Biology subjects

Hampson, K.

Publications and source records attributed to Hampson, K..

16 recordsLinked to original sources

bioRxiv2026

Lateral flow devices can fast-track rabies virus genomic surveillance

Viral genomic data can resolve rabies transmission and guide outbreak response, but surveillance is often limited less by sequencing capacity than by getting suitable specimens from remote collection sites to a laboratory, a process that can take months. Here, we show that lateral flow devices (LFDs) used for rabies diagnosis can also serve as genomic specimens, integrating diagnosis and genomic sampling into a single workflow without additional specimen collection. We evaluated LFDs and FTA cards for rabies virus genome recovery under laboratory and field conditions. During surveillance across the island provinces of MIMAROPA, Philippines, the Bionote LFD had 99.1% sensitivity and 100% specificity against the gold-standard direct fluorescent antibody test (n = 319), with results available a median of 1 day after sampling versus 5 days for DFAT confirmation. Under laboratory conditions simulating field storage (ambient temperature or 37 degrees Celsius for up to 21 days), both residual LFD material and FTA cards supported near-complete genome sequencing, although genome recovery declined with storage duration, particularly at elevated temperatures. Consistent with this, field-collected LFDs yielded near-complete genomes up to 23 days of ambient storage but only partial genomes after 29-77 days, indicating a practical window of around three weeks for use. Repurposing LFDs already embedded in diagnostic workflows offers a practical route to decentralised genomic surveillance without additional sample collection or a cold chain. FTA cards provide a complementary preservation option, while further optimisation of specimen preparation, extraction and storage could improve genome recovery and extend the sequencing window.

molecular biology↗

bioRxiv2026

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↗

bioRxiv2026

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↗

bioRxiv2026

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↗

bioRxiv2024

A randomized controlled trial of the effectiveness of a community-based rabies vaccination strategy

BackgroundApproximately 60,000 people die from dog-mediated rabies annually. Low and heterogeneous coverage reduces the effectiveness of dog vaccination campaigns that can eliminate rabies. Campaigns typically involve teams travelling annually to villages to deliver cold chain stored vaccines from centralized headquarters. Thermotolerant vaccines enable novel decentralized delivery of locally-stored vaccines by communities throughout the year. We compared the effectiveness of annual team-based versus continuous community-based dog vaccination strategies. MethodsWe conducted a cluster randomized controlled trial across Mara region, Tanzania. Trial clusters were administrative wards (112, on average four villages each). For the team-based arm vaccinators hosted annual static-point clinics, whilst for the community-based arm, a ward-based animal health officer with a village community leader managed vaccinations using vaccines stored within the ward. We measured vaccination coverage, the primary outcome, twice annually per cluster (month 1 and 11) through household surveys over three years (November 2020 to October 2023) and examined spatial and temporal coverage variations as secondary outcomes. FindingsCommunity-based delivery achieved significantly higher coverage (49-62%) than team-based delivery (22-46%), and consistently exceeded the critical threshold for herd immunity (40%), Odds ratio (OR): 1.48-3.49. The lower less uniform coverage achieved through team-based delivery had a higher monthly probability of falling below the critical threshold (0.6, 95% CI: 0.38-0.81) vs 0.18 (95% CI: 0.04-0.40). Greater declines in coverage over the year were recorded in the team-based arm compared to the community-based ConclusionCommunity-based mass dog vaccination achieves higher more consistent coverage than team-based delivery across settings typical of many sub-Saharan African countries. This approach could play an important role in national rabies elimination programmes aiming to end human rabies deaths by 2030 as part of the global zero by 30 strategy. FundingDepartment of Health and Human Services of the National Institutes of Health (R01AI141712), Wellcome Trust (207569/Z/17/Z, 224520/Z/21/Z) and MSD Animal Health. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.

immunology↗

bioRxiv2024

Reducing spatial heterogeneity in coverage improves the effectiveness of dog vaccination against rabies

Vaccination programs are the mainstay of control for many infectious diseases. Heterogeneous coverage is hypothesised to reduce vaccination programme effectiveness, but this impact has not been quantified in real systems. We address this gap using fine-scale data from two decades of rabies contact tracing and dog vaccination campaigns in Serengeti district, Tanzania. We also aimed to identify drivers of continued circulation of rabies in the district despite annual vaccination campaigns. Using generalised linear mixed models, we find that current focal (village-level) dog rabies incidence decreases with increasing recent focal vaccination coverage. However, current focal incidence depends most on recent incidence, both focally and in the wider district, consistent with high population connectivity. Removing the masking effects of prior non-focal incidence shows that, for the same average prior non-focal (wider-district) vaccination coverage, increased heterogeneity in coverage among the non-focal villages leads to increased focal incidence. These effects led to outbreaks following years when vaccination campaigns missed many villages, whereas when heterogeneity in coverage was reduced, incidence declined to low levels (<0.4 cases/1,000 dogs annually and no human deaths) and short vaccination lapses thereafter did not lead to resurgence. Through transmission-tree reconstruction, we inferred frequent incursions into the district each year (mean of 7). Inferred incursions substantially increased as a percentage of all cases in recent years, reaching 50% in 2022, suggesting regional connectivity is driving residual transmission. Overall, we empirically demonstrate how population connectivity and spatial heterogeneity in vaccination can impact disease outcomes, highlighting the importance of fine-scale monitoring in managing vaccination programs.

ecology↗

bioRxiv2024

Genomic Characterization of a Dog-Mediated Rabies Outbreak in El Pedregal, Arequipa, Peru

BackgroundRabies, a re-emerging zoonosis with the highest known human case fatality rate, has been largely absent from Peru, except for endemic circulation in the Puno region on the Bolivian border and re-emergence in Arequipa City in 2015, where it has persisted. In 2021, an outbreak occurred in the rapidly expanding city of El Pedregal near Arequipa, followed by more cases in 2022 after nearly a year of epidemiological silence. While currently under control, questions persist regarding the origin of the El Pedregal outbreak and implications for maintaining rabies control in Peru. MethodsWe sequenced 25 dog rabies virus (RABV) genomes from the El Pedregal outbreak (n=11) and Arequipa City (n=14) from 2021-2023 using Nanopore sequencing in Peru. Historical genomes from Puno (n=4, 2010-2012) and Arequipa (n=5, 2015-2019), were sequenced using an Illumina approach in the UK. In total, 34 RABV genomes were analyzed, including archived and newly obtained samples. The genomes were analyzed phylogenetically to understand the outbreaks context and origins. ResultsPhylogenomic analysis identified two genetic clusters in El Pedregal: 2021 cases stemmed from a single introduction unrelated to Arequipa cases, while the 2022 sequence suggested a new introduction from Arequipa rather than persistence. In relation to canine RABV diversity in Latin America, all new sequences belonged to a new minor clade, Cosmopolitan Am5, sharing relatives from Bolivia, Argentina, and Brazil. ConclusionGenomic insights into the El Pedregal outbreak revealed multiple introductions over a 2-year window. Eco-epidemiological conditions, including migratory worker patterns, suggest human-mediated movement drove introductions. Despite outbreak containment, El Pedregal remains at risk of dog-mediated rabies due to ongoing circulation in Arequipa, Puno, and Bolivia. Human-mediated movement of dogs presents a major risk for rabies re-emergence in Peru, jeopardizing regional dog-mediated rabies control. Additional sequence data is needed for comprehensive phylogenetic analyses.

genomics↗

bioRxiv2024

Reassessing global historical R0 estimates of canine rabies

Rabies spread by domestic dogs continues to cause tens of thousands of human deaths every year in low- and middle-income countries. Nevertheless rabies is often neglected, perhaps because it has already been eliminated from high-income countries through dog vaccination. Estimates of canine rabiess intrinsic reproductive number ([R]0), a metric of disease spread, from a wide range of times and locations are relatively low (values < 2), with narrow confidence intervals. Given rabiess persistence, this consistently low and narrow range of estimates is surprising. We combined incidence data from historical outbreaks of canine rabies from around the world with in-depth contact-tracing data from Tanzania to investigate initial growth rates (r0), generation-interval distributions (G), and reproductive numbers ([R]0). We improved on earlier estimates by choosing outbreak windows algorithmically; fitting r0 using a more appropriate statistical method that accounts for decreases through time; and incorporating uncertainty from both r0 and G in our confidence intervals on[R] 0. Our[R] 0 estimates are larger than previous estimates, with wider confidence intervals. These revised[R] 0 estimates suggest that a greater level of vaccination effort will be required to eliminate rabies than previously thought, but that the level of coverage required remains feasible. Our hybrid approach for estimating[R] 0 and its uncertainty is applicable to other disease systems where researchers estimate[R] 0 by combining data-based estimates of r0 and G.

ecology↗

bioRxiv2023

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↗

bioRxiv2022

Development, feasibility and potential effectiveness of community-based continuous mass dog vaccination delivery strategies: lessons for optimization and replication

ObjectivesDog vaccination can eliminate rabies, but annual delivery strategies do not sustain vaccination coverage between campaigns. We describe the development of a community-based continuous mass dog vaccination (CBC-MDV) approach designed to improve and maintain vaccination coverage in Tanzania and examine the feasibility of delivering this approach as well as lessons for its optimization. MethodsWe developed three delivery strategies of CBC-MDV and tested them against the current annual vaccination strategy following the UK MRCs guidance: i) developing an evidence-based theoretical framework of intervention pathways and ii) piloting to test feasibility and inform optimization. For our process evaluation of CBC-MDV we collected data using non-participant observations, meeting reports and implementation audits and in-depth interviews, as well as household surveys of vaccination coverage to assess potential effectiveness. We analyzed qualitative data thematically and quantitative data descriptively. ResultsThe final design included delivery by veterinary teams supported by village-level one health champions. In terms of feasibility, we found that less than half of CBC-MDVs components were implemented as planned. Fidelity of delivery was influenced by the strategy design, implementer availability and appreciation of value intervention components, and local environmental and socioeconomic events (e.g. elections, funerals, school cycles). CBC-MDV activities decreased sharply after initial campaigns, partly due to lack of supervision. Community engagement and involvement was not strong. Nonetheless, the CBC-MDV approaches achieved vaccination coverage above the critical threshold (40%) all-year-round. CBC-MDV components such as identifying vaccinated dogs, which village members work as one health champions and how provision of continuous vaccination is implemented need further optimization prior to scale up. InterpretationCBC-MDV is feasible to deliver and can achieve good vaccination coverage. Community involvement in the development of CBC-MDV, to better tailor components to contextual situations, and improved supervision of activities are likely to improve vaccination coverage in future. AUTHOR SUMMARYAnnual mass dog vaccination campaigns that reach at least 70% of the dog population, should maintain sufficient herd immunity between campaigns to interrupt rabies transmission. However, it is often challenging to reach 70% of the dog population with annual vaccination campaigns. We hypothesized that a community-based continuous approach to dog vaccination could better maintain high levels of vaccination coverage all-year-round. We describe the development of a community-based continuous approach to dog vaccination in Tanzania, and assessed the feasibility of delivering its components, its potential effectiveness and lessons for its optimization. We found that the approach was well accepted, as its development involved key stakeholders. Although less than half of the components of the community-based continuous approach were delivered exactly as planned, over 70% of dogs were vaccinated and the approach maintained coverage above the critical vaccination threshold throughout the year. We conclude that it is feasible to deliver a community-based continuous approach to dog vaccination, but that some components need further improvement; more supervision and community involvement should lead to better outcomes.

immunology↗

bioRxiv2021

Spatial scale of transmission explains how acute infections circulate at low prevalence

Fundamental questions remain about the regulation of acute pathogens in the absence of acquired immunity. This is especially true for canine rabies, a universally fatal zoonosis. From tracing rabies transmission in a population of 50,000 dogs in Tanzania between 2002-2016 we unravel the processes through which rabies is regulated and persists, fitting individual-based models to spatially-resolved data to investigate the mechanisms modulating transmission and the scale over which they operate. We find that while prevalence never exceeds 0.15%, we detect significant susceptible depletion at local scales commensurate with rabid dog movement, reducing transmission through clustering of rabies deaths and individuals incubating infection. Individual variation in rabid dog behaviour facilitates virus dispersal and co-circulation of lineages, enabling metapopulation persistence. These mechanisms likely operate in many pathogens circulating in spatially structured populations, with important implications for prediction and control, yet are unobservable unless the scale of host interactions is identified. One-Sentence SummaryIdentifying the spatial scale of contact reveals the mechanisms that limit the size of rabies outbreaks and that are critical for predicting transmission dynamics.

ecology↗

bioRxiv2021

Making Genomic Surveillance Deliver: A Lineage Classification and Nomenclature System to Inform Rabies Virus Elimination

The availability of pathogen sequence data and use of genomic surveillance is rapidly increasing. Genomic tools and classification systems need updating to reflect this. Here, rabies virus is used as an example to showcase the potential value of updated genomic tools to enhance surveillance to better understand epidemiological dynamics and improve disease control. Previous studies have described the evolutionary history of rabies virus; however, the resulting taxonomy lacks the definition necessary to identify incursions, lineage turnover and transmission routes at high resolution. Here we propose a lineage classification system based on the dynamic nomenclature used for SARS-CoV-2, defining a lineage by phylogenetic methods, for tracking virus spread and comparing sequences across geographic areas. We demonstrate this system through application to the globally distributed Cosmopolitan clade of rabies virus, defining 73 total lineages within the clade, beyond the 22 previously reported. We further show how integration of this tool with a new rabies virus sequence data resource (RABV-GLUE) enables rapid application, for example, highlighting lineage dynamics relevant to control and elimination programmes, such as identifying importations and their sources, and areas of persistence and transmission, including transboundary incursions. This system and the tools developed should be useful for coordinating and targeting control programmes and monitoring progress as we work towards eliminating dog-mediated rabies, as well as having potential for broad application to the surveillance of other viruses. Author SummaryThe importance of the ability to track the diversity and spread of viruses in a universal way that can be clearly communicated has been highlighted during the SARS-CoV-2 pandemic. This, accompanied with the increase in the availability and use of pathogen sequence data, means the development of new genomic tools and classification systems can strengthen outbreak response and disease control. Here, we present an easy-to-use objective and transferable classification tool for tracking viruses at high resolution. We use rabies virus, a neglected zoonotic disease that causes around 59,000 human deaths each year, as an example use case of this tool. Applying our tool to a global clade of rabies virus, we find an over 200% increase in the definition at which we can classify the virus, allowing us to identify areas of persistence and transmission that were not previously apparent, and patterns of virus spread. Insights from the application of this tool should prove valuable in targeting vaccination campaigns and improving surveillance as countries work towards the elimination of dog-mediated rabies.

genomics↗

bioRxiv2020

Wavefront-sensorless adaptive optics with a laser-free spinning disk confocal microscope

Adaptive optics is being applied widely to a range of microscopies in order to improve imaging quality in the presence of specimen-induced aberrations. We present here the first implementation of wavefront-sensorless adaptive optics for a laser-free, aperture correlation, spinning disk microscope. This widefield method provides confocal-like optical sectioning through use of a patterned disk in the illumination and detection paths. Like other high-resolution microscopes, its operation is compromised by aberrations due to refractive index mismatch and variations within the specimen. Correction of such aberrations shows improved signal level, contrast and resolution.

cell biology↗

bioRxiv2020

Dynamics of viral index infections in novel hosts

Whether a pathogen entering a new host species results in a single infection or in onward transmission, and potentially an outbreak, depends upon the progression of infection in the index case. Although index infections are rarely observable in nature, experimental inoculations of pathogens into novel host species have a long history in biomedical research. This provides a rich and largely unexploited data source for meta-analyses to identify the host and pathogen determinants of variability in infection outcomes. Here, we analysed the progressions of 514 experimental cross-species inoculations of rabies virus, a widespread zoonotic pathogen which in nature exhibits both dead end infections and varying levels of sustained transmission in novel hosts. Inoculations originating from bats rather than carnivores, and from warmer to cooler-bodied species caused infections with shorter incubation periods that were associated with diminished virus excretion. Inoculations between distantly related hosts tended to result in shorter clinical disease periods, which will also impede transmission. All effects were modulated by infection dose and together suggest that increased virulence as host species become more dissimilar is the limiting factor preventing onward transmission. These results explain observed constraints on rabies virus host shifts, allow us to evaluate the risk of novel reservoirs establishing, and give mechanistic insights into why host shifts are less likely between genetically distant species. More generally, our study highlights meta-analyses of experimental infections as a tractable approach to quantify the complex interactions between virus, reservoir, and novel host that shape the outcome of cross-species transmission. Significance statementEmerging disease epidemics often result from a pathogen establishing transmission in a novel host species. However, most cross-species transmissions fail to establish in the newly infected species for reasons that remain poorly understood. Examining cross-species inoculations involving rabies, a widespread viral zoonosis, we show that mismatches in virulence, which are predictable from host and viral factors, make sustained transmission in the novel host less likely. In particular, disease progression was accelerated and virus excretion decreased when the reservoir and novel host were physiologically or genetically more dissimilar. These mechanistic insights help to explain and predict host shift events and highlight meta-analyses of existing experimental inoculation data as a powerful and generalisable approach for understanding the dynamics of index infections in novel species.

ecology↗

bioRxiv2019

Local rabies transmission and regional spatial coupling in European foxes

Infectious diseases are often transmitted through local interactions. Yet, both surveillance and control measures are implemented within administrative units. Capturing local transmission processes and spatial coupling between regions from aggregate level data is therefore a technical challenge that can shed light on both theoretical questions and practical decisions.\n\nFox rabies has been eliminated from much of Europe through oral rabies vaccination (ORV) programmes. The European Union (EU) co-finances ORV to maintain rabies freedom in EU member and border states via a cordon sanitaire. Models to capture local transmission dynamics and spatial coupling have immediate application to the planning of these ORV campaigns and to other parts of the world considering oral vaccination.\n\nWe fitted a hierarchical Bayesian state-space model to data on three decades of fox rabies cases and ORV campaigns from Eastern Germany. Specifically, we find that (i) combining regional spatial coupling and heterogeneous local transmission allows us to capture regional rabies dynamics; (ii) incursions from other regions account for less than 1% of cases, but allow for re-emergence of disease; (iii) herd immunity achieved through bi-annual vaccination campaigns is short-lived due to population turnover. Together, these findings highlight the need for regular and sustained vaccination efforts and our modelling approach can be used to provide strategic guidance for ORV delivery. Moreover, we show that biological understanding can be gained from inference from partially observed data on wildlife disease.

ecology↗

bioRxiv2016

Surveillance to Establish Elimination of Transmission and Freedom from Dog-mediated Rabies

BackgroundWith a global target set for zero human deaths from dog-mediated rabies by 2030 and some regional programmes close to eliminating canine rabies, there is an urgent need for enhanced surveillance strategies suitable for declaring freedom from disease and elimination of transmission with known confidence.\n\nMethodsUsing exhaustive contact tracing across settings in Tanzania we generated detailed data on rabies incidence, rabid dog biting behaviour and health-seeking behaviour of bite victims. Using these data we compared case detection of sampling-based and enhanced surveillance methodologies and investigated elimination verification procedures.\n\nFindingsWe demonstrate that patients presenting to clinics with bite injuries are sensitive sentinels for identifying dog rabies cases. Triage of patients based on bite history criteria and investigation of suspicious incidents can confirm >10% of dog rabies cases and is an affordable approach that will enable validation of disease freedom following two years without case detection. Approaches based on sampling the dog population without using bite-injury follow-up were found to be neither sensitive nor cost-effective.\n\nInterpretationThe low prevalence of rabies, and short window in which disease can be detected, preclude sampling-based surveillance. Instead, active case finding guided by bite-patient triage is needed as elimination is approached. Our proposed methodology is affordable, practical and supports the goal of eliminating human rabies deaths by improving administration of lifesaving post-exposure prophylaxis for genuinely exposed but untreated contacts. Moreover, joint investigations by public health and veterinary workers will strengthen intersectoral partnerships and capacity for control of emerging zoonoses.

epidemiology↗