Publications
13 results found
Cuomo-Dannenburg G, McCain K, McCabe R, et al., 2023, Marburg virus disease outbreaks, mathematical models, and disease parameters: a systematic review, Lancet Infectious Diseases, ISSN: 1473-3099
Recent Marburg virus disease (MVD) outbreaks in Equatorial Guinea and Tanzania highlighted the importance of better understanding this highly lethal infectious pathogen. We conducted a systematic review (PROSPERO CRD42023393345), reported according to PRISMA guidelines, of peer-reviewed papers reporting historical outbreaks, modelling studies and epidemiological parameters focused on MVD. We searched PubMed and Web of Science until 31/03/2023. Two reviewers evaluated all titles and abstracts, with consensus-based decision-making. To ensure agreement, 31% (13/42) of studies were double-extracted and a custom-designed quality assessment questionnaire was used for risk of bias assessment. We present detailed information on 478 reported cases and 385 deaths from MVD. Analysis of historical outbreaks and seroprevalence estimates suggests the possibility of undetected MVD outbreaks, asymptomatic transmission and/or cross-reactivity with other pathogens. Only one study presented a mathematical model of MVD transmission. We estimate an unadjusted, pooled total random effect case fatality ratio for MVD of 61.9% (95% CI: 38.8-80.6%, I^2=93%). We identify important epidemiological parameters relating to transmission and natural history for which there are few estimates. This review and the accompanying database provide a comprehensive overview of MVD epidemiology, and identify key knowledge gaps, contributing crucial information for mathematical models to support future MVD epidemic responses.
Bhatia S, Parag KV, Wardle J, et al., 2023, Retrospective evaluation of real-time estimates of global COVID-19 transmission trends and mortality forecasts, PLOS ONE, Vol: 18, ISSN: 1932-6203
Bhatia S, Wardle J, Nash R, et al., 2023, Extending EpiEstim to estimate the transmission advantage of pathogen variants in real-time: SARS-CoV-2 as a case-study, Epidemics: the journal of infectious disease dynamics, Vol: 44, Pages: 1-8, ISSN: 1755-4365
The evolution of SARS-CoV-2 has demonstrated that emerging variants can set back the global COVID-19 response. The ability to rapidly assess the threat ofnew variants is critical for timely optimisation of control strategies.We present a novel method to estimate the effective transmission advantage of a new variant compared to a reference variant combining information across multiple locations and over time. Through an extensive simulation study designed to mimic real-time epidemic contexts, we show that our method performs well across a range of scenarios and provide guidance on its optimal useand interpretation of results. We also provide an open-source software implementation of our method. The computational speed of our tool enables users torapidly explore spatial and temporal variations in the estimated transmission advantage.We estimate that the SARS-CoV-2 Alpha variant is 1.46 (95% Credible Interval 1.44-1.47) and 1.29, (95% CrI 1.29-1.30) times more transmissible than the wild type, using data from England and France respectively. We furtherestimate that Delta is 1.77 (95% CrI: 1.69-1.85) times more transmissible than Alpha (England data).Our approach can be used as an important first step towards quantifying the threat of emerging or co-circulating variants of infectious pathogens in real-time.
Nash RK, Bhatt S, Cori A, et al., 2023, Estimating the epidemic reproduction number from temporally aggregated incidence data: A statistical modelling approach and software tool, PLOS COMPUTATIONAL BIOLOGY, Vol: 19, ISSN: 1553-734X
Challenger J, Nash RK, Ngufor C, et al., 2023, Assessing the variability in experimental hut trials evaluating insecticide-treated nets against malaria vectors, Current Research in Parasitology & Vector-Borne Diseases, Vol: 3, Pages: 1-11, ISSN: 2667-114X
Experimental hut trials (EHTs) are used to evaluate indoor vector control interventions against malaria vectors in a controlled setting. The level of variability present in the assay will influence whether a given study is well powered to answer the research question being considered. We utilised disaggregated data from 15 previous EHTs to gain insight into the behaviour typically observed. Using simulations from generalised linear mixed models to obtain power estimates for EHTs, we show how factors such as the number of mosquitoes entering the huts each night and the magnitude of included random effects can influence study power. A wide variation in behaviour is observed in both the mean number of mosquitoes collected per hut per night (ranging from 1.6 to 32.5) and overdispersion in mosquito mortality. This variability in mortality is substantially greater than would be expected by chance and should be included in all statistical analyses to prevent false precision of results. We utilise both superiority and non-inferiority trials to illustrate our methodology, using mosquito mortality as the outcome of interest. The framework allows the measurement error of the assay to be reliably assessed and enables the identification of outlier results which could warrant further investigation. EHTs are increasingly playing an important role in the evaluation and regulation of indoor vector control interventions so it is important to ensure that these studies are adequately powered.
Nash RK, Cori A, Nouvellet P, 2022, Estimating the epidemic reproduction number from temporally aggregated incidence data: a statistical modelling approach and software tool
<jats:sec><jats:title>Background</jats:title><jats:p>The time-varying reproduction number (R<jats:sub>t</jats:sub>) is an important measure of epidemic transmissibility; it can directly inform policy decisions and the optimisation of control measures. EpiEstim is a widely used software tool that uses case incidence and the serial interval (SI, time between symptoms in a case and their infector) to estimate R<jats:sub>t</jats:sub>in real-time. The incidence and the SI distribution must be provided at the same temporal resolution, which limits the applicability of EpiEstim and other similar methods, e.g. for pathogens with a mean SI shorter than the frequency of incidence reporting.</jats:p></jats:sec><jats:sec><jats:title>Methods</jats:title><jats:p>We use an expectation-maximisation algorithm to reconstruct daily incidence from temporally aggregated data, from which R<jats:sub>t</jats:sub>can then be estimated using EpiEstim. We assess the validity of our method using an extensive simulation study and apply it to COVID-19 and influenza data. The method is implemented in the opensource R package EpiEstim.</jats:p></jats:sec><jats:sec><jats:title>Findings</jats:title><jats:p>For all datasets, the influence of intra-weekly variability in reported data was mitigated by using aggregated weekly data. R<jats:sub>t</jats:sub>estimated on weekly sliding windows using incidence reconstructed from weekly data was strongly correlated with estimates from the original daily data. The simulation study revealed that R<jats:sub>t</jats:sub>was well estimated in all scenarios and regardless of the temporal aggregation of the data. In the presence of weekend effects, R<jats:sub>t</jats:sub>estimates from reconstructed data were more successful at recovering the true value of R<jats:sub>t</jats:sub>than those
Nash RK, Nouvellet P, Cori A, 2022, Real-time estimation of the epidemic reproduction number: Scoping review of the applications and challenges, PLOS Digital Health, Vol: 1, Pages: e0000052-e0000052, ISSN: 2767-3170
The time-varying reproduction number (Rt) is an important measure of transmissibility during outbreaks. Estimating whether and how rapidly an outbreak is growing (Rt > 1) or declining (Rt < 1) can inform the design, monitoring and adjustment of control measures in real-time. We use a popular R package for Rt estimation, EpiEstim, as a case study to evaluate the contexts in which Rt estimation methods have been used and identify unmet needs which would enable broader applicability of these methods in real-time. A scoping review, complemented by a small EpiEstim user survey, highlight issues with the current approaches, including the quality of input incidence data, the inability to account for geographical factors, and other methodological issues. We summarise the methods and software developed to tackle the problems identified, but conclude that significant gaps remain which should be addressed to enable easier, more robust and applicable estimation of Rt during epidemics.
Sherrard-Smith E, Winskill P, Hamlet A, et al., 2022, Optimising the deployment of vector control tools against malaria: a data-informed modelling study, The Lancet Planetary Health, Vol: 6, Pages: e100-e109, ISSN: 2542-5196
Background Concern that insecticide resistant mosquitoes are threatening malaria control has driven the development of new types of insecticide treated nets (ITNs) and indoor residual spraying (IRS). Malaria control programmes have a choice of vector control interventions though it is unclear which should be used to combat the disease.MethodsThe entomological impact of ITNs combining a pyrethroid insecticide with the synergist piperonyl butoxide (PBO) is characterised from experimental hut trials and used to parameterise a malaria transmission dynamics model. Model projections are validated for two sites by comparing results to data from pyrethroid-PBO ITN and IRS randomised control trials (RCTs). Models are used to identify optimum intervention packages for scenarios with varying budget, price, entomological and epidemiological factors. Findings Combining entomological data and models can reasonably predict changes in malaria in the Tanzanian and Ugandan RCTs. Models indicate switching from pyrethroid-only to pyrethroid-PBO ITNs could avert up to twice as many cases, though the additional benefit is highly variable and depends upon setting. Annual delivery of long-lasting, non-pyrethroid IRS is projected to prevent substantially more cases over 3-years, but pyrethroid-PBO ITNs tend to be the most cost-effective intervention per case averted. An online tool (MINT) provides users with a method of designing intervention packages given their setting and budget. InterpretationThe most cost-effective vector control package will vary locally. Models able to recreate results of RCTs can be used to extrapolate outcomes elsewhere to support evidence-based decision making for investment in vector control.FundingMedical Research Council, IVCC, Wellcome Trust.
Bhatia S, Wardle J, Nash RK, et al., 2021, A generic method and software to estimate the transmission advantage of pathogen variants in real-time : SARS-CoV-2 as a case-study
<jats:title>Abstract</jats:title><jats:p>Recent months have demonstrated that emerging variants may set back the global COVID-19 response. The ability to rapidly assess the threat of new variants in real-time is critical for timely optimisation of control strategies.</jats:p><jats:p>We extend the EpiEstim R package, designed to estimate the time-varying reproduction number (<jats:italic>R</jats:italic><jats:sub><jats:italic>t</jats:italic></jats:sub>), to estimate in real-time the effective transmission advantage of a new variant compared to a reference variant. Our method can combine information across multiple locations and over time and was validated using an extensive simulation study, designed to mimic a variety of real-time epidemic contexts.</jats:p><jats:p>We estimate that the SARS-CoV-2 Alpha variant is 1.46 (95% Credible Interval 1.44-1.47) and 1.29, (95% CrI 1.29-1.30) times more transmissible than the wild type, using data from England and France respectively. We further estimate that Beta and Gamma combined are 1.25 (95% CrI 1.24-1.27) times more transmissible than the wildtype (France data). All results are in line with previous estimates from literature, but could have been obtained earlier and more easily with our off-the-shelf open-source tool.</jats:p><jats:p>Our tool can be used as an important first step towards quantifying the threat of new variants in real-time. Given the popularity of EpiEstim, this extension will likely be used widely to monitor the co-circulation and/or emergence of multiple variants of infectious pathogens.</jats:p><jats:sec><jats:title>Significance Statement</jats:title><jats:p>Early assessment of the transmissibility of new variants of an infectious pathogen is critical for anticipating their impact and designing appropriate interventions. However, this often requires complex and bespoke analyses relying
Bhatia S, Wardle J, Nash R, et al., 2021, Report 47: A generic method and software to estimate the transmission advantage of pathogen variants in real-time : SARS-CoV-2 as a case-study
Recent months have demonstrated that emerging variants may set back the global COVID-19 response.The ability to rapidly assess the threat of new variants in real-time is critical for timely optimisation ofcontrol strategies.We extend the EpiEstim R package, designed to estimate the time-varying reproduction number (Rt),to estimate in real-time the e ective transmission advantage of a new variant compared to a referencevariant. Our method can combine information across multiple locations and over time and was validatedusing an extensive simulation study, designed to mimic a variety of real-time epidemic contexts.We estimate that the SARS-CoV-2 Alpha variant is 1.46 (95% Credible Interval 1.44-1.47) and 1.29,(95% CrI 1.29-1.30) times more transmissible than the wild type, using data from England and Francerespectively. We further estimate that Beta and Gamma combined are 1.25 (95% CrI 1.24-1.27) timesmore transmissible than the wildtype (France data). All results are in line with previous estimates fromliterature, but could have been obtained earlier and more easily with our o -the-shelf open-source tool.Our tool can be used as an important rst step towards quantifying the threat of new variants inreal-time. Given the popularity of EpiEstim, this extension will likely be used widely to monitor theco-circulation and/or emergence of multiple variants of infectious pathogens.
Nash RK, Lambert B, NGuessan R, et al., 2021, Systematic review of the entomological impact of insecticide-treated nets evaluated using experimental hut trials in Africa, Current Research in Parasitology & Vector-Borne Diseases, Vol: 1, Pages: 1-13, ISSN: 2667-114X
Resistance of anopheline mosquitoes to pyrethroid insecticides is spreading rapidly across sub-Saharan Africa, diminishing the efficacy of insecticide-treated nets (ITNs) – the primary tool for preventing malaria. The entomological efficacy of indoor vector control interventions can be measured in experimental hut trials (EHTs), where hut structures resemble local housing, but allow the collection of mosquitoes that entered, exited, blood-fed and/or died. There is a need to understand how the spread of resistance changes ITN efficacy and to elucidate factors influencing EHT results, including differences in experimental hut design, to support the development of novel vector control tools. A comprehensive database of EHTs was compiled following a systematic review to identify all known trials investigating ITNs or indoor residual spraying across sub-Saharan Africa. This analysis focuses on EHTs investigating ITNs and uses Bayesian statistical models to characterise the complex interaction between ITNs and mosquitoes, the between-study variability, and the impact of pyrethroid resistance. As resistance rises, the entomological efficacy of ITNs declines. They induce less mortality and are less likely to deter mosquitoes from entering huts. Despite this, ITNs continue to offer considerable personal protection by reducing mosquito feeding until resistance reaches high levels. There are clear associations between the different entomological impacts of ITNs, though there is still substantial variability between studies, some of which can be accounted for by hut design. The relationship between EHT outcomes and the level of resistance (as measured by discriminating dose bioassays) is highly uncertain. The meta-analyses show that EHTs are an important reproducible assay for capturing the complex entomological efficacy of ITNs on blood-feeding mosquitoes. The impact of pyrethroid resistance on these measures appears broadly consistent across a wide geographical area onc
Okell L, Whittaker C, Ghani A, et al., 2021, Global patterns of submicroscopic Plasmodium falciparum malaria infection: insights from a systematic review and meta-analysis of population surveys, The Lancet Microbe, Vol: 2, Pages: e366-e374, ISSN: 2666-5247
Background: Adoption of molecular techniques to detect Plasmodium falciparum infection has revealed many previously undetected (by microscopy) yet transmissible low-density infections. The proportion of these infections is typically highest in low transmission settings, but drivers of submicroscopic infection remain unclear. Here, we update a previously conducted systematic review of asexual P. falciparum prevalence by microscopy and polymerase chain reaction (PCR) in the same population. We conduct a meta-analysis to explore potential drivers of submicroscopic infection and identify the locations where submicroscopic infections are most common. Methods: PubMed and Web of Science databases were searched up to 11th October 2020 for cross-sectional studies reporting data on asexual P.falciparum prevalence by both microscopy and PCR. Surveys of pregnant women, where participants had been chosen based on symptoms/treatment or that did not involve a population from a defined location were excluded. Both the number of individuals tested and positive by microscopy and PCR for P. falciparum infection were extracted from each reference. Bayesian regression modelling was used to explore determinants of the size of the submicroscopic reservoir including geography, seasonality, age, methodology and current/historical patterns of transmission.Findings: A total of 166 references containing 551 cross-sectional survey microscopy/PCR prevalence pairs were included. Our results highlight that submicroscopic infections predominate in low transmission settings across all settings, but also reveal marked geographical variation, with the proportion of infections that are submicroscopic being highest in South American surveys and lowest in West African studies. Whilst current transmission levels partly explain these results, we find that historical transmission intensity also represents a crucial determinant of the size of the submicroscopic reservoir, as does the demographic structure of
Nash RK, Lambert B, NGuessan R, et al., 2021, Systematic review of the entomological impact of insecticide-treated nets evaluated using experimental hut trials in Africa
<jats:title>Abstract</jats:title><jats:sec><jats:title>Background</jats:title><jats:p>Resistance of anopheline mosquitoes to pyrethroid insecticides is spreading rapidly across sub-Saharan Africa, diminishing the efficacy of insecticide-treated nets (ITNs) — the primary tool for preventing malaria. The entomological efficacy of indoor vector control interventions can be measured in experimental hut trials (EHTs), which are specially designed to quantify the protection provided under controlled conditions. Experimental hut structures resemble local housing but allow collection of surviving exiting mosquitoes as well as dead or dying mosquitoes. There is a need to understand how the spread of resistance changes ITN efficacy and to elucidate factors influencing EHT results, including differences in experimental hut construction and design features, to support the development of novel vector control tools.</jats:p></jats:sec><jats:sec><jats:title>Methods</jats:title><jats:p>A comprehensive database of EHTs was compiled and summarised following a systematic review to identify all known trials investigating ITNs or indoor residual spraying (IRS) across sub-Saharan Africa. This analysis focuses on EHTs investigating ITNs and uses Bayesian statistical models to characterise the complex interaction between ITNs and mosquitoes, the variability between studies, and the impact of pyrethroid resistance.</jats:p></jats:sec><jats:sec><jats:title>Results</jats:title><jats:p>As resistance rises, the entomological efficacy of ITNs declines. They induce less mortality and are less likely to deter mosquitoes from entering huts. Despite this, ITNs continue to offer considerable personal protection by reducing mosquito feeding until resistance reaches high levels. There are clear associations between the different entomological impacts of ITNs, though there is still substanti
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