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Background: Sulfadoxine-pyrimethamine (SP) is recommended in Africa in several antimalarial preventive regimens including Intermittent Preventive Treatment in pregnant women (IPTp), Intermittent Preventive Treatment in infants (IPTi) and Seasonal Malaria Chemoprevention (SMC). The effectiveness of SP-based preventive treatments are threatened in areas where Plasmodium falciparum resistance to SP is high. The prevalence of mutations in the dihydropteroate synthase gene (pfdhps) can be used to monitor SP effectiveness. IPTi-SP is recommended only in areas where the prevalence of the pfdhps540E mutation is below 50%. It has also been suggested that IPTp-SP does not have a protective effect in areas where the pfdhps581G mutation, exceeds 10%. However, pfdhps mutation prevalence data in Africa are extremely heterogenous and scattered, with data completely missing from many areas. Methods and findings: The WWARN SP Molecular Surveyor database was designed to summarize dihydrofolate reductase (pfdhfr) and pfdhps gene mutation prevalence data. In this paper, pfdhps mutation prevalence data was used to generate continuous spatiotemporal surface maps of the estimated prevalence of the SP resistance markers pfdhps437G, pfdhps540E, and pfdhps581G in Africa from 1990 to 2020 using a geostatistical model, with a Bayesian inference framework to estimate uncertainty. The maps of estimated prevalence show an expansion of the pfdhps437G mutations across the entire continent over the last three decades. The pfdhps540E mutation emerged from limited foci in East Africa to currently exceeding 50% estimated prevalence in most of East and South East Africa. pfdhps540E distribution is expanding at low or moderate prevalence in central Africa and a predicted focus in West Africa. Although the pfdhps581G mutation spread from one focus in East Africa in 2000, to exceeding 10% estimated prevalence in several foci in 2010, the predicted distribution of the marker did not expand in 2020, however our analysis indicated high uncertainty in areas where pfdhps581G is present. Uncertainty was higher in spatial regions where the prevalence of a marker is intermediate or where prevalence is changing over time. Conclusions: The WWARN SP Molecular Surveyor database and a set of continuous spatiotemporal surface maps were built to provide users with standardized, current information on resistance marker distribution and prevalence estimates. According to the maps, the high prevalence of pfdhps540E mutation was to date restricted to East and South East Africa, which is reassuring for continued use of IPTi and SMC in West Africa, but continuous monitoring is needed as the pfdhps540E distribution is expanding. Several foci where pfdhps581G prevalence exceeded 10% were identified. More data on the pfdhps581G distribution in these areas needs to be collected to guide IPTp-SP recommendations. Prevalence and uncertainty maps can be utilized together to strategically identify sites where increased surveillance can be most informative. This study combines a molecular marker database and predictive modelling to highlight areas of concern, which can be used to support decisions in public health, highlight knowledge gaps in certain regions, and guide future research. Author summary: Despite great success in reducing death and illness from malaria over the last 20 years, the disease is still one of the main leading causes of death in low-income countries with estimated 229 million cases and 409,000 deaths annually. One of the main obstacles in malaria control is the development and spread of drug resistance. Several intermittent preventive treatments depend on the efficacy of the antimalarial drug sulfadoxine-pyrimethamine (SP); Intermittent Preventive Treatment in pregnant women (IPTp), Intermittent Preventive Treatment in infants (IPTi) and Seasonal Malaria Chemoprevention (SMC). Mutations in the dihydropteroate synthase gene (pfdhps) can cause resistance to SP treatment. In this paper, we use pfdhps mutation prevalence data to generate continuous spatiotemporal surface maps of the estimated prevalence of the SP resistance markers in Africa from 1990 to 2020 using a Bayesian geostatistical model. These predictive maps provide much needed insight about where SP can be used as part of preventive treatments. Spatial information on the spread of antimalarial resistance is critical for health organizations to prioritize surveillance measures, and plan control and elimination efforts. [ABSTRACT FROM AUTHOR]

In recent years there has been growing availability of individual-level spatio-temporal disease data, particularly due to the use of modern communicating devices with GPS tracking functionality. These detailed data have been proven useful for inferring disease transmission to a more refined level than previously. However, there remains a lack of statistically sound frameworks to model the underlying transmission dynamic in a mechanistic manner. Such a development is particularly crucial for enabling a general epidemic predictive framework at the individual level. In this paper we propose a new statistical framework for mechanistically modelling individual-to-individual disease transmission in a landscape with heterogeneous population density. Our methodology is first tested using simulated datasets, validating our inferential machinery. The methodology is subsequently applied to data that describes a regional Ebola outbreak in Western Africa (2014-2015). Our results show that the methods are able to obtain estimates of key epidemiological parameters that are broadly consistent with the literature, while revealing a significantly shorter distance of transmission. More importantly, in contrast to existing approaches, we are able to perform a more general model prediction that takes into account the susceptible population. Finally, our results show that, given reasonable scenarios, the framework can be an effective surrogate for susceptible-explicit individual models which are often computationally challenging. [ABSTRACT FROM AUTHOR]

Birth-death models play a key role in phylodynamic analysis for their interpretation in terms of key epidemiological parameters. In particular, models with piecewise-constant rates varying at different epochs in time, to which we refer as episodic birth-death-sampling (EBDS) models, are valuable for their reflection of changing transmission dynamics over time. A challenge, however, that persists with current time-varying model inference procedures is their lack of computational efficiency. This limitation hinders the full utilization of these models in large-scale phylodynamic analyses, especially when dealing with high-dimensional parameter vectors that exhibit strong correlations. We present here a linear-time algorithm to compute the gradient of the birth-death model sampling density with respect to all time-varying parameters, and we implement this algorithm within a gradient-based Hamiltonian Monte Carlo (HMC) sampler to alleviate the computational burden of conducting inference under a wide variety of structures of, as well as priors for, EBDS processes. We assess this approach using three different real world data examples, including the HIV epidemic in Odesa, Ukraine, seasonal influenza A/H3N2 virus dynamics in New York state, America, and Ebola outbreak in West Africa. HMC sampling exhibits a substantial efficiency boost, delivering a 10- to 200-fold increase in minimum effective sample size per unit-time, in comparison to a Metropolis-Hastings-based approach. Additionally, we show the robustness of our implementation in both allowing for flexible prior choices and in modeling the transmission dynamics of various pathogens by accurately capturing the changing trend of viral effective reproductive number. Author summary: Epidemic control and forecasting relies on accurate quantification of transmission and recovery dynamics. This quantification is achievable through the analysis of phylogenetic relationships among pathogen strains obtained from infected individuals. As a key analytical tool for such inference, we concentrate on the study of the episodic birth-death-sampling (EBDS) models. These models define a probability distribution on time-calibrated phylogenies that enable estimation of time-varying rates of pathogens' transmission, recovery, and sampling. Advances in sequencing technology, however, have led to an increasing amount of genetic data collected from these pathogens. Consequently, the traditional computational methods for analyzing these large-scale data under EBDS models have become inadequate due to their high computational load. We aimed to break this computational bottleneck by developing a new approach, based on the Hamiltonian Monte Carlo sampling, that considerably accelerates inference of all rate parameters compared to the traditional random-walk Metropolis-Hasting method. Our method greatly improves the ability to explore the complex distributions that arise when we want to understand disease dynamics at a more granular temporal resolution. This advancement delivers value to public health as it helps rapid data-driven decision-making during outbreaks and enhances our understanding of the spread of infectious diseases. [ABSTRACT FROM AUTHOR]

Coalescent theory combined with statistical modeling allows us to estimate effective population size fluctuations from molecular sequences of individuals sampled from a population of interest. When sequences are sampled serially through time and the distribution of the sampling times depends on the effective population size, explicit statistical modeling of sampling times improves population size estimation. Previous work assumed that the genealogy relating sampled sequences is known and modeled sampling times as an inhomogeneous Poisson process with log-intensity equal to a linear function of the log-transformed effective population size. We improve this approach in two ways. First, we extend the method to allow for joint Bayesian estimation of the genealogy, effective population size trajectory, and other model parameters. Next, we improve the sampling time model by incorporating additional sources of information in the form of time-varying covariates. We validate our new modeling framework using a simulation study and apply our new methodology to analyses of population dynamics of seasonal influenza and to the recent Ebola virus outbreak in West Africa. Author summary: Estimating changes in the number of individuals in a given population is a challenging problem in some settings. For example, estimating population size trajectories of the number of people infected by a pathogen (e.g., Influenza virus) is a difficult problem, because many infections in a large population remain unobserved/hidden. One indirect way of assessing population size changes is to take a sample of individuals from the population of interest and analyze genetic sequences from these individuals (e.g., Influenza virus genomes). Intuitively, genetic data is informative about population size changes, because genetic diversity increases/decreases together with the population size. However, if we sample more individuals when the population size increases and less when it decreases, this strategy produces biased results. To avoid this bias, we propose a method that explicitly and flexibly models potential dependency of genetic sequence sampling on the population size. An added bonus of this new modeling framework is more precise estimation of population size changes. We demonstrate strengths of our new methodology on simulated data and on genetic sequences of Influenza and Ebola viruses. [ABSTRACT FROM AUTHOR]

Cassava brown streak disease (CBSD) is a rapidly spreading viral disease that affects a major food security crop in sub-Saharan Africa. Currently, there are several proposed management interventions to minimize loss in infected fields. Field-scale data comparing the effectiveness of these interventions individually and in combination are limited and expensive to collect. Using a stochastic epidemiological model for the spread and management of CBSD in individual fields, we simulate the effectiveness of a range of management interventions. Specifically we compare the removal of diseased plants by roguing, preferential selection of planting material, deployment of virus-free 'clean seed' and pesticide on crop yield and disease status of individual fields with varying levels of whitefly density crops under low and high disease pressure. We examine management interventions for sustainable production of planting material in clean seed systems and how to improve survey protocols to identify the presence of CBSD in a field or quantify the within-field prevalence of CBSD. We also propose guidelines for practical, actionable recommendations for the deployment of management strategies in regions of sub-Saharan Africa under different disease and whitefly pressure. Author summary: Cassava is the second largest source of calories in sub-Saharan Africa and is particularly important for the poorest farmers in the region. Cassava brown streak disease is a viral disease that causes cassava tubers to rot, rendering the roots inedible. Recently, the disease has begun to spread towards major cassava growing regions in West Africa from East Africa, where it continues to cause significant yield losses. Improved approaches for disease control are needed to enable small-holder farmers to prepare for and minimize the impact of the disease when their fields become infected. Using a combination of computational methods and mathematical models enables us to screen a much larger range of potential treatments for their likely effectiveness in managing disease and reducing crop loss than would be possible in conventional field trials, which are expensive and logistically difficult to conduct. Our results indicate that regularly planting part of the field with virus-free cassava greatly improves the yield. Removing visibly infected plants and replanting using visibly uninfected plants also improves yield, even when some of these plants may be infected but not yet showing symptoms. We also show how the survey protocol can be optimized to improve estimates of disease severity leading to more effective tailored advice to farmers in regions with different disease pressures. [ABSTRACT FROM AUTHOR]