Transmission dynamics and prospects for the elimination of canine rabies

Rabies has been eliminated from domestic dog populations in Western Europe and North America, but continues to kill many thousands of people throughout Africa and Asia every year. A quantitative understanding of transmission dynamics in domestic dog populations provides critical information to assess whether global elimination of canine rabies is possible. We report extensive observations of individual rabid animals in Tanzania and generate a uniquely detailed analysis of transmission biology, which explains important epidemiological features, including the level of variation in epidemic trajectories. We found that the basic reproductive number for rabies, R<sub>0</sub>, is very low in our study area in rural Africa (∼1.2) and throughout its historic global range (<2). This finding provides strong support for the feasibility of controlling endemic canine rabies by vaccination, even near wildlife areas with large wild carnivore populations. However, we show that rapid turnover of domestic dog populations has been a major obstacle to successful control in developing countries, thus regular pulse vaccinations will be required to maintain population-level immunity between campaigns. Nonetheless our analyses suggest that with sustained, international commitment, global elimination of rabies from domestic dog populations, the most dangerous vector to humans, is a realistic goal

Genomic dynamics of transposable elements in the western clawed frog (Silurana tropicalis)

Transposable elements (TEs) are repetitive DNA sequences that can make new copies of themselves that are inserted elsewhere in a host genome. The abundance and distributions of TEs vary considerably among phylogenetically diverse hosts. With the aim of exploring the basis of this variation, we evaluated correlations between several genomic variables and the presence of TEs and non-TE repeats in the complete genome sequence of the Western clawed frog (Silurana tropicalis). This analysis reveals patterns of TE insertion consistent with gene disruption but not with the insertional preference model. Analysis of non-TE repeats recovered unique features of their genome-wide distribution when compared with TE repeats, including no strong correlation with exons and a particularly strong negative correlation with GC content. We also collected polymorphism data from 25 TE insertion sites in 19 wild-caught S. tropicalis individuals. DNA transposon insertions were fixed at eight of nine sites and at a high frequency at one of nine, whereas insertions of long terminal repeat (LTR) and non-LTR retrotransposons were fixed at only 4 of 16 sites and at low frequency at 12 of 16. A maximum likelihood model failed to attribute these differences in insertion frequencies to variation in selection pressure on different classes of TE, opening the possibility that other phenomena such as variation in rates of replication or duration of residence in the genome could play a role. Taken together, these results identify factors that sculpt heterogeneity in TE distribution in S. tropicalis and illustrate that genomic dynamics differ markedly among TE classes and between TE and non-TE repeats.published_or_final_versio

Speciation over the edge: Gene flow among non-human primate species across a formidable biogeographic barrier

Many genera of terrestrial vertebrates diversified exclusively on one or the other side of Wallace’s Line, which lies between Borneo and Sulawesi islands in Southeast Asia, and demarcates one of the sharpest biogeographic transition zones in the world. Macaque monkeys are unusual among vertebrate genera in that they are distributed on both sides of Wallace‘s Line, raising the question of whether dispersal across this barrier was an evolutionary one-off or a more protracted exchange—and if the latter, what were the genomic consequences. To explore the nature of speciation over the edge of this biogeographic divide, we used genomic data to test for evidence of gene flow between macaque species across Wallace’s Line after macaques colonized Sulawesi. We recovered evidence of post-colonization gene flow, most prominently on the X chromosome. These results are consistent with the proposal that gene flow is a pervasive component of speciation—even when barriers to gene flow seem almost insurmountable

Evaluating undercounts in epidemics: response to Maruotti et al. 2022

Maruotti et al. 2022 used a mark-recapture approach to estimate bounds on the true number of monkeypox infections in various countries. These approaches are fundamentally flawed; it is impossible to estimate undercounting based solely on a single stream of reported cases. Simulations based on a Richards curve for cumulative incidence show that, for reasonable epidemic parameters, the proposed methods estimate bounds on the ascertainment ratio of $\approx 0.2-0.5$ roughly independently of the true ascertainment ratio. These methods should not be used

Bifurcations and chaotic dynamics in a tumour-immune-virus system

Despite mounting evidence that oncolytic viruses can be effective in treating cancer, understanding the details of the interactions between tumour cells, oncolytic viruses and immune cells that could lead to tumour control or tumour escape is still an open problem. Mathematical modelling of cancer oncolytic therapies has been used to investigate the biological mechanisms behind the observed temporal patterns of tumour growth. However, many models exhibit very complex dynamics, which renders them difficult to investigate. In this case, bifurcation diagrams could enable the visualisation of model dynamics by identifying (in the parameter space) the particular transition points between different behaviours. Here, we describe and investigate two simple mathematical models for oncolytic virus cancer therapy, with constant and immunity-dependent carrying capacity. While both models can exhibit complex dynamics, namely fixed points, periodic orbits and chaotic behaviours, only the model with immunity-dependent carrying capacity can exhibit them for biologically realistic situations, i.e., before the tumour grows too large and the experiment is terminated. Moreover, with the help of the bifurcation diagrams we uncover two unexpected behaviours in virus-tumour dynamics: (i) for short virus half-life, the tumour size seems to be too small to be detected, while for long virus half-life the tumour grows to larger sizes that can be detected; (ii) some model parameters have opposite effects on the transient and asymptotic dynamics of the tumour.Publisher PDFPeer reviewe

Toward a comprehensive system for constructing compartmental epidemic models

Compartmental models are valuable tools for investigating infectious diseases. Researchers building such models typically begin with a simple structure where compartments correspond to individuals with different epidemiological statuses, e.g., the classic SIR model which splits the population into susceptible, infected, and recovered compartments. However, as more information about a specific pathogen is discovered, or as a means to investigate the effects of heterogeneities, it becomes useful to stratify models further -- for example by age, geographic location, or pathogen strain. The operation of constructing stratified compartmental models from a pair of simpler models resembles the Cartesian product used in graph theory, but several key differences complicate matters. In this article we give explicit mathematical definitions for several so-called ``model products'' and provide examples where each is suitable. We also provide examples of model stratification where no existing model product will generate the desired result

Using random networks to study the dynamics of respiratory syncytial virus (RSV) in the Spanish region of Valencia

[EN] Seasonal fluctuations in the incidence of several respiratory infections are a feature of epidemiological surveys all around the world. This phenomenon is characteristic of influenza and respiratory syncytial virus pandemics. However, the explanation of the seasonal outbreaks of these diseases remains poorly understood. Many statistical studies have been carried out in order to provide a correlation of the outbreaks with climatic or social factors without achieving a definitive conclusion. Here we show that, in a random social network, self-sustained seasonal epidemics emerge as a process modulated by the infection probability and the immunity period after recovering from the infection. This is a purely endogenous phenomenon that does not require any exogenous forcing. Assuming that this is the dominant mechanism for seasonal epidemics, many implications for public health policies for infectious respiratory diseases could be drawn. (C) 2010 Elsevier Ltd. All rights reserved.Supported by a grant from the Universidad Politecnica de Valencia PAID-06-09 ref: 2588.Acedo Rodríguez, L.; Moraño Fernández, JA.; Villanueva Micó, RJ.; Villanueva Oller, FJ.; Díez Domingo, J. (2011). Using random networks to study the dynamics of respiratory syncytial virus (RSV) in the Spanish region of Valencia. Mathematical and Computer Modelling. 54(7-8):1650-1654. https://doi.org/10.1016/j.mcm.2010.11.068S16501654547-

Reconstructing influenza incidence by deconvolution of daily mortality time series

We propose a mathematically straightforward method to infer the incidence curve of an epidemic from a recorded daily death curve and time-to-death distribution; the method is based on the Richardson-Lucy deconvolution scheme from optics. We apply the method to reconstruct the incidence curves for the 1918 influenza epidemic in Philadelphia and New York State. The incidence curves are then used to estimate epidemiological quantities, such as daily reproductive numbers and infectivity ratios. We found that during a brief period before the official control measures were implemented in Philadelphia, the drop in the daily number of new infections due to an average infector was much larger than expected from the depletion of susceptibles during that period; this finding was subjected to extensive sensitivity analysis. Combining this with recorded evidence about public behavior, we conclude that public awareness and change in behavior is likely to have had a major role in the slowdown of the epidemic even in a city whose response to the 1918 influenza epidemic is considered to have been among the worst in the U.S

Influenza in Tropical Regions

Viboud and colleagues discuss the implications of a new study by Peiris et al. that assesses the burden of influenza in Hong Kong

Optimal Dosing and Dynamic Distribution of Vaccines in an Influenza Pandemic

Limited production capacity and delays inherent in vaccine development are major hurdles to the widespread use of vaccines to mitigate the effects of a new influenza pandemic. Antigen-sparing vaccines have the most potential to increase population coverage but may be less efficacious. The authors explored this trade-off by applying simple models of influenza transmission and dose response to recent clinical trial data. In this paper, these data are used to illustrate an approach to comparing vaccines on the basis of antigen supply and inferred efficacy. The effects of delays in matched vaccine availability and seroconversion on epidemic size during pandemic phase 6 were also studied. The authors infer from trial data that population benefits stem from the use of low-antigen vaccines. Delayed availability of a matched vaccine could be partially alleviated by using a 1-dose vaccination program with increased coverage and reduced time to full protection. Although less immunogenic, an overall attack rate of up to 6% lower than a 2-dose program could be achieved. However, if prevalence at vaccination is above 1%, effectiveness is much reduced, emphasizing the need for other control measures