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Background: Brucellosis, as a serious zoonotic infectious disease, has been recognized as a re-emerging disease in the developing countries worldwide. In china, the incidence of brucellosis is increasing each year, seriously threatening the health of humans as well as animal populations. Despite a quite number of diagnostic methods currently being used for brucellosis, innovative technologies are still needed for its rapid and accurate diagnosis, especially in area where traditional diagnostic is unavailable., Methodology/principal Findings: In this study, a total of 22 B cell linear epitopes were predicted from five Brucella outer membrane proteins (OMPs) using an immunoinformatic approach. These epitopes were then chemically synthesized, and with the method of indirect ELISA (iELISA), each of them displayed a certain degree of capability in identifying human brucellosis positive sera. Subsequently, a fusion protein consisting of the 22 predicted epitopes was prokaryotically expressed and used as diagnostic antigen in a newly established brucellosis testing method, nano-ZnO modified paper-based ELISA (nano-p-ELISA). According to the verifying test using a collection of sera collected from brucellosis and non-brucellosis patients, the sensitivity and specificity of multiepitope based nano-p-ELISA were 92.38% and 98.35% respectively. The positive predictive value was 98.26% and the negative predictive value was 91.67%. The multiepitope based fusion protein also displayed significantly higher specificity than Brucella lipopolysaccharide (LPS) antigen., Conclusions: B cell epitopes are important candidates for serologically testing brucellosis. Multiepitope fusion protein based nano-p-ELISA displayed significantly sensitivity and specificity compared to Brucella LPS antigen. The strategy applied in this study will be helpful to develop rapid and accurate diagnostic method for brucellosis in human as well as animal populations., Competing Interests: The authors have declared that no competing interests exist.

The purpose of this study was to determine the diagnostic efficacy of Xpert MTB/RIF assay for rapid diagnosis of Tuberculosis (TB) and detection of rifampicin (RIF) resistance in patients suspected of having EPTB, assessing it against traditional culture and drug susceptibility test (DST) by proportional method, and the ability to predict multidrug resistance TB by Xpert MTB/RIF assay. In this study, the Xpert MTB/RIF assay was applied to 1,614 extrapulmonary specimens. Compared with TB culture and Composite Reference Standard (CRS), the Xpert MTB/RIF assay had a high sensitivity and specificity for detection of EPTB. Depending on the culture method or CRS as the standard, sensitivity of the Xpert MTB/RIF assay for detection of MTB in pleural effusion, cerebrospinal fluid, thoracic drainage fluid and throat swabs specimens were lower than that of other specimens. According to the experimental results, we have reason to believe that Xpert MTB/RIF assay is a rapid and simple technique with high sensitivity and specificity for diagnosing EPTB and detecting drug resistance in variety of specimens. Xpert MTB/RIF assay combined with DST maybe identify more cases of multi-drug resistant tuberculosis (MDR-TB). Author summary: Tuberculosis (TB) is the second most deadly infectious disease after COVID-19. Improving the accessibility of WHO recommended rapid molecular diagnostic tests to achieve earlier and more accurate diagnosis of TB is an important part of strengthening TB laboratory work in the strategy of ending the epidemic of tuberculosis. Extrapulmonary tuberculosis (EPTB) accounts for 15% of all tuberculosis cases. Due to the unique biological samples of different classified EPTB and the occult nature of their onset, their diagnosis is more challenging. Smear microscopy is often insensitive and culture methods are prolonged. With the introduction of Xpert MTB/RIF assay (Cepheid Inc.), this has changed TB diagnostics by providing a rapid accessible platform to diagnose TB and identify rifampicin(RIF) resistance within 2h. Xpert MTB/RIF assay is a suite of semi-nested real-time fluorescent quantitative PCR in vitro diagnostic technologies with good detection efficiency. In recent years, WHO has limited recommended Xpert MTB/RIF assay to detect various types of samples other than sputum for preliminary diagnosis of EPTB. The purpose of this paper is to systematically evaluate the practical application effect of Xpert MTB/RIF assay in the clinical diagnosis of EPTB, and provide scientific guidance for clinicians.ű [ABSTRACT FROM AUTHOR]

The reported cases of scrub typhus (ST) have continued to escalate, with outbreaks occurring regionally in China. These pose an increasing public health threat at a time when public health has been overwhelmed. During the period from July to August 2022, in Rongjiang County, Guizhou Province, China, 13 out of 21 fever patients were diagnosed with scrub typhus, based on epidemiological investigation and blood test analysis. The major clinical symptoms of these patients showed fever, chills, headache, eschar, fatigue and pneumonia, which were accompanied by a rise in C-reactive protein, neutrophils, alanine transaminase (ALT) and aspartate aminotransferase (AST). Furthermore, nearly half of them exhibited abnormal electrocardiogram activity. Through semi-nested PCR, Sanger sequencing and phylogenetic tree construction, the Karp strain of Orientia tsutsugamushi (O. tsutsugamushi) was confirmed as the pathogen causing ST in Rongjiang County, which shared the same evolutionary branch with O. tsutsugamushi isolated from wild mouse liver or spleen, indicating that the wild mouse plays an important role in transmitting the disease. In contrast to the sporadic cases in the past, our study is the first to disclose an epidemic and the corresponding clinical characteristics of ST in Guizhou province, which is of great significance for the prevention and treatment of regional illnesses. Author summary: In this study, 13 cases of ST were identified through clinical and laboratory diagnosis in Rongjiang County, which is the first outbreak of the disease in Guizhou province, China. It is worth noting that ST was caused by the Karp strain, which can be transmitted by wild mice, and the infected population generally had a clear history of outdoor activity. In addition to the typical clinical symptoms such as fever, chills and pneumonia, nearly half of patients with ST also exhibited abnormal electrocardiogram activity. In conclusion, our study presents a method to confirm ST through the combination of clinical and laboratory diagnosis, which provides a reference for the development of effective strategies and measures to tackle ST, and has important public health significance. [ABSTRACT FROM AUTHOR]

Background: Cryptosporidiosis is an emerging infectious disease of public health significance worldwide. The burden of disease caused by Cryptosporidium varies between and within countries/areas. To have a comprehensive understanding of epidemiological status and characteristics of human Cryptosporidium infection in China since the first report in 1987, a retrospective epidemiological analysis was conducted by presenting differences in the prevalence of Cryptosporidium by province, year, population, living environment and season and possible transmission routes and risk factors as well as genetic characteristics of Cryptosporidium in humans. Methodology/Principal findings: A systematic search was conducted to obtain epidemiological papers of human Cryptosporidium infection/cryptosporidiosis from PubMed and Chinese databases. Finally, 164 papers were included in our analysis. At least 200,054 people from 27 provinces were involved in investigational studies of Cryptosporidium, with an average prevalence of 2.97%. The prevalence changed slightly over time. Variable prevalences were observed: 0.65–11.15% by province, 1.89–47.79% by population, 1.77–12.87% and 0–3.70% in rural and urban areas, respectively. The prevalence peak occurred in summer or autumn. Indirect person-to-person transmission was documented in one outbreak of cryptosporidiosis in a pediatric hospital. 263 Cryptosporidium isolates were obtained, and seven Cryptosporidium species were identified: C. hominis (48.3%), C. andersoni (22.43%), C. parvum (16.7%), C. meleagridis (8.36%), C. felis (3.04%), C. canis (0.76%) and C. suis (0.38%). Conclusions/Significances: This systematic review reflects current epidemiological status and characteristics of Cryptosporidium in humans in China. These data will be helpful to develop efficient control strategies to intervene with and prevent occurrence of human Cryptosporidium infection/cryptosporidiosis in China as well as have a reference effect to other countries. Further studies should focus on addressing a high frequency of C. andersoni in humans and a new challenge with respect to cryptosporidiosis with an increasing population of elderly people and patients with immunosuppressive diseases. Author summary: Cryptosporidium is a major cause of diarrheal disease in humans globally. Due to the lack of effective drug treatment and vaccine prevention against cryptosporidiosis, it is particularly important to develop efficient control strategies to intervene with and prevent Cryptosporidium infection in humans. The present review presented and analyzed epidemiological status and characteristics of Cryptosporidium infection in humans in China since the first report in 1987. To date, epidemiological investigations of Cryptosporidium infecion have been carried out in different populations in 27 provinces, autonomous regions, and municipalities. Average prevalence of Cryptosporidium was 2.97% (5,933/200,054). Like other infectious disease, due to poor sanitation conditions in rural areas, people living in rural areas had a significantly higher prevalence of Cryptosporidium (1.77–12.87%) than those living in urban areas (0–3.70%). Seven Cryptosporidium species were identified, including C. hominis, C. andersoni, C. parvum, C. meleagridis, C. felis, C. canis and C. suis. This retrospective epidemiological analysis indicates wide geographical distribution of human Cryptosporidium infection/cryptosporidiosis in China. [ABSTRACT FROM AUTHOR]

Background: As China is moving onto schistosomiasis elimination/eradication, diagnostic methods with both high sensitivity and specificity for Schistosoma japonicum infections in humans are urgently needed. Microscopic identification of eggs in stool is proven to have poor sensitivity in low endemic regions, and antibody tests are unable to distinguish between current and previous infections. Polymerase chain reaction (PCR) technologies for the detection of parasite DNA have been theoretically assumed to show high diagnostic sensitivity and specificity. However, the reported performance of PCR for detecting S. japonicum infection varied greatly among studies. Therefore, we performed a meta-analysis to evaluate the overall diagnostic performance of variable-temperature PCR technologies, based on stool or blood, for detecting S. japonicum infections in humans from endemic areas. Methods: We searched literatures in eight electronic databases, published up to 20 January 2021. The heterogeneity and publication bias of included studies were assessed statistically. The risk of bias and applicability of each eligible study were assessed using the Quality Assessment of Diagnostic Accuracy Studies 2 tool (QUADAS-2). The bivariate mixed-effects model was applied to obtain the summary estimates of diagnostic performance. The hierarchical summary receiver operating characteristic (HSROC) curve was applied to visually display the results. Subgroup analyses and multivariate regression were performed to explore the source of heterogeneity. This research was performed following the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines and was registered prospectively in PROSPERO (CRD42021233165). Results: A total of 2791 papers were retrieved. After assessing for duplications and eligilibity a total of thirteen publications were retained for inclusion. These included eligible data from 4268 participants across sixteen studies. High heterogeneity existed among studies, but no publication bias was found. The pooled analyses of PCR data from all included studies resulted in a sensitivity of 0.91 (95% CI: 0.83 to 0.96), specificity of 0.85 (95% CI: 0.65 to 0.94), positive likelihood ratio of 5.90 (95% CI: 2.40 to 14.60), negative likelihood ratio of 0.10 (95% CI: 0.05 to 0.20) and a diagnostics odds ratio of 58 (95% CI: 19 to 179). Case-control studies showed significantly better performances for PCR diagnostics than cross-sectional studies. This was further evidenced by multivariate analyses. The four types of PCR approaches identified (convention PCR, qPCR, Digital droplet PCR and nested PCR) differed significantly, with nested PCRs showing the best performance. Conclusions: Variable-temperature PCR has a satisfactory performance for diagnosing S. japonicum infections in humans in endemic areas. More high quality studies on S. japonicum diagnostic techniques, especially in low endemic areas and for the detection of dual-sex and single-sex infections are required. These will likely need to optimise a nested PCR alongside a highly sensitive gene target. They will contribute to successfully monitoring endemic areas as they move towards the WHO 2030 targets, as well as ultimately helping areas to achieve these goals. Author summary: Schistosoma japonicum is a parasite that can cause serious intestinal schistosomiasis. The infection is mainly diagnosed by parasitological and immunological methods, such as Kato-Katz test and indirect hemagglutination assay. However, both of these are not sensitive enough to accurately assess schistosomiasis elimination/eradication. PCR assays, detecting parasite DNA, are theoretically a highly suitable, sensitive and specific, alternative. However, reported performance varies greatly among studies. Therefore, we performed this meta-analysis (PROSPERO, registered No. CRD42021233165) to analyze and summarize the data from relevant studies of variable-temperature PCR for the diagnosis of S. japonicum infections, using stool or blood samples from humans in endemic areas. We retrieved a total of 13 articles including data from 4268 participants across 16 studies. There was high heterogeneity among studies, but no publication bias was found. Analyses revealed that PCR techniques had a satisfactory performance for diagnosing S. japonicum infections in humans in endemic areas, with both high sensitivity and specificity. Further research on S. japonicum diagnostic techniques, especially in low endemicity areas and for detection of dual-sex and single-sex infections are required. These may be best using highly sensitive gene targets in nested PCR reactions. [ABSTRACT FROM AUTHOR]

Background: Understanding and mapping the distribution of sandflies and sandfly-associated pathogens (SAPs) is crucial for guiding the surveillance and control effort. However, their distribution and the related risk burden in China remain poorly understood. Methods: We mapped the distribution of sandflies and SAPs using literature data from 1940 to 2022. We also mapped the human visceral leishmaniasis (VL) cases using surveillance data from 2014 to 2018. The ecological drivers of 12 main sandfly species and VL were identified by applying machine learning, and their distribution and risk were predicted in three time periods (2021–2040, 2041–2060, and 2061–2080) under three scenarios of climate and socioeconomic changes. Results: In the mainland of China, a total of 47 sandfly species have been reported, with the main 12 species classified into three clusters according to their ecological niches. Additionally, 6 SAPs have been identified, which include two protozoa, two bacteria, and two viruses. The incidence risk of different VL subtypes was closely associated with the distribution risk of specific vectors. The model predictions also revealed a substantial underestimation of the current sandfly distribution and VL risk. The predicted areas affected by the 12 major species of sandflies and the high-risk areas for VL were found to be 37.9–1121.0% and 136.6% larger, respectively, than the observed range in the areas. The future global changes were projected to decrease the risk of mountain-type zoonotic VL (MT-ZVL), but anthroponotic VL (AVL) and desert-type zoonotic VL (DT-ZVL) could remain stable or slightly increase. Conclusions: Current field observations underestimate the spatial distributions of main sandfly species and VL in China. More active surveillance and field investigations are needed where high risks are predicted, especially in areas where the future risk of VL is projected to remain high or increase. Author summary: Our research provides a comprehensive understanding of the distribution of sandflies and SAPs in China. We have identified 47 sandfly species and 6 SAPs, with 12 main sandfly species forming three distinct ecological clusters. Our machine learning models predict the distribution and risk of sandfly species and VL under various climate and socioeconomic scenarios. The model predictions reveal a significant underestimation of the current sandfly distribution and VL risk. Future global changes are projected to decrease the risk of MT-ZVL, but AVL and DT-ZVL could remain stable or slightly increase. These findings underscore the need for more active surveillance and field investigations of vectors, especially where the future risk of VL is projected to remain high or increase. This study provides important theoretical support for guiding the surveillance and control of sandflies and SAPs. [ABSTRACT FROM AUTHOR]

Objective: To understand the epidemiological distribution characteristics of mountain-type zoonotic visceral leishmaniasis (MT-ZVL) in Yangquan City, Shanxi Province, China, from 2006 to 2021, to explore the influencing factors leading to the re-emergence of the epidemic, and to provide a basis for the formulation of targeted control strategies. Methods: Case information spanning from 2006 to 2021 in Yangquan City was collected for a retrospective case-control study conducted from June to September 2022. A 1:3 matched ratio was employed. A questionnaire was utilized to gather data on basic information, demographic characteristics, awareness of MT-ZVL knowledge, residence, and dog breeding and living habits. The study employed a multifactorial conditional stepwise logistic regression model to analyze the influencing factors. Results: A total of 508 subjects was analyzed. Risk factors for MT-ZVL included the use of soil/stone/concrete as building materials (OR = 3.932), presence of nearby empty/stone stack houses (OR = 2.515), dog breeding (OR = 4.215), presence of stray dogs (OR = 2.767), and neighbor's dog breeding (OR = 1.953). Protective factors comprised knowledge of MT-ZVL (OR = 0.113) and using mosquito repellents (OR = 0.388). The findings indicate significant associations between environmental and behavioral factors and MT-ZVL incidence in Yangquan City, Shanxi Province, China, from 2006 to 2021. These results underscore the importance of public awareness campaigns and targeted interventions aimed at reducing exposure to risk factors and promoting protective measures to mitigate the re-emergence of MT-ZVL outbreaks. Conclusion: House building materials, presence of neighboring empty houses, breeding domestic dogs and distribution of stray dogs surrounding the home are risk factors for MT-ZVL. Awareness of MT-ZVL and implementation of preventive measures during outdoor activities in summer and autumn are protective and may reduce the risk of MT-ZVL. Author summary: In recent years, a rapid reemergence of mountain-type zoonotic visceral leishmaniasis (MT-ZVL) has been seen in the extension region of the Loess Plateau that had previously achieved elimination in China. In this study, we investigate the epidemiological characteristics of MT-ZVL and identify the factors associated with the rapid rise in MT-ZVL epidemics using a case-control design. A questionnaire was used to collect basic information, demographic characteristics, awareness of MT-ZVL knowledge, residence, and dog breeding and living habits. A multifactorial conditional stepwise logistic regression model was used to analyze the influencing factors. The study revealed that there has been a rising trend in the MT-ZVL endemic areas. House building materials, presence of neighboring empty houses, breeding domestic dogs and distribution of stray dogs surrounding the home are risk factors for MT-ZVL. Awareness of MT-ZVL and implementation of preventive measures during outdoor activities in summer and autumn are protective and may reduce the risk of MT-ZVL. We believe that our study makes a significant contribution to the literature to develop strategy for control the ongoing local transmission of MT-ZVL in hill districts. By analyzing the epidemiological characteristics and influencing factors of MT-ZVL, this research provides a basis for further optimizing the targeted control strategies. [ABSTRACT FROM AUTHOR]

Background: Echinococcosis is a natural focal, highly prevalent disease in China. Factors influencing the spread of echinococcosis are not only related to personal exposure but also closely related to the environment itself. The purpose of this study was to explore the influence of environmental factors on the prevalence of human echinococcosis and to provide a reference for prevention and control of echinococcosis in the future. Methods: Data were collected from 370 endemic counties in China in 2018. By downloading Modis, DEM and other remote-sensing images in 2018. Data on environmental factors, i.e., elevation, land surface temperature (LST) and normalized difference vegetation index (NDVI) were collected. Rank correlation analysis was conducted between each environmental factor and the prevalence of echinococcosis at the county level. Negative binomial regression was used to analyze the impact of environmental factors on the prevalence of human echinococcosis at the county level. Results: According to rank correlation analysis, the prevalence of human echinococcosis in each county was positively correlated with elevation, negatively correlated with LST, and negatively correlated with NDVI in May, June and July. Negative binomial regression showed that the prevalence of human echinococcosis was negatively correlated with annual LST and summer NDVI, and positively correlated with average elevation and dog infection rate. The prevalence of human cystic echinococcosis was inversely correlated with the annual average LST, and positively correlated with both the average elevation and the prevalence rate of domestic animals. The prevalence of human alveolar echinococcosis was positively correlated with both NDVI in autumn and average elevation, and negatively correlated with NDVI in winter. Conclusion: The prevalence of echinococcosis in the population is affected by environmental factors. Environmental risk assessment and prediction can be conducted in order to rationally allocate health resources and improve both prevention and control efficiency of echinococcosis. Author summary: Echinococcosis is a natural focal, highly prevalent disease in China. Factors influencing the spread of echinococcosis are not only related to personal exposure but also closely related to the environment itself. This study covered all endemic counties in China and studied the main environmental factors affecting the epidemic of echinococcosis. to explore the influence of environmental factors on the prevalence of human echinococcosis, and to provide a reference for prevention and control of echinococcosis in the future. Data were collected from 370 endemic counties in China in 2018. By downloading Modis, DEM and other remote-sensing images in 2018. The prevalence of human echinococcosis in each county was positively correlated with elevation, negatively correlated with LST, and negatively correlated with NDVI in May, June and July. Prevalence of human echinococcosis was negatively correlated with annual LST and summer NDVI, and positively correlated with average elevation and dog infection rate. Prevalence of human cystic echinococcosis was inversely correlated with the annual average LST, and positively correlated with both the average elevation and the prevalence rate of domestic animals. The prevalence of human alveolar echinococcosis was positively correlated with both NDVI in autumn and average elevation, and negatively correlated with NDVI in winter. [ABSTRACT FROM AUTHOR]

Background: Advanced schistosomiasis is the most serious outcome of infection and has a negative impact on both physical fitness and mental health of patients, the latter of which has long been overlooked. Therefore, we performed this systematic review and meta-analysis to estimate the overall prevalence of depressive symptoms, one of the most common mental problems, in patients with advanced schistosomiasis in China. Methods: Six electronic databases were searched for studies reporting the prevalence of depressive symptoms in the targeted patients. Assessments were pooled using a fixed- or random-effects model based on heterogeneity test. Subgroup analyses were further performed and differences between/among groups were examined using the chi-squared test. The protocol had previously been registered in PROSPERO (CRD42023406708). Results: A total of 11 studies with 1,673 participants were included. The pooled prevalence of depressive symptoms in advanced schistosomiasis in China was 62.01% (95% CI: 51.30% - 72.72%), with a significant heterogeneity among studies. Depressive symptoms were more prevalent in patients with complications and more than half of the patients suffered a mild- or moderate-level of depression. No publication bias was found, and sensitivity analysis showed a stable result. Conclusions: The overall prevalence of depressive symptoms in advanced schistosomiasis in China was high enough to warrant psychotherapeutic interventions, especially for patients with complications. This would greatly prevent or/and reduce depression and improve their quality of life. Author summary: Schistosomiasis is a neglected tropical disease (NTD) which affects more than 250 million people across 78 countries worldwide. The three major schistosomes infecting humans are Schistosoma mansoni, S. japonicum, and S. haematobium. In China, after 70 years of control efforts, tremendous progress has been made, and now the number of schistosomiasis japonica infections is at its lowest historical level. However, advanced schistosomiasis, which is the most serious outcome of schistosome infection, poses a great threat as an increasing number of the patients have been diagnosed. Depression is a frequently occurring mental health issue caused by the disease that has long been overlooked. Therefore, we performed this meta-analysis to estimate the overall prevalence of depressive symptoms in patients with advanced schistosomiasis in China and its possible influential factors. We found that the pooled prevalence was 62.01% (95% CI: 51.30% - 72.72%) in the targeted patients and the estimate was associated with complications of the disease. Our study would call for psychological interventions to improve quality of life for patients with advanced schistosomiasis. [ABSTRACT FROM AUTHOR]

Background: Talaromycosis is one of the most common opportunistic infections in human immunodeficiency virus (HIV) infected patients. However, few researches have explored the prevalence in Southern China and fully assessed the value of the Mp1p antigen screening for the diagnosis of talaromycosis. Methodology/Principal findings: We performed a cross-sectional study of HIV-infected antiretroviral therapy (ART)-naïve adult patients who were seen in 2018 at Guangzhou Eighth People's Hospital, Guangzhou Medical University. Serum samples collected from all the 784 enrolled patients were tested for Mp1p antigen using double-antibody sandwich enzyme-linked immunosorbent assay. A culture of pathogen was conducted in 350 clinically suspected patients to confirm talaromycosis. The overall prevalence of talaromycosis based on the Mp1p antigen detection was 11.4% (89/784) and peaked at 32.2% (75/233) in patients with CD4+ ≤50 Nr/μl. Logistic regression analysis found Mp1p antigen positive rate decreased with the increase in CD4+ counts (OR 0.982, 95% CI 0.977–0.987, P<0.01). The optimal cut-off point of the CD4+ count was 50 Nr/μl or less. Among the 350 patients received both fungal culture and Mp1p antigen detection, 95/350 (27.1%) patients were culture-positive for a Talaromyces marneffei, 75/350 (21.4%) patients were Mp1p antigen positive. The Mp1p antigen assay showed a good agreement to the culture of pathogen, and the sensitivity, specificity, positive predictive value, negative predictive value and kappa value was 71.6% (68/95), 97.3% (248/255), 90.7% (68/75), 90.2% (248/275), and 0.737, respectively. The screening accuracy of the Mp1p antigen assay in patients with CD4+ counts of ≤50 Nr/μl was superior to that in those with higher CD4+ counts. Conclusions/Significance: Mp1p antigen screening can be an effective tool for more efficient diagnosis of Talaromycosis, especially in HIV/AIDS patients with low CD4+ counts. Future validation studies are needed. Author summary: Talaromyces marneffei (T. marneffei) is an important human immunodeficiency virus (HIV)-associated opportunistic pathogen in Southern China, and its infection is a leading cause of HIV-associated death. Properly and early antifungal treatment and timely antiretroviral therapy (ART) would reduce the mortality. Currently, the gold standard of diagnosis for talaromycosis is culture. The Mp1p antigen assay, the detection for a T. marneffei-specific protein, would be a reliable biomarker of T. marneffei infection in clinical practices. The CD4+ counts are an indicator of human immune system. The less CD4+ counts the weaker immune function and much possible the infection of opportunistic pathogen. In this study, we found that HIV patients with talaromycosis had a lower CD4+ count and more advanced disease compared to those without. The prevalence of talaromycosis based on the Mp1p antigen detection was significantly higher in patients with low CD4+ count than those with without. What's more, the Mp1p antigen screening was an effective tool to motivate the diagnosis for talaromycosis in patients with CD4+ ≤ 50 Nr/μl, and in turn to drive the initiation of antifungal treatment and ART, which would help the reduction of mortality and the improvement of treatment outcome. [ABSTRACT FROM AUTHOR]

Background: Bacillary dysentery (BD) has brought a significant public health concern in China. Temperature is one of the main factors affecting BD incidence. Due to the largely different temperature ranges between regions, the classic multi-region time series studies could only explore the relative temperature-BD association and showed that BD incidence is positively associated with relative temperature (i.e., temperature percentile), which does not conform to the laboratory knowledge that both high and low temperature interfere with the survival of bacteria. The association on relative temperature scale also limits the intuition of epidemiological meanings. Methods: A novel two-stage strategy was proposed to investigate the association between monthly temperature and BD incidence on the original temperature scale in 31 provinces, China. In the first stage, truncated polynomial splines, as the substitute of the common natural splines or B-splines in generalized additive models, were used to characterize the temperature-BD association on the original temperature scale in each province. In the second stage, a multivariate meta-analysis compatible with missing values was used to pool the associations. The classic strategy based on relative temperature was used as a reference. Results: The average temperature-BD association presented a U-inverted shape, but not a monotonically increasing shape obtained using the classic strategy. This inverted U-shaped association conforms more to the laboratory knowledge and the original-scale association also provided an intuitive perspective and an easily explanatory result. Another advantage is that the novel strategy can extrapolate the province-specific association outside the observed temperature ranges by utilizing information from other provinces, which is meaningful considering the frequent incidences of extreme temperatures. Conclusions: The association between temperature and BD incidence presented a U-inverted shape. The proposed strategy can efficiently characterize the association between exposure and outcome on original scale in a multi-region study with largely different exposure ranges. Author summary: Temperature is one of the main factors affecting BD incidence. Due to the largely different temperature ranges between regions, the classic multi-region time series studies could only explore the relative temperature-BD association and showed that BD incidence is positively associated with relative temperature (i.e., temperature percentile), which does not conform to the laboratory knowledge that both high and low temperatures interfere with the survival of bacteria. The relative-scale association also limits the intuition of epidemiological meanings. In this study, we proposed a novel two-stage strategy to characterize the association between BD and original temperature in 31 provinces, China. We examined an inverted U-shaped association, but not a monotonically increasing shape obtained using the classic strategy. This new finding conforms more to the laboratory knowledge and the original-scale association also provided an intuitive perspective and an easily explanatory result. Another advantage is that the novel strategy can extrapolate the province-specific association outside the observed temperature ranges by utilizing information from other provinces, which is meaningful considering the frequent incidences of extreme temperatures. [ABSTRACT FROM AUTHOR]

In order to investigate how the movement of dogs affects the geographically inter-provincial spread of rabies in Mainland China, we propose a multi-patch model to describe the transmission dynamics of rabies between dogs and humans, in which each province is regarded as a patch. In each patch the submodel consists of susceptible, exposed, infectious, and vaccinated subpopulations of both dogs and humans and describes the spread of rabies among dogs and from infectious dogs to humans. The existence of the disease-free equilibrium is discussed, the basic reproduction number is calculated, and the effect of moving rates of dogs between patches on the basic reproduction number is studied. To investigate the rabies virus clades lineages, the two-patch submodel is used to simulate the human rabies data from Guizhou and Guangxi, Hebei and Fujian, and Sichuan and Shaanxi, respectively. It is found that the basic reproduction number of the two-patch model could be larger than one even if the isolated basic reproduction number of each patch is less than one. This indicates that the immigration of dogs may make the disease endemic even if the disease dies out in each isolated patch when there is no immigration. In order to reduce and prevent geographical spread of rabies in China, our results suggest that the management of dog markets and trades needs to be regulated, and transportation of dogs has to be better monitored and under constant surveillance. Author Summary: In 1999, human rabies cases were reported in about 120 counties in Mainland China, mainly in the southern provinces. Now outbreaks of human rabies have been reported in about 1000 counties and the disease has spread geographically from the south to the north. Phylogeographic analyses of rabies virus strains indicate that prevalent strains in northern provinces are indeed related to the remote southern provinces. It is believed that the geographical spread of rabies virus is caused by the transportation of dogs. In this paper, a multi-patch model is proposed to describe the spatial transmission dynamics of rabies in China and to investigate how the immigration of dogs affects the geographical spread of rabies. The expression and sensitivity analysis of the basic reproduction number indicates that the movement of dogs plays an essential role in the spatial transmission dynamics of rabies. Numerical simulations on the effect of the immigration rate in three pairs of provinces, Guizhou and Guangxi, Hebei and Fujian, Sichuan and Shaanxi, are also performed. It is shown that the immigration of dogs is the main factor for the long-distance inter-provincial spread of rabies and it is necessary to manage such inter-provincial transportation of dogs. [ABSTRACT FROM AUTHOR]

Iron is a trace metal element that is essential for the survival of cells and parasites. The role of iron in cerebral toxoplasmosis (CT) is still unclear. Deferiprone (DFP) is the orally active iron chelator that binds iron in a molar ratio of 3:1 (ligand:iron) and promotes urinary iron excretion to remove excess iron from the body. The aims of this experiment were to observe the alterations in iron in brains with Toxoplasma gondii (T. gondii) acute infections and to investigate the mechanism of ferroptosis in CT using DFP. We established a cerebral toxoplasmosis model in vivo using TgCtwh3, the dominant strains of which are prevalent in China, and treated the mice with DFP at a dose of 75 mg/kg/d. Meanwhile, we treated the HT-22 cells with 100 μM DFP for half an hour and then infected cells with TgCtwh3 in vitro. A qRT-PCR assay of TgSAG1 levels showed a response to the T. gondii burden. We used inductively coupled plasma mass spectrometry, an iron ion assay kit, Western blot analysis, glutathione and glutathione disulfide assay kits, a malonaldehyde assay kit, and immunofluorescence to detect the ferroptosis-related indexes in the mouse hippocampus and HT-22 cells. The inflammatory factors interferon-γ, tumor necrosis factor-α, transforming growth factor-β, and arginase 1 in the hippocampus and cells were detected using the Western blot assay. Hematoxylin and eosin staining, electron microscopy, and the Morris water maze experiment were used to evaluate the brain injuries of the mice. The results showed that TgCtwh3 infection is followed by the activation of ferroptosis-related signaling pathways and hippocampal pathological damage in mice. The use of DFP led to ferroptosis resistance and attenuated pathological changes, inflammatory reactions and T. gondii burden of the mice, prolonging their survival time. The HT-22 cells with TgCtwh3 activated the ferroptosis pathway and was inhibit by DFP in vitro. In TgCtwh3-infected cells, inflammatory response and mitochondrial damage were severe, but these effects could be reduced by DFP. Our study elucidates the mechanism by which T. gondii interferes with the host's iron metabolism and activates ferroptosis, complementing the pathogenic mechanism of CT and further demonstrating the potential value of DFP for the treatment of CT. Author summary: Iron metabolism is closely linked to host's immunity and is involved in inflammatory and infectious processes. Iron is an important target for the host in its fight against pathogens. Meanwhile, iron is likewise a nutritional factor of pathogens and is closely associated to the survival and reproduction of T. gondii. The iron acquisition mechanisms of T. gondii may interfere with or disrupt host iron homeostasis and may induce ferroptosis in the host. Cerebral toxoplasmosis (CT) is a life-threatening infection caused by T. gondii. A comprehensive understanding of the iron metabolism status of hippocampal cells in the cerebral toxoplasmosis mouse model will help to understand the T. gondii iron acquisition pattern. To provide clues for subsequent studies on the specific mechanisms by which T. gondii regulates host iron metabolism and the development of relevant anti-Toxoplasma drugs. Here, our results showed that ferroptosis and inflammation appeared in the hippocampus after T. gondii infection. The DFP inhibits ferroptosis and attenuates inflammation, improving overall health and hippocampal pathological manifestations in infected mice. Our findings highlight that maintaining iron homeostasis and targeting ferroptosis may be a potential therapeutic approach for toxoplasmosis. [ABSTRACT FROM AUTHOR]

Background: Schistosomiasis is of great public health concern with a wide distribution and multiple determinants. Due to the advances in schistosomiasis elimination and the need for precision prevention and control, identifying determinants at a fine scale is urgent and necessary, especially for resource deployment in practice. Our study aimed to identify the determinants for the seropositive rate of schistosomiasis at the village level and to explore their spatial variations in local space. Methodology: The seropositive rates of schistosomiasis were collected from 1714 villages or communities in Human Province, and six spatial regression models including ordinary least squares (OLS), spatial lag model (SLM), spatial error model (SEM), geographically weighted regression (GWR), robust GWR (RGWR) and multiscale GWR (MGWR) were used to fit the data. Principal/Findings: MGWR was the best-fitting model (R2: 0.821, AICc:2727.092). Overall, the nearest distance from the river had the highest mean negative correlation, followed by proportion of households using well water and the annual average daytime surface temperature. The proportions of unmodified toilets showed the highest mean positive correlation, followed by the snail infested area, and the number of cattle. In spatial variability, the regression coefficients for the nearest distance from the river, annual average daytime surface temperature and the proportion of unmodified toilets were significant in all villages or communities and varied little in local space. The other significant determinants differed substantially in local space and had significance ratios ranging from 41% to 70%, including the number of cattle, the snail infested area and the proportion of households using well water. Conclusions/Significance: Our study shows that MGWR was well performed for the spatial variability of schistosomiasis in Hunan province. The spatial variability was different for different determinants. The findings for the determinants for the seropositive rate and mapped variability for some key determinants at the village level can be used for developing precision intervention measure for schistosomiasis control. Author summary: The elimination of schistosomiasis depends critically on the identification of a set of determinants. A site-specific analysis of the determinants allows organizers to adjust and clarify the focus areas for the next round. This analysis, based on anecdotal evidence and investigations specific to a narrow geographic area at a fine scale, would enhance our understanding of the determinants. Especially for areas where elimination goals are to be achieved, local spatial variation in determinants is worth exploring in depth. In this analysis we included the seropositive rates of schistosomiasis from 1714 villages or communities and established six spatial regression models. Benefiting from determinants with different bandwidths, MGWR was good at simulating schistosomiasis. We also explored the spatial variability of multiple determinants and mapped variability for some key determinants at the village level. We hope the findings will be used for developing precision intervention measure for schistosomiasis control. [ABSTRACT FROM AUTHOR]

Objective: This study aims to explore the spatiotemporal distribution of schistosomiasis in Jiangling County, and provide insights into the precise schistosomiasis control. Methods: The descriptive epidemiological method and Joinpoint regression model were used to analyze the changes in infection rates of humans, livestock, snails, average density of living snails and occurrence rate of frames with snails in Jiangling County from 2005 to 2021. Spatial epidemiology methods were used to detect the spatiotemporal clustering of schistosomiasis transmission risk in Jiangling county. Results: The infection rates in humans, livestock, snails, average density of living snails and occurrence rate of frames with snails in Jiangling County decreased from 2005 to 2021 with statistically significant. The average density of living snails in Jiangling County was spatially clustered in each year, and the Moran's I varied from 0.10 to 0.26. The hot spots were mainly concentrated in some villages of Xionghe Town, Baimasi Town and Shagang Town. The mean center of the distribution of average density of living snails in Jiangling County first moved from northwest to southeast, and then returned from southeast to northwest after 2014. SDE azimuth fluctuated in the range of 111.68°-124.42°. Kernal density analysis showed that the high and medium-high risk areas of Jiangling County from 2005 to 2021 were mainly concentrated in the central and eastern of Jiangling County, and the medium-low and low risk areas were mainly distributed in the periphery of Jiangling County. Conclusions: The epidemic situation of schistosomiasis decreased significantly in Jiangling County from 2005 to 2021, but the schistosomiasis transmission risk still had spatial clustering in some areas. After transmission interruption, targeted transmission risk intervention strategies can be adopted according to different types of schistosomiasis risk areas. Author summary: Schistosoma (S.) japonicum was once hyper-endemic in southern China. Jiangling County is one of the key endemic areas of schistosomiasis in Hubei Province, P.R. China. Although the prevalence of schistosomiasis in Jiangling County has decreased significantly, the geographical location of Jiangling County is suitable for snails breeding due to the crisscrossed ditches, so the risk of schistosomiasis transmission is still widespread. This study analyzed the schistosomiasis transmission risk in different regions in Jiangling County from 2005 to 2021, and targeted transmission risk intervention strategies can be adopted in different endemic areas after schistosomiasis transmission interruption. The areas with high risk of schistosomiasis transmission in Jiangling County were mainly distributed in the central part of Jiangling County near the west main ditch and the eastern part of Jiangling County. It is suggested strengthen schistosomiasis risk monitoring in Jiangling County, especially snails monitoring and snails elimination. In addition, health education intervention should be strengthened in key areas to prevent the spread of transmission risk to surrounding areas, in order to achieve the goal of eliminating schistosomiasis as soon as possible. [ABSTRACT FROM AUTHOR]

The legends of Fig 1 and Fig 2 are in the correct location, but the images are reversed in order. Reference 1 Liang H, Zheng L, Xia H, Tang J (2020) SARS-CoV-2 infection in China - Before the pandemic. Graph: Fig 1 Approximate number of days from infection to onset, to first medical visit, to hospitalization, to laboratory diagnosis, and to discharge with COVID-19 patients. [Extracted from the article]

Background: Hemorrhagic fever with renal syndrome (HFRS) is a widespread zoonotic disease seriously threatening Chinese residents' health. HFRS of Weihe Basin remains highly prevalent in recent years and attracts wide attention. With the acceleration of urbanization and related environmental changes, the interaction among anthropogenic activities, environmental factors, and host animals becomes more complicated in this area, which posed increasingly complex challenges for implementing effective prevention measures. Identifying the potential influencing factors of continuous HFRS epidemics in this typical area is critical to make targeted prevention and control strategies. Methods: Spatiotemporal characteristics of HFRS epidemic were analyzed based on HFRS case point data in Weihe Basin from 2005 to 2020. MaxEnt models were constructed to explore the main influencing factors of HFRS epidemic based on HFRS data, natural environment factors and socioeconomic factors. Results: Results showed that the HFRS epidemics in Weihe Basin were temporally divided into three periods (the relatively stable period, the rapid rising period, and the fluctuating rising period) and were spatially featured by relatively concentrated in the plains alongside the Weihe River. Landscape played controlling effect in this area while land use, vegetation and population in the area interacted with each other and drove the change of HFRS epidemic. The potential high-risk area for HFRS epidemic was 419 km2, where the HFRS case density reached 12.48 cases/km2, especially in the northern plains of Xi'an City. Conclusion: We suggested that the temporal and spatial variations in the HFRS epidemics, as well as their dominant influencing factors should be adequately considered for making and/or adjusting the targeted prevention and control strategies on this disease in Weihe Basin. Author summary: In recent years, the incidence rate of hemorrhagic fever with renal syndrome (HFRS) has declined in most area of China, although the acceleration of urbanization caused increasingly complicated interactions among anthropogenic activities, environmental factors, and host animals during the past decades. However, there were still some typical regions with serious HFRS epidemics in this country like the Weihe Basin in Shaanxi Province, in which more efforts should be paid for identifying the potential influencing factors and their driving mechanisms. Our study employed the MaxEnt modeling to reveal the spatio-temporal variations in the influencing factors on the epidemics of this disease from 2005 to 2020 in the Weihe Basin. We found that the landscape played controlling effect in this area while land use, vegetation and population in the area interacted with each other and drove the change of HFRS epidemic. The underling influencing factors and the stimulation of HFRS epidemic would provide detailed information for targeted strategy formulation, and the also provide reference for similar studies. [ABSTRACT FROM AUTHOR]

Snakebite envenoming adversely affects human health and life worldwide. Presently, no suitable diagnostic tools for snakebite envenoming are available in China. Therefore, we sought to develop reliable diagnostic tests for snakebite management. We conducted affinity purification experiments to prepare species-specific antivenom antibody (SSAb). In brief, affinity chromatography with an antibody purification column (Protein A) was conducted to purify immunoglobulin G from Bungarus multicinctus (BM) venom hyperimmunized rabbit serum. The cross-reactive antibodies were removed from commercial BM antivenin by immune adsorption on the affinity chromatography columns of the other three venoms, Bungarus Fasciatus (FS), Naja atra (NA), and O. hannah (OH), generating SSAb. The results of western blot analysis and enzyme-linked immunosorbent assay (ELISA) showed the high specificity of the prepared SSAb. The obtained antibodies were then applied to ELISA and lateral flow assay (LFA) to detect BM venom. The resulting ELISA and LFA could specifically and rapidly detect BM venom in various samples with the limits of quantification as 0.1 and 1 ng/ml, respectively. This method could effectively detect snake venom in experimentally envenomed rats (simulating human envenomation), which could distinguish positive and negative samples within 10–15 min. This method also showed promise in serving as a highly useful tool for a rapid clinical distinguishing of BM bites and rational use of antivenom in emergency centers. The study also revealed cross-reactivity between BM and heterogenous venoms, suggesting that they shared common epitopes, which is of great significance for developing detection methods for venoms of the snakes belonging to the same family. Author summary: The abundance of snake species and snakebites is a prominent issue in many tropical and subtropical developing countries. Thus, rapid diagnosis and selection of appropriate and effective antivenoms are the concomitant challenges that must be addressed. Neurotoxic snakebites, such as BM bites, usually occur late at night or accidentally, and local symptoms are not obvious after the bite, which results in difficulty in identifying the biting species. Administering a specific antivenom remains the most effective treatment for snakebite envenoming, thereby necessitating reliable, sensitive, and rapid diagnostic kits for BM bites. We constructed a sandwich enzyme-linked immunosorbent assay (ELISA) and a lateral flow assay (LFA) using two antibodies from different species to increase the sensitivity for venom detection and specifically identified BM venom. We found the device to be highly effective in samples of experimentally envenomed rats. The application of LFA will be conducive to appropriate antivenom administration and prevent adverse reactions. [ABSTRACT FROM AUTHOR]

Background: Viruses of the family Flaviviridae, including Japanese encephalitis virus (JEV), dengue virus (DENV), yellow fever virus (YFV) and hepatitis C virus (HCV), are widely distributed worldwide. JEV, DENV and YFV belong to the genus Flavivirus, whereas HCV belongs to the genus Hepacivirus. Children's symptoms are usually severe. As a result, rates of hospitalization due to infection with these viruses are high. The epidemiology and disease burden of hospitalized children have rarely been described in detail to date. The objective of this study was to report the general epidemiological characteristics, clinical phenotype, length of stay (LOS), burden of disease, and potential risk factors for hospitalized children infected with JEV, DENV, YFV, or HCV in Chinese pediatric hospitals. Methodology: A cross-sectional study of epidemiology and disease burden of children hospitalized for Flaviviridae virus infections between December 2015 and December 2020 in China was performed. Face sheets of discharge medical records (FSMRs) were collected from 27 tertiary children's hospitals in the Futang Research Center of Pediatric Development and aggregated into FUTang Update medical REcords (FUTURE). Information on sociodemographic variables, clinical phenotype, and LOS as well as economic burden was included in FSMRs and compared using appropriate statistical tests. Findings: The study described 490 children aged 0–15 years hospitalized for infections with Flaviviridae viruses. Japanese encephalitis (JE) cases are the highest, accounting for 92.65% of the total hospitalization cases caused by Flaviviridae virus infection. The incidence of JE peaked from July to October with a profile of a high proportion of severe cases (68.06%) and low mortality (0.44%). Rural children had a significantly higher incidence than urban children (91.63%). Most hospitalized dengue cases were reported in 2019 when dengue outbreaks occurred in many provinces of China, although only 14 dengue cases were collected during the study period. Yellow fever (YF) is still an imported disease in China. The hospitalizations for children with hepatitis C (HC) were not high, and mild chronic HC was the main clinical phenotype of patients. Among the four viral infections, JE had the highest disease burden (LOS and expenditure) for hospitalized children. Conclusion: First, the present study reveals that JE remains the most serious disease due to Flaviviridae virus infection and threatens children's health in China. Many pediatric patients have severe illnesses, but their mortality rate is lower, suggesting that existing treatment is effective. Both JEV vaccination and infection control of rural children should represent a focus of study. Second, although the dual risks of indigenous epidemics and imports of DENV still exist, the prevalence of DENV in children is generally manageable. Third, YFV currently shows no evidence of an epidemic in China. Finally, the proportion of children with chronic hepatitis C (CHC) is relatively large among hospitalized children diagnosed with HCV. Thus, early and effective intervention should be offered to children infected with HCV to ease the burden of CHC on public health. Author summary: We performed a general epidemiological and disease burden assessment of 490 hospitalized children infected with any virus from the family Flaviviridae [Japanese encephalitis virus (JEV), dengue virus (DENV), yellow fever virus (YFV) and hepatitis C virus (HCV)] from December 2015 to December 2020 with confirmed clinical presentation and laboratory results. Our study found that hospitalization for Japanese encephalitis (JE) predominated in children who lived in rural areas, and the infection was rate was considerably higher in summer and autumn (July–October) compared with other months. In addition, children hospitalized with JE have the largest share of disease burden. However, the overall low rate of hospitalization and mortality of children shows that China's JE prevention and control policies remain effective. However, the prevention, control and surveillance of JEV in rural areas should not be neglected. Dengue and yellow fever have not yet caused serious public health concerns among children in China, but the spatial and temporal distributions of viral infection must be assessed to be alert to the indigenous spread of imported cases. CHC is a refractory phenotype of HCV infection in children; thus, early screening and intervention are encouraged given the insidious appearance of symptoms in the early stages after HCV infection. These findings can help to understand the epidemic status of viruses classified in the family Flaviviridae in children and the disease burden of hospitalized children, which is conducive to precise prevention and control, optimization of the allocation of resources, and the formulation of more reasonable and effective policies. [ABSTRACT FROM AUTHOR]

Background: Hookworm disease is endemic in China and is widespread globally. The disease burden to humans is great. Methods: The study described the national surveillance of hookworm implemented in 31 provinces/autonomous regions/municipalities (P/A/Ms) of China in 2019. Each P/A/M determined the number and location of surveillance spots (counties). A unified sampling method was employed, and at least 1000 subjects were investigated in each surveillance spot. The modified Kato-Katz thick smear method was employed for stool examination. Fifty samples positive with hookworm eggs were cultured in each surveillance spot to discriminate species between A. duodenale and N. americanus. Twenty-five soil samples were collected from each surveillance spot and examined for hookworm larva. The 2019 surveillance results were analyzed and compared with that of 2016–2018. Results: A total of 424766 subjects were investigated in 31 P/A/Ms of China in 2019, and the overall hookworm infection rate was 0.85% (3580/424766). The weighted infection and standard infection rates were 0.66% (4288357/648063870) and 0.67% (4343844/648063870), respectively. Sichuan province had the highest standard infection rate (4.75%) in 2019, followed by Chongqing (2.54%) and Hainan (2.44%). The standard infection rates of other P/A/Ms were all below 1%, with no hookworm detected in 15 P/A/Ms. The standard hookworm infection rate in the males and the females were 0.61% (2021216/330728900) and 0.71% (2267141/317334970), respectively, with a significant difference between different genders (χ2 = 17.23, P<0.0001). The highest standard hookworm infection rate (1.97%) was among age ≥ 60 years, followed by 45~59 years (0.77%), 15~44 years (0.37%), and 7~14 years (0.20%). The lowest standard infection rate was among the 0~6 years age group (0.12%). A significant difference was observed among different age groups (χ2 = 2 305.17, P<0.0001). The constitute ratio for N. americanus, A. duodenale, and coinfection was 78.70% (1341/1704), 2.03% (346/1704), and 1.00% (17/1704), respectively. The detection rate of hookworm larva from soil was 3.45% (71/2056). Conclusion: The national surveillance showed that the hookworm infection rate has been decreasing annually from 2016 to 2019, and it is now below 1%. China has made significant progress in controlling hookworm. The national surveillance system is an important way to understand the endemic status and provide important information in this process and thus needs to be continually optimized. Author summary: Hookworm disease is endemic in China. The national surveillance system on important parasitic diseases including hookworm infection has been established in China. Stool samples were collected from participants, and the Kato-Katz method was applied to detect helminth eggs while samples with hookworm eggs were further cultured to differentiate the species of the parasite. Additionally, soil samples were collected and examined for hookworm larva. In 2019, the overall infection rate of hookworm in China was 0.85% (3580/424766). High prevalence was demonstrated in Western and Southern China, including Sichuan (4.75%), Chongqing (2.54%) and Hainan (2.44%). The prevalence was high in the females (0.71%) than in the males (0.61%), while it was high in older population especially those age over 60 years. N. americanus dominated the hookworm species. The prevalence of hookworm in soil was 3.45%. Overally, hookworm infection decreased to a low level in China. However, there still exist high endemic areas. Thus, intervention needs to be applied in the high endemic areas and elder population. [ABSTRACT FROM AUTHOR]

Background: Visceral leishmaniasis (VL) has been declared as one of the six major tropical diseases by the World Health Organization. This disease has been successfully controlled in China, except for some areas in the western region, such as the Xinjiang Autonomous Region, where both anthroponotic VL (AVL) and desert type zoonotic VL (DT-ZVL) remain endemic with sporadic epidemics. Methodology/Principal findings: Here, an eleven-year survey (2004–2014) of Leishmania species, encompassing both VL types isolated from patients, sand-fly vectors and Tarim hares (Lepus yarkandensis) from the Xinjiang Autonomous Region was conducted, with a special emphasis on the hares as a potential reservoir animal for DT-ZVL. Key diagnostic genes, ITS1, hsp70 and nagt (encoding N-acetylglucosamine-1-phosphate transferase) were used for phylogenetic analyses, placing all Xinjiang isolates into one clade of the L. donovani complex. Unexpectedly, AVL isolates were found to be closely related to L. infantum, while DT-ZVL isolates were closer to L. donovani. Unrooted parsimony networks of haplotypes for these isolates also revealed their relationship. Conclusions/Significance: The above analyses of the DT-ZVL isolates suggested their geographic isolation and independent evolution. The sequence identity of isolates from patients, vectors and the Tarim hares in a single DT-ZVL site provides strong evidence in support of this species as an animal reservoir. Author summary: Black faver, also known as visceral leishmaniasis (VL), is caused by pathogens of Leishmania species, spread by the bites of infected sand flies. This disease has been successfully controlled in China, except for some areas in the western region, such as Xinjiang. However, the knowledge on Leishmania in these areas remains a few important gaps. Particularly, what is the animal reservoir for desert type zoonotic VL (DT-ZVL), as sand flies get infected in areas free of patient or infected dogs? To address this question, an eleven-year survey (2004–2014) in Xinjiang for Leishmania species was carried out. We found that VLs in Xinjiang are contributed to Leishmania donovani complex, and Tarim hares is likely the reservoir animal for DT-ZVL. [ABSTRACT FROM AUTHOR]

Background: Based on two national surveys, the prevalence of soil-transmitted helminthiasis (STH) in China had decreased from 53.58% in 1988–1992 to 19.56% in 2001–2004. To update the epidemiology and characteristics of STH in China, a third national survey was implemented in 2014–2015. Methodology/Principal findings: This survey covered rural areas in 31 provinces in mainland of China. Multiple-stage stratified cluster sampling was employed, which included three levels (provinces, ecozones and economical levels). Stool samples were collected and the Kato-Katz method was applied for helminth eggs detection. Samples with hookworm eggs were selected and hatched to differentiate the species based on larval morphology. Between June 2014 and May 2015, a total of 484,210 participants from 604 counties were enrolled. The weighted prevalence of STH overall was 4.49% (95% confidential interval (CI): 2.45%-6.53%), including 2.62% (95% CI: 0.86%-4.38%) hookworm infections, 1.36% (95% CI: 0.49%-2.23%) ascariasis, and 1.02% (95% CI: 0.15%-1.89%) trichuriasis. The estimated population infected was 29.12 million (95% CI: 15.88 million-42.32 million) for all STH; 16.97 million (95% CI: 5.57 million-28.39 million) for hookworm infections; 8.83 million (95% CI: 3.18 million-14.45 million) for ascariasis; and 6.60 million (95% CI: 0.97 million-12.25 million) for trichuriasis. Overall, the prevalence of ascariasis and trichuriasis was relatively high in children, while hookworm infections were more common in the older population, especially those over 60. STH was highly prevalent in western China, and moderately in central areas, but low in eastern and northern regions. Out of 3,579 hookworm cases with species differentiation, 479 cases (13.38%) were infected with only Ancylostoma spp., 2,808 cases (78.46%) with only Necator americanus, and another 292 cases (8.16%) with both species. Conclusions/Significance: This survey demonstrated the continuous decrease of STH in rural China. However, endemicity still prevails in the western areas of the country. Hookworm, especially N. americanus, is becoming the predominant species. Older farmers in western China should be prioritized for control due to the high prevalence of hookworm. Author summary: Soil-transmitted helminthiasis (STH) had decreased significantly in China based on the two national surveys implemented in 1988–1992 and 2001–2004, respectively. In 2014–2015, an updated national survey on STH was implemented in rural China. This survey covered rural areas of 31 provinces in mainland of China and multiple-stage stratified cluster sampling was employed. Stool samples were collected and examined for helminth eggs. Totally, 484,210 villagers from 604 counties in 31 provinces participated in the survey. The adjusted prevalence of STH was 4.49%, and that of hookworm infections, ascariasis, trichuriasis was 2.62%, 1.36%, 1.02%, respectively. The estimated population with STH was 29.12 million, while that with hookworm infections, ascariasis, trichuriasis was 16.97 million, 8.83 million, 6.60 million, respectively. Children showed a high prevalence in ascariasis and trichuriasis, while the older population had a high prevalence of hookworm infections. STH was still highly prevalent in western parts, moderately in central areas, and low in eastern and northern regions. Further efforts are needed to control STH in China. [ABSTRACT FROM AUTHOR]

Background: Timely and appropriate administration of post-exposure prophylaxis (PEP) is an essential component of human rabies prevention programs. We evaluated patient care at rabies clinics in a high-risk county in Hunan Province, China to inform strategies needed to achieve dog-mediated human rabies elimination by 2030. Methods: We collected information on PEP, staff capacity, and service availability at the 17 rabies clinics in the high-risk county during onsite visits and key staff interviews. Additionally, we conducted observational assessments at five of these clinics, identified through purposive sampling to capture real-time information on patient care during a four-week period. Wound categories assigned by trained observers were considered accurate per national guidelines for comparison purposes. We used the kappa statistic and an alpha level of 0.05 to assess agreement between observers and clinic staff. Results: In 2015, the 17 clinics provided PEP to 5,261 patients. Although rabies vaccines were available at all 17 clinics, rabies immune globulin (RIG) was only available at the single urban clinic in the county. During the assessment period in 2016, 196 patients sought care for possible rabies virus exposures. According to observers, 88 (44%) patients had category III wounds, 104 (53%) had category II wounds and 4 (2%) had category I wounds. Observers and PEP clinic staff agreed on approximately half of the assigned wound categories (kappa = 0.55, p-value< 0.001). Agreement for the urban county-level CDC clinic (kappa = 0.93, p-value<0.001) was higher than that of the rural township clinics (kappa = 0.16, p-value = 0.007). Using observer assigned wound categories, 142 (73%) patients received rabies vaccinations and RIG as outlined in the national guidelines. Conclusion: Rabies PEP services were available at each town of the project county; however, gaps between clinical practice of PEP and recommendations of national rabies guidelines were identified. We used these findings to develop and implement a training to rabies clinic staff on wound categorization, wound care, and appropriate use of PEP. Additional risk-based approaches for evaluating human rabies virus exposures may be needed as China progresses towards elimination. Author summary: Members of the United Nations agreed on a goal of eliminating dog-mediated rabies by 2030. To achieve this goal, China and other endemic rabies countries will need to increase dog rabies vaccination coverage as well as ensure proper administration of rabies post-exposure prophylaxis (PEP) for patients with animal wounds. PEP includes wound washing, timely vaccination, and rabies immune globulin (RIG) according to the type and severity of patients' wounds. The authors conducted an observational assessment of PEP clinics in a high-risk county in Hunan Province. Most patients at these clinics received PEP according to the national guidelines; however, certain patients received PEP, when not warranted, and others did not receive RIG, as recommended for severe animal wounds. Wound type categorization and corresponding use of PEP were most accurate at the single urban clinic and least accurate at the rural clinics in the project county. RIG was only available at the single urban clinic. These findings highlight the importance of improving the use of PEP and access to RIG, particularly in rural areas, and exploring the use of risk-based approaches for evaluating human rabies virus exposures. These steps can contribute to eliminating dog-mediated rabies in the project county as well as elsewhere in China. [ABSTRACT FROM AUTHOR]

Background: Bovine tuberculosis (bTB), caused by members of the Mycobacterium tuberculosis complex bacteria, mainly Mycobacterium bovis (M. bovis), is a major threat to public health and economic development. There has been no systematic epidemiological assessment concerning bTB in dairy cattle in China. Methodology/principal findings: Literature related to bTB in China was retrieved from China National Knowledge Infrastructure (CNKI), PubMed, ScienceDirect, VIP Chinese Journals Database, and Wan Fang Database to build the first meta-analysis for estimating the prevalence and infection moderators of bTB in dairy cattle in China. A total of 100 relevant studies published from 2010 to 2019 were included. We estimated the overall prevalence of bTB was 2.4% (95% CI: 2.1–2.8) during this decade. In the sampling year subgroup, the prevalence was lowest in 2017 or later at 0.8% (95% CI: 0.3–1.5). The lowest prevalence was 0.7% (95% CI: 0.5–1.0) in Northwestern China. The lowest prevalence was 2.1% (95% CI: 1.8–2.5) using SIT test. Heifer cows had the highest prevalence, which was 27.1% (95% CI: 9.7–49.2). The prevalence in scale farming was 3.7% (95% CI: 3.1–4.3), significantly higher than that in free-range farming (1.7%, 95% CI: 1.1–2.4). The prevalence of bTB was highest in summer at 4.0% (95% CI: 1.7–7.0). In addition, the influence of different geographical factors (altitude, longitude, latitude, precipitation, temperature, humidity) on the prevalence was analyzed. Conclusions/significance: The results showed that bTB was widespread in China but has been gradually reduced through concerted national intervention. It is suggested that different countries should formulate corresponding prevention and control measures according to the epidemic situation in its cattle industry. Enhanced monitoring of warm and humid areas may play an important role in reducing the incidence of bTB. In addition, when large-scale breeding is promoted, attention should be paid to standardizing breeding management and improving animal welfare to reduce the prevalence of bTB in cattle. Author summary: bTB is a neglected zoonotic disease caused by members of the Mycobacterium tuberculosis complex bacteria (M. bovis, mainly), which is also called "TB disease from bovine sources" when it occurs in humans. It is still widespread in China although the prevalence has gradually reduced through national intervention. Because beef and dairy products are important human dietary sources of protein, bTB has a great impact on public health and safety. We constructed the first meta-analysis to assess the epidemic of bTB in dairy cattle in China over the past 10 years and analyzed the potential moderators of bTB. A total of 100 studies were included. The results showed that bTB was common and unevenly distributed in China. The potential moderators affecting the bTB epidemic were region, sampling year, detection methods, age of dairy cattle, feeding mode, season, and certain geographical and climatic factors (longitude, precipitation, mean temperature, humidity, and altitude). These important findings may help in the formulation of policies to control the prevalence of bTB in cattle, thereby reducing the economic losses caused by bTB and reducing the threat of bTB to human health. [ABSTRACT FROM AUTHOR]

Background: Mosquitoes host and transmit numerous arthropod-borne viruses (arboviruses) that cause disease in both humans and animals. Effective surveillance of virome profiles in mosquitoes is vital to the prevention and control of mosquito-borne diseases in northwestern China, where epidemics occur frequently. Methods: Mosquitoes were collected in the Shaanxi-Gansu-Ningxia region (Shaanxi Province, Gansu Province, and Ningxia Hui Autonomous Region) of China from June to August 2019. Morphological methods were used for taxonomic identification of mosquito species. High-throughput sequencing and metagenomic analysis were used to characterize mosquito viromes. Results: A total of 22,959 mosquitoes were collected, including Culex pipiens (45.7%), Culex tritaeniorhynchus (40.6%), Anopheles sinensis (8.4%), Aedes (5.2%), and Armigeres subalbatus (0.1%). In total, 3,014,183 (0.95% of clean reads) viral sequences were identified and assigned to 116 viral species (including pathogens such as Japanese encephalitis virus and Getah virus) in 31 viral families, including Flaviviridae, Togaviridae, Phasmaviridae, Phenuiviridae, and some unclassified viruses. Mosquitoes collected in July (86 species in 26 families) showed greater viral diversity than those from June and August. Culex pipiens (69 species in 25 families) and Culex tritaeniorhynchus (73 species in 24 families) carried more viral species than Anopheles sinensis (50 species in 19 families) or Aedes (38 species in 20 families) mosquitoes. Conclusion: Viral diversity and abundance were affected by mosquito species and collection time. The present study elucidates the virome compositions of various mosquito species in northwestern China, improving the understanding of virus transmission dynamics for comparison with those of disease outbreaks. Author summary: Most traditional viral research methods are limited to screening for a few types of viruses with low throughput. Here, we relied on metagenomic sequencing, which is a broadly non-specific screen for any virus, for monitoring of mosquito-borne viruses in the Shaanxi-Gansu-Ningxia region of China in 2019. The baseline of viral abundance and diversity in local Culex pipiens, Culex tritaeniorhynchus, Anopheles sinensis, and Aedes mosquitoes were investigated, with 116 viral species identified in 31 viral families, including Flaviviridae, Togaviridae, Phasmaviridae, Phenuiviridae, and some unclassified viruses. This study provides a baseline survey of the viromes of mosquitoes in the study area, highlighting the necessity of strengthened monitoring of mosquito-borne pathogens. [ABSTRACT FROM AUTHOR]

Streptomycin is considered to be one of the effective antibiotics for the treatment of plague. In order to investigate the streptomycin resistance of Y. pestis in China, we evaluated streptomycin susceptibility of 536 Y. pestis strains in China in vitro using the minimal inhibitory concentration (MIC) and screened streptomycin resistance-associated genes (strA and strB) by PCR method. A clinical Y. pestis isolate (S19960127) exhibited high-level resistance to streptomycin (the MIC was 4,096 mg/L). The strain (biovar antiqua) was isolated from a pneumonic plague outbreak in 1996 in Tibet Autonomous Region, China, belonging to the Marmota himalayana Qinghai–Tibet Plateau plague focus. In contrast to previously reported streptomycin resistance mediated by conjugative plasmids, the genome sequencing and allelic replacement experiments demonstrated that an rpsL gene (ribosomal protein S12) mutation with substitution of amino-acid 43 (K43R) was responsible for the high-level resistance to streptomycin in strain S19960127, which is consistent with the mutation reported in some streptomycin-resistant Mycobacterium tuberculosis strains. Streptomycin is used as the first-line treatment against plague in many countries. The emergence of streptomycin resistance in Y. pestis represents a critical public health problem. So streptomycin susceptibility monitoring of Y. pestis isolates should not only include plasmid-mediated resistance but also include the ribosomal protein S12 gene (rpsL) mutation, especially when treatment failure is suspected due to antibiotic resistance. Author summary: The plague natural foci are widely distributed in the world, and correspondingly, the plague still poses a significant threat to human health in some countries with endemic plague foci. Streptomycin is used as the first-line treatment against plague in many countries for the antibiotic is considered to be one of the effective antibiotics, particularly for the treatment of pneumonic plague. The resistance to streptomycin had been reported in Y. pestis strains from Madagascar in previous studies. In this study, we reported the high-level resistance to streptomycin in a clinical isolate of Y. pestis from a pneumonic patient in Tibet Autonomous Region, China, and a novel mechanism of streptomycin resistance, i.e. mutation in the rpsL gene were identified. The knowledge acquired about streptomycin resistance in Y. pestis will remain of great practical value. For the emergence of resistance to streptomycin in Y. pestis would render the treatment failure, thus corresponding antibiotic monitoring should be routinely carried out in countries threatened by plague. In addition, based on our further understanding about streptomycin resistance of Y. pestis isolates, such monitoring should not only include plasmid-mediated resistance but also include the ribosomal protein S12 gene (rpsL) mutation in Y. pestis isolates. [ABSTRACT FROM AUTHOR]

Background: Echinococcosis (canine Echinococcus disease) is a neglected tropical disease that causes serious public harm. Dogs, as a terminal host of Echinococcus spp., are a key part of the Echinococcus epidemic. Echinococcosis spreads easily in humans and animals in some areas of China and it is therefore necessary to fully understand the prevalence of Echinococcus spp. in dogs. Methodology/Principal findings: PubMed, ScienceDirect, Chongqing VIP, China National Knowledge Infrastructure (CNKI), and WanFang databases were searched for relevant articles published in the past 10 years. A final total of 108 studies were included. The overall prevalence of Echinococcus spp. in dogs in China was 7.3%, with the highest point estimate found in sampling year 2015 (8.2%) and publication year 2015 (16.5%). Northwestern China (7.9%) had the highest infection rate in China. Qinghai Province (13.5%) showed the highest prevalence among the 11 provinces we included. We also found that geographical and climatic factors are related to the incidence of canine echinococcosis. We further investigated the source of heterogeneity by analysis of subgroups (sampling district, detection method, dog type, season, parasite species, medication, and study quality level). Conclusions/Significance: Our research indicated that Echinococcus spp. were still prevalent in some areas in China. More localized prevention and control policies should be formulated, including improving drinking water hygiene and strengthening hygiene promotion. We recommend the rational use of anti-Echinococcus drugs. In addition, treatment of livestock offal and feces and improving the welfare of stray dogs may play an important role in reducing canine Echinococcus infections. Author summary: Echinococcosis is a neglected zoonotic disease caused by the larval form of Echinococcus spp. tapeworms. It is prevalent in parts of China although unevenly distributed. The dog is one of the terminal hosts of Echinococcus spp., which is key in controlling the epidemic of canine echinococcosis. We constructed the first meta-analysis to assess the epidemic of Echinococcus in dogs in China over the past 10 years, and analyzed potential risk factors. We analyzed 108 studies of Echinococcus in dogs in China and evaluated the infection status and potential risk factors. The influential factors included province, geographical and climatic factors, publication year, sampling district category, detection methods, dog classification, medication, and the quality level of included studies. These important findings explain the differences in prevalence of canine echinococcosis in parts of China, and help to prevent the disease and reduce the risk to the public. [ABSTRACT FROM AUTHOR]

In 2015, China and other member states of the United Nations adopted the goal of eliminating dog-mediated rabies by 2030. China has made substantial progress in reducing dog-mediated human rabies since peaking with more than 3,300 reported cases in 2007. To further improve coordination and planning, the Chinese Center for Disease Control and Prevention, in collaboration with the United States Centers for Disease Control and Prevention, conducted a Stepwise Approach towards Rabies Elimination (SARE) assessment in March 2019. Assessment goals included outlining progress and identifying activities critical for eliminating dog-mediated rabies. Participants representing national, provincial and local human and animal health sectors in China used the SARE assessment tool to answer 115 questions about the current dog-mediated rabies control and prevention programs in China. The established surveillance system for human rabies cases and availability of post-exposure prophylaxis were identified as strengths. Low dog vaccination coverage and limited laboratory confirmation of rabid dogs were identified gaps, resulting in an overall score of 1.5 on a scale of 0 to 5. Participants outlined steps to increase cross-sectoral information sharing, improve surveillance for dog rabies, increase dog vaccination coverage, and increase laboratory capacity to diagnose rabies at the provincial level. All assessment participants committed to strengthening cross-sector collaboration using a One Health approach to achieve dog-mediated human rabies elimination by 2030. Author summary: Rabies is an acute zoonosis with a mortality rate of almost 100% following the onset of symptoms. In China, the increased access to post-exposure prophylaxis has substantially reduced the number of human rabies deaths. However, rabies continues to circulate in many rural parts of the country, resulting in hundreds of rabid dog-related exposures and deaths each year. In 2015, member states of the United Nations adopted the goal of eliminating dog-mediated rabies by 2030. We conducted a Stepwise Approach towards Rabies Elimination (SARE) assessment to outline progress and identify steps needed to achieve the elimination goal in China. The assessment involved representatives from the national and 12 selected provincial-level human and animal health sectors. The 12 provinces were purposefully selected based on the current dog-mediated rabies burden, an interest in participating, and the ability to complete the SARE assessment tool. This cross-sector–or One Health—approach was useful for improving coordination and planning. In particular, the assessment identified opportunities to improve collaboration between sectors on laboratory diagnostic capacity, implementing mass dog vaccination campaigns and conducting epidemiologic investigations on dog-mediated rabies exposures. An integrated One Health strategy should be strengthened in China as well as in other countries aiming to eliminate dog-mediated rabies. [ABSTRACT FROM AUTHOR]

Dengue is considered non-endemic to mainland China. However, travellers frequently import the virus from overseas and local mosquito species can then spread the disease in the population. As a consequence, mainland China still experiences large dengue outbreaks. Temperature plays a key role in these outbreaks: it affects the development and survival of the vector and the replication rate of the virus. To better understand its implication in the transmission risk of dengue, we developed a delay differential equation model that explicitly simulates temperature-dependent development periods and tested it with collected field data for the Asian tiger mosquito, Aedes albopictus. The model predicts mosquito occurrence locations with a high accuracy (Cohen's κ of 0.78) and realistically replicates mosquito population dynamics. Analysing the infection dynamics during the 2014 dengue outbreak that occurred in Guangzhou showed that the outbreak could have lasted for another four weeks if mosquito control interventions had not been undertaken. Finally, we analyse the dengue transmission risk in mainland China. We find that southern China, including Guangzhou, can have more than seven months of dengue transmission per year while even Beijing, in the temperate north, can have dengue transmission during hot summer months. The results demonstrate the importance of using detailed vector and infection ecology, especially when vector-borne disease transmission risk is modelled over a broad range of climatic zones. Author summary: Dengue is a mosquito-borne disease and the transmission of its virus depends on four factors: The presence of 1) the virus, 2) the human host, 3) the mosquito vector, and 4) the suitability of environmental conditions. Mainland China faces regular dengue outbreaks. Because the virus is constantly imported by infected travellers into the susceptible populations of Chinese metropolises, factors 1) and 2) are almost always met. We now investigate factors 3) and 4) to see when and where the risk for outbreaks is greatest. We use a novel model that considers the development of both the mosquitoes and the viruses under different climate conditions. Our findings suggest that the Asian tiger mosquito (Aedes albopictus) can potentially transmit dengue virus over large parts of mainland China; the biggest transmission risk is simulated over southern China where large outbreaks have occurred historically, but also over the temperate north, as far as Beijing, where smaller dengue outbreaks could occur during hot summer months. [ABSTRACT FROM AUTHOR]

Background: Hand, foot, and mouth disease (HFMD) is a global infectious disease; particularly, it has a high disease burden in China. This study was aimed to explore the temporal and spatial distribution of the disease by analyzing its epidemiological characteristics, and to calculate the early warning signals of HFMD by using a logistic differential equation (LDE) model. Methods: This study included datasets of HFMD cases reported in seven regions in Mainland China. The early warning time (week) was calculated using the LDE model with the key parameters estimated by fitting with the data. Two key time points, "epidemic acceleration week (EAW)" and "recommended warning week (RWW)", were calculated to show the early warning time. Results: The mean annual incidence of HFMD cases per 100,000 per year was 218, 360, 223, 124, and 359 in Hunan Province, Shenzhen City, Xiamen City, Chuxiong Prefecture, Yunxiao County across the southern regions, respectively and 60 and 34 in Jilin Province and Longde County across the northern regions, respectively. The LDE model fitted well with the reported data (R2 > 0.65, P < 0.001). Distinct temporal patterns were found across geographical regions: two early warning signals emerged in spring and autumn every year across southern regions while one early warning signals in summer every year across northern regions. Conclusions: The disease burden of HFMD in China is still high, with more cases occurring in the southern regions. The early warning of HFMD across the seven regions is heterogeneous. In the northern regions, it has a high incidence during summer and peaks in June every year; in the southern regions, it has two waves every year with the first wave during spring spreading faster than the second wave during autumn. Our findings can help predict and prepare for active periods of HFMD. Author summary: Hand, foot, and mouth disease (HFMD), a global infectious disease, has a high disease burden in China. This study aimed to explore the temporal and spatial distribution of the disease by analyzing its epidemiological characteristics and to calculate the early warning signals of HFMD by using a logistic differential equation (LDE) model. Our findings showed that 1) the HFMD disease burden in China remained high and HFMD incidence in the southern region was higher than that in the northern region; and 2) the HFMD early warnings times across China were heterogeneous. One high incidence period occurred in the northern regions during summer, peaking in June every year, while in the southern regions two waves emerged every year. Over the southern regions, the disease appeared to spread faster in the spring wave than in the autumn wave. These results provide important information for public health authorities such as the Centers for Disease Control and Prevention staff to predict and prepare for the onset of the high active periods of HFMD, especially by indicating the heterogeneous warning times of HFMD outbreak across different geographical regions in Mainland China. [ABSTRACT FROM AUTHOR]

Background: Hand foot and mouth disease (HFMD) is becoming one of the common human infectious diseases in China. Previous studies have described HFMD in tropical or coastal areas of Asia-Pacific countries. However, limited studies have thoroughly studied the epidemiology and potential risk factors for HFMD in inland areas with complex environmental conditions. Methodology/Principal findings: Using the data from 2009 to 2018 on reported cases of Xinjiang Uighur Autonomous Region, we characterized the epidemic features of HFMD. Panel negative binomial model was used to identify climate, geographical and demographic determinants for HFMD incidence. A total of 70856 HFMD cases (average annual incidence: 305 per million persons) were reported in Xinjiang during the 10-year study period, of which 10393 (14.7%) were laboratory-confirmed and 98 (0.1%) were severe. HFMD peaked in summer every year during the study period, and incidence in 2012, 2015, 2016 and 2018 had minor peaks in autumn. After adjusting the school or holiday month, multiple factors were found to affect HFMD epidemiology: urban area being major land cover type (incidence risk ratio, IRR 2.08; 95% CI 1.50, 2.89), higher gross domestic product per capita (IRR 1.14; 95% CI 1.11, 1.16), rise in monthly average temperature (IRR 1.65; 95% CI 1.61, 1.69) and monthly accumulative precipitation (IRR 1.20; 95% CI 1.16, 1.24) predicted increase in the incidence of HFMD; farmland being major land cover type (IRR 0.72; 95% CI 0.64, 0.81), an increase of percentage of the minority (IRR 0.91; 95% CI 0.89, 0.93) and population density (IRR 0.98; 95% CI 0.98, 0.99) were related to a decrease in the incidence of HFMD. Conclusions/Significance: In conclusion, the epidemic status of HFMD in Xinjiang is characterized by low morbidity and fatality. Multiple factors have significant influences on the occurrence and transmission of HFMD in Xinjiang. Author summary: Hand foot and mouth disease (HFMD) is one of the common human infectious disease threating Asia-Pacific countries. To explore the epidemiology and environmental risk factors for HFMD in inland China, we utilized 10-year HFMD surveillance data in Xinjiang Uighur Autonomous Region and combined multiple spatial-temporal statistical analyses. We identified spatial-temporal clusters of HFMD incidence and found that multiple factors could affect HFMD incidence: urban area being major land cover type, higher gross domestic product per capita, rise in monthly average temperature and monthly accumulative precipitation predicted increase in the incidence of HFMD; farmland being major land cover type, an increase of percentage of the minority and population density were related to a decrease in the incidence of HFMD. Our findings facilitate the understanding of HFMD epidemiology and risk factors in different geographic regions, which are crucial for conducting prevention and control strategies of HFMD. [ABSTRACT FROM AUTHOR]

Background: China's "13th 5-Year Plan" (2016–2020) for the prevention and control of sudden acute infectious diseases emphasizes that epidemic monitoring and epidemic focus surveys in key areas are crucial for strengthening national epidemic prevention and building control capacity. Establishing an epidemic hot spot areas and prediction model is an effective means of accurate epidemic monitoring and surveying. Objective: This study predicted hemorrhagic fever with renal syndrome (HFRS) epidemic hot spot areas, based on multi-source environmental variable factors. We calculated the contribution weight of each environmental factor to the morbidity risk, obtained the spatial probability distribution of HFRS risk areas within the study region, and detected and extracted epidemic hot spots, to guide accurate epidemic monitoring as well as prevention and control. Methods: We collected spatial HFRS data, as well as data on various types of natural and human social activity environments in Hunan Province from 2010 to 2014. Using the information quantity method and logistic regression modeling, we constructed a risk-area-prediction model reflecting the epidemic intensity and spatial distribution of HFRS. Results: The areas under the receiver operating characteristic curve of training samples and test samples were 0.840 and 0.816. From 2015 to 2019, HRFS case site verification showed that more than 82% of the cases occurred in high-risk areas. Discussion: This research method could accurately predict HFRS hot spot areas and provided an evaluation model for Hunan Province. Therefore, this method could accurately detect HFRS epidemic high-risk areas, and effectively guide epidemic monitoring and surveyance. Author summary: Hunan, the main epidemic area of HRFS in China. Hunan has had a cumulative incidence of 117,000 cases since 1963. During this time Hunan experienced two high incidence periods in the 1980s and 1990s. We used an Information quantity + Logistic regression model (I+LR model) to predict high-incidence and potential epidemic HFRS areas. Normalized difference vegetation index(NDVI)contributed most to HFRS risk. Per capita GDP, population size, land-use type, rainfall, elevation, and soil type were all factors found to influence HFRS risk. Our study is useful for risk prediction, prevention, and control of HFRS. [ABSTRACT FROM AUTHOR]

New coronavirus cases and related deaths are continuing to occur worldwide. Early identification of the emergence of novel outbreaks of infectious diseases is critical to the generation of timely responses. We performed a comparative study to determine the feasibility of the early detection of the COVID-19 outbreak in China based on influenza surveillance data and the internet-based Baidu search index to evaluate the timelines of the alert signals compared with the traditional case reporting and response systems. An abnormal increase in the number of influenza-like illnesses (ILI) occurred at least one month earlier than the clinical reports of pneumonia with unknown causes and the conventional monitoring system. The peak of the search volume was 20 days earlier than the issuance of the massive official warning about the epidemic. The findings from this study suggest that monitoring abnormal surges of ILI and identifying peaks of online searches of key terms can provide early signals of novel disease outbreaks. We emphasize the importance of broadening the potential of syndromic surveillance, internet searches, and social media data together with the traditional disease surveillance system to enhance early detection and understanding of emerging infectious diseases. Synopsis: Early identification of the emergence of an outbreak of a novel infectious disease is critical to generating a timely response. The traditional monitoring system is adequate for detecting the outbreak of common diseases; however, it is insufficient for the discovery of novel infectious diseases. In this study, we used COVID-19 as an example to compare the delay time of different tools for identifying disease outbreaks. The results showed that both the abnormal spike in influenza-like illnesses and the peak of online searches of key terms could provide early signals. We emphasize the importance of testing these findings and discussing the broader potential to use syndromic surveillance, internet searches, and social media data together with traditional disease surveillance systems for early detection and understanding of novel emerging infectious diseases. [ABSTRACT FROM AUTHOR]

China once suffered greatly from schistosomiasis japonica, a major zoonotic disease. Nearly 70 years of multidisciplinary efforts have achieved great progress in disease control, with infections in both humans and bovines significantly reduced to very low levels. However, reaching for the target of complete interruption of transmission at the country level by 2030 still faces great challenges, with areas of ongoing endemicity and/or re-emergence within previously 'eliminated' regions. The objectives of this study were, by using meta-analytical methods, to estimate the overall prevalence of Schistosoma japonicum infections in abundant commensal rodent species in mainland China after the introduction of praziquantel for schistosomiasis treatment in humans and bovines in 1980s. In doing so we thereby aimed to further assess the role of wild rodents as potential reservoirs in ongoing schistosome transmission. Published studies on infection prevalence of S. japonicum in wild rodents in mainland China since 1980 were searched across five electronic bibliographic databases and lists of article references. Eligible studies were selected based on inclusion and exclusion criteria. Risks of within and across study biases, and the variations in prevalence estimates attributable to heterogeneities were assessed. The pooled infection prevalence and its 95% confidence intervals (CIs) were calculated with the Freeman-Tukey double arcsine transformation. We identified a total of 37 relevant articles involving 61 field studies which contained eligible data on 8,795 wild rodents across mainland China. The overall pooled infection prevalence was 3.86% (95% CI: 2.16–5.93%). No significant change in the overall pooled prevalence was observed between 1980–2003 (n = 23 studies) and 2004-current (n = 38 studies). However, whilst the estimated prevalence decreased over time in the marshland and lake regions, there was an apparent increase in prevalence within hilly and mountainous regions. Among seven provinces, a significant prevalence reduction was only seen in Jiangsu where most endemic settings are classified as the marshland and lakes. These estimates changed over season, ranging from 0.58% in spring to 22.39% in winter, in association with increases in rodent density. This study systematically analyzed S. japonicum infections in wild rodents from the published literature over the last forty years after the introduction of praziquantel for schistosomiasis treatment in humans and bovines in 1980s. Although numbers of schistosomiasis cases in humans and bovines have been greatly reduced, no such comparable overall change of infection prevalence in rodents was detected. Furthermore, there appeared to be an increase in S. japonicum prevalence in rodents over time within hilly and mountainous regions. Rodents have been projected to become the dominant wildlife in human-driven environments and the main reservoir of zoonotic diseases in general within tropical zones. Our findings thus suggest that it is now necessary to include monitoring and evaluation of potential schistosome infection within rodents, particularly in hilly and mountainous regions, if we are ever to reach the new 2030 elimination goals and to maximize the impact of future public, and indeed One Health, interventions across, regional, national and international scales. Author summary: Consistent with the revised WHO Global Goals, China has set the target of complete interruption of transmission (elimination) of zoonotic Schistosoma japonicum by 2030 at the entire country level. Much remains to be known, however, regarding the complex multi-host disease dynamics of schistosomiasis. Multi-disciplinary disease control programs within China, including mass treatment with praziquantel for over 40 years, have successfully targeted human and bovine definitive hosts, significantly reducing infection prevalence to extremely low levels. However, S. japonicum has at least 40 species of potential definitive host reservoirs. Most notably, and perhaps most challenging in terms of targeted control, high prevalence of S. japonicum has been detected in rodent wildlife within recent years, particularly in hilly and mountainous regions of China. Molecular/phylogenetic studies have revealed matched S. japonicum genotypes indicative of shared transmission between rodents and humans. Similarly, mathematical models, incorporating parasitological and molecular data, have indicated that rodents may be sufficient to maintain ongoing transmission of schistosomiasis within some Chinese regions, most notably that of hilly and mountainous habitats. In order to help elucidate further the potential association between prevalence of S. japonicum in humans with rodent wildlife across China, and to assess whether this balance may be changing following the introduction of mass drug administration with praziquantel to humans (and bovines) in the 1980s, we performed a meta-analyses aimed to estimate the overall prevalence of S. japonicum infections in commensal species rodents in China over this period. Published studies on S. japonicum infections in wild rodents in China since 1980 were searched for across five electronic bibliographic databases, together with lists of cited articles. We identified a total of 37 relevant articles involving 61 studies with eligible data on 8795 rodents. The pooled prevalence level was 3.86% (95% CI: 2.16–5.93%). No significant change in overall pooled prevalence levels within rodents was observed between 1980–2003 and 2004-current, despite the integrated control strategies performed across China within the latter period. However, whilst the prevalence estimates did decrease within marshland and lake regions since 2004, in the hilly and mountainous regions, in contrast, there was a significant increase in the rodent infection prevalence. The estimate increased from the smallest 0.58% in spring to the highest 22.39% in winter. It also increased with the density of rodents. Therefore, we suggest that future systematic monitoring of schistosome infection levels within potential wildlife reservoirs, particularly within hilly and mountainous regions within China and/or areas aiming for verification of interruption of transmission, should be incorporated in order to reliably evaluate impact, risk and ultimately help ensure the sustainability of elimination interventions across, regional, national and international scales. [ABSTRACT FROM AUTHOR]

In order to rapidly inform polices in the international response to the ongoing pandemic of coronavirus disease 19 (COVID-19), we summarize in this review current evidence on epidemiological and clinical features of the infection, transmission routes, problems of nucleic-acid testing, the epidemiological trend in China and impact of interventional measures, and some lessons learned. We concluded that the epidemic is containable with traditional nonpharmacological interventions, mainly through social distancing and finding and isolating suspected patients and close contacts. Nonpharmacological interventions are the only effective measures currently accessible and have suppressed some 90% of the infections in China. Close contacts are the major mechanism of transmission, which makes it possible to control this epidemic through nonpharmacological methods. Nucleic-acid testing alone may miss some 50% of infected patients, and other methods such as chest computerized tomography (CT) or serology should be considered to supplement molecular testing. The development of vaccines and drugs is important, but hesitation to make use of nonpharmacological interventions may mean missing golden opportunities for effective actions. Author summary: In particular, we summarize the origin of the pathogen, epidemiological and clinical features of the infection, transmission routes and transmissibility, problems of nucleic-acid testing and diagnostic criteria, the epidemiological trend in China and its relation to interventional measures, and special issues including infection in doctors and children and the role of vaccines versus traditional nonpharmacological interventions in control of the epidemic. Importantly, evidence clearly suggests the following: The epidemic is containable with traditional nonpharmacological interventions, largely by social distancing and testing and isolation of suspected patients and close contacts. Nonpharmacological interventions are the most immediately accessible effective measures and have helped suppress some 90% of infections in China. Close contacts through droplets and fomites are the major mechanism of transmission, and asymptomatic infections and aerosols are unlikely important in spreading the virus. This is a major feature of the virus and explains why it is containable through nonpharmacological methods. Nucleic-acid testing alone may miss many truly infected patients, and chest CT should always be used if available to supplement molecular testing. Development of vaccines and drugs are important, but any hesitation to use nonpharmacological interventions may mean missing golden opportunities for useful actions against the epidemic. [ABSTRACT FROM AUTHOR]

Background: Zhejiang Province has the fifth-highest incidence of severe fever with thrombocytopenia syndrome (SFTS) in China. While the top four provinces are all located in northern and central China, only Zhejiang Province is located in the Yangtze River Delta region of southeast China. This study was undertaken to identify the epidemiological characteristics of SFTS in Zhejiang from 2011 to 2018. Methods: The epidemic data from SFTS cases in Zhejiang Province from January 2011 to December 2018 were obtained from the China Information Network System of Disease Prevention and Control. Meteorological data were collected from the China Meteorological Data Sharing Service System. A multivariate time series model was used to analyze the heterogeneity of spatial-temporal transmission of the disease. Random forest analysis was performed to detect the importance of meteorological factors and the dose-response association of the incidence of SFTS with these factors. Results: In total, 412 SFTS cases (49 fatal) were reported from January 2011 to December 2018 in Zhejiang Province, China. The number of SFTS cases and the number of affected counties increased year by year. The case fatality rate in Zhejiang Province was 11.89%, which was the highest in China. Elderly patients and farmers were the most affected. The total effect values of the autoregressive component, spatiotemporal component and endemic component of the model in all ranges were 0.4580, 0.0377 and 0.0137, respectively. There was obvious heterogeneity across counties for the mean values of the spatiotemporal component and the autoregressive component. The autoregressive component was obviously the main factor driving the occurrence of SFTS, followed by the spatiotemporal component. The importance scores of the monthly mean pressure, mean temperature, mean relative humidity, mean two-minute wind speed, duration of sunshine and precipitation were 10.64, 8.34, 8.16, 6.37, 5.35 and 2.81, respectively. The relationship between these factors and the incidence of SFTS is complicated and nonlinear. A suitable range of meteorological factors for this disease was also detected. Conclusions: The autoregressive and spatiotemporal components played an important role in driving the transmission of SFTS. Targeted preventive efforts should be made in different areas based on the main component contributing to the epidemic. For most areas, early measures several months ahead of the suitable season for the occurrence of SFTS should be implemented. The level of reporting and diagnosis of this disease should be further improved. Author summary: SFTS is listed as one of the nine most infectious diseases on the WHO priority list. The transmission route and the factors driving the epidemic were complex. Ninety percent of worldwide cases have been reported from China, and Zhejiang Province in China has a high case fatality rate and a high incidence of SFTS. In our study, we found that the numbers of affected counties increased year by year, and the interval from illness onset to confirmation in SFTS was still too long. Furthermore, spatial heterogeneity in the risk factors driving the transmission of SFTS was detected. In addition, the range of suitable weather values for the transmission of SFTS was identified. This suggests that targeted preventive efforts should be made in different areas based on the main factor contributing to the epidemic. In particular, early measures several months ahead of the suitable season for the occurrence of SFTS should be implemented. Enhancement of the level of reporting and diagnosis of this disease should strengthen ongoing research with the incorporation of more risk factors. [ABSTRACT FROM AUTHOR]

Background: Essential oils may represent an alternative strategy for controlling scabies, a neglected tropical disease caused by the infestation of mite from the species Sarcoptes scabiei. Lemongrass (Cymbopogen citratus) oil is reported to possess pharmacological properties including antiparasitc, antioxidant, antimicrobial and anti-inflammatory. The aim of the present study was to assess the potential efficacy of lemongrass oil against the mites and eggs of Sarcoptes scabiei. Methodology/Principal findings: Mass spectrometry analysis confirmed that the main component presented in lemongrass oil was citral. Lemongrass oil at concentrations of 10% and 5% killed all Sarcoptes mites within 10 and 25 min, respectively. The median lethal concentration value was 1.37%, 1.08%, 0.91%, 0.64%, and 0.48% at 1, 3, 6, 12, and 24 h, respectively. Lemongrass oil at all concentrations (10%, 5%, 1%, 0.5%, 0.1%) was able to significantly decrease the hatching rate of Sarcoptes eggs. Conclusions/Significance: Lemongrass oil should be considered as a promising miticidal and ovicidal agent for scabies control. Author summary: Scabies is a parasitic infestation which affects about 455 million people annually, with a particularly high prevalence in low income tropical regions. The disease is frequently complicated by bacterial infections. Currently available treatments do not meet the ideal profile which includes miticides, ovicidal, antibacterial and anti-inflammatory/antipruritic properties. Cymbopogon citratus is a plant widely cultivated in tropical and subtropical regions. The essential oil from C. citratus is known as lemongrass oil with reported antimicrobial and anti-inflammatory properties. We conducted experiments to assess the miticidal and ovicidal efficacy of lemongrass oil against Sarcoptes mites collected from naturally infected rabbits in China. The results demonstrated that lemongrass oil can kill the motile stages of Sarcoptes mites effectively and presented a significant ovicidal activity. Considering all these properties, lemongrass oil should be considered a promissing miticide against scabies. [ABSTRACT FROM AUTHOR]

Hand, foot, and mouth disease (HFMD) has become a major public health issue in China. The disease incidence varies substantially over time and across space. To understand the heterogeneity of HFMD transmission, we compare the spatiotemporal dynamics of HFMD in Qinghai and Shanghai by conducting combined analysis of epidemiological, wavelet time series, and mathematical methods to county-level data from 2009 to 2016. We observe hierarchical epidemic waves in Qinghai, emanating from Huangzhong and in Shanghai from Fengxian. Besides population, we also find that the traveling waves are significantly associated with socio-economic and geographical factors. The population mobility also varies between the two regions: long-distance movement in Qinghai and between-neighbor commuting in Shanghai. Our findings provide important evidence for characterizing the heterogeneity of HFMD transmission and for the design and implementation of interventions, such as deploying optimal vaccine and changing local driving factors in the transmission center, to prevent or limit disease spread in these areas. Author summary: Hand, foot, and mouth disease (HFMD) has been a concern in Asian regions since the late 1990s. To disclose the transmission mechanism of HFMD and its driving factors, we combined epidemiological, spatial, and mathematical analysis, using HFMD cases in two provinces (Qinghai and Shanghai) of China as an example. We found the phenomenon of traveling waves in the process of HFMD transmission for the first time and identified different types of traveling waves associated with different driving factors. HFMD in Qinghai decline year by year with the characteristics of cross-region population mobility, while epidemics in Shanghai are persistent in the suburban areas with low incidence in the urban areas and neighboring population movement dominates the pattern. Our findings facilitate the understanding of HFMD transmission mechanisms over geographic regions, which are crucial for designing a jointly effective HFMD prevention and control strategy. [ABSTRACT FROM AUTHOR]

Schistosomiasis is a serious worldwide parasitic disease. One of the best ways to control schistosomiasis is to control the population of Oncomelania hupensis snails. We sought to identify a high-efficiency biogenic molluscicide against Oncomelania with low toxicity, to avoid chemical molluscicide contamination and toxicity in aquatic organisms. We extracted quaternary benzo[c]phenanthridine alkaloids (QBAs) from Macleaya cordata fruits. Molluscicidal activity of the QBAs against Oncomelania was determined using bioassay. Our results showed that the extracted QBAs had a strong molluscicidal effect. In treatment of O. hupensis with QBAs for 48 h and 72 h, the lethal concentration (LC50) was 2.89 mg/L and 1.29 mg/L, respectively. The molluscicidal activity of QBAs was close to that of niclosamide (ethanolamine salt), indicating that QBAs have potential development value as novel biogenic molluscicides. We also analyzed physiological toxicity mechanisms by examining the activity of several important detoxification enzymes. We measured the effect of the extracted QBAs on the activities of glutathione S-transferase (GST), carboxylesterase (CarE), acid phosphatase (ACP), and alkaline phosphatase (AKP) in the liver of O. hupensis. We found that the effects of QBAs on detoxification metabolism in O. hupensis were time and concentration dependent. The activities of GST, CarE, AKP, and ACP in the liver of snails increased significantly in the early stage of treatment (24 h), but decreased sharply in later stages (120 h), compared with these activities in controls. GST, CarE, AKP, and ACP activity in the liver of snails treated with LC50 QBAs for 120 h decreased by 62.3%, 78.1%, 59.2%, and 68.6%, respectively. Our results indicate that these enzymes were seriously inhibited by the extracted QBAs and the detoxification and metabolic functions of the liver gradually weakened, leading to poisoning, which could be the main cause of death in O. hupensis snails. Quaternary benzo[c]phenanthridine alkaloids (QBAs) have antimicrobial, antifungal, anti-inflammatory, and anticancer activities (anticancer, antibiosic, and antiphlogistic functions) and have been explored for use as bioantibiotics in livestock. Macleaya cordata fruits have a high QBA content. We isolated QBAs from M. cordata to evaluate molluscicidal activity against Oncomelania and to analyze the physiological toxicity mechanisms. Our results showed that QBAs had strong molluscicidal activity, similar to that of niclosamide. The activities of several important detoxification enzymes (glutathione S-transferase, carboxylesterase, acid phosphatase, and alkaline phosphatase) in the liver of O. hupensis snails were severely inhibited by QBAs. The detoxification and metabolic liver functions gradually weakened via poisoning, which could be the main cause of death in these snails. In China, there are abundant wild plant resources of M. cordata, which is often used in traditional Chinese medicine. QBAs comprising a natural combination of sanguinarine and chelerythrine bisulfate in about a 2:1 ratio had stronger molluscicidal activity than sanguinarine alone. This natural composition could serve as a scientific basis for future development of novel biomolluscicides using these active ingredients and proportions, which could provide an environmentally friendly alternative to the problem of contamination with chemical molluscicides used to combat schistosomiasis in endemic areas. [ABSTRACT FROM AUTHOR]

Background: Schistosoma japonicum is a parasitic flatworm that causes human schistosomiasis, which is a significant cause of morbidity in China and the Philippines. A single draft genome was available for S. japonicum, yet this assembly is very fragmented and only covers 90% of the genome, which make it difficult to be applied as a reference in functional genome analysis and genes discovery. Findings: In this study, we present a high-quality assembly of the fluke S. japonicum genome by combining 20 G (~53X) long single molecule real time sequencing reads with 80 G (~ 213X) Illumina paired-end reads. This improved genome assembly is approximately 370.5 Mb, with contig and scaffold N50 length of 871.9 kb and 1.09 Mb, representing 142.4-fold and 6.2-fold improvement over the released WGS-based assembly, respectively. Additionally, our assembly captured 85.2% complete and 4.6% partial eukaryotic Benchmarking Universal Single-Copy Orthologs. Repetitive elements account for 46.80% of the genome, and 10,089 of the protein-coding genes were predicted from the improved genome, of which 96.5% have been functionally annotated. Lastly, using the improved assembly, we identified 20 significantly expanded gene families in S. japonicum, and those genes were primarily enriched in functions of proteolysis and protein glycosylation. Conclusions: Using the combination of PacBio and Illumina Sequencing technologies, we provided an improved high-quality genome of S. japonicum. This improved genome assembly, as well as the annotation, will be useful for the comparative genomics of the flukes and more importantly facilitate the molecular studies of this important parasite in the future. [ABSTRACT FROM AUTHOR]

Background: Enterocytozoon bieneusi is the most common microsporidian species causing diarrhea and other intestinal disorders in humans and animals. Like other infectious diseases, microsporidiosis usually disproportionately affects poor populations. In China, some ethnic minority areas remain poor. Currently, no information of E. bieneusi infection is available in minority populations. The present aims were to understand occurrence and genetic characterizations of E. bieneusi in ethnic minority groups from a poverty-stricken ethnic township in Yunnan Province, and to assess risk factors for E. bieneusi infection. Methodology/Principal findings: 289 fecal specimens were collected from Yao people (one specimen each) with and without diarrhea, in Yunnan Province. E. bieneusi was identified and genotyped by PCR and sequence analysis of the ITS region of the rRNA gene. An average prevalence of 8.30% (24/289) was observed and four genotypes were identified—genotype Peru6 (n = 21) and three novel genotypes (one each). Genotype Peru6 was detected in two family members in each of three families. In a phylogenetic analysis, all of four genotypes fell into group 1 with zoonotic potential. The people owning individual pit toilets had a statistically higher prevalence of E. bieneusi (16.67%, 12/72) than those using public pit toilets (6.06%, 12/198). Conclusions/Significance: This is the first report on occurrence and genetic characteristics of E. bieneusi in ethnic minority groups in China. Genotype Peru6 was found in humans in China for the first time and showed dominance in Yao people. The same genotype was found in some family members and all the genotypes fell into group 1, suggesting the possibility of anthroponotic and zoonotic transmissions. The majority (83.33%, 20/24) of E. bieneusi positive individuals did not present diarrhea. In any case, it is important to recognize their existence and the importance that asymptomatic individuals to E. bieneusi may have from an epidemiological point of view, as transmitters of this pathogen. The analysis of risk factors provides scientific evidence for the development of effective strategies for prevention and control of E. bieneusi infection. [ABSTRACT FROM AUTHOR]

This article discusses a case report of a 26-year-old female in China who was diagnosed with advanced schistosomiasis japonica, a severe form of the parasitic disease schistosomiasis. The patient underwent a splenectomy, which resulted in the reversal of liver fibrosis. The article highlights the importance of early operation and effective decompression of the portal system in improving liver fibrosis in advanced schistosomiasis cases. It also emphasizes the need for regular ultrasound examinations in endemic regions to prevent the progression of the disease. [Extracted from the article]

Currently, malaria rapid diagnostic tests (RDTs) are widely used for malaria diagnosis, but test performance and the factors that lead to failure of Plasmodium ovale detection are not well understood. In this study, three pLDH-based RDTs were evaluated using cases in China that originated in Africa. The sensitivity of Wondfo Pf/Pan, CareStart pLDH PAN and SD BIOLINE Pf/Pan in P. ovale detection was 70, 55 and 18%, respectively. CareStart was worse at detecting P. o. curtisi (36.5%) than at detecting P. o. wallikeri (75.0%), and SD could not detect P. o. curtisi. The overall detection ratio of all three RDTs decreased with parasite density and pLDH concentration. Wondfo, CareStart and SD detected only 75.0, 78.1 and 46.9% of the P. ovale cases, respectively, even when the parasitemia were higher than 5000 parasites/μL. Subspecies of P. ovale should be considered while to improve RDT quality for P. ovale diagnosis to achieve the goal of malaria elimination. [ABSTRACT FROM AUTHOR]

Hantaviruses can cause hantavirus pulmonary syndrome (HPS) in the Americas and hemorrhagic fever with renal syndrome (HFRS) in Eurasia. In recent decades, repeated outbreaks of hantavirus disease have led to public concern and have created a global public health burden. Hantavirus spillover from natural hosts into human populations could be considered an ecological process, in which environmental forces, behavioral determinants of exposure, and dynamics at the human–animal interface affect human susceptibility and the epidemiology of the disease. In this review, we summarize the progress made in understanding hantavirus epidemiology and rodent reservoir population biology. We mainly focus on three species of rodent hosts with longitudinal studies of sufficient scale: the striped field mouse (Apodemus agrarius, the main reservoir host for Hantaan virus [HTNV], which causes HFRS) in Asia, the deer mouse (Peromyscus maniculatus, the main reservoir host for Sin Nombre virus [SNV], which causes HPS) in North America, and the bank vole (Myodes glareolus, the main reservoir host for Puumala virus [PUUV], which causes HFRS) in Europe. Moreover, we discuss the influence of ecological factors on human hantavirus disease outbreaks and provide an overview of research perspectives. [ABSTRACT FROM AUTHOR]

Background: China used to be among the countries with a high prevalence of trachoma. At the launch of The Global Elimination of Trachoma (GET) 2020 campaign by the World Health Organization (WHO) in 1996, China was placed on the list of countries endemic for trachoma based on historical data. However, empirical observation and routinely collected eye care data were suggesting that trachoma was no longer a public health problem. To determine whether the GET 2020 goals had been met in P. R. China, we conducted a targeted assessment with national scope. Methodology/principal finding: Province assessment teams, trained in WHO Trachoma Rapid Assessment (TRA) methodology and in WHO simplified trachoma grading system, carried out assessments in 16 provinces (among them, 2 provinces conducted pilot assessment). Based on the published literature, including national and international reports, suspected trachoma-endemic areas within each province were identified. Within these areas, trachomatous inflammation- follicular (TF) assessments were carried out in at least 50 grade-one children in primary schools serving villages with the lowest socio-economic development. Trachomatous trichiasis (TT) and corneal opacity (CO) assessments were conducted among persons aged 15 and over in villages within the catchment area of the selected schools. Of 8,259 children examined in 128 primary schools in 97 suspected trachoma endemic areas, only 16 cases of conjunctivitis were graded as TF. 38 cases with TT were found among the 339,013 examined residents in villages surrounding the schools. Among these 97 suspected trachoma endemic areas in only three was the prevalence of TT more than 0.2%. Conclusions/significance: This large study suggested that trachoma was not a public health problem in 16 provinces that had been previously suspected to be endemic. These findings will facilitate planning for elimination of trachoma from PR China. [ABSTRACT FROM AUTHOR]

Background: Plague, caused by the bacterium Yersinia pestis, is a highly infectious, zoonotic disease. Hundreds of human plague cases are reported across the world annually. Qinghai Plateau is one of the most severely affected plague regions in China, with more than 240 fatal cases of Y. pestis in the last 60 years. Conventional epidemiologic analysis has effectively guided the prevention and control of local plague transmission; however, molecular genetic analysis is more effective for investigating population diversity and transmission. In this report, we employed different genetic markers to analyze the population structure of Y. pestis in Qinghai Plateau. Methodology/Principal finding: We employed a two-step hierarchical strategy to analyze the phylogeny of 102 Qinghai Plateau isolates of Y. pestis, collected between 1954 and 2011. First, we defined the genealogy of Y. pestis by constructed minimum spanning tree based on 25 key SNPs. Seven groups were identifi7ed, with group 1.IN2 being identified as the dominant population. Second, two methods, MLVA and CRISPR, were applied to examine the phylogenetic detail of group 1.IN2, which was further divided into three subgroups. Subgroups of 1.IN2 revealed a clear geographic cluster, possibly associated with interaction between bacteriophage and Y. pestis. More recently, Y. pestis populations appear to have shifted from the east toward the center and west of Qinghai Plateau. This shift could be related to destruction of the local niche of the original plague focus through human activities. Additionally, we found that the abundance and relative proportion of 1.IN2 subgroups varied by decade and might be responsible for the fluctuations of plague epidemics in Qinghai Plateau. Conclusion/Significance: Molecular genotyping methods provided us with detailed information on population diversity and the spatial-temporal distribution of dominant populations of Y. pestis, which will facilitate future surveillance, prevention, and control of plague in Qinghai Plateau. [ABSTRACT FROM AUTHOR]

Background: This study aimed to investigate the spatiotemporal clustering and socio-environmental factors associated with dengue fever (DF) incidence rates at street level in Guangzhou City, China. Methods: Spatiotemporal scan technique was applied to identify the high risk region of DF. Multiple regression model was used to identify the socio-environmental factors associated with DF infection. A Poisson regression model was employed to examine the spatiotemporal patterns in the spread of DF. Results: Spatial clusters of DF were primarily concentrated at the southwest part of Guangzhou City. Age group (65+ years) (Odd Ratio (OR) = 1.49, 95% Confidence Interval = 1.13 to 2.03), floating population (OR = 1.09, 95% CI = 1.05 to 1.15), low-education (OR = 1.08, 95% CI = 1.01 to 1.16) and non-agriculture (OR = 1.07, 95% CI = 1.03 to 1.11) were associated with DF transmission. Poisson regression results indicated that changes in DF incidence rates were significantly associated with longitude (β = -5.08, P<0.01) and latitude (β = -1.99, P<0.01). Conclusions: The study demonstrated that social-environmental factors may play an important role in DF transmission in Guangzhou. As geographic range of notified DF has significantly expanded over recent years, an early warning systems based on spatiotemporal model with socio-environmental is urgently needed to improve the effectiveness and efficiency of dengue control and prevention. [ABSTRACT FROM AUTHOR]

Background: There was a dengue epidemic in several regions of China in 2013. No study has explored the dynamics of dengue transmission between different geographical locations with dengue outbreaks in China. The purpose of the study is to analyze the epidemiological characteristics and to explore the dynamic transmission of dengue in China, 2013. Methodology and Principal Findings: Records of dengue cases of 2013 were obtained from the China Notifiable Disease Surveillance System. Full E-gene sequences of dengue virus detected from the outbreak regions of China were download from GenBank. Geographical Information System and heatmaps were used to describe the epidemiological characteristics. Maximum Likelihood phylogenetic and Bayesian phylogeographic analyses were conducted to explore the dengue dynamic transmission. Yunnan Province and Guangdong Province had the highest imported cases in the 2013 epidemic. In the locations with local dengue transmission, most of imported cases occurred from June to November 2013 while local dengue cases developed from July to December, 2013. There were significant variations for the incidences of dengue, in terms of age distributions, among different geographic locations. However, gender differences were identified in Guangzhou, Foshan and Xishuangbanna. DENV 1–3 were detected in all locations with the disease outbreaks. Some genotypes were detected in more than one locations and more than one genotypes have been detected in several locations. The dengue viruses introduced to outbreak areas were predominantly from Southeast Asia. In Guangdong Province, the phylogeographical results indicated that dengue viruses of DENV 1 were transmitted to neighboring cities Foshan and Zhongshan from Guangzhou city, and then transmitted to Jiangmen city. The virus in DENV 3 was introduced to Guangzhou city, Guangdong Province from Xishuangbanna prefecture, Yunnan Province. Conclusions: Repeated dengue virus introductions from Southeast Asia and subsequent domestic dengue transmission within different regions may have contributed to the dengue epidemics in China, 2013. [ABSTRACT FROM AUTHOR]

Background: Rabies in China remains a public health problem. In 2014, nearly one thousand rabies-related deaths were reported while rabies geographic distribution has expanded for the recent years. This report used surveillance data to describe the epidemiological characteristics of human rabies in China including determining high-risk areas and seasonality to support national rabies prevention and control activities. Methods: We analyzed the incidence and distribution of human rabies cases in mainland China using notifiable surveillance data from 1960–2014, which includes a detailed analysis of the recent years from 2004 to 2014. Results: From 1960 to 2014, 120,913 human rabies cases were reported in mainland China. The highest number was recorded in 1981(0.7/100,000; 7037 cases), and in 2007(0.3/100,000; 3300 cases). A clear seasonal pattern has been observed with a peak in August (11.0% of total cases), Human rabies cases were reported in all provinces with a yearly average of 2198 from 1960 to 2014 in China, while the east and south regions were more seriously affected compared with other regions. From2004 to 2014, although the number of cases decreased by 65.2% since 2004 from 2651 to 924 cases, reported areas has paradoxically expanded from 162 prefectures to 200 prefectures and from southern to the central and northern provinces of China. Farmers accounted most of the cases (65.0%); 50–59 age group accounted for the highest proportion (20.5%), and cases are predominantly males with a male-to-female ratio of 2.4:1 on average. Conclusions: Despite the overall steady decline of cases since the peak in 2007, the occurrence of cases in new areas and the spread trend were obvious in China in recent years. Further investigations and efforts are warranted in the areas have high rabies incidence to control rabies by interrupting transmission from dogs to humans and in the dog population. Furthermore, elimination of rabies should be eventually the ultimate goal for China. [ABSTRACT FROM AUTHOR]

Background: Anthrax, a global re-emerging zoonotic disease in recent years is enzootic in mainland China. Despite its significance to the public health, spatiotemporal distributions of the disease in human and livestock and its potential driving factors remain poorly understood. Methodology/Principal Findings: Using the national surveillance data of human and livestock anthrax from 2005 to 2013, we conducted a retrospective epidemiological study and risk assessment of anthrax in mainland China. The potential determinants for the temporal and spatial distributions of human anthrax were also explored. We found that the majority of human anthrax cases were located in six provinces in western and northeastern China, and five clustering areas with higher incidences were identified. The disease mostly peaked in July or August, and males aged 30–49 years had higher incidence than other subgroups. Monthly incidence of human anthrax was positively correlated with monthly average temperature, relative humidity and monthly accumulative rainfall with lags of 0–2 months. A boosted regression trees (BRT) model at the county level reveals that densities of cattle, sheep and human, coverage of meadow, coverage of typical grassland, elevation, coverage of topsoil with pH > 6.1, concentration of organic carbon in topsoil, and the meteorological factors have contributed substantially to the spatial distribution of the disease. The model-predicted probability of occurrence of human cases in mainland China was mapped at the county level. Conclusions/Significance: Anthrax in China was characterized by significant seasonality and spatial clustering. The spatial distribution of human anthrax was largely driven by livestock husbandry, human density, land cover, elevation, topsoil features and climate. Enhanced surveillance and intervention for livestock and human anthrax in the high-risk regions, particularly on the Qinghai-Tibetan Plateau, is the key to the prevention of human infections. [ABSTRACT FROM AUTHOR]