mers地壇醫(yī)院感染性疾病診療中心

1、北京地壇醫(yī)院感染性疾病診療中心蔣榮猛2015.6.9中東呼吸綜合征(MERS)提綱MERS經過類SARS？人傳人？診斷和治療個人防護on the day of admission2 days later 疫情信息截至2015年5月31日，全球報告了1185例確診病例，其中443例死亡（37.4%）。其中95%以上的病例發(fā)生在中東。 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韓國中國東亞：韓國和中國韓國：截至

3、6月8日：87例，其中死亡6例6家醫(yī)院三星醫(yī)學中心（34例）平澤市圣母醫(yī)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多人隔離,1800多個學校關閉中國：韓國第三例（首例同病房76歲）的兒子（44歲）MERS CoVWHO，2013年5月23日命名為“中東呼吸綜合征”（Middle East Respiratory Syndrome，MERS）MERS CoVhCoV-EMC (Erasmus Medical C

4、enter).人類冠狀病毒最早在1965年發(fā)現，其代表株是HCoV-229E 1967年病毒學家又從感冒病人中分離到了另一種人類冠狀病毒，其代表株為HCoV-OC43只會導致普通感冒，發(fā)生咳嗽，鼻塞等癥狀，并不會引起惡性感染或者是死亡新型冠狀病毒SARS-CoV（嚴重急性呼吸系統綜合征冠狀病毒），截止2003年7月，SARS-CoV共擴散到了37個國家，8273人感染，死亡775人，致死率達9.6%。2004年和2005年又分別發(fā)現了兩株人類冠狀病毒HCoV-NL63 和HCoV-HKU1 冠狀病毒發(fā)現歷史MERS CoV來源？美國國家過敏癥和傳染病研究所（NIAID）和沙特國王大學等機構合作

5、，在沙特全國范圍內采集了 200 多頭單峰駝血液樣本，結果發(fā)現74的樣本中都存在這種病毒病毒主要存在于駱駝的呼吸道中而非糞便中1992 年至 2010 年間采集的駱駝血液樣本的分析表明，這種病毒在駱駝中存在的歷史至少可追溯到 1992 年，只不過攜帶病毒的駱駝沒有表現出任何感染癥狀蝙蝠中也發(fā)現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; 370:2499-2505十幾起聚集病例have been reported by many countries (France, Italy, Jordan, Saudi Arabia, Tunisia, the UK and South Korea) Clusters2012年10月和11月，沙特一個家庭4名成員診斷莫斯，2人死亡。其他24名家庭成員和124名醫(yī)務工作者沒有發(fā)病。2013年4月，沙特26例聚集病例，大多數和一家醫(yī)院有關聯，其中16例死亡。2例為醫(yī)務人員感染。2013年5月，法國一名男子從阿聯酋回國后發(fā)病，診

7、斷莫斯，死亡。與他同住一個房間的一個病人被感染。超過100名醫(yī)務工作者被檢測，沒有感染證據，而且許多還沒有個人防護用品。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).沙特和阿聯酋醫(yī)院感染暴發(fā)2

9、014年4月，沙特和阿聯酋超過500人感染大多數在沙特Jeddah的14家醫(yī)院暴發(fā)感染，一共為255例沒有確切的證據表明有持續(xù)的社區(qū)傳播能力許多第二代病例發(fā)生在醫(yī)務人員，但癥狀輕微或無癥狀，但15%的醫(yī)務人員表現為重癥或死亡接觸的家庭成員554人中有7人被感染（傳播率為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？聚集病例超級傳播者癥狀氣溶膠密切接觸病死率8%蝙蝠？駱駝？部分傳染來源不清楚部分無發(fā)熱、無呼吸道癥狀部分腹瀉為首發(fā)癥狀部分早期出現腎衰致死性更強 Published online June 3, 201 Published online June 3, 201識別與診斷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發(fā)病到住院中位數天數：4天發(fā)病到入住ICU ：5 天需要機械通氣時間：16天ICU stay：30天發(fā)病到死亡時間：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、腎功能衰竭、慢性肺部疾病和免疫功能不全的人一旦感染莫斯病毒，是重癥的高危因素。Lancet Infect Dis 2013; 13:752761Clin Infect Dis 2014; 59:160165中國大陸第3版-2014年9月中東呼吸綜合征病例診療方案（2014年版）疑似病例患者符合流行病學史和臨床表現，但尚無實驗室確認依據。1.流行病學史。發(fā)病前14天內有中東地區(qū)旅游或居住史

16、；或與疑似/臨床診斷/確診病例有密切接觸史。2.臨床表現。難以用其他病原感染解釋的發(fā)熱（體溫38）伴呼吸道癥狀。臨床診斷病例1滿足疑似病例標準，僅有實驗室陽性篩查結果（如僅呈單靶標PCR或單份血清抗體陽性）的患者。2滿足疑似病例標準，因僅有單份采集或處理不當的標本而導致實驗室檢測結果陰性或無法判斷結果的患者。確診病例疑似和臨床診斷病例具備下述4項之一：1.至少雙靶標PCR檢測陽性。2.單個靶標PCR陽性產物，經基因測序確認。3.從呼吸道標本中分離出中東呼吸綜合征冠狀病毒。4.恢復期血清中東呼吸綜合征冠狀病毒抗體較急性期血清抗體水平陽轉或呈4倍以上升高。無癥狀感染者無臨床癥狀，但具備實驗室確診依

17、據4項之一者。WHO修訂的MERS病例定義14 July 2014確診病例需要至少間隔14天采集2個樣本，通過篩選（ELISA，IFA）和中和試驗等顯示血清學轉換。確診病例：可能病例：確診病例：有MERS感染的實驗室診斷證據，不必考慮臨床癥狀和體征。可能病例：1.有臨床，影像學，或肺實質病變的組織病理學證據的急性發(fā)熱呼吸系統疾?。ㄈ绶窝谆蚣毙院粑狡染C合征）和與確診的MERS病例有直接的流行病學關聯和不可檢測MERS-Cov，或單份采集處理不當的標本檢測陰性或不確定可能病例：2. 有臨床，影像學，或肺實質病變的組織病理學證據的急性發(fā)熱呼吸系統疾?。ㄈ绶窝谆蚣毙院粑狡染C合征）和在中東國家居住或

18、旅行，或在已知單峰駱駝血液有MERS-CoV循環(huán)或最近發(fā)生人感染病例的國家居住或旅行和MERS-Cov檢測結果不確定可能病例：3.任何嚴重的急性發(fā)熱呼吸系統疾病和和確診的MERS病例有流行病學關聯和MERS-Cov檢測結果不確定laboratory confirmedrRT-PCR：2個特異性基因靶標陽性或一個靶標陽性同時第二個靶標序列陽性恢復期血清中東呼吸綜合征冠狀病毒抗體較急性期（間隔14天以上）血清抗體水平呈4倍以上升高（ screening (ELISA, IFA)和中和抗體）鑒別診斷：發(fā)病早期癥狀無特異性流感病毒SARS冠狀病毒等What to do and what not to

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

20、2b combination therapy has signicant antiviral effects氯喹，氯丙嗪，洛哌丁胺，洛匹那韋，環(huán)孢素A和霉酚酸對 MERS-CoV 有活性抗病毒治療anti-CD26 monoclonal antibodies： 2F9 YS110 m336human MicroRNAs密切監(jiān)測病情變化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.抗菌藥物和液體管理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醫(yī)院感染控制根據沙特阿拉伯對402例MERS感染病例的統計資料顯示，醫(yī)務人員感染者占27%，醫(yī)務人員感染者中57.8%無癥狀或癥狀輕微。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.發(fā)熱門（急）診醫(yī)務人員在診療工作中應當遵循標準預防和額外預防相結合的原則。嚴格執(zhí)行手衛(wèi)生、消毒、隔離及個人防護等措施。在診療所有患者時應當戴外科口罩，診療疑似、臨床診

26、斷或確診患者時應當戴醫(yī)用防護口罩。戴口罩前和摘口罩后應當進行洗手或手消毒。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.病區(qū)（房）對疑似、臨床診斷和確診病例應當及時采取隔離措施；疑似及臨床診斷病例應當進行單間隔離，經實驗室確診的相同感染征患者

28、可以多人安置于同一房間?；颊叩幕顒釉瓌t上限制在隔離病房內，若確需離開隔離病房或隔離區(qū)域時，應當采取相應措施防止造成交叉感染。嚴格探視制度，不設陪護。醫(yī)務人員的防護醫(yī)務人員應當按照標準預防和額外預防的原則，根據其傳播途徑采取飛沫隔離、空氣隔離和接觸隔離。手衛(wèi)生正確穿脫防護用品醫(yī)務人員應當根據導致感染的風險程度采取相應的防護措施。醫(yī)務人員的防護（1）接觸患者的血液、體液、分泌物、排泄物、嘔吐物及污染物品時應當戴清潔手套，脫手套后洗手。（2）可能受到患者血液、體液、分泌物等物質噴濺時，應當戴外科口罩或醫(yī)用防護口罩、護目鏡、穿隔離衣。（3）對疑似、臨床診斷或確診患者進行氣管插管等有創(chuàng)操作時，應當戴外科口罩或醫(yī)用防護口罩、醫(yī)用乳膠手套、護目鏡、防護面屏、穿防滲隔離衣。（4）外科口罩、醫(yī)