[Progress and challenge in intelligent syndromic surveillance for infectious diseases].

Intelligent syndromic surveillance is an important part of multi-point triggering and multi-channel surveillance system of intelligent early warning of infectious diseases in China, and an inevitable development process of traditional syndromic surveillance as the constant emergence of new technologies. Intelligent syndromic surveillance collects not only the medical data of patients seeking medical care in hospitals but also massive non-medical information. However, along with its rapid development, challenges in intelligent syndromic surveillance have emerged, such as information explosion, cost-effective balance, information sharing, data security and privacy. This paper summarizes the concept and development of intelligent syndromic surveillance to provide references for the method and technique development of intelligent early warning of infectious diseases and new thought for the prevention and control of infectious diseases in China and in the world.

[Research progress on early warning model of influenza].

Influenza is an acute respiratory infectious disease caused by influenza virus. It usually exhibits seasonal transmission, but the novel influenza strain can lead to a pandemic with severe human health and socioeconomic consequences. Early warning of influenza epidemic is an important strategy and means for influenza prevention and control. On the basis of reviewing the main influenza surveillance and early warning systems, this study summarizes the principles, applications, advantages and disadvantages, and development prospects of common influenza early warning models, in order to provide reference for research and application of early warning technology for influenza and other acute respiratory infectious diseases.

[Summary and prospect of early warning models and systems for infectious disease outbreaks].

This paper summarizes the basic principles and models of early warning for infectious disease outbreaks, introduces the early warning systems for infectious disease based on different data sources and their applications, and discusses the application potential of big data and their analysing techniques, which have been studied and used in the prevention and control of COVID-19 pandemic, including internet inquiry, social media, mobile positioning, in the early warning of infectious diseases in order to provide reference for the establishment of an intelligent early warning mechanism and platform for infectious diseases based on multi-source big data.

[Establishment of multi-point trigger and multi-channel surveillance mechanism for intelligent early warning of infectious diseases in China].

This paper reviews the limitations of current infectious disease surveillance and early warning system in China, analyzes the concepts and countermeasures of the establishment of an intelligent early warning platform of infectious diseases based on multi-point trigger mechanism and multi-channel surveillance mechanism and proposes the realization routes for the purpose of facilitating capacity building and improvement of surveillance and early warning of infectious diseases in China.

[Comparison of epidemiological characteristics of human infection with avian influenza A (H5N1) virus in five countries of Asia and Africa].

Objective: To understand characteristics of demographic, seasonal and spatial distribution of H5N1 cases in major countries of Asia (Indonesia, Cambodia, Vietnam, China) and Africa (Egypt). Methods: Through searching public data resource and published papers, we collected cases information in five countries from May 1st, 1997 to November 6th, 2017, including general characteristics, diagnosis, onset and exposure history, etc. Different characteristics of survived and death cases in different countries were described and χ(2) test was used to compare the differences among death cases and odds ratio (OR) and 95%CI value was used to compare death risk in different countries. Results: A total of 856 cases were reported in five countries with Egypt had the most cases (44.3%). The highest number of cases were reported in 2015 (18.3%). 53% cases were reported from January to March, and 96.1% of cases had the history of poultry exposure. 64.2% (43 cases) cases in China had live poultry market exposure, but the sick/dead poultry exposure was the major exposure for cases in other four countries. 452 death cases were reported in five countries, and the fatality rate was 52.8%. With Egypt as the reference group, the highest death risk was seen in Indonesia (OR (95%CI): 11.52 (7.46-17.77)), followed by Cambodia (OR (95%CI): 4.27(2.37-7.69)) and China (OR (95%CI): 2.87 (1.73-4.74)). The age distribution of death cases among 5 countries was statistically significant, and the highest fatality rate was in 15-54 years group in Egypt (83.6%, 102 cases), while in Cambodia the highest fatality rate was in 0-14 years group (76.9%, 30 cases). The highest number of deaths were reported in 2006, and 48.3% were reported from January to March. There was difference in exposure routes among 5 countries (χ(2)=43.85, P=0.001), 63.2% (24 cases) of the death cases in China had live poultry market exposure. 92.9% (79 cases), 83.3% (40 cases) and 100.0% (38 cases) death cases in Indonesia, Vietnam and Camodia had sick/dead poultry exposure, respectively;and 81.6% (31 cases) of the death cases in Egypt had backyard poultry exposure. Conclusion: The geographical distribution, seasonal age, gender, exposure matter and outcome of H5N1 cases in five countries were different.

A cross-sectional study of acute diarrhea in Pudong, Shanghai, China: prevalence, risk factors, and healthcare-seeking practices.

Diarrhea is a common cause of morbidity and mortality and the incidence of diarrhea in the world has changed little over the past four decades. To assess the prevalence of and healthcare practices for diarrhea, a cross-sectional study was conducted in Pudong, Shanghai, China. In October 2014, a total of 5324 community residents were interviewed. Respondents were asked if they had experienced diarrhea (defined as ⩾3 passages of watery, loose, bloody, or mucoid stools within a 24-h period) in the previous month prior to the interview. The monthly prevalence of diarrhea was 4·1% (95% CI: 3·3-4·8), corresponding to an incidence rate of 0·54 episodes per person-year. The proportion of individuals with diarrhea who sought healthcare was 21·2% (95% CI: 13·4-29·0). Diarrhea continues to impose a considerable burden on the community and healthcare system in Pudong. Young age and travel were identified as predictors of increased diarrhea occurrence.

[Epidemiological characteristics of diarrheagenic Escherichia coli among diarrhea outpatients in China, 2012-2015].

Objective: To understand the epidemiological characteristics of diarrheagenic Escherichia (E.) coli (DEC) among diarrhea outpatients in China. Methods: Diarrhea surveillance program was conducted in outpatient and emergency departments from 170 hospitals that under the sentinel programs in 27 provinces, from 2012-2015. Clinical and epidemiological data regarding diarrhea patients were collected, with fecal specimens sampled and tested for DEC in 92 network-connected laboratories. Results: Among all the 46 721 diarrhea cases, 7.7% of them appeared DEC positive in those with geographic heterogeneity. In 2 982 cases (6.4%) with available data on PCR subtypes of DEC, enteroaggregative E. coli (EAEC, 1 205 cases, 40.4%) appeared the most commonly seen pathogens, followed by enteropathogenic E. coli (EPEC, 815 cases, 27.3%), and enterotoxigenic E.coli (ETEC, 653 cases, 21.9%). The highest positive rate of DEC was observed in outpatients of 25-34 years old (10.1%), living in the warm temperate zones (11.1%), and with mucous-like stool (9.4%). The positive rate of DEC showed a strong seasonal pattern, with peaks in summer, for all the subtypes. Conclusions: DEC seemed easy to be detected among diarrhea outpatients in China, with EAEC, EPEC and ETEC the most commonly identified subtypes. Epidemiological characteristics regarding the heterogeneities of DEC appeared different, in regions, age groups and seasons. Long-term surveillance programs should be strengthened to better understand the epidemiology of DEC, in China.

[Analysis on the epidemiological features of human brucellosis in northern and southern areas of China, 2015-2016].

Objective: To analyze the epidemiological characteristics of human brucellosis in northern and southern areas of China, and to develop national strategies for brucellosis prevention and control. Methods: Individual data on human brucellosis was collected from the National Notifiable Infectious Disease Reporting Information System to describe the situation of brucellosis in China during 2015-2016. Epidemiological features of the disease in northern and southern areas of China were analyzed. Results: A total of 104 125 cases were reported in mainland China during 2015-2016, with an average incidence rate as 3.81/100 000. The overall incidence rate from the northern provinces was 7.77/100 000 in 2016, a 18.6% decrease from 2015 (9.55/100 000), whereas the incidence rate in the southern provinces was 0.27/100 000 in 2016, with an increase of 28.6% than 0.21/100 000 in 2015. 90.0% of the newly infected counties mainly distributed in southern China. As for the locations of reporting cases, most of them were in the same counties in the northern areas (52.3%) while most cases in the southern areas (59.6%) were imported from other counties. The median age of the cases was 48 (IQR: 38-58) years, with male-to-female ratios as 2.7∶1 in the north and 2.2∶1 in the south. Majority of the cases were occupation-related, from both the northern (86.8%) and southern (62.7%) areas. Human brucellosis occurred every month throughout the year but with an obvious seasonal increase between March and July. Conclusions: Different epidemiological features of human brucellosis appeared in both northern and southern areas of China. The disease was seen endemic in the northern and dispersal in the southern provinces. Appropriate strategies for brucellosis prevention and control should be developed, according to the different epidemiological characteristics in the northern or southern areas.

Investigation of JAKs/STAT-3 in lipopolysaccharide-induced intestinal epithelial cells.

Janus-activated kinase (JAKs)-signal transducer and activator of transcription 3 (STAT-3) signalling play critical roles in immunoregulation and immunopathology, which involve inflammatory responses and enteritis. JAK phosphorylates STAT-3 in response to stimulation by cytokines or growth factors, and then activates or represses the gene expression. STAT-3 is activated persistently in cancer cells and contributes to the malignant progression of various types of cancer and inflammation. To elucidate the different roles of JAKs in the activation of STAT-3, the lipopolysaccharide-induced primary intestinal epithelial cell (IEC) acute inflammatory model was established. Small interference RNAs (siRNAs) were then employed to attenuate the expression levels of JAKs. Real-time quantitative reverse transcription-polymerase chain reaction (PCR) (qRT-PCR) revealed that JAK mRNA levels were reduced efficiently by JAK-specific siRNAs. Under the IEC inflammatory model transfected with si-JAK, which equates to effective silencing, qRT-PCR and Western blot assays, suggested that knockdowns of JAK attenuated the JAK-induced down-regulation of STAT-3 at the mRNA or protein levels. In particular, JAK1 played a key role, which was consistent with the RNA-Seq results. Subsequently, the expression levels of proinflammatory cytokines interleukin (IL)-1ß and tumour necrosis factor (TNF)-α were down-regulated in the IEC inflammatory model transfected with si-JAK1. JAK1 appears as a direct activator for STAT-3, whereas treatments targeting JAK1 repressed STAT-3 sufficiently pathways in the IEC inflammatory model. Therefore, the control of JAK1 using siRNAs has the potential to be an effective strategy against enteritis.

Association analysis between feed efficiency studies and expression of hypothalamic neuropeptide genes in laying ducks.

Residual feed intake (RFI) is now considered a more reasonable metric to evaluate animal feed efficiency. In this study, the correlation between RFI and other feed efficiency traits was investigated and gene expression within the hypothalamus was determined in low RFI (LRFI) and high RFI (HRFI) ducks. Further, several hypothalamic neuropeptide genes were measured using quantitative real-time PCR. The mean feed intake value was 160 g/day, whereas the egg mass laid (EML) and body weight were approximately 62.4 g/day and 1.46 kg respectively. Estimates for heritability of RFI, feed conversion ratio (FCR) and feed intake were 0.26, 0.18 and 0.23 respectively. RFI is phenotypically positively correlated with feed intake and FCR (P < 0.01). The expression of neuropeptide Y (NPY) and neuropeptide Y receptor Y5 (NPY5R) mRNA was higher in HRFI ducks compared with LRFI ducks (P < 0.05), whereas that of proopiomelanocortin (POMC), melanocortin 4 receptor (MC4R) and cholecystokinin (CCK) was lower (P < 0.05). The mRNA expression of gonadotropin-releasing hormone 1 (luteinizing-releasing hormone) (GNRH1) and prolactin receptor (PRLR) was unchanged between LRFI and HRFI ducks. The results indicate that selection for LRFI could reduce feed intake without significant changes in EML, whereas selection on FCR will increase EML.

[Comparison of demographical characteristics of malaria cases from malaria control to elimination in China].

OBJECTIVE: To further identify the high-risk population at malaria elimination phase, and to provide the scientific evident for targeted prevention and control measures, we compared the demographical feature and its change trend for malaria cases between malaria control stage and elimination stage in China. METHODS: The data of individual case (probable and confirmed) and population during 2007-2014 were collected from China National Notifiable Infectious Disease Reporting Information System, and the data of epidemiological investigation for malaria case (imported and indigenous) during 2011-2014 were collected from China Parasite Disease Prevention and Control Information System. All of the data didn't include China's Hongkong, Macao, Taiwan and foreign cases. We described the demographic features of malaria cases, e.g. sex, age, occupation and mobility, to compare the differences of cases between malaria control stage (2007-2010) and the elimination phase (2011-2014). RESULTS: From 2007 to 2014, a total of 108 076 malaria cases were reported nationwide, which 13 355 cases were reported at the elimination stage. The proportion of male cases considerably increased from 65.1% (6 1625 cases) at the control stage to 91.4% (12 209 cases) at the elimination phase, with the cases aged 15-64 years among male cases dramatically rose from 74.3% (45 793 cases) to 97.2% (11 870 cases). In terms of occupation, the proportion of children and students decreased from 17.8% (16 891 cases) to 2.7% (356 cases), while the percentage of migrant workers, workers and other professional cases increased from 8.5% (8 031 cases), 3.5% (3 319 cases) and 3.6% (3 435 cases) to 13.1% (1 757 cases), 11.5% (1 534 cases) and 11.4% (1 517 cases), respectively. During the elimination stage,P. faliparium cases have higher proportion of male (96.4%, 7 179 cases) and adult aged 15-64 year (99.4%, 7 399 cases) than that of P. vivax cases , 83.9% (4 344 cases) and 90.3% (4 679 cases), respectively. Moreover, the proportion of imported cases rose from 63.6% (2 599 cases) in 2011 to 97.7% (2 854 cases) in 2014, and the proportion of the migrants in indigenous cases also showed an increasing trend from 13.5% (201 cases) in 2011 to 28.4% (19 cases) in 2014. CONCLUSION: Compared with the control stage, great changes of demographical characteristics of malaria cases occurred at the elimination stage. Male adults aged 15-64 year-old, imported cases and domestic migrants were the high-risk population for targeted control and prevention at the malaria elimination stage.

[Epidemiological analysis of the deaths of malaria in China, 2005-2014].

OBJECTIVE: To explore the epidemiological features of deaths of malaria from 2005 to 2014, so as to provide the evidence for subsequently more effective strategic planning of malaria elimination in China. METHODS: The data of individual malaria cases (including probable and confirmed cases, population data, geographic distribution, diagnosis and reporting information) were obtained from the National Notifiable Infectious Disease Reporting Information System from 2005 to 2014 and the epidemiological investigation information (including the clinical systems and the imported and indigenous cases) was extracted from Parasite Disease Prevention and Control Information System from 2011 to 2014. All of the data didn't include Hongkong, Macao, Taiwan and foreign cases. The population characteristics, clinical systems, geographic distribution, diagnosis and reporting and sources of infections of deaths were analyzed. RESULTS: From 2005 to 2014, a total of 228 deaths of malaria were reported, with 203 (89.0%) of P. falciparum malaria, 13 (5.7%) of P. vivax malaria, 1 (0.5%) of P. malariae malaria and 11(4.8%) other cases. The fatality rate of malaria increased since 2010. Among the deaths, 48 (81.4% ) had serious complications, which included cerebral lesion, coma, severe renal and hepatic injuries and hemolysis and so on. In 2005-2010, the geographical distribution of malaria deaths was mainly in Yunnan (78 deaths, 56.1%), Sichuan (13 deaths, 9.4%), Henan (7 deaths, 5.0%), Shandong (6 deaths, 4.3%) and Zhejiang (5 deaths, 3.6%) province. However, since the initiation of malaria elimination program in 2010, the areas with malaria deaths have changed, which mainly distributed in Henan (10 deaths, 11.2%), Sichuan (9 deaths, 10.1%), Shandong (8 deaths, 9.0%), Jiangsu (7 deaths, 7.9%) and Hunan province (7 deaths, 7.9%). Besides there were nine deaths (10.0%) reported in non-endemic areas of malaria (Beijing, Inner Mongolia, Jilin, and Ningxia) in 2011-2014. The median time from illness onset to diagnosis for deaths was 5.5 (P25-P75: 3.0-8.5) d, which was longer than 3.0 (2.0-6.0)d for survivors. Moreover, for deaths, the median P50 (P25-P75)(6.0, 4.0-9.0 d) from illness onset to diagnosis in 2011-2014 was longer than that in 2005-2010 (5.0, 3.0-9.0 d). Among imported deaths, 77 deaths (90.6%) originated from Africa and 8 deaths (9.4%) from Southeast Asia. CONCLUSION: Although the reported deaths of malaria were stable in 2005-2014, the geographical distribution of malaria deaths changed significantly and the time from illness onset to the diagnosis was longer since 2010. Special attention should be paid to the diagnosis and treatment of imported cases to reduce the fatality at the malaria elimination stage.

Health and production traits in bovine are associated with single nucleotide polymorphisms in the NOD2 gene.

The NOD2 gene plays a fundamental role in initiating the inflammatory and subsequent immune response. NOD2 was previously identified as a susceptibility locus for inflammatory bowel diseases in humans. In this study, we detected 2 mutations in exon 12 (A→T, G→A) among 5 cattle breeds (N = 315) and analyzed their associations with production traits and genetic resistance against bovine mastitis in Chinese Holstein and Chinese Simmental breeds (N = 218). The transitions (A→T) at position 114 bp were associated with somatic cell score (P < 0.01). The G→A at position 1594 bp plays a critical role in increasing 305-day milk yields. In Chinese Holstein and Chinese Simmental breeds, the BB genotype may contribute to disease susceptibility. Compared to all genotypic combinations, the A, B, and FF genotypes are beneficial not only for reducing somatic cell score but also for increasing production.

Messenger RNA expression and immunolocalization of psoriasin in the goat mammary gland and its milk concentration after an intramammary infusion of lipopolysaccharide.

Psoriasin (S100A7) is a member of the S100 protein family of calcium-binding proteins and plays a crucial role in local host defenses. The present study aimed to identify the expression of S100A7 in the goat mammary gland and in milk. The goat S100A7 coding DNA sequence was identified using direct sequencing. An S100A7 antibody was raised in rabbits by immunization with a synthetic S100A7 peptide consisting of 13 amino acids. Messenger RNA expression and protein localization in different regions of a healthy mammary gland were detected by reverse transcription-polymerase chain reaction and immunohistochemistry. Changes in the concentration of S100A7 in the milk after an intramammary infusion of Escherichia coli lipopolysaccharide (LPS) were examined by an enzyme immunoassay. The goat S100A7 peptide had 98% and 86% sequence similarity to that of sheep and bovines, respectively. The S100A7 mRNA expression was higher in the teat and udder skin than in the cistern and parenchyma of the mammary gland. Immunoreactive S100A7 was localized in the epithelial cells of the alveolus and gland cistern, and stratified squamous epithelium of the teat. Psoriasin as a secreted protein was detectable in healthy milk, and an intramammary LPS infusion increased the concentration of S100A7 in the milk. The results suggest that S100A7 is produced in the epithelial cells of the mammary gland and is secreted into the milk.

Spatiotemporal pattern of hand-foot-mouth disease in China: an analysis of empirical orthogonal functions.

OBJECTIVES: Hand-foot-mouth disease (HFMD) is the most common infectious disease in China. Spatial and temporal patterns of HFMD in China provide valuable information on the relationship between HFMD and the geographical environment, and help in the prediction of HFMD transmission. STUDY DESIGN: Cross-sectional study. METHODS: Total HFMD morbidity per 10 days from May 2008 to March 2009 was recorded in 1966 counties in China. Empirical orthogonal function (EOF) analysis was used to obtain spatial and temporal patterns of HFMD. RESULTS: The first five modes of HFMD morbidity explained 84.24% of the total variance. The dominant mode (first mode showing the highest variance) showed high HFMD morbidity in the western counties of Bohai Bay, the mid-south of China, the Yangtze River delta, the Pearl River delta and the areas bordering Vietnam from early May to late July 2008. The second mode showed high HFMD morbidity in the western counties of Bohai Bay, the north-east of China, north of Xinjiang and the Yangtze River delta from late May to the middle of August 2008. The third mode showed high HFMD morbidity in the Yangtze River delta, the Pearl River delta and the middle of the Huaihe River basin in early May 2008. CONCLUSIONS: EOF analysis of HFMD morbidity shows the main spatiotemporal patterns and can explain variance in HFMD in China.

Dectin-1 gene polymorphism is associated with susceptibility to nonspecific digestive disorders and cytokine expression in rabbits.

Dectin-1 plays a critical role in the pathogenesis of intestinal inflammation by recognizing the pathogenic agents and mediating cytokine responses. The objective of this study was to establish the association between dectin-1 polymorphisms and susceptibility to nonspecific digestive disorders (NSDD) and cytokine expression in rabbits. A total of 7 coding SNP were detected in dectin-1 gene. The genetic association between SNP (ss707197675A > G) and susceptibility to NSDD was evaluated using a case-control study (178 cases and 174 controls). The results revealed that the A allele was associated with an increased risk of developing NSDD in rabbits. The AA genotype significantly increased the genetic susceptibility to NSDD with odds ratio of 4.76 (95% confidence interval, 1.92-12.50, P = 0.0002) compared with GG and GA genotypes. We also experimentally induced NSDD in another independent growing rabbit population by feeding a low-fiber diet and subsequently investigated the cytokine mRNA expression. Among the 4 studied cytokines, the expression of interferon-γ, IL-17F, and IL-22 were increased 2.8 to 6.0-fold in AA genotype compared with GG genotype (P < 0.01). The greater IL-17F and IL-22 mRNA expressions indicated a positive correlation with severe intestinal inflammation (P < 0.05). The decreased expression of IL-10 was associated with severe intestinal inflammation (P = 0.006), but IL-10 expression was not influenced by dectin-1 genotype. In conclusion, polymorphism ss707197675 of dectin-1 is related with susceptibility to NSDD and increased expression of proinflammatory cytokines, and dectin-1 could be an important candidate gene associated with NSDD in rabbits.

Mitochondrial DNA sequence diversity and origin of Chinese domestic yak.

In order to clarify the origin and genetic diversity of yak in China, we analysed mitochondrial DNA (mtDNA) control region sequences (approximately 891 bp) in 52 individuals from four domestic yak (Poephagus grunniens) breeds, as well as from a hybrid between yak and cattle (Pianniu). Twenty-five samples were further selected for partial (420 bp) cytochrome b sequencing based on control region sequence information. Two yak samples shared sequences with Chinese cattle (Bos taurus); the remaining yak mtDNAs converged into two major clades in the phylogenetic analysis. Genetic diversity varied substantially among the breeds, with the hybrid Pianniu yak demonstrating the highest diversity. Our results suggest that the Chinese yak was domesticated from two distinct matrilineal sources or from a heterogeneous pool containing both divergent lineages, with occasional gene introgression from cattle.

Use of direct-probe mass spectrometry as a toxicology confirmation method for demoxepam in urine following high-performance liquid chromatography.

The identification of the metabolite demoxepam in human urine establishes that chlordiazepoxide, a common benzodiazepine, has been administered. Like N-oxide metabolites of other drugs, demoxepam cannot be detected by gas chromatography-mass spectrometry (GC-MS), due to thermal decomposition, and the product, nordiazepam, is a metabolite common to many benzodiazepines. Demoxepam can be readily screened using a high-performance liquid chromatography (HPLC) system such as REMEDi HS; at 35 degrees C, no thermal decomposition will occur. Currently, there is no confirmation method available for the detection of demoxepam in urine samples. In this study, we demonstrated that following collection of the HPLC fraction, demoxepam can be confirmed using the technique of direct-probe MS. The mass spectra of demoxepam and nordiazepam differ and are easily distinguishable from each other. Ten urine samples that were analyzed by HPLC and determined to contain demoxepam were evaluated; demoxepam was confirmed in each case by direct-probe MS.

The development of a broad-spectrum toxicology screening program in Taiwan.

Our institute serves as a centralized clinical laboratory for municipal and private hospitals in Taipei, a major international metropolis in the Asian region. Two key considerations leading to the development of our toxicology program are: a large number of foreign visitors and local residents returning from overseas trips may bring in chemicals which are less commonly seen in this region; and the lack of readily available assays for a large percentage of commonly used medicines, including prescription and over-the-counter drugs. Our toxicology screening program addresses the needs of both the Emergency Department Drug Screening and Drug of Abuse Screening. In Emergency Department Drug Screening, REMEDi HS is used as the general screening method. In Drug of Abuse Screening, the TDx is used for the initial screening of amphetamine-like substances and opiates, followed by REMEDi HS for the confirmation of positive samples. Emergency Department data collected at our institute over one year (September 1992 to August 1993) identified 57 different drugs in 713 samples. Opiates, narcotics and central stimulants accounted for 24% of the encountered drugs. Presently, there is no extensive reporting of misuse of benzodiazepines in this region. The detection of herbal ingredients like ephedrine and methylephedrine (from the Ma-Huang plant) in patient samples illustrates a large area often overlooked by western toxicology.