Shanqian Huang

Avian influenza H5N1 viral and bird migration networks in Asia

Significance Highly pathogenic avian influenza virus H5N1 first emerged in Asia and subsequently unfolded into the first avian influenza panzootic, causing major economic losses in the poultry sector. However, we still do not understand the regional long-distance transmission and seasonal patterns of H5N1. In this study, we addressed this issue by combining H5N1 outbreak records, whole-genome sequences of viral samples, and satellite tracking data for four species of migratory birds in Asia. We show that timing of H5N1 outbreaks and viral migration are closely associated with known bird migration routes. The flyway is the major viral transmission barrier to the intracontinental spread of H5N1 by migratory birds in Asia, whereas geographic distances within the flyways have little effect on H5N1 transmission. 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.

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.

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.

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.

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

Significance Interannual cycles of many zoonotic diseases are considered to be driven by climate variability. However, the role of climate forcing in the modulation of zoonotic dynamics has been highly controversial, chiefly due to the difficulty in quantifying the links between climate forcing, animal population dynamics, and disease dynamics. Here, we address this issue by using a unique field surveillance dataset from Central China, covering one-half century. Our results shed light on the drivers behind interannual variability and the dynamic patterns of disease ecology, and the links between interannual climate variability and the human–animal interface, adding up to 3-mo lead time over outbreak warnings. 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.

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

BackgroundThe 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.MethodsWe 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.ResultsResults 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.ConclusionsOur 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.

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.

Using Satellite Data for the Characterization of Local Animal Reservoir Populations of Hantaan Virus on the Weihe Plain, China

Striped field mice (Apodemus agrarius) are the main host for the Hantaan virus (HTNV), the cause of hemorrhagic fever with renal syndrome (HFRS) in central China. It has been shown that host population density is associated with pathogen dynamics and disease risk. Thus, a higher population density of A. agrarius in an area might indicate a higher risk for an HFRS outbreak. Here, we surveyed the A. agrarius population density between 2005 and 2012 on the Weihe Plain, Shaanxi Province, China, and used this monitoring data to examine the relationships between the dynamics of A. agrarius populations and environmental conditions of crop-land, represented by remote sensing based indicators. These included the normalized difference vegetation index, leaf area index, fraction of photosynthetically active radiation absorbed by vegetation, net photosynthesis (PsnNet), gross primary productivity, and land surface temperature. Structural equation modeling (SEM) was applied to detect the possible causal relationship between PsnNet, A. agrarius population density and HFRS risk. The results showed that A. agrarius was the most frequently captured species with a capture rate of 0.9 individuals per hundred trap-nights, during 96 months of trapping in the study area. The risk of HFRS was highly associated with the abundance of A. agrarius, with a 1–5-month lag. The breeding season of A. agrarius was also found to coincide with agricultural activity and seasons with high PsnNet. The SEM indicated that PsnNet had an indirect positive effect on HFRS incidence via rodents. In conclusion, the remote sensing-based environmental indicator, PsnNet, was highly correlated with HTNV reservoir population dynamics with a 3-month lag (r = 0.46, p < 0.01), and may serve as a predictor of potential HFRS outbreaks.

Risk analysis of H5N1 highly pathogenic avian influenza in poultry at the Poyang Lake area, China

Migratory birds have been known to spread the highly pathogenic avian influenza virus (HPAIV) H5N1 over large distances. Moreover, previous studies have shown it to be widely circulated in live-bird markets. However, how live-bird markets in addition to wild birds affect the local persistence of avian influenza virus (AIV) remains uncertain. The abundance of fresh water and widely distributed wetlands make the Poyang lake area a suitable overwintering site for migratory birds. The intensive local poultry industry and poor biosecurity potentially increase the risk of interactions between the wild and domestic birds. These factors likely contributed to the spread and persistence of AIVs in the Poyang lake area in these years. Here, a cross-sectional survey together with sampling was conducted randomly in the Poyang lake area to investigate the local distribution of the H5N1 viruses. In total, 891 poultry isolates from 31 villages around the Poyang lake area were randomly sampled in poultry sectors and tested for the presence of avian influenza using RT-PCR assays. Environmental factors such as poultry density, road accessibility, and wild bird biodiversity together with breeding characteristics derived from these questionnaires were collected and utilized for risk analysis modelling. Our results revealed that distance to the nearest wetlands with a high number of birds and accessibility by road were the main risk factors for the occurrence HPAIV H5N1, suggesting that the high density of road networks may facilitate the transmission of this virus. Investigating the regional distribution characteristics of the virus is of great significance, therefore the general public would benefit from an early warning, prevention, and taking control measures in high-risk regions.