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  • Journal article
    Penn MJ, Laydon DJ, Penn J, Whittaker C, Morgenstern C, Ratmann O, Mishra S, Pakkanen MS, Donnelly CA, Bhatt Set al., 2023,

    Intrinsic randomness in epidemic modelling beyond statistical uncertainty

    , Communications Physics, Vol: 6

    Uncertainty can be classified as either aleatoric (intrinsic randomness) or epistemic (imperfect knowledge of parameters). The majority of frameworks assessing infectious disease risk consider only epistemic uncertainty. We only ever observe a single epidemic, and therefore cannot empirically determine aleatoric uncertainty. Here, we characterise both epistemic and aleatoric uncertainty using a time-varying general branching process. Our framework explicitly decomposes aleatoric variance into mechanistic components, quantifying the contribution to uncertainty produced by each factor in the epidemic process, and how these contributions vary over time. The aleatoric variance of an outbreak is itself a renewal equation where past variance affects future variance. We find that, superspreading is not necessary for substantial uncertainty, and profound variation in outbreak size can occur even without overdispersion in the offspring distribution (i.e. the distribution of the number of secondary infections an infected person produces). Aleatoric forecasting uncertainty grows dynamically and rapidly, and so forecasting using only epistemic uncertainty is a significant underestimate. Therefore, failure to account for aleatoric uncertainty will ensure that policymakers are misled about the substantially higher true extent of potential risk. We demonstrate our method, and the extent to which potential risk is underestimated, using two historical examples.

  • Journal article
    Walker M, Lambert S, Neves MI, Worsley AD, Traub R, Colella Vet al., 2023,

    Modeling the effectiveness of One Health interventions against the zoonotic hookworm Ancylostoma ceylanicum

    , Frontiers of Medicine, Vol: 10, ISSN: 1673-7342

    Hookworm disease is a major global public health concern, annually affecting 500-700 million of the world's poorest people. The World Health Organization is targeting the elimination of hookworm as a public health problem by 2030 using a strategy of mass drug administration (MDA) to at-risk human populations. However, in Southeast Asia and the Pacific the zoonotic hookworm species, Ancylostoma ceylanicum, is endemic in dogs and commonly infects people. This presents a potential impediment to the effectiveness of MDA that targets only humans. Here, we develop a novel multi-host (dog and human) transmission model of A. ceylanicum and compare the effectiveness of human-only and "One Health" (human plus dog) MDA strategies under a range of eco-epidemiological assumptions. We show that One Health interventions-targeting both dogs and humans-could suppress prevalence in humans to ≤ 1% by the end of 2030, even with only modest coverage (25-50%) of the animal reservoir. With increasing coverage, One Health interventions may even interrupt transmission. We discuss key unresolved questions on the eco-epidemiology of A. ceylanicum, the challenges of delivering MDA to animal reservoirs, and the growing importance of One Health interventions to human public health.

  • Journal article
    Ledien J, Cucunubá ZM, Parra-Henao G, Rodríguez-Monguí E, Dobson AP, Adamo SB, Castellanos LG, Basáñez M-G, Nouvellet Pet al., 2023,

    From serological surveys to disease burden: a modelling pipeline for Chagas disease.

    , Philosophical Transactions of the Royal Society B: Biological Sciences, Vol: 378, Pages: 1-12, ISSN: 0962-8436

    In 2012, the World Health Organization (WHO) set the elimination of Chagas disease intradomiciliary vectorial transmission as a goal by 2020. After a decade, some progress has been made, but the new 2021–2030 WHO roadmap has set even more ambitious targets. Innovative and robust modelling methods are required to monitor progress towards these goals. We present a modelling pipeline using local seroprevalence data to obtain national disease burden estimates by disease stage. Firstly, local seroprevalence information is used to estimate spatio-temporal trends in the Force-of-Infection (FoI). FoI estimates are then used to predict such trends across larger and fine-scale geographical areas. Finally, predicted FoI values are used to estimate disease burden based on a disease progression model. Using Colombia as a case study, we estimated that the number of infected people would reach 506 000 (95% credible interval (CrI) = 395 000–648 000) in 2020 with a 1.0% (95%CrI = 0.8–1.3%) prevalence in the general population and 2400 (95%CrI = 1900–3400) deaths (approx. 0.5% of those infected). The interplay between a decrease in infection exposure (FoI and relative proportion of acute cases) was overcompensated by a large increase in population size and gradual population ageing, leading to an increase in the absolute number of Chagas disease cases over time.This article is part of the theme issue ‘Challenges and opportunities in the fight against neglected tropical diseases: a decade from the London Declaration on NTDs’.

  • Journal article
    Collyer BS, Truscott JE, Mwandawiro CS, Njenga SM, Anderson RMet al., 2023,

    How important is the spatial movement of people in attempts to eliminate the transmission of human helminth infections by mass drug administration?

    , Philos Trans R Soc Lond B Biol Sci, Vol: 378

    Human mobility contributes to the spatial dynamics of many infectious diseases, and understanding these dynamics helps us to determine the most effective ways to intervene and plan surveillance. In this paper, we describe a novel transmission model for the spatial dynamics of hookworm, a parasitic worm which is a common infection across sub-Saharan Africa, East Asia and the Pacific islands. We fit our model, with and without mobility, to data obtained from a sub-county in Kenya, and validate the model's predictions against the decline in prevalence observed over the course of a clustered randomized control trial evaluating methods of administering mass chemotherapy. We find that our model which incorporates human mobility is able to reproduce the observed patterns in decline of prevalence during the TUMIKIA trial, and additionally, that the widespread bounce-back of infection may be possible over many years, depending on the rates of people movement between villages. The results have important implications for the design of mass chemotherapy programmes for the elimination of human helminth transmission. This article is part of the theme issue 'Challenges and opportunities in the fight against neglected tropical diseases: a decade from the London Declaration on NTDs'.

  • Journal article
    Forbes K, Basáñez M-G, Hollingsworth TD, Anderson RMet al., 2023,

    Introduction to the special issue: challenges and opportunities in the fight against neglected tropical diseases: a decade from the London Declaration on NTDs

    , Philosophical Transactions of the Royal Society B: Biological Sciences, Vol: 378, Pages: 1-8, ISSN: 0962-8436

    Twenty neglected tropical diseases (NTDs) are currently prioritised by the World Health Organization for eradication, elimination as a public health problem, elimination of transmission or control by 2030. This issue celebrates progress made since the 2012 London Declaration on NTDs and discusses challenges currently faced to achieve these goals. It comprises 14 contributions spanning NTDs tackled by intensified disease management to those addressed by preventive chemotherapy. Although COVID-19 negatively affected NTD programmes, it also served to spur new multisectoral approaches to strengthen school-based health systems. The issue highlights the needs to improve impact survey design, evaluate new diagnostics, understand the consequences of heterogeneous prevalence and human movement, the potential impact of alternative treatment strategies and the importance of zoonotic transmission. This article is part of the theme issue 'Challenges and opportunities in the fight against neglected tropical diseases: a decade from the London Declaration on NTDs'.

  • Journal article
    Kura K, Milton P, Hamley JID, Walker M, Bakajika DK, Kanza EM, Opoku NO, Howard H, Nigo MM, Asare S, Olipoh G, Attah SK, Mambandu GL, Kennedy KK, Kataliko K, Mumbere M, Halleux CM, Hopkins A, Kuesel AC, Kinrade S, Basáñez M-Get al., 2023,

    Can mass drug administration of moxidectin accelerate onchocerciasis elimination in Africa?

    , Philosophical Transactions of the Royal Society B: Biological Sciences, Vol: 378, Pages: 1-11, ISSN: 0962-8436

    Epidemiological and modelling studies suggest that elimination of Onchocerca volvulus transmission (EoT) throughout Africa may not be achievable with annual mass drug administration (MDA) of ivermectin alone, particularly in areas of high endemicity and vector density. Single-dose Phase II and III clinical trials demonstrated moxidectin's superiority over ivermectin for prolonged clearance of O. volvulus microfilariae. We used the stochastic, individual-based EPIONCHO-IBM model to compare the probabilities of reaching EoT between ivermectin and moxidectin MDA for a range of endemicity levels (30 to 70% baseline microfilarial prevalence), treatment frequencies (annual and biannual) and therapeutic coverage/adherence values (65 and 80% of total population, with, respectively, 5 and 1% of systematic non-adherence). EPIONCHO-IBM's projections indicate that biannual (six-monthly) moxidectin MDA can reduce by half the number of years necessary to achieve EoT in mesoendemic areas and might be the only strategy that can achieve EoT in hyperendemic areas. Data needed to improve modelling projections include (i) the effect of repeated annual and biannual moxidectin treatment; (ii) inter- and intra-individual variation in response to successive treatments with moxidectin or ivermectin; (iii) the effect of moxidectin and ivermectin treatment on L3 development into adult worms; and (iv) patterns of adherence to moxidectin and ivermectin MDA.

  • Journal article
    Murphy C, Lim WW, Mills C, Wong JY, Chen D, Xie Y, Li M, Gould S, Xin H, Cheung JK, Bhatt S, Cowling BJ, Donnelly CAet al., 2023,

    Effectiveness of social distancing measures and lockdowns for reducing transmission of COVID-19 in non-healthcare, community-based settings.

    , Philos Trans A Math Phys Eng Sci, Vol: 381

    Social distancing measures (SDMs) are community-level interventions that aim to reduce person-to-person contacts in the community. SDMs were a major part of the responses first to contain, then to mitigate, the spread of SARS-CoV-2 in the community. Common SDMs included limiting the size of gatherings, closing schools and/or workplaces, implementing work-from-home arrangements, or more stringent restrictions such as lockdowns. This systematic review summarized the evidence for the effectiveness of nine SDMs. Almost all of the studies included were observational in nature, which meant that there were intrinsic risks of bias that could have been avoided were conditions randomly assigned to study participants. There were no instances where only one form of SDM had been in place in a particular setting during the study period, making it challenging to estimate the separate effect of each intervention. The more stringent SDMs such as stay-at-home orders, restrictions on mass gatherings and closures were estimated to be most effective at reducing SARS-CoV-2 transmission. Most studies included in this review suggested that combinations of SDMs successfully slowed or even stopped SARS-CoV-2 transmission in the community. However, individual effects and optimal combinations of interventions, as well as the optimal timing for particular measures, require further investigation. This article is part of the theme issue 'The effectiveness of non-pharmaceutical interventions on the COVID-19 pandemic: the evidence'.

  • Journal article
    Díaz AV, Walker M, Webster JP, 2023,

    Reaching the World Health Organization elimination targets for schistosomiasis: the importance of a One Health perspective.

    , Philos Trans R Soc Lond B Biol Sci, Vol: 378

    The past three years has seen the launch of a new World Health Organization (WHO) neglected tropical diseases (NTDs) roadmap, together with revised control and elimination guidelines. Across all, there is now a clear emphasis on the need to incorporate a One Health approach, recognizing the critical links between human and animal health and the environment. Schistosomiasis, caused by Schistosoma spp. trematodes, is a NTD of global medical and veterinary importance, with over 220 million people and untold millions of livestock currently infected. Its burden remains extremely high in certain regions, particularly within sub-Saharan Africa, despite over two decades of mass preventive chemotherapy (mass drug administration), predominantly to school-aged children. In Africa, in contrast to Asia, any zoonotic component of schistosomiasis transmission and its implications for disease control has, until recently, been largely ignored. Here, we review recent epidemiological, clinical, molecular, and modelling work across both Asia and Africa. We outline the evolutionary history and transmission dynamics of Schistosoma species, and emphasize the emerging risk raised by both wildlife reservoirs and viable hybridization between human and animal schistosomes. To achieve the 2030 WHO roadmap elimination targets, a truly multi-disciplinary One Health perspective must be implemented. This article is part of the theme issue 'Challenges and opportunities in the fight against neglected tropical diseases: a decade from the London Declaration on NTDs'.

  • Journal article
    Volz E, 2023,

    Fitness, growth and transmissibility of SARS-CoV-2 genetic variants.

    , Nat Rev Genet, Vol: 24, Pages: 724-734

    The massive scale of the global SARS-CoV-2 sequencing effort created new opportunities and challenges for understanding SARS-CoV-2 evolution. Rapid detection and assessment of new variants has become one of the principal objectives of genomic surveillance of SARS-CoV-2. Because of the pace and scale of sequencing, new strategies have been developed for characterizing fitness and transmissibility of emerging variants. In this Review, I discuss a wide range of approaches that have been rapidly developed in response to the public health threat posed by emerging variants, ranging from new applications of classic population genetics models to contemporary synthesis of epidemiological models and phylodynamic analysis. Many of these approaches can be adapted to other pathogens and will have increasing relevance as large-scale pathogen sequencing becomes a regular feature of many public health systems.

  • Journal article
    Moreira FRR, Menezes MTD, Salgado-Benvindo C, Whittaker C, Cox V, Chandradeva N, Paula HHSD, Martins AF, Chagas RRD, Brasil RDV, Cândido DDS, Herlinger AL, Ribeiro MDO, Arruda MB, Alvarez P, Tôrres MCDP, Dorigatti I, Brady O, Voloch CM, Tanuri A, Iani F, Souza WMD, Cardozo SV, Faria NR, Aguiar RSet al., 2023,

    Epidemiological and genomic investigation of chikungunya virus in Rio de Janeiro state, Brazil, between 2015 and 2018.

    , PLoS Negl Trop Dis, Vol: 17

    Since 2014, Brazil has experienced an unprecedented epidemic caused by chikungunya virus (CHIKV), with several waves of East-Central-South-African (ECSA) lineage transmission reported across the country. In 2018, Rio de Janeiro state, the third most populous state in Brazil, reported 41% of all chikungunya cases in the country. Here we use evolutionary and epidemiological analysis to estimate the timescale of CHIKV-ECSA-American lineage and its epidemiological patterns in Rio de Janeiro. We show that the CHIKV-ECSA outbreak in Rio de Janeiro derived from two distinct clades introduced from the Northeast region in mid-2015 (clade RJ1, n = 63/67 genomes from Rio de Janeiro) and mid-2017 (clade RJ2, n = 4/67). We detected evidence for positive selection in non-structural proteins linked with viral replication in the RJ1 clade (clade-defining: nsP4-A481D) and the RJ2 clade (nsP1-D531G). Finally, we estimate the CHIKV-ECSA's basic reproduction number (R0) to be between 1.2 to 1.6 and show that its instantaneous reproduction number (Rt) displays a strong seasonal pattern with peaks in transmission coinciding with periods of high Aedes aegypti transmission potential. Our results highlight the need for continued genomic and epidemiological surveillance of CHIKV in Brazil, particularly during periods of high ecological suitability, and show that selective pressures underline the emergence and evolution of the large urban CHIKV-ECSA outbreak in Rio de Janeiro.

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