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Epidemic Bacterial Meningitis and Japanese Encephalitis Surveillance Project 流行性细菌性脑膜炎和乙型脑炎监测项目 Surveillance System Overview 监测系统总结 Dr. Stephen Hadler, MD WHO China 世界卫生组织驻华代表处 April 2007 Outline of this presentation 提纲 Objectives of field surveillance for meningitis and encephalitis 脑膜炎和脑炎现场监测的目的 Clinical presentations and case definitions 临床表现和病例定义 What do surveillance staff do? 监测人员需要做什么? What does a hospital focal point do? 医院监测负责人需要做什么? Specimen collection, prioritization, aliquoting and transport 标本采集、优先性、分装和运送 Objectives of Meningitis / Encephalitis Surveillance 脑膜炎和脑炎监测的目的 Identify all cases of meningitis and encephalitis in project areas 发现项目地区所有的脑膜炎和脑炎病例 Rapidly identify and investigate outbreaks 迅速发现和 调查爆发 Assure prompt laboratory investigation of each case in sentinel hospitals 保证哨点监测医院的每个病例立即进行 实验室方面的调查 Complete case investigations for all cases 对所有病例完成病例调查 Sentinel hospitals full investigation 哨点监测医院-全面调查 Other hospitals key clinical and laboratory information 非哨点监测医院-关键临床和实验室信息 Clinical Presentations and Case definition 临床表现和病例定义 Case Definition of Acute Encephalitis Meningitis Syndrome (AMES) 急性脑炎脑膜炎综合症(AMES)病例定义 A case of acute meningitis encephalitis syndrome is defined as a person of any age, at any time of year, with the acute onset of: 急性脑炎脑膜炎综合症被定义为任何年龄、一年 中任何时间急性起病,有下列表现者: 1. Fever 发热1 WITH 伴有 2. Change in mental status 精神状态的改变 2 3 AND / OR 和/或 3. Meningeal signs, neck stiffness, headache 脑膜刺激征、颈项强直、头痛 1 Usually 38.5 C rectal or 38.0 C axillary 通常直肠肠体温 38.5 C 或腋下体温 38.0 C 2 Symptoms like new onset seizures, confusion, disorientation, coma, somnolence, irritability or inability to talk, abnormal behavior greater than that seen with usual febrile illness 如新发发惊厥、精神混乱、定向障碍、昏迷、嗜睡、易激惹或不能讲话讲话,常 见发热见发热性疾病少见见的异常行为为 3 Excluding simple febrile seizures 排除单纯单纯的发热发热性惊厥 Distinguishing Encephalitis and Meningitis 脑炎和脑膜炎的鉴别 It is often not possible to distinguish encephalitis and meningitis based on clinical symptoms or routine laboratory tests 根据临床表现和常规实验室检 测通常不能区别脑炎和脑膜炎 Many patients have signs and symptoms of both parenchymal and meningeal involvement (e.g., altered mental status and stiff neck) 许多病例兼有脑 实质和脑膜病变的表现(如精神状态的改变和颈项强直) More important to recognize that the patient may have a CNS infection and treat accordingly 较为重要的是认识到其是一个中枢神经系统感染的病人 ,并给予相应的治疗处理 Encephalitis 脑炎 Meningitis 脑膜炎 Constitutional symptoms 基本 症状 Fever 发热Yes 有Yes 有 Headache 头痛Yes 有Yes 有 Nausea/ vomiting 恶心/呕吐Yes 有Yes 有 Neck stiffness 颈项强直No 无Yes 有 Neurologic dysfunction 神经系统功能障碍 Seizures 惊厥Yes 有 Less common不 常见 Paralysis 瘫痪Rare 罕见No 无 Cranial nerve palsies 颅神经麻 痹 Yes 有No 无 Altered mental status 精神状态改变Yes 有Minimal 轻微 Distinguishing encephalitis and meningitis 脑炎和脑膜炎的鉴别 Case Presentations can overlap 脑炎和脑膜炎病例临床症状交叉重叠图 Distinct encephalitis cases 典型的脑炎病例 Distinct meningitis cases 典型的脑膜炎病例 Overlapping Presentation 交叉重叠症状 Common Diagnostic Categories for Suspect Cases Found in Hospital Logs 医院病历中疑似病例常见的诊断病名 Japanese encephalitis 乙型脑脑炎 Viral encephalitis 病毒性脑脑炎 Encephalitis 脑脑炎 Viral meningoencephalitis 病毒性脑脑膜脑脑炎 Epidemic meningitis 流脑脑 Viral meningitis 病毒性脑脑膜炎 Meningitis 脑脑膜炎 Cerebrospinal meningitis 脑脑脊髓膜炎 TB meningitis 结结核性脑脑膜炎 TB meningoencephalitis 结结核性脑脑膜脑脑炎 Pyogenic or purulent meningitis 化脓脓性脑脑膜炎 Other suspect meningitis or encephalitis (eg: rabies) 其他脑脑膜炎或脑脑炎疑似病例 (如:狂犬病) Febrile illness with new onset seizures 具有新发发惊厥的发热发热性疾病 1 Other diagnosis 其他诊诊断(list注明)_ 1 Excluding simple febrile seizures defined as a seizure that occurs in a child aged 6 months to less than 6 years old, whose only finding is fever and one generalized convulsion lasting less than 15 minutes, and who recovers consciousness within 60 minutes of the seizure. 排除单纯单纯的发热发热性惊厥指 6个月至6岁的儿童,仅有发热及一般性的少于15分钟的抽搐,在抽搐后60 分钟恢复知觉 Example 例子: Hubei Province: Large central hospital, urban setting, 800 beds 湖北省一家城区800床位的大医院 203 CSF cultures : 2005 2005 年到访问时 203份CSF 8 (4%) positive cultures 8份(4%)培养阳性 No Hib, S pneumo or Neisseria meningitidis 没有Hib,Sp,NM 194 CSF wbc counts 白细胞计数: March 2005 October 2005: 47 (24%) with cell count = 10x106 wbc / liter 29 (83%) of 35 wbc differentials had =20% PMNs 166 cases meningitis and encephalitis diagnosed May 2004 Oct 2005: 67 viral encephalitis 病毒性脑炎 43 viral meningitis 病毒性脑膜炎 11 tuberculosis meningitis 结核性脑膜炎 10 pyogenic meningitis 化脓性脑膜炎 9 mumps encephalitis 腮腺炎脑炎 5 encephalitis 脑炎 11 viral meningoencephalitis 病毒性脑膜脑炎 10 miscellaneous meningitis/encephalitis 其他名称的脑膜炎/脑炎 Multiple Dx 诊断病名多样 Few would be reported in NNDRS 很少是NNDRS要求报告 的 Suggests possible bacterial cause 提示可能为细菌引起 CSF collected Routinely 常规采集CSF Project Surveillance Strategies项目监测策略 Province 省 Selected Prefectures 地区 Selected counties 所选择的县 Investigation and lab confirmation of outbreaks 爆发的调查和实验室确诊 Active surveillance for meningitis / encephalitis 脑膜炎/脑炎主动监测 Case investigation each case 病例调查每 一例病人 Active surveillance主动监测 Case investigation病例调查 Enhanced Lab confirmation at 6-8 selected hospitals 在6-8所医院强化实验室确诊 Meningitis / Encephalitis Project Field Surveillance Staff 脑膜炎/脑炎项目现场监测官员 County surveillance officers 县监测官员 Hospital focal point (surveillance officers) 医院监测负责人(监测官员) Will require contact person at each hospital 每个 医院都应指定联系人 Support county surveillance officers in work at hospital 支持到医院工作的县监测官员 What will County Surveillance Staff do?县监测人员的职责是什么 Active surveillance visits to every hospital every 10 days 每10天到 各医院进行一次主动监测 访问 Sentinel hospital visits more often 对哨点监测医院访问更多 Complete case investigations 完成病例调查 Outbreak investigations 爆发调查 Active Surveillance Visits to Hospitals Every 10 days 每10天到各医院进行主动监测访问 Meet with hospital focal point (surveillance officer) 与医院监测负责人(监测官员)见面 Search hospital record logs 搜索医院病历记录 Pediatrics, neurology, internal medicine, infectious disease wards, others as appropriate 儿科、神经科、内科、传染病房、其他相关部门 Review data on new AMES cases 查阅新发AMES病例的相关资料 Complete active surveillance record form 完成主动监测记录表 Complete case investigation line lists (short forms), (already begun by focal point) 完成病例调查一览表(简短的表) If a cluster appears to be starting, investigate 如果显示可能有聚集性发病,进行调查 Discuss Active Surveillance 10 day visit record 就旬主动监测访问记录进行讨论 Record each visit to each hospital 记录每所访问的医院 Numbers of encephalitis/meningitis cases investigated 调查的脑炎/脑膜炎病例数 Number cases found 发现的病例数 Number reported 报告的病例数 Number not reported 漏报的病例数 Example of form 表样 Attached list 3 Acute meningitis and encephalitis disease surveillance data sheet 附表3 流脑、乙脑等疾病监测主动监测记录表 填报单位 年 月 旬 访视 日期 查阅病 例数 发现病例数 已报告病例数 漏报病例数 被访 视 医生 签字 被访视 单位负 责人签 字 访 视人 签 字 上 中 下 Active Surveillance Visits 主动监测访问 Non-Sentinel Hospitals 非哨点监测医院 Complete line list information 完成病例一览表信息 Case investigation key information 病例调查-关键信 息 Clinical sx and diagnosis, laboratory testing 临床表现和诊断,实验室检测 Hospital focal point (surveillance officer) can help 医院监测负责人(监测官员)提供帮助 Differs from the case investigation form 与长表的区别 Limited information collected 只收集有限的信息 All results from hosp laboratories (CSF examination, cultures, etc) 所有收集的信息都是医院已有的(CSF检测结果、培养等 ) Case Line List Information病例一览表信息 Non-Sentinel Hospitals 非哨点监测医院 Active Surveillance Visits 主动监测访问 Sentinel Hospitals 哨点监测医院 Officer may visit more often 监测官员可能要访问更多次 Meet with hospital focal point (surveillance officer) 与医院监测负责人(监测官员)会面 Search hospital record logs 搜索医院病历记录 Pediatrics, neurology, internal medicine, infectious disease wards, others as appropriate 儿科、神经科、内科、传染病房、其他相关部 门 Review data on AMES cases 查阅急性脑膜炎脑炎综合症病例的相关资料 Complete case investigation forms, with support of focal point 在医院监测人员支持下,完成病例调查表(长表) Active Surveillance Visits 主动监测访问 Sentinel Hospitals 哨点监测医院- 2 Assure clinical specimens obtained for each patient 保证从每例病例都采集到临床标本 Visit laboratory to review results and identify problems 对实验室进行访问,审阅结果,发现问题 Help maintain quality control of aliquoting and upkeep of specimens 帮助维持标本分装诉质量控制及保存上送 Arrange transport of specimens to prefecture / province lab 安排将标本运送到地区/省 If a cluster appears to be starting, investigate 如果有发生聚集性发病的倾向,立即进行调查 Sentinel Hospitals Case Investigation Form 哨点监测医院病例调查表 Complete for all cases 对所有病例进行调查 Information required 需要的信息 Name, age, location, other demographic 姓名、年龄、地址、其他人口学资 料 Hospitalization dates and diagnosis 住院日期及诊断 Clinical symptoms 临床症状 Vaccination history (JE Epidemic meningitis, Hib) 疫苗接种史(乙脑疫苗、流脑疫苗、Hib) Exposures 暴露情况 Hospital laboratory results CSF, blood, etc 医院实验室结果-CSF、血液 等 Final diagnosis 最后诊断 Treatment and final outcomes 治疗和最后转归 Hospital focal point (surveillance officer) can help fill in 医院监测负责人(监测官员)可以协助填写 Clinical specimens obtained for all cases 采集所有病例的临床标本 May require several visits 可能需要多次访问 What do Hospital Focal Points do ? 医院监测人员的职责? Notify County Surveillance staff about cases * 将病例报告给县监测人员 Help fill out forms 帮助填表 Coordinate with clinical laboratories 与临床实验室进行协调 Follow-up on specimens tested, aliquoted 追踪样品的分装和检测 Assure all parts of forms completed * Within 12 hours if at Sentinel hospital * 哨点监测医院应在12小时内报告 If an Outbreak is Suspected 若怀疑有暴发流行 Investigate ! 立即进行调查 Work in key hospitals to rapidly gather line list information 在主要医院迅速收集病例一览表中的资料 Work with key hospitals and with prefecture/ provincial labs to confirm the diagnosis in at least 5 patients 与主要医院及与 地区和省疾控中心实验室一起至少对5个病例进行实验室核实诊断 Complete case investigation (Long) forms, already begun by focal point 完成个案病例调查表(长表),基层人员可能已开始填 写 Help transport specimens to prefecture/province lab if appropriate 尽可能帮助将样品妥善的运送到地区和省疾控中心实验室 Outbreak Definitions and Linelist 爆发定义和病例一览表 Definition of an outbreak爆发的定义: 3 or more cases of meningitis encephalitis syndrome within 14 days in a village, residential community, school 14天之内在一个村庄、居民区或学校发生三例或三例以上的 脑膜炎-脑炎综合症病例 3 or more cases in a township within 14 days 14天内在一个乡镇发生3例或3例以上病例 5 + cases in a county within one month 一个月内在一个县发生5例或以上病例 Example of Outbreak line list (next slide) 爆发病例一览表示例(下一张幻灯片) Hospital: _ Cang Zhui City Hospital City/county: Cang Zhui Prefecture: Hong Bao Province: Chang Cheng _ Date: YYYYMMDD _2006/05/30 Investigator _Li Ping _ Hospital ID # Patient Name Se x M/ F Ag e Address City,village Admission Date YYMMDD Onset Date YYMMD D Clinical Diagnosis # CSF collected Y/N Comments 1756-9 Wang Wu M 2 Suang Xi 06/05/043 Encephaliti s Y On antibiotics at admission 1626-9 Shu Hui F 1 8 Suang Xi 06/05/195 Epidemic meningitis Y 1366-9 Chen Daxin M 1 7 Bao Bao 06/05/26 7 Meningitis N On antibiotics at admission 1526-9 Li HongF2 Cang Zhui 06/05/2 1 1 Japanese encephalitis Y On antibiotics at admission 1226-4 Wang YongM21 Bao Bao 06/05/2 9 3 Encephaliti s Y Hospital ID: is the number of patient in hospital records Address: city or village, and county Clinical Diagnosis: 1=Japanese encephalitis 5= Epidemic meningitis 9 = TB meningitis13=New onset seizures * 2=Viral encephalitis6= Viral meningitis 10=TB meningoencephalitis14= Other diagnosis(list)_ 3=Encephalitis 7= Meningitis11= Pyogenic or purulent meningitis 4=Viral meningoencephalitis8= Cerebrospinal meningitis12= Other suspect meningitis or encephalitis (eg: rabies) *Excluding simple febrile seizures- defined as a seizure that occurs in a child aged 6 months to less than 6 years old, whose only finding is fever and a single generalized convulsion lasting less than 15 minutes, and who recovers consciousness within 60 minutes of the seizure 医院 病例号 码 病人姓名 性别 男/女 年 龄 地址 市,村 入院日期 年月日 发病日 期 年月日 临床诊断 号码 # 脑脊液 是否收 集 是/否 建议 1756-9 王五 男 2 双喜 06/05/043 脑炎是入院时用抗生素 1626-9 舒惠 女 18 双喜 06/05/195 流行性脑 膜炎 是 1366-9 陈大新 男 17 宝宝 06/05/267 脑脊髓膜炎 否入院时用抗生素 1526-9 李红 女 2 长醉 06/05/2 1 1 日本脑炎 是入院时用抗生素 1226-4 王红 男 21 宝宝 06/05/2 9 3 脑炎 是 病例号码: 病人在医院记录中的号码 地址:市,县或者村 临床诊断: 1 日本脑炎 2 病毒性脑炎(列举_ _) 3 脑炎 4 病毒性脑膜脑炎 5 流行性脑膜炎 6 病毒性脑膜炎 7 脑脊髓膜炎 8 脑脊髓型脑膜炎 9 结核性脑膜炎 1 0 结核脑膜脑炎 11 化脓性脑膜炎 12 其它可疑脑膜炎或脑炎(比如,狂犬病) 13 新发癫痫 * 14 其它诊断(请列举) _ *不包括单纯热性癫痫 其定义为在6个月至 6岁的儿童由发热引起的癫痫. 唯一的表现是发热以及少于 医院: _ 长醉市医院 市/县: 长醉 地区: 洪堡 省: 长城 _ 日期: 年 月 日 _2006/05/30 调查者 _李平 _ Collection and Management of Laboratory Specimens 实验室标本的采集和管理 Specimens needed for laboratory confirmation 实验室确诊所需标本 from suspect AMES cases 疑似急性脑膜炎脑炎综合症病例的标本 identified at sentinel hospitals 在哨点监测医院发现的病例 How to aliquot and prioritize specimens 标本如何分装及使用的优先顺序 Transport of specimens to prefecture and province 运送标本到地区和省 Specimens to be Collected in Sentinel Hospitals 哨点监测医院要采集的标本 CSF 3.0 ml (1.5 ml for project) Hospital testing 医院检测 Aliquots for prefecture and province 分装送地区和省 Blood 血液 Culture 培养 Serologic testing 血清学检测 Stool 粪便 All cases 所有病例 Lab Submission form 讨论实验室提交样品的表格 Patient name and identifying information 病例姓 名和身份证信息 Diagnosis 诊断 Type of specimen 标本类型 Date/time of specimen 标本采集的日期/时间 Time delivered in lab 运送到实验室的时间 Condition of specimen 标本状态 Adequate 合格表格 Proper shipping 正确运送 No leakage 没有泄漏 Paperwork complete 表格填写完整 Specimen Adequacy Criteria 实验室标本验收指标 Name of person to whom laboratory results should be sent 实验室结果接受人姓名: Address 地址: Telephone number电话号码:Fax number 传真号码: For use by the receiving laboratory 以下仅用于接收实验室: Name of laboratory 实验室名称: Name of person receiving the specimen 标本接收者姓名: Specimen type标本类 型 Date Received in Lab 接收日期 Is specimen adequate? 标本是否完 好? * Type of test 实验类型 Date of test 实验日期 Test result 实验结果 Date result reported 结果报告 日期 Date sample sent to Reference Lab 标本送到参比 实验室日期 *Is specimen ADEQUATE? YES / NO ? * 标本是否完好? 是/否 Adequate means 标本完好指标 1. NO leakeage无泄漏, 2. Specimen volume is sufficient 样本体积充足 3. Ice packs are still cold 冰排状态良好 4. Paperwork is complete 送检单完全 5. NO hemolysis in CSF or serum specimens 脑脊液样品或血清无溶血 If Sample is NOT adequate, what is the problem? 若样品有问题, 什么问题? Leakage泄漏 Not enough sample样本体积充足 Ice packs are warm, sample arrived warm冰排融化,样本变暖 incomplete documentation送检单不完全 Hemolysis in specimen样本溶血 Other其他 (please list请注明)_ CSF Distribution脑脊液的分配 Ship to Prefecture lab 运送到地区实验室 -0.5 ml aliquot for JE IgM ELISA 分装0.5 ml 用于乙脑 IgM ELISA检测 - duplicate set of primary plates in candle jar or inoculated TI vial 两套原始平板置于烛缸或接种TI管 Ship to Provincial CDC lab 运送到省CDC实验室 - 0.5 ml aliquots 0.5 ml 分装 -0.5 ml aliquot in PCR extraction buffer 0.5 ml 加入核酸提取缓冲液 Hospital lab processing 医院实验室处理(1.5ml) - Aliquot per protocol 根据实验方案进行分装 - Add extraction buffer to PCR aliquots 在PCR那一份加核酸提取缓冲液 - Freeze (20 C) prior to shipment 运输前冻存于零下20 C Hospital lab testing (1.5ml)医院实验室检查(1.5毫升 ) - Protein/glucose蛋白/葡萄糖(0.15ml) - Cell count细胞计数(0.25ml) - Other其他 (0.5ml) Gram stain革兰染色 Bacterial latex agglutination 细菌乳胶凝集试验 Culture 1 for hospital 医院培养1 Culture 2 for prefecture lab 地区实验室培养2 duplicate set of primary plates, or inoculate transport isolate vial (TI) 两套原始平板,或使用TI培养管 1.5ml 1.5ml Collect at least 3.0 ml CSF (if possible) 至少采集3.0 ml CSF (如果可能) CSF Aliquoting (hospital lab) 脑脊液的分装(医院实验室) CSF: 3.0 ml, if possible如 果可能 1.5 ml 0.5 ml First priority 第一优先 (hospital lab 医院实验室) JE IgM ELISA PCR, viral culture Storage PCR,病毒培养 储存 0.5 ml aliquots按 0.5 ml 分装 (at least 2 至少两 份) Routine exam Culture 常规检测 培养 Third priority 第三优先* (Prefecture lab 地区实验室 ) Second priority 第二优先 (Prov and Natl CCDC lab 省和国 家CDC实验室) Blood and Serum Distribution 血液和血清的分配 Hospital lab processing for culture 医院实验室培养样品的处理 - Immediately inoculate each of 2 blood culture bottles with whole blood 立即将全血接种到3个培养瓶 Ship to Prefecture lab 运送到地区实验室 -0.5 ml aliquot for JE IgM ELISA 0.5 毫升用于乙脑 IgM ELISA 检测 Ship to Provincial CDC lab 运送到省CDC实验室 -0.5 ml aliquots for JE IgM ELISA, PCR 0.5毫升用于乙脑 IgM ELISA, PCR 检测 Hospital lab processing for serum 医院实验室血清样品的处理 - Allow remaining blood to clot 让剩余的血液凝固 - Separate serum from clot分离血清 - Aliquot serum per protocol 根据实验方案分装血清 - Freeze (20 C) prior to shipment 运送前冷冻于零下20 C - Ship serum per protocol 根据实验方案分发血清 Volume to collect 采集量: 5-10 ml (adult 成人) 2-5 ml (child 儿童) 0.5-2 ml (infant 婴儿) 28 July 2007 Aliquoting serum at hospital lab 医院实验室血清的分装 Serum 血清: 0.5 ml 0.5 ml Third priority 第三优先 (Natl CCDC lab 国家CDC) First priority 第一优先 (Prefecture lab 地区实验室) Second priority 第二优先 (Provincial lab 省实验室) JE IgM ELISA JE IgM ELISA (Quality control 质量控制) JE IgM ELISA, PCR, storage 储存 5-10 ml (adult 成人) 2-5 ml (child 儿童) 0.5-2 ml (infant 婴儿) All remaining volume into 0.5 ml aliquots 所有剩余血清均 按0.5ml分装 Storage of Specimens 标本储存 Freezer冷冻 CSF 脑脊液 - 20 C Serum and blood 血清和血标本 - 20 C Stools 便标本 - 20 C Bacterial isolates 细菌分离物 20-36 C Transport of Specimens to Prefecture and Province 运送标本到地区和省 Prefecture serum and CSF for JE testing 地区-血清和CSF,以检测乙脑 Province 省 CSF for PCR CSF以进行PCR检测 Bacterial isolates for characterization 细菌分离株以进一步鉴 定 Serum for JE testing 血清以开展乙脑检测 How to transfer follow national biosafety guidelines 如何运送-遵循国家生物安全规定 Timeliness rapid transfer to next level 时效性快速运送到上一级 Transporting Specimens 运送标本 Place CSF or serum specimen in cold box below 8C between frozen ice packs 将CSF或血标本置于冰排之间8C以下 Complete lab request form for each case, including the following information 每例均应填写实验室申请表,并包括以下内容: date collected 采集日期 case identification 病例身份信息 date of onset 发病日期 Place lab request form in separate and sealed plastic bag 实验室申请表置于单独、密封的塑料袋 内 Implementation Issues 1 有关的几个问题 Sentinel H

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