Imperial College London

DrPatrickWalker

Faculty of MedicineSchool of Public Health

Senior Lecturer
 
 
 
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Contact

 

+44 (0)20 7594 3946patrick.walker06

 
 
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Location

 

UG12Norfolk PlaceSt Mary's Campus

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Summary

 

Publications

Publication Type
Year
to

100 results found

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

Samuels AM, Towett O, Seda B, Wiegand RE, Otieno K, Chomba M, Lucchi N, Ljolje D, Schneider K, Walker PGT, Kwambai TK, Slutsker L, Ter Kuile FO, Kariuki SKet al., 2022, Diagnostic Performance of Loop-Mediated Isothermal Amplification and Ultrasensitive Rapid Diagnostic Tests for Malaria Screening Among Pregnant Women in Kenya., J Infect Dis, Vol: 226, Pages: 696-707

BACKGROUND: Screen-and-treat strategies with sensitive diagnostic tests may reduce malaria-associated adverse pregnancy outcomes. We conducted a diagnostic accuracy study to evaluate new point-of-care tests to screen pregnant women for malaria at their first antenatal visit in western Kenya. METHODS: Consecutively women were tested for Plasmodium infection by expert microscopy, conventional rapid diagnostic test (cRDT), ultra sensitive RDT (usRDT), and loop-mediated isothermal amplification (LAMP). Photoinduced electron-transfer polymerase chain reaction (PET-PCR) served as the reference standard. Diagnostic performance was calculated and modelled at low parasite densities. RESULTS: Between May and September 2018, 172 of 482 screened participants (35.7%) were PET-PCR positive. Relative to PET-PCR, expert microscopy was least sensitive (40.1%; 95% confidence interval [CI], 32.7%-47.9%), followed by cRDT (49.4%; 95% CI, 41.7%-57.1), usRDT (54.7%; 95% CI, 46.9%-62.2%), and LAMP (68.6%; 95% CI, 61.1%-75.5%). Test sensitivities were comparable in febrile women (n = 90). Among afebrile women (n = 392), the geometric-mean parasite density was 29 parasites/µL and LAMP (sensitivity = 61.9%) and usRDT (43.2%) detected 1.74 (95% CI, 1.31-2.30) and 1.21 (95% CI, 88-2.21) more infections than cRDT (35.6%). Per our model, tests performed similarly at densities >200 parasites/µL. At 50 parasites/µL, the sensitivities were 45%, 56%, 62%, and 74% with expert microscopy, cRDT, usRDT, and LAMP, respectively. CONCLUSIONS: This first-generation usRDT provided moderate improvement in detecting low-density infections in afebrile pregnant women compared to cRDTs.

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

de Cola MA, Sawadogo B, Richardson S, Ibinaiye T, Traore A, Compaore CS, Oguoma C, Oresanya O, Tougri G, Rassi C, Roca-Feltrer A, Walker P, Okell LCet al., 2022, Impact of seasonal malaria chemoprevention on prevalence of malaria infection in malaria indicator surveys in Burkina Faso and Nigeria, BMJ Global Health, Vol: 7, Pages: 1-11, ISSN: 2059-7908

Background In 2012, the WHO issued a policy recommendation for the use of seasonal malaria chemoprevention (SMC) to children 3–59 months in areas of highly seasonal malaria transmission. Clinical trials have found SMC to prevent around 75% of clinical malaria. Impact under routine programmatic conditions has been assessed during research studies but there is a need to identify sustainable methods to monitor impact using routinely collected data.Methods Data from Demographic Health Surveys were merged with rainfall, geographical and programme data in Burkina Faso (2010, 2014, 2017) and Nigeria (2010, 2015, 2018) to assess impact of SMC. We conducted mixed-effects logistic regression to predict presence of malaria infection in children aged 6–59 months (rapid diagnostic test (RDT) and microscopy, separately).Results We found strong evidence that SMC administration decreases odds of malaria measured by RDT during SMC programmes, after controlling for seasonal factors, age, sex, net use and other variables (Burkina Faso OR 0.28, 95% CI 0.21 to 0.37, p<0.001; Nigeria OR 0.40, 95% CI 0.30 to 0.55, p<0.001). The odds of malaria were lower up to 2 months post-SMC in Burkina Faso (1-month post-SMC: OR 0.29, 95% CI 0.12 to 0.72, p=0.01; 2 months post-SMC: OR: 0.33, 95% CI 0.17 to 0.64, p<0.001). The odds of malaria were lower up to 1 month post-SMC in Nigeria but was not statistically significant (1-month post-SMC 0.49, 95% CI 0.23 to 1.05, p=0.07). A similar but weaker effect was seen for microscopy (Burkina Faso OR 0.38, 95% CI 0.29 to 0.52, p<0.001; Nigeria OR 0.53, 95% CI 0.38 to 0.76, p<0.001).Conclusions Impact of SMC can be detected in reduced prevalence of malaria from data collected through household surveys if conducted during SMC administration or within 2 months afterwards. Such evidence could contribute to broader evaluation of impact of SMC programmes.

Journal article

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

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

de Cola MA, Sawadogo B, Ibinaiye T, Richardson S, Roca-Feltrer A, Rassi C, Walker P, Okell Let al., 2021, AN ECOLOGICAL ANALYSIS EXPLORING THE IMPACT OF SEASONAL MALARIA CHEMOPREVENTION IN BURKINA FASO AND NIGERIA USING NATIONAL HOUSEHOLD SURVEYS (2010-2018), Publisher: AMER SOC TROP MED & HYGIENE, Pages: 338-338, ISSN: 0002-9637

Conference paper

Nhiga SL, Kinyina A, Assenga M, Lash R, Almeida A, Kitojo C, Florey L, Reaves E, Kombe M, Suhowatsky S, Griffith K, Drake M, Lemwayi R, Aron S, Chacky F, Walker P, Gutman Jet al., 2021, ASSESSING THE UTILITY OF ANTENATAL CARE SURVEILLANCE IN TANZANIA FOR MONITORING COVERAGE OF MALARIA CONTROL INTERVENTIONS, Publisher: AMER SOC TROP MED & HYGIENE, Pages: 348-348, 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

Mangal T, Whittaker C, Nkhoma D, Ng'ambi W, Watson O, Walker P, Ghani A, Revill P, Colbourn T, Phillips A, Hallett T, Mfusto-Bengo Jet al., 2021, The potential impact of intervention strategies on COVID-19 transmission in Malawi: a mathematical modelling study, BMJ Open, Vol: 11, ISSN: 2044-6055

BackgroundCOVID-19 mitigation strategies have been challenging to implement in resource-limited settings due to the potential for widespread disruption to social and economic well-being. Here we predict the clinical severity of COVID-19 in Malawi, quantifying the potential impact of intervention strategies and increases in health system capacity.MethodsThe infection fatality ratios (IFR) were predicted by adjusting reported IFR for China accounting for demography, the current prevalence of comorbidities and health system capacity. These estimates were input into an age-structured deterministic model, which simulated the epidemic trajectory with non-pharmaceutical interventions and increases in health system capacity. Findings The predicted population-level IFR in Malawi, adjusted for age and comorbidity prevalence, is lower than estimated for China (0.26%, 95% uncertainty interval [UI] 0.12 – 0.69%, compared with 0.60%, 95% CI 0.4% – 1.3% in China), however the health system constraints increase the predicted IFR to 0.83%, 95% UI 0.49% – 1.39%. The interventions implemented in January 2021 could potentially avert 54,400 deaths (95% UI 26,900 – 97,300) over the course of the epidemic compared with an unmitigated outbreak. Enhanced shielding of people aged ≥ 60 years could avert a further 40,200 deaths (95% UI 25,300 – 69,700) and halve ICU admissions at the peak of the outbreak. A novel therapeutic agent, which reduces mortality by 0.65 and 0.8 for severe and critical cases respectively, in combination with increasing hospital capacity could reduce projected mortality to 2.5 deaths per 1,000 population (95% UI 1.9 – 3.6).ConclusionWe find the interventions currently used in Malawi are unlikely to effectively prevent SARS-CoV-2 transmission but will have a significant impact on mortality. Increases in health system capacity and the introduction of novel therapeutics are likely to further reduce the projected numbers of deaths.

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

Djaafara A, Whittaker C, Watson OJ, Verity R, Brazeau N, Widyastuti, Oktavia D, Adrian V, Salama N, Bhatia S, Nouvellet P, Sherrard-Smith E, Churcher T, Surendra H, Lina RN, Ekawati LL, Lestari KD, Andrianto A, Thwaites G, Baird JK, Ghani A, Elyazar IRF, Walker Pet al., 2021, Using syndromic measures of mortality to capture the dynamics of COVID-19 in Java, Indonesia in the context of vaccination roll-out, BMC Medicine, Vol: 19, ISSN: 1741-7015

Background: As in many countries, quantifying COVID-19 spread in Indonesia remains challenging due to testing limitations. In Java, non-pharmaceutical interventions (NPIs) were implemented throughout 2020. However, as a vaccination campaign launches, cases and deaths are rising across the island. Methods: We used modelling to explore the extent to which data on burials in Jakarta using strict COVID-19 protocols (C19P) provide additional insight into the transmissibility of the disease, epidemic trajectory, and the impact of NPIs. We assess how implementation of NPIs in early 2021 will shape the epidemic during the period of likely vaccine roll-out. Results: C19P burial data in Jakarta suggest a death toll approximately 3.3 times higher than reported. Transmission estimates using these data suggest earlier, larger, and more sustained impact of NPIs. Measures to reduce sub-national spread, particularly during Ramadan, substantially mitigated spread to more vulnerable rural areas. Given current trajectory, daily cases and deaths are likely to increase in most regions as the vaccine is rolled-out. Transmission may peak in early 2021 in Jakarta if current levels of control are maintained. However, relaxation of control measures is likely to lead to a subsequent resurgence in the absence of an effective vaccination campaign. Conclusions: Syndromic measures of mortality provide a more complete picture of COVID-19 severity upon which to base decision-making. The high potential impact of the vaccine in Java is attributable to reductions in transmission to date and dependent on these being maintained. Increases in control in the relatively short-term will likely yield large, synergistic increases in vaccine impact.

Journal article

McCabe R, Kont M, Schmit N, Whittaker C, Lochen A, Baguelin M, Knock E, Whittles L, Lees J, Brazeau N, Walker P, Ghani A, Ferguson N, White P, Donnelly C, Hauck K, Watson Oet al., 2021, Modelling ICU capacity under different epidemiological scenarios of the COVID-19 pandemic in three western European countries, International Journal of Epidemiology, Vol: 50, Pages: 753-767, ISSN: 0300-5771

Background: The coronavirus disease 2019 (COVID-19) pandemic has placed enormous strain on intensive care units (ICUs) in Europe. Ensuring access to care, irrespective of COVID-19 status, in winter 2020/21 is essential.Methods: An integrated model of hospital capacity planning and epidemiological projections of COVID-19 patients is used to estimate the demand for and resultant spare capacity of ICU beds, staff, and ventilators under different epidemic scenarios in France, Germany, and Italy across the 2020/21 winter period. The effect of implementing lockdowns triggered by different numbers of COVID-19 patients in ICU under varying levels of effectiveness is examined, using a ‘dual-demand’ (COVID-19 and non-COVID-19) patient model.Results: Without sufficient mitigation, we estimate that COVID-19 ICU patient numbers will exceed those seen in the first peak, resulting in substantial capacity deficits, with beds being consistently found to be the most constrained resource. Reactive lockdowns could lead to large improvements in ICU capacity during the winter season, with pressure being most effectively alleviated when lockdown is triggered early and sustained under a higher level of suppression. The success of such interventions also depends on baseline bed numbers and average non-COVID-19 patient occupancy.Conclusions: Reductions in capacity deficits under different scenarios must be weighed against the feasibility and drawbacks of further lockdowns. Careful, continuous decision-making by national policymakers will be required across the winter period 2020/21.

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

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

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

Journal article

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

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

Smith TP, Dorigatti I, Mishra S, Volz E, Walker PGT, Ragonnet-Cronin M, Tristem M, Pearse WDet al., 2021, Environmental drivers of SARS-CoV-2 lineage B.1.1.7 transmission intensity

<jats:title>Abstract</jats:title><jats:p>Previous work has shown that environment affects SARS-CoV-2 transmission, but it is unclear whether emerging strains show similar responses. Here we show that, like other SARS-CoV-2 strains, lineage B.1.1.7 spread with greater transmission in colder and more densely populated parts of England. However, we also find evidence of B.1.1.7 having a transmission advantage at warmer temperatures compared to other strains. This implies that spring and summer conditions are unlikely to slow B.1.1.7’s invasion in Europe and across the Northern hemisphere - an important consideration for public health interventions.</jats:p>

Journal article

Diawara H, Walker P, Cairns M, Steinhardt LC, Diawara F, Kamate B, Duval L, Sicuri E, Sagara I, Sadou A, Mihigo J, Eckert E, Dicko A, Conteh Let al., 2021, Cost-effectiveness of district-wide seasonal malaria chemoprevention when implemented through routine malaria control programme in Kita, Mali using fixed point distribution, Malaria Journal, Vol: 20, Pages: 1-14, ISSN: 1475-2875

Background: Seasonal malaria chemoprevention (SMC) is a strategy for malaria control recommended by the World Health Organization (WHO) since 2012 for Sahelian countries. The Mali National Malaria Control Programme adopted a plan for pilot implementation and nationwide scale-up by 2016. Given that SMC is a relatively new approach, there is an urgent need to assess the costs and cost effectiveness of SMC when implemented through the routine health system to inform decisions on resource allocation.Methods: Cost data were collected from pilot implementation of SMC in Kita district, which targeted 77,497 children aged 3–59 months. Starting in August 2014, SMC was delivered by fixed point distribution in villages with the first dose observed each month. Treatment consisted of sulfadoxine-pyrimethamine and amodiaquine once a month for four consecutive months, or rounds. Economic and financial costs were collected from the provider perspective using an ingredients approach. Effectiveness estimates were based upon a published mathematical transmission model calibrated to local epidemiology, rainfall patterns and scale-up of interventions. Incremental cost effectiveness ratios were calculated for the cost per malaria episode averted, cost per disability adjusted life years (DALYs) averted, and cost per death averted.Results: The total economic cost of the intervention in the district of Kita was US $357,494. Drug costs and personnel costs accounted for 34% and 31%, respectively. Incentives (payment other than salary for efforts beyond routine activities) accounted for 25% of total implementation costs. Average financial and economic unit costs per child per round were US $0.73 and US $0.86, respectively; total annual financial and economic costs per child receiving SMC were US $2.92 and US $3.43, respectively. Accounting for coverage, the economic cost per child fully adherent (receiving all four rounds) was US $6.38 and US $4.69, if weighted highly adherent, (receivin

Journal article

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

Nouvellet P, Bhatia S, Cori A, Ainslie K, Baguelin M, Bhatt S, Boonyasiri A, Brazeau N, Cattarino L, Cooper L, Coupland H, Cucunuba Perez Z, Cuomo-Dannenburg G, Dighe A, Djaafara A, Dorigatti I, Eales O, van Elsland S, NASCIMENTO F, Fitzjohn R, Gaythorpe K, Geidelberg L, green W, Hamlet A, Hauck K, Hinsley W, Imai N, Jeffrey, Jeffrey B, Knock E, Laydon D, Lees J, Mangal T, Mellan T, Nedjati Gilani G, Parag K, Pons Salort M, Ragonnet-Cronin M, Riley S, Unwin H, Verity R, Vollmer M, Volz E, Walker P, Walters C, Wang H, Watson O, Whittaker C, Whittles L, Xi X, Ferguson N, Donnelly Cet al., 2021, Reduction in mobility and COVID-19 transmission, Nature Communications, Vol: 12, ISSN: 2041-1723

In response to the COVID-19 pandemic, countries have sought to control SARS-CoV-2 transmission by restricting population movement through social distancing interventions, thus reducing the number of contacts.Mobility data represent an important proxy measure of social distancing, and here, we characterise the relationship between transmission and mobility for 52 countries around the world.Transmission significantly decreased with the initial reduction in mobility in 73% of the countries analysed, but we found evidence of decoupling of transmission and mobility following the relaxation of strict control measures for 80% of countries. For the majority of countries, mobility explained a substantial proportion of the variation in transmissibility (median adjusted R-squared: 48%, interquartile range - IQR - across countries [27-77%]). Where a change in the relationship occurred, predictive ability decreased after the relaxation; from a median adjusted R-squared of 74% (IQR across countries [49-91%]) pre-relaxation, to a median adjusted R-squared of 30% (IQR across countries [12-48%]) post-relaxation.In countries with a clear relationship between mobility and transmission both before and after strict control measures were relaxed, mobility was associated with lower transmission rates after control measures were relaxed indicating that the beneficial effects of ongoing social distancing behaviours were substantial.

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

Kitojo C, Chacky F, Kigadye ES, Mugasa JP, Lusasi A, Mohamed A, Walker P, Reaves EJ, Gutman JR, Ishengoma DSet al., 2020, Evaluation of a single screen and treat strategy to detect asymptomatic malaria among pregnant women from selected health facilities in Lindi region, Tanzania, Malaria Journal, Vol: 19, Pages: 1-8, ISSN: 1475-2875

BackgroundIn areas of high transmission, malaria in pregnancy (MiP) primarily causes asymptomatic infections; these infections nonetheless increase the risk of adverse maternal and fetal outcomes. In 2014, Tanzania initiated a single screening and treatment (SST) strategy for all pregnant women at their first antenatal care (ANC) visit using malaria rapid diagnostic tests (RDT) for surveillance purposes. However, there is paucity of data on the effectiveness of SST in the prevention of MiP. The objective of this study was to estimate the number of asymptomatic infections among pregnant women detected by SST, which would have been missed in the absence of the policy.MethodsData from pregnant women attending their first ANC visits between October 2017 and June 2018, including gestational age, history of fever, and RDT results, were abstracted from ANC registers in eight health centres in two randomly selected districts, Kilwa and Lindi, in Lindi Region. The proportion of symptomatic (with history of fever in the past 48 h) and asymptomatic pregnant women with positive RDTs were calculated and stratified by trimester (first, second and third). The study areas were categorized as low transmission with prevalence < 10% or moderate/high with ≥ 10%.ResultsOver the study period, 1,845 women attended their first ANC visits; 22.1% were in the first trimester (< 12 weeks gestation age). Overall 15.0% of the women had positive RDTs, and there was a trend towards higher malaria prevalence in the first (15.9%) and second (15.2%) trimesters, compared to the third (7.1%), although the differences were not statistically significant (p = 0.07). In total, 6.9% of women reported fever within the past 48 h and, of these, 96.1% were RDT positive. For every 100 pregnant women in the moderate/high and low transmission areas, SST identified 60 and 26 pregnant women, respectively, with asymptomatic infections that would have otherwise

Journal article

Unwin H, Mishra S, Bradley V, Gandy A, Mellan T, Coupland H, Ish-Horowicz J, Vollmer M, Whittaker C, Filippi S, Xi X, Monod M, Ratmann O, Hutchinson M, Valka F, Zhu H, Hawryluk I, Milton P, Ainslie K, Baguelin M, Boonyasiri A, Brazeau N, Cattarino L, Cucunuba Z, Cuomo-Dannenburg G, Dorigatti I, Eales O, Eaton J, van Elsland S, Fitzjohn R, Gaythorpe K, Green W, Hinsley W, Jeffrey B, Knock E, Laydon D, Lees J, Nedjati-Gilani G, Nouvellet P, Okell L, Parag K, Siveroni I, Thompson H, Walker P, Walters C, Watson O, Whittles L, Ghani A, Ferguson N, Riley S, Donnelly C, Bhatt S, Flaxman Set al., 2020, State-level tracking of COVID-19 in the United States, Nature Communications, Vol: 11, Pages: 1-9, ISSN: 2041-1723

As of 1st June 2020, the US Centers for Disease Control and Prevention reported 104,232 confirmed or probable COVID-19-related deaths in the US. This was more than twice the number of deaths reported in the next most severely impacted country. We jointly model the US epidemic at the state-level, using publicly available deathdata within a Bayesian hierarchical semi-mechanistic framework. For each state, we estimate the number of individuals that have been infected, the number of individuals that are currently infectious and the time-varying reproduction number (the average number of secondary infections caused by an infected person). We use changes in mobility to capture the impact that non-pharmaceutical interventions and other behaviour changes have on therate of transmission of SARS-CoV-2. We estimate thatRtwas only below one in 23 states on 1st June. We also estimate that 3.7% [3.4%-4.0%] of the total population of the US had been infected, with wide variation between states, and approximately 0.01% of the population was infectious. We demonstrate good 3 week model forecasts of deaths with low error and good coverage of our credible intervals.

Journal article

Watson O, Abdelmagid N, Ahmed A, Ahmed Abd Elhameed AE, Whittaker C, Brazeau N, Hamlet A, Walker P, Hay J, Ghani A, Checchi F, Dahab Met al., 2020, Report 39: Characterising COVID-19 epidemic dynamics and mortality under-ascertainment in Khartoum, Sudan

Report

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

McCabe R, Kont M, Schmit N, Whittaker C, Lochen A, Baguelin M, Knock E, Whittles L, Lees J, Walker P, Ghani A, Ferguson N, White P, Donnelly C, Hauck K, Watson Oet al., 2020, Report 36: Modelling ICU capacity under different epidemiological scenarios of the COVID-19 pandemic in three western European countries

The coronavirus disease 2019 (COVID-19) pandemic has placed enormous strain on healthcare systems, particularly intensive care units (ICUs), with COVID-19 patient care being a key concern of healthcare system planning for winter 2020/21. Ensuring that all patients who require intensive care, irrespective of COVID-19 status, can access it during this time is essential. This study uses an integrated model of hospital capacity planning and epidemiological projections of COVID-19 patients to estimate the spare capacity of key ICU resources under different epidemic scenarios in France, Germany and Italy across the winter period of 2020/21. In particular, we examine the effect of implementing suppression strategies of varying effectiveness, triggered by different numbers of COVID-19 patients in ICU. The use of a ‘dual-demand’ (COVID-19 and non-COVID-19) patient model and the consideration of multiple ICU resources that determine capacity (beds, doctors, nurses and ventilators) and the interdependencies between them, provides a detailed insight into potential capacity constraints this winter. Without sufficient mitigation, we estimate that COVID-19 ICU patient numbers will exceed those seen in the first peak, resulting in substantial capacity deficits, with beds being consistently found to be the most constrained resource across countries. Lockdowns triggered based on ICU capacity could lead to large improvements in spare capacity during the winter season, with pressure being most effectively alleviated when lockdown is triggered early and implemented at a higher level of suppression. In many cases, maximum deficits are reduced to lower levels which can then be managed by expanding supply-side hospital capacity, to ensure that all patients can receive treatment. The success of such interventions also depends on baseline ICU bed numbers and average non-COVID-19 patient occupancy. We find that lockdowns of longer duration reduce the total number of days in defic

Report

Thompson H, Hogan A, Walker P, White M, Cunnington A, Ockenhouse C, Ghani Aet al., 2020, Modelling the roles of antibody titre and avidity in protection from Plasmodium falciparum malaria infection following RTS,S/AS01 vaccination, Vaccine, Vol: 38, Pages: 7498-7507, ISSN: 0264-410X

Anti-circumsporozoite antibody titres have been established as an essential indicator for evaluating the immunogenicity and protective capacity of the RTS,S/AS01 malaria vaccine. However, a new delayed-fractional dose regime of the vaccine was recently shown to increase vaccine efficacy, from 62.5% (95% CI 29.4–80.1%) under the original dosing schedule to 86.7% (95% CI, 66.8–94.6%) without a corresponding increase in antibody titres. Here we reanalyse the antibody data from this challenge trial to determine whether IgG avidity may help to explain efficacy better than IgG titre alone by adapting a within-host mathematical model of sporozoite inoculation. We demonstrate that a model incorporating titre and avidity provides a substantially better fit to the data than titre alone. These results also suggest that in individuals with a high antibody titre response that also show high avidity (both metrics in the top tercile of observed values) delayed-fractional vaccination provided near perfect protection upon first challenge (98.2% [95% Credible Interval 91.6–99.7%]). This finding suggests that the quality of the vaccine induced antibody response is likely to be an important determinant in the development of highly efficacious pre-erythrocytic vaccines against malaria.

Journal article

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