Purpose of review Despite great progress in decoding disease mechanisms, rabies remains one of the leading causes of human death worldwide. Towards the elimination of human rabies deaths by 2030, feasible and affordable post (PEP) and pre-exposure prophylaxis (PrEP) must be available with expansion to rural areas in rabies endemic countries. Vaccination and population control of dogs, principal reservoirs and transmitters, must be done in concert. Recent finding Advances in the understanding of rabies neuropathogenesis and pathophysiology are reviewed, including recent experimental findings on host- and virus-specific mechanisms mediating neuronal survival and explaining clinical differences in furious and paralytic rabies. The forthcoming World Health Organization guide on rabies based on pathogenesis and immunization mechanisms data with support by clinical evidence provide new accelerated 1 week intradermal PrEP and PEP schedules. Rabies immunoglobulin injected into the wound only is endorsed at amounts not exceeding the dose interfering with active immunization. Potential therapeutics as designed in accord with rabies neuro-pathophysiology are plausible. Summary Clinical practice and rabies awareness can be leveraged by transboundary collaboration among different areas. Advancement in prophylaxis and perspectives on animal control offer a new path to conquer rabies by 2030.

Rabies: changing prophylaxis and new insights in pathophysiology.

Background Rabies is a fatal yet vaccine-preventable disease. In the last two decades, domestic dog populations have been shown to constitute the predominant reservoir of rabies in developing countries, causing 99% of human rabies cases. Despite substantial control efforts, dog rabies is still widely endemic and is spreading across previously rabies-free areas. Developing a detailed understanding of dog rabies dynamics and the impact of vaccination is essential to optimize existing control strategies and developing new ones. In this scoping review, we aimed at disentangling the respective contributions of mathematical models and phylodynamic approaches to advancing the understanding of rabies dynamics and control in domestic dog populations. We also addressed the methodological limitations of both approaches and the remaining issues related to studying rabies spread and how this could be applied to rabies control. Methodology/principal findings We reviewed how mathematical modelling of disease dynamics and phylodynamics have been developed and used to characterize dog rabies dynamics and control. Through a detailed search of the PubMed, Web of Science, and Scopus databases, we identified a total of n = 59 relevant studies using mathematical models (n = 30), phylodynamic inference (n = 22) and interdisciplinary approaches (n = 7). We found that despite often relying on scarce rabies epidemiological data, mathematical models investigated multiple aspects of rabies dynamics and control. These models confirmed the overwhelming efficacy of massive dog vaccination campaigns in all settings and unraveled the role of dog population structure and frequent introductions in dog rabies maintenance. Phylodynamic approaches successfully disentangled the evolutionary and environmental determinants of rabies dispersal and consistently reported support for the role of reintroduction events and human-mediated transportation over long distances in the maintenance of rabies in endemic areas. Potential biases in data collection still need to be properly accounted for in most of these analyses. Finally, interdisciplinary studies were determined to provide the most comprehensive assessments through hypothesis generation and testing. They also represent new avenues, especially concerning the reconstruction of local transmission chains or clusters through data integration. Conclusions/significance Despite advances in rabies knowledge, substantial uncertainty remains regarding the mechanisms of local spread, the role of wildlife in dog rabies maintenance, and the impact of community behavior on the efficacy of control strategies including vaccination of dogs. Future integrative approaches that use phylodynamic analyses and mechanistic models within a single framework could take full advantage of not only viral sequences but also additional epidemiological information as well as dog ecology data to refine our understanding of rabies spread and control. This would represent a significant improvement on past studies and a promising opportunity for canine rabies research in the frame of the One Health concept that aims to achieve better public health outcomes through cross-sector collaboration.

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Mathematical modelling and phylodynamics for the study of dog rabies dynamics and control: A scoping review.

Background COVID-19 was first reported in 2019, and the Chinese government immediately carried out stringent and effective control measures in response to the epidemic. Objective Nonpharmaceutical interventions (NPIs) may have impacted incidences of other infectious diseases as well. Potential explanations underlying this reduction, however, are not clear. Hence, in this study, we aim to study the influence of the COVID-19 prevention policies on other infectious diseases (mainly class B infectious diseases) in China. Methods Time series data sets between 2017 and 2021 for 23 notifiable infectious diseases were extracted from public data sets from the National Health Commission of the People’s Republic of China. Several indices (peak and trough amplitudes, infection selectivity, preferred time to outbreak, oscillatory strength) of each infectious disease were calculated before and after the COVID-19 outbreak. Results We found that the prevention and control policies for COVID-19 had a strong, significant reduction effect on outbreaks of other infectious diseases. A clear event-related trough (ERT) was observed after the outbreak of COVID-19 under the strict control policies, and its decreasing amplitude is related to the infection selectivity and preferred outbreak time of the disease before COVID-19. We also calculated the oscillatory strength before and after the COVID-19 outbreak and found that it was significantly stronger before the COVID-19 outbreak and does not correlate with the trough amplitude. Conclusions Our results directly demonstrate that prevention policies for COVID-19 have immediate additional benefits for controlling most class B infectious diseases, and several factors (infection selectivity, preferred outbreak time) may have contributed to the reduction in outbreaks. This study may guide the implementation of nonpharmaceutical interventions to control a wider range of infectious diseases. 

/pdf/changes-in-temporal-properties-of-notifiable-infectious-esergxz9.pdf

Changes in Temporal Properties of Notifiable Infectious Disease Epidemics in China During the COVID-19 Pandemic: Population-Based Surveillance Study

Rabies is a neglected zoonotic disease which is caused by negative strand RNA-viruses belonging to the genus Lyssavirus. Within this genus, rabies viruses circulate in a diverse set of mammalian reservoir hosts, is present worldwide, and is almost always fatal in non-vaccinated humans. Approximately 59,000 people are still estimated to die from rabies each year, leading to a global initiative to work towards the goal of zero human deaths from dog-mediated rabies by 2030, requiring scientific efforts from different research fields. The past decade has seen a much increased use of phylogeographic and phylodynamic analyses to study the evolution and spread of rabies virus. We here review published studies in these research areas, making a distinction between the geographic resolution associated with the available sequence data. We pay special attention to environmental factors that these studies found to be relevant to the spread of rabies virus. Importantly, we highlight a knowledge gap in terms of applying these methods when all required data were available but not fully exploited. We conclude with an overview of recent methodological developments that have yet to be applied in phylogeographic and phylodynamic analyses of rabies virus.

On the Use of Phylogeographic Inference to Infer the Dispersal History of Rabies Virus: A Review Study

A variety of infectious diseases occur in mainland China every year. Cyclic oscillation is a widespread attribute of most viral human infections. Understanding the outbreak cycle of infectious diseases can be conducive for public health management and disease surveillance. In this study, we collected time-series data for 23 class B notifiable infectious diseases from 2004 to 2020 using public datasets from the National Health Commission of China. Oscillatory properties were explored using power spectrum analysis. We found that the 23 class B diseases from the dataset have obvious oscillatory patterns (seasonal or sporadic), which could be divided into three categories according to their oscillatory power in different frequencies each year. These diseases were found to have different preferred outbreak months and infection selectivity. Diseases that break out in autumn and winter are more selective. Furthermore, we calculated the oscillation power and the average number of infected cases of all 23 diseases in the first eight years (2004 to 2012) and the next eight years (2012 to 2020) since the update of the surveillance system. A strong positive correlation was found between the change of oscillation power and the change in the number of infected cases, which was consistent with the simulation results using a conceptual hybrid model. The establishment of reliable and effective analytical methods contributes to a better understanding of infectious diseases' oscillation cycle characteristics. Our research has certain guiding significance for the effective prevention and control of class B infectious diseases.

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Enlightenment on oscillatory properties of 23 class B notifiable infectious diseases in the mainland of China from 2004 to 2020.

Objectives
To explore the epidemiological, phylogeographic and migration characteristics of human rabies in Shaanxi Province, China from 2009 to 2015.

Methods
The collected data were described and the sequenced glycoprotein (G) and nucleoprotein (N) genes were implemented to estimate the evolutionary rates and phylogeographic patterns using BEAST v.1.8.2.

Results
269 rabies cases were reported and 70.26% of the cases were male and 61.71% were between the ages of 19 to 59. The majority of the cases were farmers (83.27%). The estimated evolutionary rate of the N genes was 2.4 × 10−4substitutions/site/year and the G genes was 3.4 × 10−4. The time of the most recent common ancestor(TMRCA) was estimated around 1990. We detected viral migration paths from Sichuan, Guizhou and Hunan to Hanzhong prefecture of Shaanxi and then spreaded to Xi'an and other prefectures.

Conclusions
The main population affected by rabies virus was male adult farmers. The evolution rate of rabies viruses in Shaanxi was similar with the prior results reported by others and the ancestor virus should be circulating in neighboring province Sichuan around 1990 and then transmitted to Shaanxi. Promptly standard wound treatment and timely post-exposure prophylaxis should be compulsory for the dog-bitten victims. This article is protected by copyright. All rights reserved

Re‐emerging of rabies in Shaanxi province, China, from 2009 to 2015

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Re‐emerging of rabies in Shaanxi province, China, from 2009 to 2015