sensitivity analyses the 3-week strategy resulted in a greater number of hospital admissions. Interpretation: England’s delayed second dose vaccination strategy was informed by early real-world vaccine effectiveness data and a careful assessment of the trade-offs in the context of limited vaccine supplies in a growing epidemic. Our study shows that rapidly providing partial (single dose) vaccine-induced protection to a larger proportion of the population was successful in reducing the burden of COVID-19 hospitalisations and deaths. Ther

Journal article

Whittaker C, Hamlet A, Sherrard-Smith E, Winskill P, Cuomo-Dannenburg G, Walker PGT, Sinka M, Pironon S, Kumar A, Ghani A, Bhatt S, Churcher TSet al., 2023, Seasonal dynamics of Anopheles stephensi and its implications for mosquito detection and emergent malaria control in the Horn of Africa, Proceedings of the National Academy of Sciences of USA, Vol: 120, Pages: 1-9, ISSN: 0027-8424

Invasion of the malaria vector Anopheles stephensi across the Horn of Africa threatens control efforts across the continent, particularly in urban settings where the vector is able to proliferate. Malaria transmission is primarily determined by the abundance of dominant vectors, which often varies seasonally with rainfall. However, it remains unclear how An. stephensi abundance changes throughout the year, despite this being a crucial input to surveillance and control activities. We collate longitudinal catch data from across its endemic range to better understand the vector's seasonal dynamics and explore the implications of this seasonality for malaria surveillance and control across the Horn of Africa. Our analyses reveal pronounced variation in seasonal dynamics, the timing and nature of which are poorly predicted by rainfall patterns. Instead, they are associated with temperature and patterns of land use; frequently differing between rural and urban settings. Our results show that timing entomological surveys to coincide with rainy periods is unlikely to improve the likelihood of detecting An. stephensi. Integrating these results into a malaria transmission model, we show that timing indoor residual spraying campaigns to coincide with peak rainfall offers little improvement in reducing disease burden compared to starting in a random month. Our results suggest that unlike other malaria vectors in Africa, rainfall may be a poor guide to predicting the timing of peaks in An. stephensi-driven malaria transmission. This highlights the urgent need for longitudinal entomological monitoring of the vector in its new environments given recent invasion and potential spread across the continent.

Journal article

Unwin H, Sherrard-Smith E, Churcher T, Ghani Aet al., 2023, Quantifying the direct and indirect protection provided by insecticide treated bed nets against malaria, Nature Communications, Vol: 14, Pages: 1-12, ISSN: 2041-1723

Long lasting insecticidal nets (LLINs) provide both direct and indirect protection against malaria. As pyrethroid resistance evolves in mosquito vectors, it will be useful to understand how the specific benefits LLINs afford individuals and communities may be affected. Here we use modelling to show that there is no minimum LLIN usage needed for users and non-users to benefit from community protection. Modelling results also indicate that pyrethroid resistance in local mosquitoes will likely diminish the direct and indirect benefits from insecticides, leaving the barrier effects intact, but LLINs are still expected to provide enhanced benefit over untreated nets even at high levels of pyrethroid resistance.

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

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

Imai N, Rawson T, Knock ES, Sonabend R, Elmaci Y, Perez-Guzman PN, Whittles LK, Kanapram DT, Gaythorpe KAM, Hinsley W, Djaafara BA, Wang H, Fraser K, FitzJohn RG, Hogan AB, Doohan P, Ghani AC, Ferguson NM, Baguelin M, Cori Aet al., 2022, Quantifying the impact of delaying the second COVID-19 vaccine dose in England: a mathematical modelling study

<jats:title>Abstract</jats:title><jats:sec><jats:title>Background</jats:title><jats:p>The UK was the first country to start national COVID-19 vaccination programmes, initially administering doses 3-weeks apart. However, early evidence of high vaccine effectiveness after the first dose and the emergence of the Alpha variant prompted the UK to extend the interval between doses to 12-weeks. In this study, we quantify the impact of delaying the second vaccine dose on the epidemic in England.</jats:p></jats:sec><jats:sec><jats:title>Methods</jats:title><jats:p>We used a previously described model of SARS-CoV-2 transmission and calibrated the model to English surveillance data including hospital admissions, hospital occupancy, seroprevalence data, and population-level PCR testing data using a Bayesian evidence synthesis framework. We modelled and compared the epidemic trajectory assuming that vaccine doses were administered 3-weeks apart against the real vaccine roll-out schedule. We estimated and compared the resulting number of daily infections, hospital admissions, and deaths. A range of scenarios spanning a range of vaccine effectiveness and waning assumptions were investigated.</jats:p></jats:sec><jats:sec><jats:title>Findings</jats:title><jats:p>We estimate that delaying the interval between the first and second COVID-19 vaccine doses from 3- to 12-weeks prevented an average 64,000 COVID-19 hospital admissions and 9,400 deaths between 8<jats:sup>th</jats:sup> December 2020 and 13th September 2021. Similarly, we estimate that the 3-week strategy would have resulted in more infections and deaths compared to the 12-week strategy. Across all sensitivity analyses the 3-week strategy resulted in a greater number of hospital admissions.</jats:p></jats:sec><jats:sec><jats:title>Interpretation</jats:title><jats:p>England&

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

Mwandigha LM, Fraser KJ, Racine A, Mouksassi S, Ghani ACet al., 2022, Power calculations for cluster randomised trials (CRTs) with truncated Poisson-distributed outcomes: a motivating example from a malaria vector control trial, International Journal of Epidemiology, Vol: 49, Pages: 954-962, ISSN: 0300-5771

Background:Cluster randomized trials (CRTs) are increasingly used to study the efficacy of interventions targeted at the population level. Formulae exist to calculate sample sizes for CRTs, but they assume that the domain of the outcomes being considered covers the full range of values of the considered distribution. This assumption is frequently incorrect in epidemiological trials in which counts of infection episodes are right-truncated due to practical constraints on the number of times a person can be tested.Methods:Motivated by a malaria vector control trial with right-truncated Poisson-distributed outcomes, we investigated the effect of right-truncation on power using Monte Carlo simulations.Results:The results demonstrate that the adverse impact of right-truncation is directly proportional to the magnitude of the event rate, λ, with calculations of power being overestimated in instances where right-truncation was not accounted for. The severity of the adverse impact of right-truncation on power was more pronounced when the number of clusters was ≤30 but decreased the further the right-truncation point was from zero.Conclusions:Potential right-truncation should always be accounted for in the calculation of sample size requirements at the study design stage.

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

Nyberg T, Ferguson NM, Nash SG, Webster HH, Flaxman S, Andrews N, Hinsley W, Bernal JL, Kall M, Bhatt S, Blomquist P, Zaidi A, Volz E, Aziz NA, Harman K, Funk S, Abbott S, Hope R, Charlett A, Chand M, Ghani AC, Seaman SR, Dabrera G, De Angelis D, Presanis AM, Thelwall Set al., 2022, Comparative analysis of the risks of hospitalisation and death associated with SARS-CoV-2 omicron (B.1.1.529) and delta (B.1.617.2) variants in England: a cohort study, The Lancet, Vol: 399, Pages: 1303-1312, ISSN: 0140-6736

BackgroundThe omicron variant (B.1.1.529) of SARS-CoV-2 has demonstrated partial vaccine escape and high transmissibility, with early studies indicating lower severity of infection than that of the delta variant (B.1.617.2). We aimed to better characterise omicron severity relative to delta by assessing the relative risk of hospital attendance, hospital admission, or death in a large national cohort.MethodsIndividual-level data on laboratory-confirmed COVID-19 cases resident in England between Nov 29, 2021, and Jan 9, 2022, were linked to routine datasets on vaccination status, hospital attendance and admission, and mortality. The relative risk of hospital attendance or admission within 14 days, or death within 28 days after confirmed infection, was estimated using proportional hazards regression. Analyses were stratified by test date, 10-year age band, ethnicity, residential region, and vaccination status, and were further adjusted for sex, index of multiple deprivation decile, evidence of a previous infection, and year of age within each age band. A secondary analysis estimated variant-specific and vaccine-specific vaccine effectiveness and the intrinsic relative severity of omicron infection compared with delta (ie, the relative risk in unvaccinated cases).FindingsThe adjusted hazard ratio (HR) of hospital attendance (not necessarily resulting in admission) with omicron compared with delta was 0·56 (95% CI 0·54–0·58); for hospital admission and death, HR estimates were 0·41 (0·39–0·43) and 0·31 (0·26–0·37), respectively. Omicron versus delta HR estimates varied with age for all endpoints examined. The adjusted HR for hospital admission was 1·10 (0·85–1·42) in those younger than 10 years, decreasing to 0·25 (0·21–0·30) in 60–69-year-olds, and then increasing to 0·47 (0·40–0·56) in those aged at leas

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

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

Ferguson N, Ghani A, Hinsley W, Volz E, on behalf of the Imperial College COVID-19 Response Teamet al., 2021, Report 50: Hospitalisation risk for Omicron cases in England

To assess differences in the risk of hospitalisation between the Omicron variant of concern (1) and the Delta variant, we analysed data from all PCR-confirmed SARS-CoV-2 cases in England with last test specimen dates between 1st and 14th December inclusive. Variant was defined using a combination of S-gene Target Failure (SGTF) and genetic data. Case data were linked by National Health service (NHS) number to the National Immunisation Management System (NIMS) database, the NHS Emergency Care (ECDS) and Secondary Use Services (SUS) hospital episode datasets. Hospital attendance was defined as any record of attendance at a hospital by a case in the 14 days following their last positive PCR test, up to and including the day of attendance. A secondary analysis examined the subset of attendances with a length of stay of one or more days. We used stratified conditional Poisson regression to predict hospitalisation status, with demographic strata defined by age, sex, ethnicity, region, specimen date, index of multiple deprivation and in some analyses, vaccination status. Predictor variables were variant (Omicron or Delta), reinfection status and vaccination status. Overall, we find evidence of a reduction in the risk of hospitalisation for Omicron relative to Delta infections, averaging over all cases in the study period. The extent of reduction is sensitive to the inclusion criteria used for cases and hospitalisation, being in the range 20-25% when using any attendance at hospital as the endpoint, and 40-45% when using hospitalisation lasting 1 day or longer or hospitalisations with the ECDS discharge field recorded as “admitted” as the endpoint (Table 1). These reductions must be balanced against the larger risk of infection with Omicron, due to the reduction in protection provided by both vaccination and natural infection. A previous infection reduces the


Ferguson N, Ghani A, Cori A, Hogan A, Hinsley W, Volz Eet al., 2021, Report 49: Growth, population distribution and immune escape of Omicron in England

To estimate the growth of the Omicron variant of concern (1) and its immune escape (2–9) characteristics, we analysed data from all PCR-confirmed SARS-CoV-2 cases in England excluding those with a history of recent international travel. We undertook separate analyses according to two case definitions. For the first definition, we included all cases with a definitive negative S-gene Target Failure (SGTF) result and specimen dates between 29/11/2021 and 11/12/2021 inclusive. For the second definition, we included cases with a positive genotype result and specimen date between 23/11/2021 and 11/12/2021 inclusive. We chose a later start date for the SGTF definition to ensure greater specificity of SGTF for Omicron.We used logistic and Poisson regression to identify factors associated with testing positive for Omicron compared to non-Omicron (mostly Delta) cases. We explored the following predictors: day, region, symptomatic status, sex, ethnicity, age band and vaccination status. Our results suggest rapid growth of the frequency of the Omicron variant relative to Delta, with the exponential growth rate of its frequency estimated to be 0.34/day (95% CI: 0.33-0.35) [2.0 day doubling time] over the study period from both SGTF and genotype data. The distribution of Omicron by age, region and ethnicity currently differs markedly from Delta, with 18–29-year-olds, residents in the London region, and those of African ethnicity having significantly higher rates of infection with Omicron relative to Delta.Hospitalisation and asymptomatic infection indicators were not significantly associated with Omicron infection, suggesting at most limited changes in severity compared with Delta.To estimate the impact of Omicron on vaccine effectiveness (VE) for symptomatic infection we used conditional Poisson regression to estimate the hazard ratio of being an Omicron case (using SGTF definition) compared with Delta, restricting our analysis to symptomatic cases and matching by da


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.


McCabe R, Kont MD, Watson O, Schmit N, Whittaker C, Lochen A, Walker PGT, Ghani AC, Ferguson NM, White PJ, Donnelly CA, Watson OJet al., 2021, Communicating uncertainty in epidemic models, Epidemics: the journal of infectious disease dynamics, Vol: 37, Pages: 1-6, ISSN: 1755-4365

While mathematical models of disease transmission are widely used to inform public health decision-makers globally, the uncertainty inherent in results are often poorly communicated. We outline some potential sources of uncertainty in epidemic models, present traditional methods used to illustrate uncertainty and discuss alternative presentation formats used by modelling groups throughout the COVID-19 pandemic. Then, by drawing on the experience of our own recent modelling, we seek to contribute to the ongoing discussion of how to improve upon traditional methods used to visualise uncertainty by providing a suggestion of how this can be presented in a clear and simple manner.

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

Sonabend R, Whittles LK, Imai N, Perez Guzman PN, Knock E, Rawson T, Gaythorpe KA, Djaafara A, Hinsley W, Fitzjohn R, Lees JA, Thekke Kanapram D, Volz E, Ghani A, Ferguson NM, Baguelin M, Cori Aet al., 2021, Non-pharmaceutical interventions, vaccination, and the SARS-CoV-2 delta variant in England: a mathematical modelling study, The Lancet, Vol: 398, Pages: 1825-1835, ISSN: 0140-6736

Background:England's COVID-19 roadmap out of lockdown policy set out the timeline and conditions for the stepwise lifting of non-pharmaceutical interventions (NPIs) as vaccination roll-out continued, with step one starting on March 8, 2021. In this study, we assess the roadmap, the impact of the delta (B.1.617.2) variant of SARS-CoV-2, and potential future epidemic trajectories.Methods:This mathematical modelling study was done to assess the UK Government's four-step process to easing lockdown restrictions in England, UK. We extended a previously described model of SARS-CoV-2 transmission to incorporate vaccination and multi-strain dynamics to explicitly capture the emergence of the delta variant. We calibrated the model to English surveillance data, including hospital admissions, hospital occupancy, seroprevalence data, and population-level PCR testing data using a Bayesian evidence synthesis framework, then modelled the potential trajectory of the epidemic for a range of different schedules for relaxing NPIs. We estimated the resulting number of daily infections and hospital admissions, and daily and cumulative deaths. Three scenarios spanning a range of optimistic to pessimistic vaccine effectiveness, waning natural immunity, and cross-protection from previous infections were investigated. We also considered three levels of mixing after the lifting of restrictions.Findings:The roadmap policy was successful in offsetting the increased transmission resulting from lifting NPIs starting on March 8, 2021, with increasing population immunity through vaccination. However, because of the emergence of the delta variant, with an estimated transmission advantage of 76% (95% credible interval [95% CrI] 69–83) over alpha, fully lifting NPIs on June 21, 2021, as originally planned might have led to 3900 (95% CrI 1500–5700) peak daily hospital admissions under our central parameter scenario. Delaying until July 19, 2021, reduced peak hospital admissions by three fol

Journal article

Mousa A, Challenger JD, Griffin J, Ghani AC, Cunnington AJ, Al-Taiar A, Anstey NM, Badaut C, Barber BE, Bassat Q, Datta D, Drakeley C, Gordeuk VR, Grigg MJ, Hugo P, John CC, Mayor A, Migot-Nabias F, Opoka RO, Pasvol G, Rees CP, Reyburn H, Riley EM, Shah BN, Sitoe A, Thuma PE, Unger SA, Viwami F, Walther M, Whitty CJ, William T, Okell LCet al., 2021, THE RELATIONSHIP BETWEEN SEVERE MALARIA PHENOTYPES AND AGE AND ESTIMATES OF BURDEN ACROSS SUB-SAHARAN AFRICA., Annual Meeting of the American-Society-of-Tropical-Medicine-and-Hygiene (ASTMH), Publisher: AMER SOC TROP MED & HYGIENE, Pages: 142-142, ISSN: 0002-9637

Conference paper

Whittaker C, Walker PGT, Alhaffar M, Hamlet A, Djaafara BA, Ghani A, Ferguson N, Dahab M, Checchi F, Watson OJet al., 2021, Under-reporting of deaths limits our understanding of true burden of covid-19, BMJ-BRITISH MEDICAL JOURNAL, Vol: 375, ISSN: 0959-535X

Journal article

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