Interannual cycles of Hantaan virus outbreaks at the human-animal interface in Central China are controlled by temperature and rainfall.

Hantavirus, a rodent-borne zoonotic pathogen, has a global distribution with 200,000 human infections diagnosed annually. In recent decades, repeated outbreaks of hantavirus infections have been reported in Eurasia and America. These outbreaks have led to public concern and an interest in understanding the underlying biological mechanisms. Here, we propose a climate-animal-Hantaan virus (HTNV) infection model to address this issue, using a unique dataset spanning a 54-y period (1960-2013). This dataset comes from Central China, a focal point for natural HTNV infection, and includes both field surveillance and an epidemiological record. We reveal that the 8-y cycle of HTNV outbreaks is driven by the confluence of the cyclic dynamics of striped field mouse (Apodemus agrarius) populations and climate variability, at both seasonal and interannual cycles. Two climatic variables play key roles in the ecology of the HTNV system: temperature and rainfall. These variables account for the dynamics in the host reservoir system and markedly affect both the rate of transmission and the potential risk of outbreaks. Our results suggest that outbreaks of HTNV infection occur only when climatic conditions are favorable for both rodent population growth and virus transmission. These findings improve our understanding of how climate drives the periodic reemergence of zoonotic disease outbreaks over long timescales.

Anthropogenically driven environmental changes shift the ecological dynamics of hemorrhagic fever with renal syndrome.

Zoonoses are increasingly recognized as an important burden on global public health in the 21st century. High-resolution, long-term field studies are critical for assessing both the baseline and future risk scenarios in a world of rapid changes. We have used a three-decade-long field study on hantavirus, a rodent-borne zoonotic pathogen distributed worldwide, coupled with epidemiological data from an endemic area of China, and show that the shift in the ecological dynamics of Hantaan virus was closely linked to environmental fluctuations at the human-wildlife interface. We reveal that environmental forcing, especially rainfall and resource availability, exert important cascading effects on intra-annual variability in the wildlife reservoir dynamics, leading to epidemics that shift between stable and chaotic regimes. Our models demonstrate that bimodal seasonal epidemics result from a powerful seasonality in transmission, generated from interlocking cycles of agricultural phenology and rodent behavior driven by the rainy seasons.

Molecular Evolution, Diversity, and Adaptation of Influenza A(H7N9) Viruses in China.

The substantial increase in prevalence and emergence of antigenically divergent or highly pathogenic influenza A(H7N9) viruses during 2016-17 raises concerns about the epizootic potential of these viruses. We investigated the evolution and adaptation of H7N9 viruses by analyzing available data and newly generated virus sequences isolated in Guangdong Province, China, during 2015-2017. Phylogenetic analyses showed that circulating H7N9 viruses belong to distinct lineages with differing spatial distributions. Hemagglutination inhibition assays performed on serum samples from patients infected with these viruses identified 3 antigenic clusters for 16 strains of different virus lineages. We used ancestral sequence reconstruction to identify parallel amino acid changes on multiple separate lineages. We inferred that mutations in hemagglutinin occur primarily at sites involved in receptor recognition or antigenicity. Our results indicate that highly pathogenic strains likely emerged from viruses circulating in eastern Guangdong Province during March 2016 and are associated with a high rate of adaptive molecular evolution.

Avian influenza H5N1 viral and bird migration networks in Asia.

The spatial spread of the highly pathogenic avian influenza virus H5N1 and its long-term persistence in Asia have resulted in avian influenza panzootics and enormous economic losses in the poultry sector. However, an understanding of the regional long-distance transmission and seasonal patterns of the virus is still lacking. In this study, we present a phylogeographic approach to reconstruct the viral migration network. We show that within each wild fowl migratory flyway, the timing of H5N1 outbreaks and viral migrations are closely associated, but little viral transmission was observed between the flyways. The bird migration network is shown to better reflect the observed viral gene sequence data than other networks and contributes to seasonal H5N1 epidemics in local regions and its large-scale transmission along flyways. These findings have potentially far-reaching consequences, improving our understanding of how bird migration drives the periodic reemergence of H5N1 in Asia.

Genetic evidence for avian influenza H5N1 viral transmission along the Black Sea-Mediterranean Flyway.

The current epidemic of highly pathogenic avian influenza H5N1 virus is considered to pose a significant threat to the health of wild and domestic avian species, and even to human beings. The Black Sea-Mediterranean Flyway is one of the most important epidemic areas of H5N1. However, the epidemic along this flyway has not been fully explored. To better understand the role of hosts in the spread and evolution of H5N1 virus along the flyway, a phylogeographic study was conducted using haemagglutinin (HA) gene sequences obtained during 2005-2013. To infer phylodynamic spread in time and space, we used a flexible Bayesian statistical framework and modelled viral spatial diffusion as a continuous-time Markov-chain process along time-measured genealogies. Our results revealed that H5N1 virus isolated from wild birds showed an increase in genetic variation of HA gene from 2005-2007. The mean genetic distance of viruses isolated from poultry reached its peak in 2010, and dropped in 2011, increasing again in 2012-2013. The reconstruction of virus circulation revealed a different viral-migration network of H5N1 virus by different hosts. Western Russia constituted a link in viral migration from Russia to Europe and Africa. Cross-species transmission of H5N1 viruses predominated in the migration network of the Black Sea-Mediterranean Flyway. This might be due to the migration of birds across long distances and interaction between local poultry and migratory birds. Additionally, the short-distance spread of H5N1 viruses among poultry followed local transportation networks. Such findings will aid in developing effective disease control and prevention strategies.

Surface water areas significantly impacted 2014 dengue outbreaks in Guangzhou, China.

Dengue transmission in urban areas is strongly influenced by a range of biological and environmental factors, yet the key drivers still need further exploration. To better understand mechanisms of environment-mosquito-urban dengue transmission, we propose an empirical model parameterized and cross-validated from a unique dataset including viral gene sequences, vector dynamics and human dengue cases in Guangzhou, China, together with a 36-year urban environmental change maps investigated by spatiotemporal satellite image fusion. The dengue epidemics in Guangzhou are highly episodic and were not associated with annual rainfall over time. Our results indicate that urban environmental changes, especially variations in surface area covered by water in urban areas, can substantially alter the virus population and dengue transmission. The recent severe dengue outbreaks in Guangzhou may be due to the surge in an artificial lake construction, which could increase infection force between vector (mainly Aedes albopictus) and host when urban water area significantly increased. Impacts of urban environmental change on dengue dynamics may not have been thoroughly investigated in the past studies and more work needs to be done to better understand the consequences of urbanization processes in our changing world.

Spatial, temporal and genetic dynamics of highly pathogenic avian influenza A (H5N1) virus in China.

BACKGROUND: The spatial spread of H5N1 avian influenza, significant ongoing mutations, and long-term persistence of the virus in some geographic regions has had an enormous impact on the poultry industry and presents a serious threat to human health. METHODS: We applied phylogenetic analysis, geospatial techniques, and time series models to investigate the spatiotemporal pattern of H5N1 outbreaks in China and the effect of vaccination on virus evolution. RESULTS: Results showed obvious spatial and temporal clusters of H5N1 outbreaks on different scales, which may have been associated with poultry and wild-bird transmission modes of H5N1 viruses. Lead-lag relationships were found among poultry and wild-bird outbreaks and human cases. Human cases were preceded by poultry outbreaks, and wild-bird outbreaks were led by human cases. Each clade has gained its own unique spatiotemporal and genetic dominance. Genetic diversity of the H5N1 virus decreased significantly between 1996 and 2011; presumably under strong selective pressure of vaccination. Mean evolutionary rates of H5N1 virus increased after vaccination was adopted in China. A clear signature of positively selected sites in the clade 2.3.2 virus was discovered and this may have resulted in the emergence of clade 2.3.2.1. CONCLUSIONS: Our study revealed two different transmission modes of H5N1 viruses in China, and indicated a significant role of poultry in virus dissemination. Furthermore, selective pressure posed by vaccination was found in virus evolution in the country.

Microbial denitrification characteristics of typical decentralized wastewater treatment processes based on 16S rRNA sequencing.

Despite the widespread application of decentralized wastewater treatment (WWT) facilities in China, relatively few research has used the multi-media biological filter (MMBF) facilities to investigate the microorganism characteristics. This study utilizes 16S rRNA high-throughput sequencing (HTS) technology to examine the microbial biodiversity of a representative wastewater treatment (WWT) system in an expressway service area. The pathways of nitrogen removal along the treatment route were analyzed in conjunction with water quality monitoring. The distribution and composition of microbial flora in the samples were examined, and the dominant flora were identified using LEfSe analysis. The FAPROTAX methodology was employed to investigate the relative abundance of genes associated with the nitrogen cycle and to discern the presence of functional genes involved in nitrogen metabolism. On average, the method has a high level of efficiency in removing COD, TN, NH3-N, and TP from the effluent. The analysis of the microbial community identified a total of 40 phyla, 111 classes, 143 orders, 263 families, and 419 genera. The phyla that were predominantly observed include Proteobacteria, Acidobacteria, Chloroflexi, Actinobacteria, Nitrospirae, Bacteroidetes. The results show that the system has achieved high performance in nitrogen removal, the abundance of nitrification genes is significantly higher than that of other nitrogen cycle genes such as denitrification, and there are six nitrogen metabolism pathways, primarily nitrification, among which Nitrospirae and Nitrospira are the core differentiated flora that can adapt to low temperature conditions and participate in nitrification, and are the dominant nitrogen removal flora in cold regions. This work aims to comprehensively investigate the diversity and functional properties of the bacterial community in decentralized WWT processes.

Evolutionary selection of biofilm-mediated extended phenotypes in Yersinia pestis in response to a fluctuating environment.

Yersinia pestis is transmitted from fleas to rodents when the bacterium develops an extensive biofilm in the foregut of a flea, starving it into a feeding frenzy, or, alternatively, during a brief period directly after feeding on a bacteremic host. These two transmission modes are in a trade-off regulated by the amount of biofilm produced by the bacterium. Here by investigating 446 global isolated Y. pestis genomes, including 78 newly sequenced isolates sampled over 40 years from a plague focus in China, we provide evidence for strong selection pressures on the RNA polymerase ω-subunit encoding gene rpoZ. We demonstrate that rpoZ variants have an increased rate of biofilm production in vitro, and that they evolve in the ecosystem during colder and drier periods. Our results support the notion that the bacterium is constantly adapting-through extended phenotype changes in the fleas-in response to climate-driven changes in the niche.

Increasing airline travel may facilitate co-circulation of multiple dengue virus serotypes in Asia.

The incidence of dengue has grown dramatically in recent decades worldwide, especially in Southeast Asia and the Americas with substantial transmission in 2014-2015. Yet the mechanisms underlying the spatio-temporal circulation of dengue virus (DENV) serotypes at large geographical scales remain elusive. Here we investigate the co-circulation in Asia of DENV serotypes 1-3 from 1956 to 2015, using a statistical framework that jointly estimates migration history and quantifies potential predictors of viral spatial diffusion, including socio-economic, air transportation and maritime mobility data. We find that the spread of DENV-1, -2 and -3 lineages in Asia is significantly associated with air traffic. Our analyses suggest the network centrality of air traffic hubs such as Thailand and India contribute to seeding dengue epidemics, whilst China, Cambodia, Indonesia, and Singapore may establish viral diffusion links with multiple countries in Asia. Phylogeographic reconstructions help to explain how growing air transportation networks could influence the dynamics of DENV circulation.

Severe Fever with Thrombocytopenia Syndrome Virus in Humans, Domesticated Animals, Ticks, and Mosquitoes, Shaanxi Province, China.

AbstractThe first human infection with severe fever with thrombocytopenia syndrome virus (SFTSV) was detected in Shaanxi Province, China, in 2013, although the virus had been reported in 13 other provinces of China since 2010. We collected and analyzed a total of 4,011 samples, including 936 human serum samples, 155 animal serum samples, 895 ticks, 1,950 mosquitoes, 30 midges, and 20 sandflies. SFTSV antibodies were found in 44 human samples (4.7%) with no significant differences between males and females or across counties. The incidence rate of severe fever with thrombocytopenia syndrome was significantly higher among individuals 20-60 years of age. Moreover, SFTSV-specific antibodies were detected in goats (66.7%), cattle (13.2%), and dogs (15.0%), but not in pigs (0%). We detected the virus in Haemaphysalis concinna ticks with a prevalence rate of 21.3% (17/80 pools). All mosquito, midge, and sandfly samples were negative for SFTSV. These results support wide circulation of the virus in western China. Haemaphysalis concinna ticks may serve as a novel SFTSV vector, and the role of these ticks requires further investigation.

How environmental conditions impact mosquito ecology and Japanese encephalitis: an eco-epidemiological approach.

Japanese encephalitis (JE) is one of the major vector-borne diseases in Southeast Asia and the Western Pacific region, posing a threat to human health. In rural and suburban areas, traditional rice farming and intensive pig breeding provide an ideal environment for both mosquito development and the transmission of JEV among human beings. Combining surveillance data for mosquito vectors, human JE cases, and environmental conditions in Changsha, China, 2004-2009, generalized threshold models were constructed to project the mosquito and JE dynamics. Temperature and rainfall were found to be closely associated with mosquito density at 1, and 4month lag, respectively. The two thresholds, maximum temperature of 22-23°C for mosquito development and minimum temperature of 25-26°C for JEV transmission, play key roles in the ecology of JEV. The model predicts that, in the upper regime, a 1g/m(3) increase in absolute humidity would on average increase human cases by 68-84%. A shift in mosquito species composition in 2007 was observed, and possibly caused by a drought. Effective predictive models could be used in risk management to provide early warnings for potential JE transmission.

Changes in rodent abundance and weather conditions potentially drive hemorrhagic fever with renal syndrome outbreaks in Xi'an, China, 2005-2012.

BACKGROUND: Increased risks for hemorrhagic fever with renal syndrome (HFRS) caused by Hantaan virus have been observed since 2005, in Xi'an, China. Despite increased vigilance and preparedness, HFRS outbreaks in 2010, 2011, and 2012 were larger than ever, with a total of 3,938 confirmed HFRS cases and 88 deaths in 2010 and 2011. METHODS AND FINDINGS: Data on HFRS cases and weather were collected monthly from 2005 to 2012, along with active rodent monitoring. Wavelet analyses were performed to assess the temporal relationship between HFRS incidence, rodent density and climatic factors over the study period. Results showed that HFRS cases correlated to rodent density, rainfall, and temperature with 2, 3 and 4-month lags, respectively. Using a Bayesian time-series Poisson adjusted model, we fitted the HFRS outbreaks among humans for risk assessment in Xi'an. The best models included seasonality, autocorrelation, rodent density 2 months previously, and rainfall 2 to 3 months previously. Our models well reflected the epidemic characteristics by one step ahead prediction, out-of-sample. CONCLUSIONS: In addition to a strong seasonal pattern, HFRS incidence was correlated with rodent density and rainfall, indicating that they potentially drive the HFRS outbreaks. Future work should aim to determine the mechanism underlying the seasonal pattern and autocorrelation. However, this model can be useful in risk management to provide early warning of potential outbreaks of this disease.