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Article ; Online: Estimated impact of RTS,S/AS01 malaria vaccine allocation strategies in sub-Saharan Africa

Alexandra B Hogan / Peter Winskill / Azra C Ghani

PLoS Medicine, Vol 17, Iss 11, p e

A modelling study.

2020 Volume 1003377

Abstract: Background The RTS,S/AS01 vaccine against Plasmodium falciparum malaria infection completed phase III trials in 2014 and demonstrated efficacy against clinical malaria of approximately 36% over 4 years for a 4-dose schedule in children aged 5-17 months. ... ...

Abstract	Background The RTS,S/AS01 vaccine against Plasmodium falciparum malaria infection completed phase III trials in 2014 and demonstrated efficacy against clinical malaria of approximately 36% over 4 years for a 4-dose schedule in children aged 5-17 months. Pilot vaccine implementation has recently begun in 3 African countries. If the pilots demonstrate both a positive health impact and resolve remaining safety concerns, wider roll-out could be recommended from 2021 onwards. Vaccine demand may, however, outstrip initial supply. We sought to identify where vaccine introduction should be prioritised to maximise public health impact under a range of supply constraints using mathematical modelling. Methods and findings Using a mathematical model of P. falciparum malaria transmission and RTS,S vaccine impact, we estimated the clinical cases and deaths averted in children aged 0-5 years in sub-Saharan Africa under 2 scenarios for vaccine coverage (100% and realistic) and 2 scenarios for other interventions (current coverage and World Health Organization [WHO] Global Technical Strategy targets). We used a prioritisation algorithm to identify potential allocative efficiency gains from prioritising vaccine allocation among countries or administrative units to maximise cases or deaths averted. If malaria burden at introduction is similar to current levels-assuming realistic vaccine coverage and country-level prioritisation in areas with parasite prevalence >10%-we estimate that 4.3 million malaria cases (95% credible interval [CrI] 2.8-6.8 million) and 22,000 deaths (95% CrI 11,000-35,000) in children younger than 5 years could be averted annually at a dose constraint of 30 million. This decreases to 3.0 million cases (95% CrI 2.0-4.7 million) and 14,000 deaths (95% CrI 7,000-23,000) at a dose constraint of 20 million, and increases to 6.6 million cases (95% CrI 4.2-10.8 million) and 38,000 deaths (95% CrI 18,000-61,000) at a dose constraint of 60 million. At 100% vaccine coverage, these impact estimates increase to 5.2 million cases (95% CrI 3.5-8.2 million) and 27,000 deaths (95% CrI 14,000-43,000), 3.9 million cases (95% CrI 2.7-6.0 million) and 19,000 deaths (95% CrI 10,000-30,000), and 10.0 million cases (95% CrI 6.7-15.7 million) and 51,000 deaths (95% CrI 25,000-82,000), respectively. Under realistic vaccine coverage, if the vaccine is prioritised sub-nationally, 5.3 million cases (95% CrI 3.5-8.2 million) and 24,000 deaths (95% CrI 12,000-38,000) could be averted at a dose constraint of 30 million. Furthermore, sub-national prioritisation would allow introduction in almost double the number of countries compared to national prioritisation (21 versus 11). If vaccine introduction is prioritised in the 3 pilot countries (Ghana, Kenya, and Malawi), health impact would be reduced, but this effect becomes less substantial (change of <5%) if 50 million or more doses are available. We did not account for within-country variation in vaccine coverage, and the optimisation was based on a single outcome measure, therefore this study should be used to understand overall trends rather than guide country-specific allocation. Conclusions These results suggest that the impact of constraints in vaccine supply on the public health impact of the RTS,S malaria vaccine could be reduced by introducing the vaccine at the sub-national level and prioritising countries with the highest malaria incidence.
Keywords	Medicine ; R
Subject code	306
Language	English
Publishing date	2020-11-01T00:00:00Z
Publisher	Public Library of Science (PLoS)
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Analysis of the potential for a malaria vaccine to reduce gaps in malaria intervention coverage

H. Juliette T. Unwin / Lazaro Mwandigha / Peter Winskill / Azra C. Ghani / Alexandra B. Hogan

Malaria Journal, Vol 20, Iss 1, Pp 1-

2021 Volume 11

Abstract: Abstract Background The 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 ...

Abstract	Abstract Background The 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. Methods Using 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. Results Uptake 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 intervention uptake and was positively associated with use of ...
Keywords	Malaria vaccine ; RTS,S/AS01 ; Expanded Programme on Immunization ; Demographic and Health Surveys ; DHS Program ; Arctic medicine. Tropical medicine ; RC955-962 ; Infectious and parasitic diseases ; RC109-216
Subject code	360
Language	English
Publishing date	2021-11-01T00:00:00Z
Publisher	BMC
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Modelling the impact of vaccine hesitancy in prolonging the need for Non-Pharmaceutical Interventions to control the COVID-19 pandemic

Daniela Olivera Mesa / Alexandra B. Hogan / Oliver J. Watson / Giovanni D. Charles / Katharina Hauck / Azra C. Ghani / Peter Winskill

Communications Medicine, Vol 2, Iss 1, Pp 1-

2022 Volume 8

Abstract: Olivera Mesa et al. model the potential impact of vaccine hesitancy in prolonging the need for non-pharmaceutical interventions (NPIs) to control the COVID-19 pandemic. They show that vaccine hesitancy could prolong the need for NPIs to remain in place ... ...

Abstract	Olivera Mesa et al. model the potential impact of vaccine hesitancy in prolonging the need for non-pharmaceutical interventions (NPIs) to control the COVID-19 pandemic. They show that vaccine hesitancy could prolong the need for NPIs to remain in place and lead to increased mortality if NPIs are relaxed.
Keywords	Medicine ; R
Language	English
Publishing date	2022-02-01T00:00:00Z
Publisher	Nature Portfolio
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Health inequities and clustering of fever, acute respiratory infection, diarrhoea and wasting in children under five in low- and middle-income countries

Peter Winskill / Alexandra B. Hogan / Julie Thwing / Lazaro Mwandigha / Patrick G. T. Walker / Ben Lambert

BMC Medicine, Vol 19, Iss 1, Pp 1-

a Demographic and Health Surveys analysis

2021 Volume 11

Abstract: Abstract 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 ... ...

Abstract	Abstract 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.
Keywords	Malaria ; Pneumonia ; Diarrhoea ; Malnutrition ; Clustering ; Child health ; Medicine ; R
Subject code	360
Language	English
Publishing date	2021-06-01T00:00:00Z
Publisher	BMC
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Prioritizing the scale-up of interventions for malaria control and elimination

Peter Winskill / Patrick G. Walker / Richard E. Cibulskis / Azra C. Ghani

Malaria Journal, Vol 18, Iss 1, Pp 1-

2019 Volume 11

Abstract: Abstract Background A core set of intervention and treatment options are recommended by the World Health Organization for use against falciparum malaria. These are treatment, long-lasting insecticide-treated bed nets, indoor residual spraying, and ... ...

Abstract	Abstract Background A core set of intervention and treatment options are recommended by the World Health Organization for use against falciparum malaria. These are treatment, long-lasting insecticide-treated bed nets, indoor residual spraying, and chemoprevention options. Both domestic and foreign aid funding for these tools is limited. When faced with budget restrictions, the introduction and scale-up of intervention and treatment options must be prioritized. Methods Estimates of the cost and impact of different interventions were combined with a mathematical model of malaria transmission to estimate the most cost-effective prioritization of interventions. The incremental cost effectiveness ratio was used to select between scaling coverage of current interventions or the introduction of an additional intervention tool. Results Prevention, in the form of vector control, is highly cost effective and scale-up is prioritized in all scenarios. Prevention reduces malaria burden and therefore allows treatment to be implemented in a more cost-effective manner by reducing the strain on the health system. The chemoprevention measures (seasonal malaria chemoprevention and intermittent preventive treatment in infants) are additional tools that, provided sufficient funding, are implemented alongside treatment scale-up. Future tools, such as RTS,S vaccine, have impact in areas of higher transmission but were introduced later than core interventions. Conclusions In a programme that is budget restricted, it is essential that investment in available tools be effectively prioritized to maximize impact for a given investment. The cornerstones of malaria control: vector control and treatment, remain vital, but questions of when to scale and when to introduce other interventions must be rigorously assessed. This quantitative analysis considers the scale-up or core interventions to inform decision making in this area.
Keywords	Malaria ; Plasmodium falciparum ; Interventions ; Prioritization ; Cost-effective ; Scale-up ; Arctic medicine. Tropical medicine ; RC955-962 ; Infectious and parasitic diseases ; RC109-216
Subject code	360
Language	English
Publishing date	2019-04-01T00:00:00Z
Publisher	BMC
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Long-term vaccination strategies to mitigate the impact of SARS-CoV-2 transmission

Alexandra B Hogan / Sean L Wu / Jaspreet Toor / Daniela Olivera Mesa / Patrick Doohan / Oliver J Watson / Peter Winskill / Giovanni Charles / Gregory Barnsley / Eleanor M Riley / David S Khoury / Neil M Ferguson / Azra C Ghani

PLoS Medicine, Vol 20, Iss 11, p e

A modelling study.

2023 Volume 1004195

Abstract: Background Vaccines have reduced severe disease and death from Coronavirus Disease 2019 (COVID-19). However, with evidence of waning efficacy coupled with continued evolution of the virus, health programmes need to evaluate the requirement for regular ... ...

Abstract	Background Vaccines have reduced severe disease and death from Coronavirus Disease 2019 (COVID-19). However, with evidence of waning efficacy coupled with continued evolution of the virus, health programmes need to evaluate the requirement for regular booster doses, considering their impact and cost-effectiveness in the face of ongoing transmission and substantial infection-induced immunity. Methods and findings We developed a combined immunological-transmission model parameterised with data on transmissibility, severity, and vaccine effectiveness. We simulated Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) transmission and vaccine rollout in characteristic global settings with different population age-structures, contact patterns, health system capacities, prior transmission, and vaccine uptake. We quantified the impact of future vaccine booster dose strategies with both ancestral and variant-adapted vaccine products, while considering the potential future emergence of new variants with modified transmission, immune escape, and severity properties. We found that regular boosting of the oldest age group (75+) is an efficient strategy, although large numbers of hospitalisations and deaths could be averted by extending vaccination to younger age groups. In countries with low vaccine coverage and high infection-derived immunity, boosting older at-risk groups was more effective than continuing primary vaccination into younger ages in our model. Our study is limited by uncertainty in key parameters, including the long-term durability of vaccine and infection-induced immunity as well as uncertainty in the future evolution of the virus. Conclusions Our modelling suggests that regular boosting of the high-risk population remains an important tool to reduce morbidity and mortality from current and future SARS-CoV-2 variants. Our results suggest that focusing vaccination in the highest-risk cohorts will be the most efficient (and hence cost-effective) strategy to reduce morbidity and mortality.
Keywords	Medicine ; R
Subject code	910
Language	English
Publishing date	2023-11-01T00:00:00Z
Publisher	Public Library of Science (PLoS)
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Global variation in force-of-infection trends for human Taenia solium taeniasis/cysticercosis

Matthew A Dixon / Peter Winskill / Wendy E Harrison / Charles Whittaker / Veronika Schmidt / Astrid Carolina Flórez Sánchez / Zulma M Cucunuba / Agnes U Edia-Asuke / Martin Walker / María-Gloria Basáñez

eLife, Vol

2022 Volume 11

Abstract: Infection by Taenia solium poses a major burden across endemic countries. The World Health Organization (WHO) 2021–2030 Neglected Tropical Diseases roadmap has proposed that 30% of endemic countries achieve intensified T. solium control in hyperendemic ... ...

Abstract	Infection by Taenia solium poses a major burden across endemic countries. The World Health Organization (WHO) 2021–2030 Neglected Tropical Diseases roadmap has proposed that 30% of endemic countries achieve intensified T. solium control in hyperendemic areas by 2030. Understanding geographical variation in age-prevalence profiles and force-of-infection (FoI) estimates will inform intervention designs across settings. Human taeniasis (HTT) and human cysticercosis (HCC) age-prevalence data from 16 studies in Latin America, Africa, and Asia were extracted through a systematic review. Catalytic models, incorporating diagnostic performance uncertainty, were fitted to the data using Bayesian methods, to estimate rates of antibody (Ab)-seroconversion, infection acquisition and Ab-seroreversion or infection loss. HCC FoI and Ab-seroreversion rates were also estimated across 23 departments in Colombia from 28,100 individuals. Across settings, there was extensive variation in all-ages seroprevalence. Evidence for Ab-seroreversion or infection loss was found in most settings for both HTT and HCC and for HCC Ab-seroreversion in Colombia. The average duration until humans became Ab-seropositive/infected decreased as all-age (sero)prevalence increased. There was no clear relationship between the average duration humans remain Ab-seropositive and all-age seroprevalence. Marked geographical heterogeneity in T. solium transmission rates indicate the need for setting-specific intervention strategies to achieve the WHO goals.
Keywords	taenia solium ; one health ; modelling ; neglected tropical diseases ; statistics ; zoonotic infections ; Medicine ; R ; Science ; Q ; Biology (General) ; QH301-705.5
Subject code	333
Language	English
Publishing date	2022-08-01T00:00:00Z
Publisher	eLife Sciences Publications Ltd
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Book ; Online: mrc-ide/squire

OJ Watson / cwhittaker1000 / Peter Winskill / Giovanni / Nicholas Brazeau / Rich FitzJohn / patrickgtwalker / Darío Hereñú

v0.4.34

2020

Abstract: SEIR transmission model of COVID-19. Documentation at: ...

Abstract	SEIR transmission model of COVID-19. Documentation at:
Keywords	covid19
Publishing date	2020-09-11
Publishing country	eu
Document type	Book ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Modelling population-level impact to inform target product profiles for childhood malaria vaccines

Alexandra B. Hogan / Peter Winskill / Robert Verity / Jamie T. Griffin / Azra C. Ghani

BMC Medicine, Vol 16, Iss 1, Pp 1-

2018 Volume 11

Abstract: Abstract Background The RTS,S/AS01 vaccine for Plasmodium falciparum malaria demonstrated moderate efficacy in 5–17-month-old children in phase 3 trials, and from 2018, the vaccine will be evaluated through a large-scale pilot implementation program. ... ...

Abstract	Abstract Background The RTS,S/AS01 vaccine for Plasmodium falciparum malaria demonstrated moderate efficacy in 5–17-month-old children in phase 3 trials, and from 2018, the vaccine will be evaluated through a large-scale pilot implementation program. Work is ongoing to optimise this vaccine, with higher efficacy for a different schedule demonstrated in a phase 2a challenge study. The objective of our study was to investigate the population-level impact of a modified RTS,S/AS01 schedule and dose amount in order to inform the target product profile for a second-generation malaria vaccine. Methods We used a mathematical modelling approach as the basis for our study. We simulated the changing anti-circumsporozoite antibody titre following vaccination and related the titre to vaccine efficacy. We then implemented this efficacy profile within an individual-based model of malaria transmission. We compared initial efficacy, duration and dose timing, and evaluated the potential public health impact of a modified vaccine in children aged 5–17 months, measuring clinical cases averted in children younger than 5 years. Results In the first decade of delivery, initial efficacy was associated with a higher reduction in childhood clinical cases compared to vaccine duration. This effect was more pronounced in high transmission settings and was due to the efficacy benefit occurring in younger ages where disease burden is highest. However, the low initial efficacy and long duration schedule averted more cases across all age cohorts if a longer time horizon was considered. We observed an age-shifting effect due to the changing immunological profile in higher transmission settings, in scenarios where initial efficacy was higher, and the fourth dose administered earlier. Conclusions Our findings indicate that, for an imperfect childhood malaria vaccine with suboptimal efficacy, it may be advantageous to prioritise initial efficacy over duration. We predict that a modified vaccine could outperform the current RTS,S/AS01, although ...
Keywords	RTS,S/AS01 ; Target product profile ; Plasmodium falciparum ; Malaria ; Efficacy ; Second-generation malaria vaccine ; Medicine ; R
Language	English
Publishing date	2018-07-01T00:00:00Z
Publisher	BMC
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Strategies for tackling Taenia solium taeniosis/cysticercosis

Matthew A Dixon / Uffe C Braae / Peter Winskill / Martin Walker / Brecht Devleesschauwer / Sarah Gabriël / Maria-Gloria Basáñez

PLoS Neglected Tropical Diseases, Vol 13, Iss 4, p e

A systematic review and comparison of transmission models, including an assessment of the wider Taeniidae family transmission models.

2019 Volume 0007301

Abstract: Background The cestode Taenia solium causes the neglected (zoonotic) tropical disease cysticercosis, a leading cause of preventable epilepsy in endemic low and middle-income countries. Transmission models can inform current scaling-up of control efforts ... ...

Abstract	Background The cestode Taenia solium causes the neglected (zoonotic) tropical disease cysticercosis, a leading cause of preventable epilepsy in endemic low and middle-income countries. Transmission models can inform current scaling-up of control efforts by helping to identify, validate and optimise control and elimination strategies as proposed by the World Health Organization (WHO). Methodology/principal findings A systematic literature search was conducted using the PRISMA approach to identify and compare existing T. solium transmission models, and related Taeniidae infection transmission models. In total, 28 modelling papers were identified, of which four modelled T. solium exclusively. Different modelling approaches for T. solium included deterministic, Reed-Frost, individual-based, decision-tree, and conceptual frameworks. Simulated interventions across models agreed on the importance of coverage for impactful effectiveness to be achieved. Other Taeniidae infection transmission models comprised force-of-infection (FoI), population-based (mainly Echinococcus granulosus) and individual-based (mainly E. multilocularis) modelling approaches. Spatial structure has also been incorporated (E. multilocularis and Taenia ovis) in recognition of spatial aggregation of parasite eggs in the environment and movement of wild animal host populations. Conclusions/significance Gaps identified from examining the wider Taeniidae family models highlighted the potential role of FoI modelling to inform model parameterisation, as well as the need for spatial modelling and suitable structuring of interventions as key areas for future T. solium model development. We conclude that working with field partners to address data gaps and conducting cross-model validation with baseline and longitudinal data will be critical to building consensus-led and epidemiological setting-appropriate intervention strategies to help fulfil the WHO targets.
Keywords	Arctic medicine. Tropical medicine ; RC955-962 ; Public aspects of medicine ; RA1-1270
Language	English
Publishing date	2019-04-01T00:00:00Z
Publisher	Public Library of Science (PLoS)
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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