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Significance Methods for analyzing individual-level geo-located disease data have existed for some time, but have rarely been used to analyze endemic human diseases. Here we apply such methods to nearly a decade’s worth of uniquely detailed epidemiological data on incidence of the deadly vector-borne disease visceral leishmaniasis (VL) and its secondary condition, post–kala-azar dermal leishmaniasis (PKDL), to quantify the spread of infection around cases in space and time by inferring who infected whom, and estimate the relative contribution of different infection states to transmission. Our findings highlight the key role long diagnosis delays and PKDL play in maintaining VL transmission. This detailed characterization of the spatiotemporal transmission of VL will help inform targeting of interventions around VL and PKDL cases., Understanding of spatiotemporal transmission of infectious diseases has improved significantly in recent years. Advances in Bayesian inference methods for individual-level geo-located epidemiological data have enabled reconstruction of transmission trees and quantification of disease spread in space and time, while accounting for uncertainty in missing data. However, these methods have rarely been applied to endemic diseases or ones in which asymptomatic infection plays a role, for which additional estimation methods are required. Here, we develop such methods to analyze longitudinal incidence data on visceral leishmaniasis (VL) and its sequela, post–kala-azar dermal leishmaniasis (PKDL), in a highly endemic community in Bangladesh. Incorporating recent data on VL and PKDL infectiousness, we show that while VL cases drive transmission when incidence is high, the contribution of PKDL increases significantly as VL incidence declines (reaching 55% in this setting). Transmission is highly focal: 85% of mean distances from inferred infectors to their secondary VL cases were

The World Health Organization recently launched its 2021-2030 roadmap, Ending the Neglect to Attain the Sustainable Development Goals, an updated call to arms to end the suffering caused by neglected tropical diseases. Modelling and quantitative analyses played a significant role in forming these latest goals. In this collection, we discuss the insights, the resulting recommendations and identified challenges of public health modelling for 13 of the target diseases: Chagas disease, dengue, gambiense human African trypanosomiasis (gHAT), lymphatic filariasis (LF), onchocerciasis, rabies, scabies, schistosomiasis, soil-transmitted helminthiases (STH), Taenia solium taeniasis/ cysticercosis, trachoma, visceral leishmaniasis (VL) and yaws. This piece reflects the three cross-cutting themes identified across the collection, regarding the contribution that modelling can make to timelines, programme design, drug development and clinical trials.

The World Health Organization recently launched its 2021-2030 roadmap, Ending the Neglect to Attain the Sustainable Development Goals, an updated call to arms to end the suffering caused by neglected tropical diseases. Modelling and quantitative analyses played a significant role in forming these latest goals. In this collection, we discuss the insights, the resulting recommendations and identified challenges of public health modelling for 13 of the target diseases: Chagas disease, dengue, gambiense human African trypanosomiasis (gHAT), lymphatic filariasis (LF), onchocerciasis, rabies, scabies, schistosomiasis, soil-transmitted helminthiases (STH), Taenia solium taeniasis/ cysticercosis, trachoma, visceral leishmaniasis (VL) and yaws. This piece reflects the three cross-cutting themes identified across the collection, regarding the contribution that modelling can make to timelines, programme design, drug development and clinical trials.

The dynamics of immunity are crucial to understanding the long-term patterns of the SARS-CoV-2 pandemic. Several cases of reinfection with SARS-CoV-2 have been documented 48–142 days after the initial infection and immunity to seasonal circulating coronaviruses is estimated to be shorter than 1 year. Using an age-structured, deterministic model, we explore potential immunity dynamics using contact data from the UK population. In the scenario where immunity to SARS-CoV-2 lasts an average of three months for non-hospitalized individuals, a year for hospitalized individuals, and the effective reproduction number after lockdown ends is 1.2 (our worst-case scenario), we find that the secondary peak occurs in winter 2020 with a daily maximum of 387 000 infectious individuals and 125 000 daily new cases; threefold greater than in a scenario with permanent immunity. Our models suggest that longitudinal serological surveys to determine if immunity in the population is waning will be most informative when sampling takes place from the end of the lockdown in June until autumn 2020. After this period, the proportion of the population with antibodies to SARS-CoV-2 is expected to increase due to the secondary wave. Overall, our analysis presents considerations for policy makers on the longer-term dynamics of SARS-CoV-2 in the UK and suggests that strategies designed to achieve herd immunity may lead to repeated waves of infection as immunity to reinfection is not permanent. This article is part of the theme issue ‘Modelling that shaped the early COVID-19 pandemic response in the UK’.

Visceral leishmaniasis (VL) is declining in India and the World Health Organization's (WHO) 2020 'elimination as a public health problem' target has nearly been achieved. Intensified combined interventions might help reach elimination, but their impact has not been assessed. WHO's Neglected Tropical Diseases 2021-2030 roadmap provides an opportunity to revisit VL control strategies. We estimated the combined effect of a district-wide pilot of intensified interventions in the highly-endemic Vaishali district, where cases fell from 3,598 in 2012-2014 to 762 in 2015-2017. The intensified control approach comprised indoor residual spraying with improved supervision; VL-specific training for accredited social health activists to reduce onset-to-diagnosis time; and increased Information Education & Communication activities in the community. We compared the rate of incidence decrease in Vaishali to other districts in Bihar state via an interrupted time series analysis with a spatiotemporal model informed by previous VL epidemiological estimates. Changes in Vaishali's rank among Bihar's endemic districts in terms of monthly incidence showed a change pre-pilot (3rd highest out of 33 reporting districts) vs. during the pilot (9th) (p

Highlights • Unit testing can reduce the number of bugs in code but is rarely used in our field. • We present a worked example of adding unit tests to a computational model. • Specific issues such as stochastic code are common in infectious disease modelling. • Unit testing can handle particular quirks of infectious disease models. • We hope to increase the use of unit testing in infectious disease epidemiology., Infectious disease epidemiology is increasingly reliant on large-scale computation and inference. Models have guided health policy for epidemics including COVID-19 and Ebola and endemic diseases including malaria and tuberculosis. Yet a coding bug may bias results, yielding incorrect conclusions and actions causing avoidable harm. We are ethically obliged to make our code as free of error as possible. Unit testing is a coding method to avoid such bugs, but it is rarely used in epidemiology. We demonstrate how unit testing can handle the particular quirks of infectious disease models and aim to increase uptake of this methodology in our field.

Emerging evidence suggests that contact tracing has had limited success in the UK in reducing the R number across the COVID-19 pandemic. We investigate potential pitfalls and areas for improvement by extending an existing branching process contact tracing model, adding diagnostic testing and refining parameter estimates. Our results demonstrate that reporting and adherence are the most important predictors of programme impact but tracing coverage and speed plus diagnostic sensitivity also play an important role. We conclude that well-implemented contact tracing could bring small but potentially important benefits to controlling and preventing outbreaks, providing up to a 15% reduction in R, and reaffirm that contact tracing is not currently appropriate as the sole control measure.

The tau statisticτ uses geolocation and, usually, symptom onset time to assess global spatiotemporal clustering from epidemiological data. We test different methods that could bias the clustering range estimate based on the statistic or affect its apparent precision, by comparison with a baseline analysis of an open access measles dataset. From re-analysing this data we find evidence against no clustering and no inhibition, p-value∈[0,0⋅022] (global envelope test). We develop a tau-specific modification of the Loh & Stein spatial bootstrap sampling method, which gives bootstrap tau estimates with 24% lower sampling error and a 110% higher estimated clustering endpoint than previously published (61⋅0 m vs. 29 m) and an equivalent increase in the clustering area of elevated disease odds by 342%. These differences could have important consequences for control efforts. Correct practice of graphical hypothesis testing of no clustering and clustering range estimation of the tau statistic are illustrated in the online Graphical abstract. We advocate proper implementation of this useful statistic, ultimately to reduce inaccuracies in control policy decisions made during disease clustering analysis., Graphical abstract, Highlights • Point estimation methods can heavily bias disease clustering range estimates. • A 110% radial clustering bias is amplified to 342% on an areal intervention scale. • A modified Loh & Stein spatial bootstrap loses less unique pair information. • Clustering endpoint estimates appear more precise using this modified bootstrap. • BCa CIs not percentile CIs are preferred for asymmetric bootstrap distributions.

Background: Visceral leishmaniasis (VL) is declining in India, but still persists in disadvantaged communities despite WHO's 2020 'elimination as a public health problem' target. Combined interventions might achieve elimination if we knew their impact. Furthermore WHO's forthcoming NTD road map has opened a policy window for strategy change for 2021-2030. We estimated the combined effect from a district-wide pilot of intensified interventions in the highly endemic Vaishali district, where cases fell from 3,598 in 2012-2014 to 708 in 2015-2017. Methods: The intensified control approach comprised indoor residual spraying with improved supervision; VL-specific training for Accredited Social Health Activists to reduce onset-to-diagnosis time; and increased Information Education and Communication activities in the community. We compared the rate of incidence decrease in Vaishali to other districts in Bihar via an interrupted time series analysis with a spatiotemporal model, and estimated the number of cases averted by the pilot. Findings: Changes in Vaishali's rank among Bihar's endemic districts in terms of monthly case numbers showed a change pre-pilot (3rd highest out of 33 reporting districts) versus during the pilot (9th) (p

BACKGROUND: Between August and November 2014, the incidence of Ebola virus disease (EVD) rose dramatically in several districts of Sierra Leone. As a result, the number of cases exceeded the capacity of Ebola holding and treatment centres. During December, additional beds were introduced, and incidence declined in many areas. We aimed to measure patterns of transmission in different regions, and evaluate whether bed capacity is now sufficient to meet future demand. METHODS: We used a mathematical model of EVD infection to estimate how the extent of transmission in the nine worst affected districts of Sierra Leone changed between 10th August 2014 and 18th January 2015. Using the model, we forecast the number of cases that could occur until the end of March 2015, and compared bed requirements with expected future capacity. RESULTS: We found that the reproduction number, R, defined as the average number of secondary cases generated by a typical infectious individual, declined between August and December in all districts. We estimated that R was near the crucial control threshold value of 1 in December. We further estimated that bed capacity has lagged behind demand between August and December for most districts, but as a consequence of the decline in transmission, control measures caught up with the epidemic in early 2015. CONCLUSIONS: EVD incidence has exhibited substantial temporal and geographical variation in Sierra Leone, but our results suggest that the epidemic may have now peaked in Sierra Leone, and that current bed capacity appears to be sufficient to keep the epidemic under-control in most districts.