mers地坛医院感染性疾病诊疗中心

1、北京地坛医院感染性疾病诊疗中心蒋荣猛2015.6.9中东呼吸综合征(MERS)提纲MERS经过类SARS？人传人？诊断和治疗个人防护on the day of admission2 days later 疫情信息截至2015年5月31日，全球报告了1185例确诊病例，其中443例死亡（37.4%）。其中95%以上的病例发生在中东。 Published online June 3, 2012012年5月-2015年6月Figure. Geographical distribution of confirmed MERS-CoV cases87/6 Published online June 3,

2、 201Countries with Lab-Confirmed MERS CasesCountries in or near the Arabian Peninsula Saudi ArabiaUnited Arab Emirates (UAE)QatarOmanJordanKuwaitYemenLebanonIranUnited Kingdom (UK)FranceTunisiaItalyMalaysiaPhilippinesGreeceEgyptUnited States of America (USA)NetherlandsAlgeriaAustria韩国中国东亚：韩国和中国韩国：截至

3、6月8日：87例，其中死亡6例6家医院三星医学中心（34例）平泽市圣母医院（37例）Asan Asan Seoul Clinic (1例)365 Yeol Lin Hospital(1例)Dae cheong Hospital和KonYang University Hospital (14例)2361多人隔离,1800多个学校关闭中国：韩国第三例（首例同病房76岁）的儿子（44岁）MERS CoVWHO，2013年5月23日命名为“中东呼吸综合征”（Middle East Respiratory Syndrome，MERS）MERS CoVhCoV-EMC (Erasmus Medical C

4、enter).人类冠状病毒最早在1965年发现，其代表株是HCoV-229E 1967年病毒学家又从感冒病人中分离到了另一种人类冠状病毒，其代表株为HCoV-OC43只会导致普通感冒，发生咳嗽，鼻塞等症状，并不会引起恶性感染或者是死亡新型冠状病毒SARS-CoV（严重急性呼吸系统综合征冠状病毒），截止2003年7月，SARS-CoV共扩散到了37个国家，8273人感染，死亡775人，致死率达9.6%。2004年和2005年又分别发现了两株人类冠状病毒HCoV-NL63 和HCoV-HKU1 冠状病毒发现历史MERS CoV来源？美国国家过敏症和传染病研究所（NIAID）和沙特国王大学等机构合作

5、，在沙特全国范围内采集了 200 多头单峰驼血液样本，结果发现74的样本中都存在这种病毒病毒主要存在于骆驼的呼吸道中而非粪便中1992 年至 2010 年间采集的骆驼血液样本的分析表明，这种病毒在骆驼中存在的历史至少可追溯到 1992 年，只不过携带病毒的骆驼没有表现出任何感染症状蝙蝠中也发现Middle Eastrespiratorysyndrome(MERS): bats or dromedary, which of them is responsible?Bull Soc Pathol Exot.2014 May;107(2):69-73.Emerg Infect Dis.2014 Ju

6、l;20(7):1231-4.N Engl J Med 2014; 370:2499-2505十几起聚集病例have been reported by many countries (France, Italy, Jordan, Saudi Arabia, Tunisia, the UK and South Korea) Clusters2012年10月和11月，沙特一个家庭4名成员诊断莫斯，2人死亡。其他24名家庭成员和124名医务工作者没有发病。2013年4月，沙特26例聚集病例，大多数和一家医院有关联，其中16例死亡。2例为医务人员感染。2013年5月，法国一名男子从阿联酋回国后发病，诊

7、断莫斯，死亡。与他同住一个房间的一个病人被感染。超过100名医务工作者被检测，没有感染证据，而且许多还没有个人防护用品。聚集病例N Engl J Med.2013 Jun 19. Hospital Outbreak of Middle East Respiratory Syndrome CoronavirusA total of 21 of the 23 cases were acquired by person-to-person transmission in hemodialysis units, intensive care units, or in-patient units in

8、three different health care facilities.Among 217 household contacts and more than 200 health care worker contacts whom we identified, MERS-CoV infection developed in 5 family members (3 with laboratory-confirmed cases) and in 2 health care workers (both with laboratory-confirmed cases).沙特和阿联酋医院感染暴发2

9、014年4月，沙特和阿联酋超过500人感染大多数在沙特Jeddah的14家医院暴发感染，一共为255例没有确切的证据表明有持续的社区传播能力许多第二代病例发生在医务人员，但症状轻微或无症状，但15%的医务人员表现为重症或死亡接触的家庭成员554人中有7人被感染（传播率为1.3%）Clinical features and virological analysis of a case of MERScoronavirusinfection.A 73-year-old man from Abu Dhabi, United Arab Emirates, was transferred to Klin

10、ikum Schwabing on March 19, 2013, on day 11 of illness.Viral loadsBronchoalveolar fluid：1.2106copies/mLon day 16 were positive, but yielded little viral RNA (5370 copies per mL). Urine samples: 2691 copies/mLStool：1031 copies/gNo virus was detected in blood.Lancet Infect Dis.2013 Jun 14. pii: S1473-

11、3099(13)70154-3.SARS AND MERS蝙蝠？聚集病例超级传播者症状气溶胶密切接触病死率8%蝙蝠？骆驼？部分传染来源不清楚部分无发热、无呼吸道症状部分腹泻为首发症状部分早期出现肾衰致死性更强 Published online June 3, 201 Published online June 3, 201识别与诊断CLINICAL FEATURESMost cases present with symptoms of inuenza-like illness (ILI) such as fever, cough (predominantly dry), malaise, my

12、algia, sore throat, headache, rhinorrhoea, nausea, vomiting, abdominal pain, diarrhoea, and even renal failure occur occasionallyDyspnoea is a frequent complaint, and the majority of the patients develop pneumonia (70%) and ultimately require admission into an ICUAnn Intern Med. 2014;160:389-397.CLI

13、NICAL FEATURES itant infections and hypoalbuminemia were identied as the predictors of severe infection in individuals aged 65 years.Most of the paediatric cases were asymptomatic and found during the screening process among close family contacts of MERS-CoV patients in the community or in hospital.

14、Ann Intern Med. 2014;160:389-397.Crit Care Med. 2015 Jun;43(6):1283-90. Crit Care Med. 2015 Jun;43(6):1283-90.CLINICAL FEATURES发病到住院中位数天数：4天发病到入住ICU ：5 天需要机械通气时间：16天ICU stay：30天发病到死亡时间：12天ICU 90天死亡率: 58%Ann Intern Med. 2014;160:389-397.PrognosisIn one epidemiological analysis, the case-fatality rati

15、o for primary cases was 74% (95% CI, 4991), whereas for secondary cases, it was 20% (95% CI, 742)老年人，糖尿病、肾功能衰竭、慢性肺部疾病和免疫功能不全的人一旦感染莫斯病毒，是重症的高危因素。Lancet Infect Dis 2013; 13:752761Clin Infect Dis 2014; 59:160165中国大陆第3版-2014年9月中东呼吸综合征病例诊疗方案（2014年版）疑似病例患者符合流行病学史和临床表现，但尚无实验室确认依据。1.流行病学史。发病前14天内有中东地区旅游或居住史

16、；或与疑似/临床诊断/确诊病例有密切接触史。2.临床表现。难以用其他病原感染解释的发热（体温38）伴呼吸道症状。临床诊断病例1满足疑似病例标准，仅有实验室阳性筛查结果（如仅呈单靶标PCR或单份血清抗体阳性）的患者。2满足疑似病例标准，因仅有单份采集或处理不当的标本而导致实验室检测结果阴性或无法判断结果的患者。确诊病例疑似和临床诊断病例具备下述4项之一：1.至少双靶标PCR检测阳性。2.单个靶标PCR阳性产物，经基因测序确认。3.从呼吸道标本中分离出中东呼吸综合征冠状病毒。4.恢复期血清中东呼吸综合征冠状病毒抗体较急性期血清抗体水平阳转或呈4倍以上升高。无症状感染者无临床症状，但具备实验室确诊依

17、据4项之一者。WHO修订的MERS病例定义14 July 2014确诊病例需要至少间隔14天采集2个样本，通过筛选（ELISA，IFA）和中和试验等显示血清学转换。确诊病例：可能病例：确诊病例：有MERS感染的实验室诊断证据，不必考虑临床症状和体征。可能病例：1.有临床，影像学，或肺实质病变的组织病理学证据的急性发热呼吸系统疾病（如肺炎或急性呼吸窘迫综合征）和与确诊的MERS病例有直接的流行病学关联和不可检测MERS-Cov，或单份采集处理不当的标本检测阴性或不确定可能病例：2. 有临床，影像学，或肺实质病变的组织病理学证据的急性发热呼吸系统疾病（如肺炎或急性呼吸窘迫综合征）和在中东国家居住或

18、旅行，或在已知单峰骆驼血液有MERS-CoV循环或最近发生人感染病例的国家居住或旅行和MERS-Cov检测结果不确定可能病例：3.任何严重的急性发热呼吸系统疾病和和确诊的MERS病例有流行病学关联和MERS-Cov检测结果不确定laboratory confirmedrRT-PCR：2个特异性基因靶标阳性或一个靶标阳性同时第二个靶标序列阳性恢复期血清中东呼吸综合征冠状病毒抗体较急性期（间隔14天以上）血清抗体水平呈4倍以上升高（ screening (ELISA, IFA)和中和抗体）鉴别诊断：发病早期症状无特异性流感病毒SARS冠状病毒等What to do and what not to

19、doClinical management of severe acute respiratory infections when novel coronavirus is suspected 临床管理抗病毒治疗5 critically ill patients: ribavirin and interferon alfa-2a therapy are signicantly associated with improved survival at 14 days, but not at 28 days抗病毒治疗In vitro: ribavirin and interferon alpha-

20、2b combination therapy has signicant antiviral effects氯喹，氯丙嗪，洛哌丁胺，洛匹那韦，环孢素A和霉酚酸对 MERS-CoV 有活性抗病毒治疗anti-CD26 monoclonal antibodies： 2F9 YS110 m336human MicroRNAs密切监测病情变化Closely monitor patients with SARI for signs of clinical deterioration, such assevere respiratory distress/respiratory failure tissu

21、e hypoperfusion/shockGive supplemental oxygen therapy to patients with SARI/ARDSGive oxygen therapy to patients with signs of severe respiratory distress, hypoxaemia (i.e. SpO2 90%) or shock. Initiate oxygen therapy at 5 L/min and titrate to SpO2 90% in non-pregnant adults and SpO2 9295 % in pregnan

22、t patients. mechanical ventilation should be instituted earlyUse a lung-protective ventilation strategy (LPV) for patients with ARDS.抗菌药物和液体管理Give empiric antimicrobials to treat suspected pathogens, including community-acquired pathogensUse conservative fluid management in patients with SARI when t

23、here is no evidence of shockDo not give high-dose systemic corticosteroids or other adjunctive therapies for viral pneumonitis outside the context of clinical trialsProlonged use of systemic high-dose corticosteroids can result in serious adverse events in patients with SARI, including opportunistic

24、 infectionavascular necrosisnew health-care-associated bacterial infection possibly prolonged viral replication医院感染控制根据沙特阿拉伯对402例MERS感染病例的统计资料显示，医务人员感染者占27%，医务人员感染者中57.8%无症状或症状轻微。Mathematical modelling suggests that ial transmission is over four times higher than community transmission.The basic rep

25、roduction number (R0) was estimated to be 0.69 (95% CI, 0.500.92). Other reported estimated R0 values were 0.74 (95% CI, 0.531.03) before June 1, 2013, and 0.32 (95%CI, 0.140.65) after that dateEpidemics 2014; 9:4051.发热门（急）诊医务人员在诊疗工作中应当遵循标准预防和额外预防相结合的原则。严格执行手卫生、消毒、隔离及个人防护等措施。在诊疗所有患者时应当戴外科口罩，诊疗疑似、临床诊

26、断或确诊患者时应当戴医用防护口罩。戴口罩前和摘口罩后应当进行洗手或手消毒。Standard precautionshand hygiene use of personal protective equipment (PPE) to avoid direct contact with patients blood, body fluids, secretions (including respiratory secretions) and non-intact skin. When providing care in close contact with a patient with respi

27、ratory symptoms (e.g. coughing or sneezing), use eye protection, because sprays of secretions may occur. prevention of needle-stick or sharps injury;safe waste management; cleaning and disinfection of equipment;cleaning of the environment.病区（房）对疑似、临床诊断和确诊病例应当及时采取隔离措施；疑似及临床诊断病例应当进行单间隔离，经实验室确诊的相同感染征患者

28、可以多人安置于同一房间。患者的活动原则上限制在隔离病房内，若确需离开隔离病房或隔离区域时，应当采取相应措施防止造成交叉感染。严格探视制度，不设陪护。医务人员的防护医务人员应当按照标准预防和额外预防的原则，根据其传播途径采取飞沫隔离、空气隔离和接触隔离。手卫生正确穿脱防护用品医务人员应当根据导致感染的风险程度采取相应的防护措施。医务人员的防护（1）接触患者的血液、体液、分泌物、排泄物、呕吐物及污染物品时应当戴清洁手套，脱手套后洗手。（2）可能受到患者血液、体液、分泌物等物质喷溅时，应当戴外科口罩或医用防护口罩、护目镜、穿隔离衣。（3）对疑似、临床诊断或确诊患者进行气管插管等有创操作时，应当戴外科口罩或医用防护口罩、医用乳胶手套、护目镜、防护面屏、穿防渗隔离衣。（4）外科口罩、医