The particulate matter with diameter of less than 2.5 µm (PM2.5) is an important risk factor for respiratory infectious diseases, such as scarlet fever, tuberculosis, and similar diseases. However, it is not clear which component of PM2.5 is more important for respiratory infectious diseases. Based on data from 31 provinces in mainland China obtained between 2013 and 2019, this study investigated the effects of different PM2.5 components, i.e., sulfate (SO42−), nitrate (NO3−), ammonium (NH4+), and organic matter (OM), and black carbon (BC), on respiratory infectious diseases incidence [pulmonary tuberculosis (PTB), scarlet fever (SF), influenza, hand, foot, and mouth disease (HFMD), and mumps]. Geographical probes and the Bayesian kernel machine regression (BKMR) model were used to investigate correlations, single-component effects, joint effects, and interactions between components, and subgroup analysis was used to assess regional and temporal heterogeneity. The results of geographical probes showed that the chemical components of PM2.5 were associated with the incidence of respiratory infectious diseases. BKMR results showed that the five components of PM2.5 were the main factors affecting the incidence of respiratory infectious diseases (PIP>0.5). The joint effect of influenza and mumps by co-exposure to the components showed a significant positive correlation, and the exposure-response curve for a single component was approximately linear. And single-component modelling revealed that OM and BC may be the most important factors influencing the high incidence of respiratory infections. Moreover, respiratory infectious diseases in southern and southwestern China may be less affected by the PM2.5 component. This study is the first to explore the relationship between different components of PM2.5 and the incidence of five common respiratory infectious diseases in 31 provinces of China, which provides a certain theoretical basis for future research.
BackgroundFrom January 2020 to December 2022, China implemented "First-level-response", "Normalized-control" and "Dynamic-COVID-zero" to block the COVID-19 epidemic; however, the immediate and long-term impact of three strategies on other infectious diseases and the difference in their impact is currently unknown. We aim to provide a more comprehensive understanding of the impact of non-pharmacological interventions (NPIs) on infectious diseases in China.MethodsWe collected data on the monthly case count of infectious diseases in China from January 2015 to July 2022. After considering long-term trends using the Cox-Stuart test, we performed the two ratio Z tests to preliminary analyze the impact of three strategies on infectious diseases. Next, we used a multistage interrupted-time-series analysis fitted by the Poisson regression to evaluate and compare the immediate and long-term impact of three strategies on infectious diseases in China.ResultsCompared to before COVID-19, the incidence of almost all infectious diseases decreased immediately at stages 1, 2, and 3; meanwhile, the slope in the incidence of many infectious diseases also decreased at the three stages. However, the slope in the incidence of all sexually transmitted diseases increased at stage 1, the slope in the incidence of all gastrointestinal infectious diseases increased at stage 2, and the slope in the incidence of some diseases such as pertussis, influenza, and brucellosis increased at stage 3. The immediate and long-term limiting effects of "Normalized-control" on respiratory-transmitted diseases were weaker than "First-level-response" and the long-term limiting effects of "Dynamic-COVID-zero" on pertussis, influenza, and hydatid disease were weaker than "Normalized-control".ConclusionsThree COVID-19 control strategies in China have immediate and long-term limiting effects on many infectious diseases, but there are differences in their limiting effects. Evidence from this study shows that pertussis, influenza, brucellosis, and hydatid disease began to recover at stage 3, and relaxation of NPIs may lead to the resurgence of respiratory-transmitted diseases and vector-borne diseases.
Mainland China included Japanese encephalitis (JE) vaccine in the national immunization program in 2008 to control the JE epidemic. However, Gansu province in Western China experienced the largest JE outbreak since 1958 in 2018. We conducted a retrospective epidemiological study to explore the causes of this outbreak. We found that adults aged ≥20 years (especially those in rural areas) were the main JE cases in Gansu Province, with a significant increase in the JE incidence in older adults aged ≥60 years in 2017 and 2018. In addition, JE outbreaks in Gansu Province were mainly located in the southeastern region, while the temperature and precipitation in Gansu Province were gradually increasing in recent years, which made the JE epidemic areas in Gansu Province gradually spread to the western of Gansu Province. We also found that adults aged ≥20 years in Gansu Province had lower JE antibody positivity than children and infants, and the antibody positivity rate decreased with age. In the summer of 2017 and 2018, the density of mosquitoes (mainly the Culex tritaeniorhynchus ) in Gansu Province was significantly higher than in other years, and the genotype of JEV was mainly Genotype‐G1. Therefore, in the future JE control in Gansu Province, we need to strengthen JE vaccination for adults. Moreover, strengthening mosquito surveillance can provide early warning of JE outbreaks and the spread of epidemic areas in Gansu Province. At the same time, strengthening JE antibody surveillance is also necessary for JE control.
BACKGROUND:The impact of COVID-19 on the epidemiology, clinical characteristics, and infection spectrum of viral and bacterial respiratory infections in Western China is unknown.METHODS:We conducted an interrupted time series analysis based on surveillance of acute respiratory infections (ARI) in Western China to supplement the available data.RESULTS:The positive rates of influenza virus, Streptococcus pneumoniae, and viral and bacterial coinfections decreased, but parainfluenza virus, respiratory syncytial virus, human adenovirus, human rhinovirus, human bocavirus, non-typeable Haemophilus influenzae, Mycoplasma pneumoniae, and Chlamydia pneumoniae infections increased after the onset of the COVID-19 epidemic. The positive rate for viral infection in outpatients and children aged <5 years increased, but the positive rates of bacterial infection and viral and bacterial coinfections decreased, and the proportion patients with clinical symptoms of ARI decreased after the onset of the COVID-19 epidemic. Non-pharmacological interventions reduced the positive rates of viral and bacterial infections in the short term but did not have a long-term limiting effect. Moreover, the proportion of ARI patients with severe clinical symptoms (dyspnea and pleural effusion) increased in the short term after COVID-19, but in the long-term, it decreased.CONCLUSIONS:The epidemiology, clinical characteristics, and infection spectrum of viral and bacterial infections in Western China have changed, and children will be a high-risk group for ARI after the COVID-19 epidemic. In addition, the reluctance of ARI patients with mild clinical symptoms to seek medical care after COVID-19 should be considered. In the post-COVID-19 era, we need to strengthen the surveillance of respiratory pathogens.
Japanese encephalitis (JE), a mosquito-borne zoonotic disease, has emerged as a major public health concern around the world. Previous research has shown that JE has serious sequelae, and the recent shift in the population from children to adults presents a significant challenge for JE treatment and prevention. Therefore, we examined the differences in clinical manifestations (clinical symptoms, clinical signs, complications, and clinical typing) of JE between children and adults over the 15 years in Gansu Province to provide a theoretical basis for better response to JE treatment. Clinical typing was found to be statistically significant in the child versus adult groups and the groups with or without vaccination. Only the dysfunction of consciousness differed statistically between children with and without vaccination, whereas neurological symptoms such as vomiting (jet vomiting), irritability, drowsiness, convulsions, and hyperspasmia differed statistically between children and adults, and the rest of the symptoms did not differ statistically. Only pupil size changes were statistically different in clinical signs between the children with and without vaccination, while blood pressure changes, change in pupil size, positive meningeal stimulation signs, and positive pathological reflexes (increased muscle tone and Babinski's sign) were statistically different between adults and children. Bronchopneumonia was the most common complication, especially in adults. Therefore, the authors believe that children and adults differ in some clinical manifestations and propose that efforts should be directed toward developing individualized treatment plans for different age groups and employing more effective supportive treatment for various populations. In addition, we suggest expanding the coverage of the JE vaccine and increasing overall vaccination rates and adopting multiple measures in conjunction with JE prevention and control.
In 2008, Mainland China included the Japanese encephalitis (JE) vaccine in the Expanded Program on Immunization (EPI) to control the JE epidemic. However, Northwest China experienced the largest JE outbreak since 1994 in 2018, and the effects of the EPI in different regions are unclear. Therefore, we used an interrupted time series design to evaluate the effects of the EPI in different regions. In this study, β1 and β1+β3 represented the slope or trend of the JE incidence before and after the EPI, respectively; β2 was the level change of the JE incidence immediately after the EPI; β3 represented the slope change of the JE incidence before and after the EPI. We found that the JE incidence in all regions showed a decreasing trend before the EPI (β1<0.000, P<0.05). The JE incidence in Mainland China (β2=-7.669, P<0.05), East China (β2=-9.791, P<0.05), Central China (β2=-10.695, P<0.05), South China (β2=-6.551, P<0.05) and Southwest China (β2=-2.216, P<0.05) decreased by 7.669/100,000, 9.791/100,000, 10.695/100,000, 6.551/100,000 and 2.216/100,000 immediately after the EPI, and the EPI had short-term effects on the JE incidence in these regions. The slope of the JE incidence in Mainland China (β3=0.272, P<0.05), East China (β3=0.337, P<0.05), Central China (β3=0.381, P<0.05), South China (β3=0.254, P<0.05) and Southwest China (β3=0.081, P<0.05) increased by 0.272, 0.337, 0.381, 0.254 and 0.081 after the EPI, and the EPI had long-term effects on the JE incidence in these regions. The JE incidence in many regions (excluding North China) showed a decreasing trend after the EPI (β1+β3 <0.000). Northwest China (GDP from 2008 to 2020 ranked last in Mainland China) and Southwest China (GDP from 2008 to 2020 ranked fifth in Mainland China), with underdeveloped economy, used to be low-epidemic regions of JE, but they have become high-epidemic regions in recent years. Economic development may contribute to the geographic variations in the effects of the EPI. Therefore, it is significant for JE control in Mainland China to increase support for underdeveloped regions and adjust the vaccine strategy according to the new epidemic situation of JE.
NAD(P)H:quinone oxidoreductase (NQO1) is a flavoprotein which catalyzes the two-electron reduction of quinones and azo-dyes and thus prevents the formation of free radicals and toxic oxygen metabolites that may be generated by the one-electron reductions catalyzed by cytochrome P450 reductase. Analysis of RNA indicated 20- to 50-fold higher levels of NQO1 gene expression in the liver tumors and in the tissue surrounding the tumors of patients with hepatocarcinoma than in normal individuals. An approximately 50-fold higher level of NQO1 mRNA was also observed in human hepatoblastoma (Hep-G2) cells than in normal liver. By deletion mutagenesis in the human NQO1 gene promoter and subsequent transfection into hepatic and nonhepatic cell lines, a 1.42 kb DNA segment has been identified to contain cis-acting elements responsible for high levels of expression of the NQO1 gene in tumor cells.
ObjectiveTo examine characteristics of pathogens identified among patients with fever and rash syndrome (RFIs) in Gansu province from 2009 to 2019, and to provide a reference for implementing targeted prevention measures and conducting pathogen surveillance. Methods Sentinel surveillance data on 5 822 RFIs cases reported in Gansu province from 2009 through 2019 were extracted from the Information Management System for Prevention and Treatment of AIDS and Viral Hepatitis and other Major Infectious Diseases. Multiple correspondence analysis was adopted to analyze characteristics of pathogens isolated from the RFIs patients. Results Enterovirus infection was confirmed in 1 653 (28.39%) of the all RFIs patients reported during the period and the number (proportion) of the patients confirmed with other pathogen infections were 548 (9.41%) for measles virus, 201 (3.45%) for rubella virus, and 495 (8.50%) for varicella-zoster virus, respectively. No pathogen infection was confirmed in 2 925 (50.24%) RFIs patients. The results of multiple correspondence analysis showed that enteroviruses infection was more frequently diagnosed in hospitalized cases in western and central Gansu province, during summer/autumn season, among scattered children aged ≤ 5 years and kindergarten children, among patients hospitalized in provincial and county-level hospitals; measles virus infection was more frequently confirmed among the patients in eastern and southern areas of Gansu province, during winter/spring season, in the adults (≥ 18 years) with some specific occupations, and among patients seeking medication at municipal hospitals; and more varicella-zoster virus and rubella virus infections were detected among the students aged 6 to 17 years. No pathogen infection was identified among the majority of the RFIs patients visiting doctors in outpatient/emergency departments. Conclusion The main pathogens inducing RFIs incidents in Gansu province from 2009 to 2019 include enterovirus, measles virus, varicella-zoster virus and rubella virus, and there were disparities in the detection rate of the pathogens among various populations, in different seasons and in various geographical areas.
Introduction:The Qinghai-Tibet Plateau is considered the most plague-heavy region in China, and skinning and eating marmots (Marmota himalayana) are understood to be the main exposure factors to plague. Yersinia pestis is relatively inactive during marmots' hibernation period. However, this case report shows plague infection risk is not reduced but rather increased during the marmot hibernation period if plague exposure is not brought under control.Case Presentation:The patient was a 45-year-old man who presented with high fever, swelling of axillary lymph nodes, and existing hand wounds on his right side. Y. pestis was isolated from his blood and lymphatic fluid. Hence, the patient was diagnosed with a confirmed case of bubonic plague. Later, his condition progressed to septicemic plague. Plague exposure through wounds and delays in appropriate treatment might have contributed to plague progression.Conclusion:This case report reveals that excavating a hibernating marmot is a significant transmission route of plague. Plague prevention and control measures are priority needs during the marmot hibernation period.
Background: We aimed to quantify the impact of each vaccine strategy (including the P3-inactivated vaccine strategy [1968-1987], the SA 14-14-2 live-attenuated vaccine strategy [1988-2007], and the Expanded Program on Immunization [EPI, 2008-2020]) on the incidence of Japanese encephalitis (JE) in regions with different economic development levels. Methods: The JE incidence in mainland China from 1961 to 2020 was summarized by year, then modeled and analyzed using an interrupted time series analysis. Results: After the P3-inactivated vaccine was used, the JE incidence in Eastern China, Central China, Western China and Northeast China in 1968 decreased by 39.80 % (IRR = 0.602, P < 0.001), 7.80 % (IRR = 0.922, P < 0.001), 10.80 % (IRR = 0.892, P < 0.001) and 31.90 % (IRR = 0.681, P < 0.001); the slope/trend of the JE incidence from 1968 to 1987 decreased by 30.80 % (IRR = 0.692, P < 0.001), 29.30 % (IRR = 0.707, P < 0.001), 33.00 % (IRR = 0.670, P < 0.001) and 41.20 % (IRR = 0.588, P < 0.001). After the SA 14-14-2 live-attenuated vaccine was used, the JE incidence in Eastern China and Northeast China in 1988 decreased by 2.60 % (IRR = 0.974, P = 0.009) and 14.70 % (IRR = 0.853, P < 0.001); the slope/trend of the JE incidence in Eastern China and Central China from 1988 to 2007 decreased by 4.60 % (IRR = 0.954, P < 0.001) and 4.70 % (IRR = 0.953, P < 0.001). After the EPI was implemented, the JE incidence in Eastern China, Central China and Western China in 2008 decreased by 10.50 % (IRR = 0.895, P = 0.013), 18.00 % (IRR = 0.820, P < 0.001) and 24.20 % (IRR = 0.758, P < 0.001), the slope/ trend of the JE incidence in Eastern China from 2008 to 2020 decreased by 17.80 % (IRR = 0.822, P < 0.001). Conclusions: Each vaccine strategy has different effects on the JE incidence in regions with different economic development. Additionally, some economically underdeveloped regions have gradually become the main areas of the JE outbreak. Therefore, mainland China should provide economic assistance to areas with low economic development and improve JE vaccination plans in the future to control the epidemic of JE.
目的 比较成人和儿童乙型脑炎减毒活疫苗(Japanese encephalitis attenuated live vaccine,JE-L)预防接种不良反应发生率.方法 通过中国和甘肃省免疫规划信息管理系统收集甘肃省2019-2020年JE-L预防接种不良反应个案和接种信息,比较40-74岁成人和0-14岁儿童JE-L不良反应报告发生率.结果 甘肃省2019-2020年40-74岁成人、0-14岁儿童JE-L预防接种不良反应报告发生率分别为19.89/10万剂(81例)、214.14/10万剂(2 798例)(RR = 0.09,95%CI:0.07-0.12);其中一般反应分别为 19.89/10万剂(81 例)、213.99/10万剂(2 796例),异常反应分别为0.00/10万剂、0.15/10万剂(2例).结论 JE-L预防接种不良反应发生率在可接受范围内,且多为轻微反应;成人不良反应发生率低于儿童.
National-based prospective surveillance of all-age patients with acute diarrhea was conducted in China between 2009‒2018. Here we report the etiological, epidemiological, and clinical features of the 152,792 eligible patients enrolled in this analysis. Rotavirus A and norovirus are the two leading viral pathogens detected in the patients, followed by adenovirus and astrovirus. Diarrheagenic Escherichia coli and nontyphoidal Salmonella are the two leading bacterial pathogens, followed by Shigella and Vibrio parahaemolyticus. Patients aged <5 years had higher overall positive rate of viral pathogens, while bacterial pathogens were more common in patients aged 18‒45 years. A joinpoint analysis revealed the age-specific positivity rate and how this varied for individual pathogens. Our findings fill crucial gaps of how the distributions of enteropathogens change across China in patients with diarrhea. This allows enhanced identification of the predominant diarrheal pathogen candidates for diagnosis in clinical practice and more targeted application of prevention and control measures.
Objective To understand the compositions of pathogens and seasonal distribution characteristics of rash and fever syndrome (RFS) in Gansu Province from 2009 to 2019, so as to provide references for further disease surveillance and scientific prevention and control. Methods Descriptive epidemiological methods were used to analyze the composition of pathogens of RFS in Gansu Province from 2009 to 2019 and the seasonal variation characteristics of the main pathogens. Results The compositions of pathogens of RFS in Gansu Province were dominated by viruses, mainly enterovirus (56.04%), measles virus (19.14%), varicella-zoster virus (16.85%) and rubella virus (7.33%). The differences of positive rate of the main pathogens in different age groups and different seasons were statistically significant (all P Conclusions From 2009 to 2019, the compositions of pathogens of RFS in Gansu Province were mainly viruses and the main pathogens have obvious seasonal characteristics. Seasonal and targeted proventive methods should be adopted for high-risk populations.
Nationwide prospective surveillance of all-age patients with acute respiratory infections was conducted in China between 2009‒2019. Here we report the etiological and epidemiological features of the 231,107 eligible patients enrolled in this analysis. Children <5 years old and school-age children have the highest viral positivity rate (46.9%) and bacterial positivity rate (30.9%). Influenza virus, respiratory syncytial virus and human rhinovirus are the three leading viral pathogens with proportions of 28.5%, 16.8% and 16.7%, and Streptococcus pneumoniae , Mycoplasma pneumoniae and Klebsiella pneumoniae are the three leading bacterial pathogens (29.9%, 18.6% and 15.8%). Negative interactions between viruses and positive interactions between viral and bacterial pathogens are common. A Join-Point analysis reveals the age-specific positivity rate and how this varied for individual pathogens. These data indicate that differential priorities for diagnosis, prevention and control should be highlighted in terms of acute respiratory tract infection patients’ demography, geographic locations and season of illness in China.
目的 探讨甘肃省2017-2018年流行性乙型脑炎(简称乙脑)的流行病学特征和疾病负担.方法 利用甘肃省2017年1月1日—2018年12月31日乙脑病例数据和随访数据,计算乙脑的发病率、死亡率、病死率以及潜在减寿年数,比较不同分组的乙脑病例病情转归情况,采用二项Logistic回归分析模型分析甘肃省乙脑患者病情转归的主要影响因素.结果 乙脑发病率、死亡率以及病死率随着年龄增长而增加.不同年龄(H=61.797,P<0.001)、不同临床分型(H=53.953,P<0.001)、有无意识障碍(H=64.367,P<0.001)以及有无脑膜刺激征(H=5.251,P=0.022)的乙脑病例病情转归比较均有统计学差异.二项Logistic逐步回归分析模型结果显示,年龄(OR=3.217,P<0.001)、临床分型(OR=1.621,P<0.001)及有无意识障碍(OR=1.969,P=0.002)对甘肃省乙脑病例病情转归的影响均有统计学意义.甘肃省2017年和2018年乙脑病例的潜在寿命损失分别为945.84人年和1 056.92人年,0~<15岁损失最小,女性损失高于男性.结论 成人乙脑发病率、死亡率及病死率均高于儿童,乙脑造成的潜在寿命损失也主要以成人为主,影响乙脑病例转归的主要因素为年龄、临床分型以及有无意识障碍.
目的 运用向量自回归(vector autoregressive,VAR)模型分析甘肃省流行性乙型脑炎(简称乙脑)发病与气象因素的动态响应关系,为不同气象条件下乙脑的防控提供科学依据.方法 用2014年1月-2018年12月乙脑发病率和同期气象数据建立VAR模型,通过脉冲响应和方差分解定量分析气象因素对乙脑发病的影响.结果 VAR(2)模型的拟合优度为0.95,调整后拟合优度为0.95,希尔不等系数(Theil inequality coefficient,TIC)为0.06.平均气温、日照时数和降雨量对乙脑发病率变化的贡献到第6期分别为9.52%、2.13%和38.62%.结论 VAR(2)模型可用于分析乙脑发病与气象因素的动态关系,乙脑的防控及预测预警可考虑结合当地气象因素.
目的 探索Group LASSO(least absolute shrinkage and selection operator)Logistic回归分析模型在研究流行性乙型脑炎(简称乙脑)早期临床症状与预后之间的关系中的应用.方法 收集整理2017-2018年甘肃省乙脑报告发病数据,建立乙脑预后影响因素的Group LASSO Logistic回归分析模型,通过交叉验证法选择惩罚参数,筛选出影响乙脑预后的早期临床症状.结果 纳入的866名乙脑患者中,有预后结局的共764名,其中死亡者占22.5%、有后遗症者占12.6%、好转者占17.8%、痊愈者占47.1%.筛选出的变量有意识障碍、呼吸衰竭、呼吸节律改变、肌张力增强及乙脑疫苗接种史.结论 通过构建Group LASSO Logistic回归分析模型可以筛选出对预后有影响的早期临床症状.
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.
Backgrounds: Seasonal influenza remains epidemic globally with a substantial health burden. Understanding the transmission patterns and epidemic features of influenza may facilitate the improvement of preventive and control measures. This study aims to assess the epidemic features of influenza among different climate zones and identify high-risk zones across Gansu province, China. Methods: We collected weekly influenza cases at county-level between 1st January 2012 and 31st December 2016, as well as climate zones classification shapefile data from Koppen-Geiger climate map. We compared the epidemic features (Frequency index (alpha), Duration index (beta) and Intensity index (gamma)) of influenza among different climate zones. Spatial cluster analysis was used to examine the high-risk areas of transmission of influenza. Results: The distribution of cases existed significant differences among eight climate zones (F-test: 267.02, p < 0.05). The highest mean weekly incidence rate (per 100,000 population) was 0.59 in snow climate with dry winter and warm summer (Dwb). The primary (relative risk (RR): 3.61, p < 0.001) and secondary (RR: 2.45, p < 0.001) clusters were located in Dwb. The highest values of alpha, beta and gamma were 1.00, 261 and 154.38 in Dwb. The hot spots (high-high clusters) of the epidemic indices were detected in Dwb. Conclusions: This study found the variability of epidemic features of influenza among eight climate zones. We highlight that Dwb was the high-risk zone where influenza clustered with the highest incidence rate and epidemic temporal indices. This provide further insight into potential improvement of preventive measures by climate zones to minimize the impact of epidemics.