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Durrant, R.

Publications and source records attributed to Durrant, R..

6 recordsLinked to original sources

One Health genomic surveillance reveals structured urban rabies transmission and major surveillance gaps

Persistent local foci remain a barrier to eliminating dog-mediated rabies. The processes sustaining micro-scale transmission, particularly in complex urban systems, remain poorly understood. We apply an integrated One Health genomic epidemiology framework to reconstruct a decade-long rabies virus (RABV) epidemic in Arequipa, Peru. Combining 133 new whole genomes with existing data, we produce the most comprehensive canine RABV dataset in Latin America and use whole-genome-informed phylogenetic, phylodynamic, and landscape analyses, to trace the epidemic from its first detection in 2015. Transmission was dominated by a single lineage estimated to be introduced around 2012, which spread for approximately 3 years before detection. We find that only 1-2% of infections are routinely detected, revealing extensive cryptic transmission and undermining case-based metrics for verifying disease freedom. Additional regional and transboundary introductions were detected, but only one resulted in sustained transmission. Within Arequipa city, transmission is highly structured, concentrated in densely populated and socioeconomically deprived areas, and shaped by urban connectivity, with roads and dry water channels facilitating spread and rivers acting as partial barriers. Together, our findings demonstrate that rabies persistence reflects interacting processes across spatial scales and support genomic-informed, spatially targeted surveillance and control strategies.

evolutionary biology↗

A simple method of estimating rabies outbreak sizes from phylogenies

The ability to estimate the size of a disease outbreak is beneficial both for coordinating an outbreak response and for retrospectively evaluating the effectiveness of response measures and surveillance. Methods such as seroprevalence surveys and epidemiological modelling can be used for this purpose, but are not suitable for every outbreak. We develop a simple formula to estimate the proportion of outbreak cases sequenced, using only the per-generation substitution rate and the length of a phylogenetic tree. This proportion can then be used to estimate the outbreak size. We validate this method using subsampled data from fully observed simulated outbreaks, and then apply it to an ongoing rabies outbreak in the Philippines. We find that this method produces accurate estimates of outbreak size and can be applied to outbreaks with substitution rates and R0 values within the estimated range for rabies. We estimated that approximately 19% of cases from the outbreak in the Philippines had been sequenced, suggesting better than average case detection, with a resulting outbreak size estimate consistent with previous analyses. With this method and the associated R package POSER (https://github.com/RowanDurrant/poser), we aim to make rabies outbreak size estimation more accessible, but further work is required to improve its applicability to other diseases.

genetics↗

Differences in codon usage between host-species-specific rabies virus clades are driven by UpA and purine content

Viral genes sometimes use certain codons more than others due to their nucleotide content, translational efficiency, and selection pressure from the host immune system. The rabies virus (RABV) is a negative strand RNA virus which can infect a broad range of mammalian hosts, with many of its clades circulating predominantly in specific host species. Previous work on codon usage in RABV has focused only on broader viral clades. We use publicly available RABV nucleoprotein gene sequences to investigate how dinucleotide content and codon usage biases differ between host-associated clades, and what drives these differences. We found that codon usage varies most between bat- and carnivore-associated RABV clades, and more subtly between host-species-specific minor clades within these groups. C1, GA3 and GT3 content were found to have a strong influence over codon usage patterns, and CpG content was higher in carnivore-associated RABV clades than in bat-associated clades. This, along with lower numbers of zinc-finger antiviral protein binding motifs than would be expected based on (di)nucleotide composition in bat-associated RABV sequences, suggests that bat-associated RABV clades may be under higher selection pressure from the hosts zinc-finger antiviral protein than carnivore-associated clades are, warranting further investigation of the mechanism underpinning this change.

microbiology↗

Examining the molecular clock hypothesis for the contemporary evolution of the rabies virus

The molecular clock hypothesis assumes that mutations accumulate on an organisms genome at a constant rate over time, but this assumption does not always hold true. While modelling approaches exist to accommodate deviations from a strict molecular clock, assumptions about rate variation may not fully represent the underlying evolutionary processes. There is considerable variability in rabies virus (RABV) incubation periods, ranging from days to over a year, during which viral replication may be reduced. This prompts the question of whether modelling RABV on a per infection generation basis might be more appropriate. We investigate how variable incubation periods affect root-to-tip divergence under per-unit time and per-generation models of mutation. Additionally, we assess how well these models represent root-to-tip divergence in time-stamped RABV sequences. We find that at low substitution rates (<1 substitution per genome per generation) divergence patterns between these models are difficult to distinguish, while above this threshold differences become apparent across a range of sampling rates. Using a Tanzanian RABV dataset, we calculate the mean substitution rate to be 0.17 substitutions per genome per generation. At RABVs substitution rate, the per-generation substitution model is unlikely to represent rabies evolution substantially differently than the molecular clock model when examining contemporary outbreaks; over enough generations for any divergence to accumulate, extreme incubation periods average out. However, measuring substitution rates per-generation holds potential in applications such as inferring transmission trees and predicting lineage emergence. Author SummaryRabies is a neglected disease that kills around 60,000 people each year. After entering the body, the incubation period of the virus is usually less than one month, but can sometimes span months to years. While we normally assume a virus accumulates mutations at a constant rate, it is possible that rabies occasional long incubation periods mean that mutations accumulate at varying rates if the virus replicates (and thus mutates) more slowly during the incubation period. We compared how the rabies virus evolves over time using two simulation models where mutations either occur per unit time or per infection generation. We also calculated the mean substitution rate per infection generation, which can be useful for inferring linkage between related rabies cases. We found that at realistic substitution rates for the rabies virus, we could not distinguish between the two models. Our calculations show that in most generations no mutations are expected to occur. Thus, over a time period long enough to observe genetic divergence, occasional long incubation periods would be "cancelled out" by shorter than average incubation periods, meaning that the two models are almost equivalent. However our work suggests that modelling substitution rates per generation may be useful for epidemiological inference.

microbiology↗

Disruption of metapopulation structure effectively reduces Tasmanian devil facial tumour disease spread at the expense of abundance and genetic diversity

Metapopulation structure (i.e. the spatial arrangement of local populations and corridors between them) plays a fundamental role in the persistence of wildlife populations, but can also drive the spread of infectious diseases. While the disruption of metapopulation connectivity can reduce disease spread, it can also impair host resilience by disrupting gene flow and colonisation dynamics. Thus, a pressing challenge for many wildlife populations is to elucidate whether the benefits of disease management methods that reduce metapopulation connectivity outweigh the associated risks. Directly transmissible cancers are clonal malignant cell lines capable to spread through host populations without immune recognition, when susceptible and infected hosts become in close contact. Using an individual-based metapopulation model we investigate the effects of the interplay between host dispersal, disease transmission rate and inter-individual contact distance for transmission (determining within-population mixing) on the spread and persistence of a transmissible cancer, Tasmanian devil facial tumour disease (DFTD), from local to regional scales. Further, we explore population isolation scenarios to devise management strategies to mitigate disease spread. Disease spread, and the ensuing population declines, are synergistically determined by individuals dispersal, disease transmission rate and within-population mixing. Low to intermediate transmission rates can be magnified by high dispersal and inter-individual transmission distance. Once disease transmission rate is high, dispersal and inter-individual contact distance do not impact the outcome of the disease transmission dynamics. Isolation of local populations effectively reduced metapopulation-level disease prevalence but caused severe declines in metapopulation size and genetic diversity. The relative position of managed (i.e. isolated) populations within the metapopulation had a significant effect on disease prevalence, highlighting the importance of considering metapopulation structure when implementing metapopulation-scale disease control measures. Our findings suggests that population isolation is not an ideal management method for preventing disease spread in species inhabiting already fragmented landscapes, where genetic diversity and extinction risk are already a concern, such as the Tasmanian devil.

ecology↗

Microbiome and Antimicrobial Resistance Gene Dynamics in International Travelers

We engaged metagenomic next generation sequencing to longitudinally assess the gut microbiota and antimicrobial resistomes of international travelers to understand global exchange of resistant organisms. Travel resulted in an increase in antimicrobial resistance genes and a greater proportion of Escherichia species within gut microbial communities without impacting diversity.

microbiology↗