Project description:Along with the prevalence of edible frog farming in China, the outbreak of a deadly infectious frog diseased, called frog meningitis (or cataracts and torticollis), has increased in frequency and geographical range dramatically. More than 10 bacterial species, belonging to 8 genera, has been reported as its potential pathogens. Diseased frogs typically manifest as torticollis, cataracts, edema and finally death, resulting in huge economic loss. Currently, the pathogenesis of this disease has not been investigated systematically. Here, we summarized the pathological stages of infected black-spotted frogs (Pelophylax nigromaculata) in Sichuan province according to their symptoms, typically progressing of pathological stage with only torticollis to stage with both torticollis and cataracts. On the basis, we analyzed the pathogenesis by a combination of comparative environmental analysis, microbiomics and transcriptomics. Results showed that more severely infected frog ponds tended to have lower water alkalinity. Elizabethkingia miricola was the only bacteria, whose abundance was positively correlated with the disease degree, and it has absolute dominance in the eyeball and brain of some torticollis-cataracts frogs. E. miricola and several other bacterial species, which belonged to pathogenic genera of meningitis, might be constitutively existed in the resident microbiome in frogs or their environment. Activations of infectious processes and immune responses related pathways were the major difference between health and diseased frogs at transcriptional level. Despite transcriptional activation of immunoglobulins was observed in both torticollis-only and torticollis-cataracts frogs, transcriptional activation of innate immune system (including MHC, toll-like receptor, and cathelicidins) in brain, inflammation system (including interleukins and receptors) in brain, and acute phase proteins (including transferrins and fibrinogens) in both liver and brain was only observed in torticollis-cataracts frogs. Activation of inflammation and the resulting higher vascular permeability in torticollis-cataracts frogs could explain the severe brain infection, cooccurrence of torticollis and cataracts, and systemic edema in torticollis-cataracts frogs. In addition, meningitis could also result in reduction in energy production in liver, and this was more severe in torticollis-cataracts frogs. In conclusion, our results suggested environment might have a role in susceptibility of frog meningitis. E. miricola was the most likely pathogen of meningitis of black-spotted frogs in Sichuan. Refer to the pathogenesis of human meningitis, excessive inflammation likely played a critical role in the progress of frog meningitis, and its resulted sepsis and organ failure might be the direct cause of infected frogs.

Project description:Background: In December 2019, an outbreak of coronavirus disease (later named as COVID-19) was identified in Wuhan, China and, later on, detected in other parts of China. Our aim is to evaluate the effectiveness of the evolution of interventions and self-protection measures, estimate the risk of partial lifting control measures and predict the epidemic trend of the virus in the mainland of China excluding Hubei province based on the published data and a novel mathematical model. Methods: A novel COVID-19 transmission dynamic model incorporating the intervention measures implemented in China is proposed. COVID-19 daily data of the mainland of China excluding Hubei province, including the cumulative confirmed cases, the cumulative deaths, newly confirmed cases and the cumulative recovered cases between 20 January and 3 March 2020, were archived from the National Health Commission of China (NHCC). We parameterize the model by using the Markov Chain Monte Carlo (MCMC) method and estimate the control reproduction number (Rc), as well as the effective daily reproduction ratio- Re(t), of the disease transmission in the mainland of China excluding Hubei province. Results: The estimation outcomes indicate that Rc is 3.36 (95% CI: 3.20-3.64) and Re(t) has dropped below 1 since 31 January 2020, which implies that the containment strategies implemented by the Chinese government in the mainland of China are indeed effective and magnificently suppressed COVID-19 transmission. Moreover, our results show that relieving personal protection too early may lead to a prolonged disease transmission period and more people would be infected, and may even cause a second wave of epidemic or outbreaks. By calculating the effective reproduction ratio, we prove that the contact rate should be kept at least less than 30% of the normal level by April, 2020. Conclusions: To ensure the pandemic ending rapidly, it is necessary to maintain the current integrated restrict interventions and self-protection measures, including travel restriction, quarantine of entry, contact tracing followed by quarantine and isolation and reduction of contact, like wearing masks, keeping social distance, etc. People should be fully aware of the real-time epidemic situation and keep sufficient personal protection until April. If all the above conditions are met, the outbreak is expected to be ended by April in the mainland of China apart from Hubei province.

Project description:Shigui Ruan. Modeling the transmission dynamics and control of rabies in China. Mathematical Biosciences 286 (2017). Human rabies was first recorded in ancient China in about 556 BC and is still one of the major public-health problems in China. From 1950 to 2015, 130,494 human rabies cases were reported in Mainland China with an average of 1977 cases per year. It is estimated that 95% of these human rabies cases are due to dog bites. The purpose of this article is to provide a review about the models, results, and simulations that we have obtained recently on studying the transmission of rabies in China. We first construct a basic susceptible, exposed, infectious, and recovered (SEIR) type model for the spread of rabies virus among dogs and from dogs to humans and use the model to simulate the human rabies data in China from 1996 to 2010. Then we modify the basic model by including both domestic and stray dogs and apply the model to simulate the human rabies data from Guangdong Province, China. To study the seasonality of rabies, in Section 4 we further propose a SEIR model with periodic transmission rates and employ the model to simulate the monthly data of human rabies cases reported by the Chinese Ministry of Health from January 2004 to December 2010. To understand the spatial spread of rabies, in Section 5 we add diffusion to the dog population in the basic SEIR model to obtain a reaction-diffusion equation model and determine the minimum wave speed connecting the disease-free equilibrium to the endemic equilibrium. Finally, in order to investigate how the movement of dogs affects the geographically inter-provincial spread of rabies in Mainland China, in Section 6 we propose a multi-patch model to describe the transmission dynamics of rabies between dogs and humans and use the two-patch submodel to investigate the rabies virus clades lineages and to simulate the human rabies data from Guizhou and Guangxi, Hebei and Fujian, and Sichuan and Shaanxi, respectively. Some discussions are provided in Section 7.

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