Profile and dynamics of infectious diseases: a population-based observational study using multi-source big data.

BACKGROUND: The current surveillance system only focuses on notifiable infectious diseases in China. The arrival of the big-data era provides us a chance to elaborate on the full spectrum of infectious diseases. METHODS: In this population-based observational study, we used multiple health-related data extracted from the Shandong Multi-Center Healthcare Big Data Platform from January 2013 to June 2017 to estimate the incidence density and describe the epidemiological characteristics and dynamics of various infectious diseases in a population of 3,987,573 individuals in Shandong province, China. RESULTS: In total, 106,289 cases of 130 infectious diseases were diagnosed among the population, with an incidence density (ID) of 694.86 per 100,000 person-years. Besides 73,801 cases of 35 notifiable infectious diseases, 32,488 cases of 95 non-notifiable infectious diseases were identified. The overall ID continuously increased from 364.81 per 100,000 person-years in 2013 to 1071.80 per 100,000 person-years in 2017 (χ2 test for trend, P < 0.0001). Urban areas had a significantly higher ID than rural areas, with a relative risk of 1.25 (95% CI 1.23-1.27). Adolescents aged 10-19 years had the highest ID of varicella, women aged 20-39 years had significantly higher IDs of syphilis and trichomoniasis, and people aged ≥ 60 years had significantly higher IDs of zoster and viral conjunctivitis (all P < 0.05). CONCLUSIONS: Infectious diseases remain a substantial public health problem, and non-notifiable diseases should not be neglected. Multi-source-based big data are beneficial to better understand the profile and dynamics of infectious diseases.

The relationship between adolescent risk perception and emotions during the COVID-19: a short-term longitudinal study.

This study explores the relationship between adolescents' perceptions of epidemic risk and their emotions through three follow-up surveys during the early stages of the COVID-19 pandemic on February 11th (T1), 18th (T2), and 25th (T3), 2020. Three hundred and four adolescents in different academic stages (junior high middle school, senior high middle school, and university) participated in the online survey, and cross-lag analysis was used to examine the causal relationship between epidemic risk perceptions and positive and negative emotions. The results found that the individual's positive emotions were significantly higher than the negative emotions in T1, T2 and T3. Cross-lag analysis found that for positive emotions, T2 positive emotions could negatively predict T3 epidemic risk perceptions, and T2 epidemic risk perceptions could negatively predict the individual's T3 positive emotions. For negative emotions, risk perceptions at T1 could positively predict negative emotions at T2, and at the same time, negative emotions at T1 could also positively predict epidemic risk perceptions at T2. This indicates that during the early stages of the COVID-19 pandemic, there was a causal relationship between the perceptions of epidemic risk and the emotions of adolescents, and this relationship had high stability among groups of different genders and academic stages.

Epidemic character and environmental factors in epidemic areas of severe fever with thrombocytopenia syndrome in Shandong Province.

Severe fever with thrombocytopenia syndrome (SFTS) is an emerging lethal tick-borne disease that has been widely prevalent in East Asia in recent years, and raised an important public health problem in China. However, a comprehensive and thorough understanding of the current SFTS epidemic areas in Shandong Province is not available. Accordingly, a descriptive analysis was applied to explore the demographic and spatio-temporal features of SFTS cases in Shandong Province from 2010 to 2015. The division between epidemic areas and non-epidemic areas was given by maximum entropy niche model (MaxEnt) based on environmental factors such as temperature and precipitation. There were 1,786 SFTS cases between 2010 and 2015 in Shandong, mainly involving middle-aged and elderly individuals (age:40-80) and farmers (84.6 %). May-October was the high-incidence period and the SFTS cases were mostly clustered in the central and eastern regions of Shandong Province. In light of MaxEnt, 3 specific environmental features between dichotomous areas were identified, including 1) most epidemic areas are covered by acidic soils (Constituent ratio: 63.8 %) while 29.1 % coverage appears in non-epidemic areas, 2) compared with non-epidemic areas, the identical kinds of agricultural areas accounted for a higher constituent ratio (64.9 % vs. 42.7 %), and 3) lower level of annual temperature in epidemic areas compared to non-epidemic areas [Median: 13.2℃ vs. 14.2℃; (25th IQR, 75th IQR): (12.5, 13.7) vs. (13.6, 14.9)]. Our study suggests middle-aged and elderly farmers are high-risk population to be focused on in future prevention and acidic soils, agricultural activities as well lower temperature that may be related to increased SFTS incidence.

Impacts of transportation and meteorological factors on the transmission of COVID-19.

The ongoing pandemic of 2019 novel coronavirus disease (COVID-19) is challenging global public health response system. We aim to identify the risk factors for the transmission of COVID-19 using data on mainland China. We estimated attack rate (AR) at county level. Logistic regression was used to explore the role of transportation in the nationwide spread. Generalized additive model and stratified linear mixed-effects model were developed to identify the effects of multiple meteorological factors on local transmission. The ARs in affected counties ranged from 0.6 to 9750.4 per million persons, with a median of 8.8. The counties being intersected by railways, freeways, national highways or having airports had significantly higher risk for COVID-19 with adjusted odds ratios (ORs) of 1.40 (p = 0.001), 2.07 (p < 0.001), 1.31 (p = 0.04), and 1.70 (p < 0.001), respectively. The higher AR of COVID-19 was significantly associated with lower average temperature, moderate cumulative precipitation and higher wind speed. Significant pairwise interactions were found among above three meteorological factors with higher risk of COVID-19 under low temperature and moderate precipitation. Warm areas can also be in higher risk of the disease with the increasing wind speed. In conclusion, transportation and meteorological factors may play important roles in the transmission of COVID-19 in mainland China, and could be integrated in consideration by public health alarm systems to better prevent the disease.

Age-dependent Gender Differences in COVID-19 in Mainland China: Comparative Study.

BACKGROUND: The ongoing pandemic of novel coronavirus disease 2019 (COVID-19) is challenging the global public health system. Sex differences in infectious diseases are a common but neglected problem. METHODS: We used the national surveillance database of COVID-19 in mainland China to compare gender differences in attack rate (AR), proportion of severe and critical cases (PSCC), and case fatality rate (CFR) in relation to age, affected province, and onset-to-diagnosis interval. RESULTS: The overall AR was significantly higher in females than in males (63.9 vs 60.5 per 1 million persons; P ˂ .001). In contrast, PSCC and CFR were significantly lower among females (16.9% and 4.0%) than among males (19.5% and 7.2%), with odds ratios of 0.87 and 0.57, respectively (both P ˂ .001). The female-to-male differences were age dependent, and were significant among people aged 50-69 years for AR and in patients aged 30 years or older for both PSCC and CFR (all P ≤ .001). The AR, PSCC, and CFR varied greatly from province to province. However, female-to-male differences in AR, PSCC, and CFR were significant in the epicenter, Hubei province, where 82.2% confirmed cases and 97.4% deaths occurred. After adjusting for age, affected province, and onset-to-diagnosis interval, the female-to-male difference in AR, PSCC, and CFR remained significant in multivariate logistic regression analyses. CONCLUSIONS: We elucidate an age-dependent gender dimorphism for COVID-19, in which females have higher susceptibility but lower severity and fatality. Further epidemiological and biological investigations are required to better understand the sex-specific differences for effective interventions.

Therapy to Obese Type 2 Diabetes Mellitus: How Far Will We Go Down the Wrong Road?

Traditional glucose-lowering chemical agents, including various types of insulin and insulin secretagogues, insulin sensitizers, gliptins, etc., are based on diabetic pathogenesis of insulin resistance (IR) and islet insufficiency. Numerous evidence-based medical studies have shown that these traditional hypoglycemic chemical agents do not provide cardiovascular benefit to patients with type 2 diabetes mellitus (T2DM) and may even increase the risk of all-cause mortality. Based on research evidence published to date, these studies show that overload of energy could increase the incidence and prevalence of T2DM, and reduction in the heat load can significantly reduce the incidence of T2DM. Therefore, the essence of T2DM is heat overload, meaning heat overload is the etiology of obese T2DM. At the same time, results of numerous studies show that heat overloading is the cause of IR. IR and islet dysfunction are protective factors in intervening with heat overload. These drugs, which are based on the mechanisms of IR and islet insufficiency, increase caloric reserve and cause or worsen obesity, which is equivalent to exacerbating the basic etiology and the cardiovascular risk factor of T2DM. Thus, a reasonable strategy for prevention and treatment of obese T2DM appears to promote the negative balance of calories and the elimination of caloric reserves. Chinese herbal medicines can promote negative balance of heat in many aspects, which can bring new hope for prevention and treatment of T2DM.

A review on advances in methods for modification of paper supports for use in point-of-care testing.

Paper is a widely used support for use in devices for point-of-care testing (POCT) in clinical diagnosis, food safety monitoring and environmental pollution. Paper is inexpensive, biocompatible, biodegradable and allows a sample fluid to flow by capillary force. Numerous method have been developed recently for chemical modification of papers in order to introduce different functionalities. This review (with 148 refs.) summarizes the recent progress in paper-based POCT devices. The introduction summarizes the state of the art of paper-based POCT devices and the physicochemical properties of existing unmodified materials (including cellulose, cellulose-based composites, cotton fibers, glass fibers, nitrocellulose, thread). Methods for paper modification for sample pretreatment are summarized next, with subsections on sample storage and collection, sample separation, nucleic acid extraction and sample preconcentration. Another main section covers approaches for paper modification for improving POCTs, with subsections on assays for proteins, nucleic acids, drugs, ion and organic molecules. The advantages and disadvantages of these approaches are compared. Several tables are presented that summarize the various modification techniques. A concluding section summarizes the current status, addresses challenges and gives an outlook on future perspectives of POCTs. Graphical abstract This review summarizes the progress that has been made in paper based point-of-care testing (POCT) and lateral flow assays (LFAs), quite often by using advanced nanomaterials for paper modification.

Genetic Diversity and the Spatio-Temporal Analyses of Hantaviruses in Shandong Province, China.

Hemorrhagic fever with renal syndrome (HFRS) is a serious public health problem in Shandong Province, China. We conducted an epizootiologic investigation and phylogeographic and phylodynamic analyses to infer the phylogenetic relationships of hantaviruses in space and time, and gain further insights into their evolutionary dynamics in Shandong Province. Our data indicated that the Seoul virus (SEOV) is distributed throughout Shandong, whereas Hantaan virus (HTNV) co-circulates with SEOV in the eastern and southern areas of Shandong. Their distribution showed strong geographic clustering. In addition, our analyses indicated multiple evolutionary paths, long-distance transmission, and demographic expansion events for SEOV in some areas. Selection pressure analyses revealed that negative selection on hantaviruses acted as the principal evolutionary force, whereas a little evidence of positive selection exists. We found that several positively selected sites were located within major functional regions and indicated the importance of these residues for adaptive evolution of hantaviruses.

The novel α-glucan YCP improves the survival rates and symptoms in septic mice by regulating myeloid-derived suppressor cells.

Sepsis is a life-threatening health condition that is initially characterized by uncontrolled inflammation, followed by the development of persistent immunosuppression. YCP is a novel α-glucan purified from the mycelium of the marine fungus Phoma herbarum YS4108, which has displayed strong antitumor activity via enhancing host immune responses. In this study, we investigated whether YCP could influence the development of sepsis in a mouse model. Caecal ligation and puncture (CLP)-induced sepsis was established in mice that were treated with YCP (20 mg/kg, ip or iv) 2 h before, 4 and 24 h after the CLP procedure, and then every other day. YCP administration greatly improved the survival rate (from 39% to 72% on d 10 post-CLP) and ameliorated disease symptoms in the septic mice. Furthermore, YCP administration significantly decreased the percentage of myeloid-derived suppressor cells (MDSCs) in the lungs and livers, which were dramatically elevated during sepsis. In cultured BM-derived cells, addition of YCP (30, 100 µg/mL) significantly decreased the expansion of MDSCs; YCP dose-dependently decreased the phosphorylation of STAT3 and increased the expression of interferon regulatory factor-8 (IRF-8). When BM-derived MDSCs were co-cultured with T cells, YCP dose-dependently increased the production of arginase-1 (Arg-1) and inducible nitric oxide synthase (iNOS), and activated the NF-κB pathway. In addition, the effects of YCP on MDSCs appeared to be dependent on toll-like receptor (TLR) 4. These results reveal that YCP inhibits the expansion of MDSCs via STAT3 while enhancing their immunosuppressive function, partially through NF-κB. Our findings suggest that YCP protects mice against sepsis by regulating MDSCs. Thus, YCP may be a potential therapeutic agent for sepsis.

Prevalence of diabetes and unrecognized diabetes in hypertensive patients aged 40 to 79 years in southwest China.

This study aimed to assess the prevalence of diabetes and unrecognized diabetes in hypertensive patients aged 40 to 79 years in Southwest China. From September 2013 to March 2014, a cross-sectional survey was conducted in 4021 hypertensive patients aged 40 to 79 years living in Chengdu and Chongqing, China. Fasting plasma glucose (FPG) and 2h plasma glucose (2-hPG) in an oral glucose-tolerance test (OGTT) were used for assessments. Whether the patients previously had diabetes (DM) was determined by their own reports. The survey was carried out by the same questionnaire for all respondents. DM prevalence was 32.0% in hypertensive patients aged 40 to 79 years in Southwest China, with the rates of 29.6% and 33.5% in men and women, respectively (P<0.001). DM prevalence increased with age age and body-mass index. DM prevalence rates were 16.9%, 24.7%, 38.2% and 41.9% in hypertensive patients aged 40-49, 50-59, 60-69 and over 70, respectively. DM prevalence were 30.6%, 27.9%, 37.1%, and 37.4%, for BMI<18.5, 18.5-24.9, 25.0-29.9, and ≥30, respectively. Prevalence of unrecognized DM were 20.8% in hypertensive patients aged 40 to 79 years in Southwest China. Using only fasting blood glucose testing without OGTT would have resulted in 65.0% of missed DM diagnosis in these newly diagnosed patients. The prevalence of DM and unrecognized DM were high in hypertensive patients aged 40 to 79 years in Southwest China.These findings indicate that hypertensive patients aged 40 to 79 years should regularly submit to community-based OGTT screening for timely DM diagnosis.

Association between serum γ-glutamyltransferase and chronic kidney disease in urban Han Chinese: a prospective cohort study.

PURPOSE: Limited numbers of literatures have focused on the association between γ-glutamyltransferase (GGT) and chronic kidney disease (CKD), and their results were controversial. Therefore, in this study, we set up a large-scale cohort of Chinese population to discover and verify the association between serum GGT and CKD. METHODS: Our cohort study was based on 21,818 patients who visited Health Management Center of Shandong Provincial Hospital, China, to receive routine health check-up during the period of 2005-2010, and we used multivariate Cox regression model to clarify whether elevated serum GGT increased the risk of CKD or not. RESULTS: During the follow-up of 57,891 person-years, 1456 patients developed CKD, giving rise to an incidence density of 25.15 per 1000 person-years (1456/57,891 person-years). After adjusting gender, age, baseline serum creatinine (SCr), body mass index (BMI), serum albumin (ALB), alanine aminotransferase (ALT), hemoglobin, white blood cell count (WBC), triglyceride (TG), total cholesterol (TC), hypertension, cardiovascular disease (CVD), diabetes, smoking and drinking status, the risk for CKD increased with the elevated serum GGT quartiles. The hazard ratio (HR) for CKD was 1.326 (95 % confidence interval (CI), 1.073-1.639) when the top quartile of serum GGT was compared with the bottom one, and the HR of log-transformed serum GGT for CKD was 1.658 (95 % CI, 1.294-2.125). The results were consistent in males but different in females when gender was stratified. CONCLUSION: The result reveals that there is a positive relationship between increasing serum GGT levels and the incidence of CKD which suggests that elevated GGT level could be a potential indicator for risk of CKD.

Letter to the Editor: The Surge of Type 2 Diabetes Mellitus in China - an International Alert: Physical Exercise and Low-Caloric Diet May Reduce the Risks of Type 2 Diabetes Mellitus and Dementia.

The prevalence of diabetes in China has surged from 0.67% before 1980 to 11.6% currently. It is even higher than the prevalence in the United States. Certainly, China's economic open-ups, improving living standard, and modernization have propagated the surge. From a traditional public-health point of view, increased food intake and decreased exercise were the main contributors. A new knowledge of colon microbiota could be applied to provide a second harvest of food energy; for example, large molecules of carbohydrates, which are undigested by the stomach and small intestine, produce by-products that the body can absorb in the colon. Colon microbiota can ferment these carbohydrates to the short-chain fatty acid butyrate. This is an energy source that may even cause nonalcoholic fatty liver. How these colon microbiota contribute to the surge of diabetes and whether this new knowledge can be used to control diabetes and metabolic syndrome are questions for future scientific studies. Clinically, however, colon microbiota have had immediate applications; fecal microbiota have been transplanted from healthy persons to treat recurrent Clostridium difficile infection at Mayo Clinic. In addition, a stool biobank of healthy persons was established at Mayo Clinic for future clinical applications.

Immunologic Characterization of Cytokine Responses to Enterovirus 71 and Coxsackievirus A16 Infection in Children.

Viral encephalitis is a serious complication of hand, foot, and mouth disease (HFMD), but characteristics of cytokines response in enterovirus 71 (EV-71) and/or coxsackievirus A16 (CV-A16) associated HFMD with or without viral encephalitis remained unclear.We performed a multigroup retrospective study and compared the serum cytokines concentrations among 16 encephalitis patients infected with EV-71 and CV-A16, 24 encephalitis patients with single EV-71 infection, 34 mild HFMD patients with EV-71 infection, 18 mild HFMD patients with CV-A16 infection, and 39 healthy control subjects.Serum levels of interleukin (IL)-4, IL-5, IL-22, and IL-23 were significantly higher in encephalitis patients than in HFMD-alone patients when adjusting for age and sex; IL-2, tumor necrosis factor (TNF)-α, IL-4, IL-22, and IL-1ß were significantly higher in HFMD-alone patients of EV-71 infection than in CV-A16 infected HFMD patients; cerebrospinal fluid level of IL-6 was lower in the EV-71/CV-A16 associated encephalitis than that in the EV-71 alone associated encephalitis patients.Over or low expression of the cytokines cascade in HFMD patients appears to play an important role in the elicitation of the immune response to EV-71 and CV-A16. These data will be used to define a cytokine profile, which might help to recognize HFMD patients with the high risk of developing encephalitis.

The effect of gliquidone on KATP channels in pancreatic ß-cells, cardiomyocytes, and vascular smooth muscle cells.

AIMS: Sulfonylurea drugs exert an insulinotropic effect through ATP-sensitive potassium (KATP) channel inhibition in pancreatic islet cells. These channels are also expressed in cardiomyocytes and vascular smooth muscle cells (VSMCs), suggesting potential for adverse cardiovascular effects. We evaluated the effects of Gliquidone (Glq) on sulfonylurea receptors in HIT-T15 cells (SUR1), cardiomyocytes (SUR2A), and VSMCs (SUR2B). METHODS: The concentration-dependent effects of Glq (0.001-500 µM) on KATP channels were assessed using whole-cell patch clamp in HIT-T15 cells, rat cardiomyocytes, and VSMCs. Parallel studies using Glibenclamide (Glb) (0.001-10 µM) and Gliclazide (Glc) (0.01-500 µM)were conducted as controls. RESULTS: In HIT-T15 cells, Glb exhibited the lowest IC50 (0.03 µM), as compared to Glq (0.45µM) and Glc (1.21µM). However, Glq had higher IC50 in cardiomyoctes and VSMCs, as compared to Glb (119.1 vs. 0.01 and 149.7 vs. 0.09 µM, respectively), suggesting that Glq is more selective to ß-cells than Glb. Thus, Glq may have fewer side effects in cardiomyoctes and VSMCs. CONCLUSIONS: Glq is a highly selective SUR secretagogue with moderate affinity to ß-cells, but low affinity to cardiomyocytes and VSMCs. Our data also reveal the non-selective nature of Glb, as evidenced by high binding affinity to KATP channels in all the three cell types examined.

Burden of disease measured by disability-adjusted life years and a disease forecasting time series model of scrub typhus in Laiwu, China.

BACKGROUND: Laiwu District is recognized as a hyper-endemic region for scrub typhus in Shandong Province, but the seriousness of this problem has been neglected in public health circles. METHODOLOGY/PRINCIPAL FINDINGS: A disability-adjusted life years (DALYs) approach was adopted to measure the burden of scrub typhus in Laiwu, China during the period 2006 to 2012. A multiple seasonal autoregressive integrated moving average model (SARIMA) was used to identify the most suitable forecasting model for scrub typhus in Laiwu. Results showed that the disease burden of scrub typhus is increasing yearly in Laiwu, and which is higher in females than males. For both females and males, DALY rates were highest for the 60-69 age group. Of all the SARIMA models tested, the SARIMA(2,1,0)(0,1,0)12 model was the best fit for scrub typhus cases in Laiwu. Human infections occurred mainly in autumn with peaks in October. CONCLUSIONS/SIGNIFICANCE: Females, especially those of 60 to 69 years of age, were at highest risk of developing scrub typhus in Laiwu, China. The SARIMA (2,1,0)(0,1,0)12 model was the best fit forecasting model for scrub typhus in Laiwu, China. These data are useful for developing public health education and intervention programs to reduce disease.

Time-specific ecologic niche models forecast the risk of hemorrhagic fever with renal syndrome in Dongting Lake district, China, 2005-2010.

BACKGROUND: Hemorrhagic fever with renal syndrome (HFRS), a rodent-borne infectious disease, is one of the most serious public health threats in China. Increasing our understanding of the spatial and temporal patterns of HFRS infections could guide local prevention and control strategies. METHODOLOGY/PRINCIPAL FINDINGS: We employed statistical models to analyze HFRS case data together with environmental data from the Dongting Lake district during 2005-2010. Specifically, time-specific ecologic niche models (ENMs) were used to quantify and identify risk factors associated with HFRS transmission as well as forecast seasonal variation in risk across geographic areas. Results showed that the Maximum Entropy model provided the best predictive ability (AUC = 0.755). Time-specific Maximum Entropy models showed that the potential risk areas of HFRS significantly varied across seasons. High-risk areas were mainly found in the southeastern and southwestern areas of the Dongting Lake district. Our findings based on models focused on the spring and winter seasons showed particularly good performance. The potential risk areas were smaller in March, May and August compared with those identified for June, July and October to December. Both normalized difference vegetation index (NDVI) and land use types were found to be the dominant risk factors. CONCLUSIONS/SIGNIFICANCE: Our findings indicate that time-specific ENMs provide a useful tool to forecast the spatial and temporal risk of HFRS.

[Soil respiration dynamics and its controlling factors of typical vegetation communities on meadow steppes in the western Songnen Plain].

In order to accurately explore the soil respiration dynamics and its controlling factors of typical vegetation types in the western Songnen Plain, soil respiration rates of Chloris virgata, Puccinellia distans, Phragmites australis and Leymus chinensis communities were measured. The results showed that the diurnal curves of soil respiration rates of the four vegetation communities had simple peak values, which appeared at 11:00-15:00, and the valley values occurred at 21:00-1:00 or 3:00-5:00. The seasonal dynamic patterns of their soil respiration rates were similar, with the maximum (3.21-4.84 micromol CO2 x m(-2) x s(-1)) occurring in July and August and the minimum (0.46-1.51 micromol CO2 x m(-2) x s(-1)) in October. The soil respiration rates of the four vegetation communities had significant exponential correlations with ambient air temperature and soil temperature. Soil moisture, however, only played an important role in affecting the soil respiration rate of C. virgata community while air humidity near the soil surface was significantly correlated with the soil respiration rates of P. australis and L. chinensis communities. The soil salt contents seriously constrained the CO2 dioxide emission, and the soil pH, electrical conductivity (EC), exchangeable sodium percentage (ESP) could explain 87%-91% spatial variations of the soil respiration rate.

Animal reservoir, natural and socioeconomic variations and the transmission of hemorrhagic fever with renal syndrome in Chenzhou, China, 2006-2010.

BACKGROUND: China has the highest incidence of hemorrhagic fever with renal syndrome (HFRS) worldwide. Reported cases account for 90% of the total number of global cases. By 2010, approximately 1.4 million HFRS cases had been reported in China. This study aimed to explore the effect of the rodent reservoir, and natural and socioeconomic variables, on the transmission pattern of HFRS. METHODOLOGY/PRINCIPAL FINDINGS: Data on monthly HFRS cases were collected from 2006 to 2010. Dynamic rodent monitoring data, normalized difference vegetation index (NDVI) data, climate data, and socioeconomic data were also obtained. Principal component analysis was performed, and the time-lag relationships between the extracted principal components and HFRS cases were analyzed. Polynomial distributed lag (PDL) models were used to fit and forecast HFRS transmission. Four principal components were extracted. Component 1 (F1) represented rodent density, the NDVI, and monthly average temperature. Component 2 (F2) represented monthly average rainfall and monthly average relative humidity. Component 3 (F3) represented rodent density and monthly average relative humidity. The last component (F4) represented gross domestic product and the urbanization rate. F2, F3, and F4 were significantly correlated, with the monthly HFRS incidence with lags of 4 months (r = -0.289, P<0.05), 5 months (r = -0.523, P<0.001), and 0 months (r = -0.376, P<0.01), respectively. F1 was correlated with the monthly HFRS incidence, with a lag of 4 months (r = 0.179, P = 0.192). Multivariate PDL modeling revealed that the four principal components were significantly associated with the transmission of HFRS. CONCLUSIONS: The monthly trend in HFRS cases was significantly associated with the local rodent reservoir, climatic factors, the NDVI, and socioeconomic conditions present during the previous months. The findings of this study may facilitate the development of early warning systems for the control and prevention of HFRS and similar diseases.