SARS 之鑑別診斷、治療與感染管制 張峰義 三軍總醫院 內科部感染科

大綱 Background overview Etiology Routes of transmission Clinical presentation and differential diagnosis Treatment and outcome Reporting and case definition 公共衛生「三段五級」預防架構及措施

Background Overview

SARS:2002新出現在人類的傳染病 WHO於2003年3月15日新公布的名稱，感染特點為發生瀰漫性肺炎及呼吸衰竭，比非典型性肺炎嚴重，因此取名為嚴重急性呼吸道症候群(Severe Acute Respiratory Syndrome, SARS)。

2002年11月中國大陸廣東地區出現「非典型性肺炎」疫情流行。 續發的香港疫情，為來自一位住宿於M酒店的廣東教授，傳給飯店人員及旅客，同時藉由受感染之旅客散佈全球。 WHO於3月底證實源頭來自廣東的「非典型性肺炎」。

疾病概述 流行病學 預防措施 防治工作  source from WHO

死亡數=71

– 全球共發現8,096例SARS病例，且造成774例死亡。 – 主要受感染國家包括： • 中國大陸：5,327例 • 香港：1,755例 根據世界衛生組織2003年12月31日的統計資料 （資料期間：2002年11月1日至2003年7月31日） – 全球共發現8,096例SARS病例，且造成774例死亡。 – 主要受感染國家包括： • 中國大陸：5,327例 • 香港：1,755例 • 臺灣：346例（37例死亡；12月底另發生1例實驗室感染病例） • 加拿大：251例 • 新加坡：238例

Etiology

致病原 「SARS-CoV病毒」 是新發現的冠狀病毒。 原冠狀病毒為導致感冒的致病原之一， 引起症狀較輕微。 2003年4月16日WHO正式命名。

Routes of Transmission

傳染窩 根據研究顯示，下列野生動物身上帶有 SARS-CoV病毒： 果子狸、貉、獾 蝙蝠、猴及蛇 老鼠

Routes of Transmission Droplets, direct and indirect contact: predominantly Household members, healthcare workers, or other patients who were not protected with contact or respiratory precautions. Fecal: less frequent The presence of virus in the stool. Amoy Gardens outbreak. Airborne transmission: less frequent Metropole hotel and the Amoy Gardens Outbreak. Clusters among healthcare workers exposed during high-risk activities.

傳染方式 SARS是近距離飛沫傳染，包括： 潛伏期 吸入病人的飛沫或體液而傳染。 接觸到病患分泌物或帶菌的體液。 2至7天，最長可達10天以上。

可傳染期、感受性及抵抗力 可傳染期 感受性及抵抗力 在尚未發燒時不會傳染給他人。 發病後7至10天內是最危險的傳染期。 發燒消退後10天即不具感染力。 感受性及抵抗力 SARS病毒為新型變種病毒，眾人皆無抗體。

Clinical Presentation and Differential Diagnosis

臨床表現 主要症狀 其他症狀 發高燒(＞38℃) 呼吸急促或呼吸困難 咳嗽 胸部X光發現肺部病變 頭痛、肌肉僵直、食慾不振、倦怠、腹瀉、意識紊亂

臨床表現 併發症 最嚴重會出現瀰漫性肺炎，氧氣交換下降，導致缺氧。 病人會呼吸困難、缺氧，甚至死亡。

Reporting and Case Definition

WHO Case Definition Suspect case A person presenting after 1 November 2002 with history of high fever (>38 °C) AND cough or breathing difficulty AND one or more of the following exposures during the 10 days prior to onset of symptoms: close contact with a person who is a suspect or probable case of SARS history of travel, to an area with recent local transmission of SARS residing in an area with recent local transmission of SARS Probable case A suspect case with radiographic evidence of infiltrates consistent with pneumonia or respiratory distress syndrome (RDS) on chest X-ray (CXR). A suspect case of SARS that is positive for SARS coronavirus by one or more assays.

法定傳染病規範~ 通報定義(1/2) 符合下列臨床條件及流行病學條件 臨床症狀：需同時符合下列四項 1.發燒（≧38℃） 2.一種或以上的下呼吸道症狀（咳嗽、呼吸困難、呼吸短促） 3.放射線診斷學上有與肺炎或呼吸窘迫症候群一致的肺浸潤的證據或者屍體解剖的發現與肺炎或呼吸窘迫症候群的病理學一致 4.無其他可替代的診斷能完全解釋疾病

法定傳染病規範~ 通報定義(2/2) 符合下列臨床條件及流行病學條件 流行病學：發病前10日有以下任一個暴露史 1.有SARS流行地區（經WHO宣布）之旅遊史 2.有SARS確定病例之接觸史 3.有與活性SARS冠狀病毒及感染SARS冠狀病毒個案臨床檢體相關之暴露史 醫師或法醫師高度懷疑

法定傳染病規範~ 病例定義 確定病例定義 實驗室診斷準則 兩次流行期之間：同時符合臨床條件、流行病學條件及檢驗條件。 爆發流行時：符合檢驗條件與流行病學條件第一項至第三項之任一條件。 實驗室診斷準則 臨床檢體分離並鑑定出SARS-CoV 病毒。 臨床檢體SARS-CoV PCR陽性。 血清學抗體檢測陽性：ELISA或IFA檢測抗體陽轉(seroconversion)。

SARS與MERS比較

Airway Defense Mechanisms LOWER AIRWAY UPPER AIRWAY Receptor on ciliated cells? Aminopeptidase N (CD13) for 229E, a sialic acid-containing R for OC43. Replication 32-34 ℃. Interferon, specific nasal secretory IgA, nasal secretory protein. Protection role? ALVEOLAR-SPACE DEFFENSE MECHANISM Alveolar lining fluid free fatty acids lysozyme iron-binding proteins IgG surfactant component Cellular components MO PMNL Lymphs

Clinical Presentation Fever body temperature of > 38.0°C (100.4°F). The most common symptom. Fever may be absent during the early stages of the disease and in individuals with co-morbidities. Chills, rigors, headache, dizziness, malaise, and myalgia. Sputum production, sore throat, coryza, nausea, and vomiting are less common. Diarrhea only seemed to be a prominent symptom in the Amoy Gardens' outbreak in Hong Kong.

Clinical Symptoms at Presentation of SARS SARS (CDC-TW ) (HK) Symptom (%) PCR(+) or Ab (+) PCR(-) or Ab(-) p value n=329 n=197 n=227 Fever 98.5 93.9 0.009 99 Cough 62 61.4 0.967 44 Diarrhea 23.4 14.2 0.015 41 Dyspnea 21.9 34.5 0.002 19 Myalgia 16.1 14.1 0.764 50 Headache 15.2 12.7 0.505 33 Chills 14 12.2 0.649 74 Sore throat 13.4 16.8 0.351 14 Sputum 12.8 17.8 0.149 20 General malaise 7.3 5.6 0.561 - Vomiting 5.5 5.1 1.000 7 Rhinorrhea 4.3 6.6 0.33 11 Nausea 4 3 0.766 - Abdominal pain 3.6 2.5 0.659 - Chest pain 2.1 3.6 0.482 9 Anorexia - - - 23 Rigor - - - 40 Wu YC et al.:Memoir of Severe Acute Respiratory Syndrome Control in Taiwan 2003:page 19 HK: Choi KW, et al., Ann Intern Med 2003 ;139

Clinical Course Incubation period: median 6 days; max. 10 days Clinical course: highly variable, ranging from mild symptoms to a severe disease process with respiratory failure and death. Clinical deterioration generally occurs 7 to 10 days after the onset of symptoms. Week 1 of illness Patients initially develop influenza-like prodromal symptoms, including fever, malaise, myalgia, headache, and rigors. Week 2 of illness Cough (initially dry), dyspnea and diarrhea may be present in the first week but more commonly reported in the second week of illness. Severe cases develop rapidly progressing respiratory distress and oxygen desaturation with about 20% requiring intensive care. Transmission occurs mainly during the second week of illness. Overall CFR estimate of approximately 11%. WHO, Alert, verification and public health management of SARS in the post-outbreak period (14 August 2003)

acute pneumonia typical atypical SARS symptoms Gradual onset Dry cough Shortness of breath Headache Myalgias Fatigue Sore throat Nausea Vomiting Diarrhea Abrupt onset of a chill, pleuritic chest pain, high spiking fever Cough productive of a rusty-colored sputum symptoms

acute pneumonia typical atypical The overlap of demographic features, presenting signs and symptoms, and laboratory and radiographic characteristics make the clear differentiation between atypical agents and typical bacterial causes of CAP problematic. - Mandell GL et al, Principles and Practice of Infectious Diseases

Causes of CAP Requiring Hospitalization in the Pre-SARS Era Cause of pneumonia Percent (%)   Streptococcus pneumoniae 10-20 Haemophilus influenzae 6-10 Chlamydia pneumoniae 6 Legionella pneumophila 2-7 Aerobic GNB 3-6 Staphylococcus aureus 3 Influenza 1-9 Mycoplasma pneumoniae 2-8 Moraxella catarrhalis 1 Coxiella burnetii 1-3 Pneumocystis carinii 2-5 Mycobacterium tuberculosis 1-3 Unknown etiology 30-50

Severe community acquired pneumonia Community-acquired pneumonia in the pre-SARS era Severe community acquired pneumonia Unknown (19-52%) H.influenzae (3-12%) Legionella (8-12%) Pneumococcus (15-33%) Mycoplasma (6-7%)

Clinical Symptoms at Presentation SARS Legionnaires Disease Symptom (%) Lee Peiris Donnelly Booth Tsai Kirby Helms Woodhead Fang Sopena n=138 n=50 n>1250 n=144 n=123 n=65 n=87 n=79 n=24 n=49 Fever 100 100 94 99 97 99 90 90 67 100 Sputum 50 49 46 53 75 42 Cough 57 62 50 69 86 92 71 94 70 69 Dyspnea p.a. 20 31 p.a. 59 36 37 45 50 46 Chest pain 23 33 26 46 14 25 Chills 73 74 65 28 74 77 51 - 42 - Malaise p.a. 50 64 31 Diarrhea 20 10 27 24 41 47 24 28 21 25 Runny nose 23 24 25 2 Myalgia 61 54 51 49 Headache 56 20 50 35 SARS: Lee N. A Major Outbreak of SARS in Hong Kong. N Engl J Med 2003; 348:1986-94. Peiris JS. Clinical progression and viral load in a community outbreak of SARS. Lancet 2003b; 361:1767-72. Donnelly CA. Epidemiological determinants of spread of causal agent of SARS in Hong Kong. Lancet 2003; 361:1761-6. Booth CM. Clinical features and short-term outcomes of 144 patients with SARS in the greater Toronto area. JAMA 2003; 289:2801-9. Legionnaires Disease : Michael S. Respiratory Infections: Page 416

The Intestinal Tropism of the SARS-CoV has Major Implication on Clinical Presentation and Viral Transmission Watery diarrhea: 20.3%(28/138); Diarrhea during the course of illness: 38.4%(53/138). Intestinal biopsy disclosed minimal architectural disruption but the presence of active viral replication within both the small and large intestine. Coronavirus was also isolated by culture from these specimens, and SARS-CoV RNA can be detected in the stool of patients for more than 10 wks after symptom onset. Leung WK et al, Gastroenterology 2003;125:1011-7

Laboratory Findings Lymphopenia: Progressive lymphopenia was found in 153/157 (98 %) . Reaching its lowest point in the second week. Reduced CD4 and CD8 T cell counts: adverse outcome. Transient leucopenia. Thrombocytopenia. Possibly caused by an immune mechanism. Reaching a low point at the end of the first week. Elevated lactate dehydrogenase (LDH). Association with extensive lung injury. An independent predictor for poor outcome. Elevated aspartate and alanine aminotransferases. Elevated creatine kinase. Low calcium, phosphorus, sodium and potassium levels. Clotting profile.

Laboratory Finding in 227 Patients with SARS Confirmed At admission Bilirubin level 7 Hemoglobin level 131 Alkaline phosphatase level 63 Leukocyte 4.9 Alanine aminotransferase level 28 Neutrophil count 3.7 Creatine phosphokinase level 1.7 Lymphocyte count 0.7 Lactate dehydrogenase level 232 Platelet count 147 C-creactive protein level 29 Prothrombin time 12.1 Sodium level 134 On serial assessment Activated partial Nadir hemoglobin level 113 thromboplastin time 33 Nadir leukocyte count 3.8 Potassium level 3.6 Nadir neutrophil count 2.7 Urea level 3.3 Nadir lymphocyte count 0.4 Creatinine level 70 Peak neutrophil count 14.5 Albumin level 37 Peak alanine Globulin level 33 aminotransferase level 52 Choi KW et al; Ann Intern Med.2003;139

SARS - Chest Radiographic Findings at Onset of Fever Abnormal: 78.3% (108/138) showed air-space consolidation. 54.6%(59/108) had unilateral focal involvement. 45.4%(49/108) had unilateral multifocal or bilateral involvement. Pleural effusion (-) Cavitation (-) Hilar lymphadenopathy (-) Lee et al. NEJM 2003:348:1986-94

Chest Radiograph in Legionnaires’ Disease at Presentation: Literature Review Radiographic finding Domingo McFarlane Muder Kroboth Dietrich % 1991,n=17 1984,n=49 1984,n=17 1983,n=34 1979,n=24 Patchy alveolar infiltrate - - 100 76 - Unilobar involvement 49 61 65 59 - Multilobar involvement 51 39 35 50 - Lower lobe involvement - - - 79 - Upper lobe involvement - - - 65 - Unilateral involvement 75 - - 50 - Bilateral involvement 25 - - - - Ground glass infiltrate - - - - 100 Pleural effusion 34 24 35 35 38 Cavitation 3 2 - 3 - Pulmonary collapse/ atelactasis - 37 - - -

CT Scans The predominant abnormalities found on initial CT scans. Sub-pleural focal consolidation with air bronchograms and ground-glass opacities. The lower lobes are preferentially affected, especially in the early stages. Obvious bronchial dilatation is generally not found. It also shares CT features with other conditions that result in subpleural air-space disease, such as the pneumonia of bronchiolitis obliterans and acute interstitial pneumonia.

Interpretation of laboratory Positive Results for SARS a) Confirmed positive PCR for SARS virus: At least 2 different clinical specimens, or The same clinical specimen collected on 2 or more days during the course of the illness, or 2 different assays or repeat PCR using the original clinical sample on each occasion of testing. b) Seroconversion by ELISA or IFA: Negative antibody test on acute serum followed by positive antibody test on convalescent serum, or Four-fold or greater rise in antibody titre between acute and convalescent phase sera tested in parallel. c) Virus isolation: Isolation in cell culture of SARS-CoV from any specimen; plus PCR confirmation using a validated method. WHO, Use of laboratory methods for SARS diagnosis

Early and Rapid Diagnosis of SARS-CoV Infection (sensitivity??) Virus nucleic acid Nested RT-PCR , multiplex RT-PCR, real-time PCR, SARS chip Serology IFA, ELISA,etc

Early and Rapid Diagnosis of Common CAP Agents Organism Rapid test Culture Serology Pneumococcus Gram stain Sputum Not commercially Urine antigen available Anaerobes Gram Stain M. pneumoniae PCR, Throat ELISA,CF Gram stain (-) NP swab Legionella spp. Urine antigen Sputum IFA DFA, PCR BAL Gram stain (-) C. pneumoniae PCR, Throat IFA

Important Clues for the Differential Diagnosis of CAP Versus SARS Hx: Travel, contact, cluster, chronic comorbidity. Clinical characteristics and laboratory findings. Serology, RT-PCR for SARS. Specific Dx for pneumonia pathogen (Co-pathogen?). Therapeutic Response.

Epidemiologic Condition Related to Specific Pathogens in Patients with Community-acquired Pneumonia (to be cont’d) Condition Commonly Encountered Pathogens Alcoholism Streptococcus pneumoniae (including DRSP), anaerobes, gram-negative bacilli, tuberculosis COPD/smoker S. pneumoniae, Hemophilus influenzae, Moraxella catarrhalis, Legionella Nursing home residency , gram-negative bacilli, H. influenzae, Staphylococcus aureus, anaerobes, Chlamydia tuberculosis Poor dental hygiene Anaerobes Epidemic Legionnaire’s disease species Exposure to bats Histoplasma capsulatum Exposure to birds psittaci, Cryptococcus neoformans, H. Exposure to rabbits Francisella tularensis

Epidemiologic Condition Related to SARS in Patients with Community-acquired Pneumonia Commonly Encountered Pathogens Travel to endemic area of SARS SARS-CoV Family cluster SARS-CoV, Mycoplasma, RS virus Contact history SARS active in community ?????SARS, Influenza, S. pneumoniae, S. aureus, H. influenzae, etc. Influenza active in community Influenza , S. pneumoniae, S. aureus, H. influenzae

Factors Influencing Transmission Determined of size of the inoculum: The distance to the index patient. The viral load in the secretion of the index patient. Nasopharyngeal aspirates: relatively low in the first few days, peak at around day 10, decrease to the levels obtained on admission at day 15. Stool: peak at day 13-14. Transmission more likely to happen in the later phase of the illness. High-Risk activities: Potent aerosol-generating procedures. Diagnostic sputum induction, bronchoscopy, endotracheal intubation, airway suction, BiPAP, neubrilization.

Host Factor Symptomatic Patients: Superspreader Only symptomatic patients may spread the SARS virus efficiently. Moderately transmissible. Superspreader A single individual has directly infected a large number of other people. Extensive viral shedding: advanced disease or possibly co-morbidities. other transmission routes or inadequate infection control measures. Unsuspected patients: atypical presentation. After Recovery 14 days of home quarantine following discharge. no reports of transmission after discharge.

Superspreaders: Number of Infected Persons and Outcome Age City O- H* Co-morbid conditions Infected persons** Out-come 64 Hong Kong 7 n.a. 13 p+s dead 47 Hanoi 3 none 20 p 26 >5 112 alive 22 Singapore 4 21 p, 3 s 27 23 p, 5 s 53 Diabetes, ischemic heart disease 23 p, 8 s 60 Chronic kidney disease, diabetes 62 p+s Ischemic heart disease, left ventricular failure 12 p, 3 s Toronto 6 Congestive heart failure 44 p 43 Taiwan Diabetes, peripheral vascular disease 137 p *Days between onset of illness and hospitalization, ** p = probable case; s =suspected case n.a. = not available

Of the first 201 probable cases reported, 103 were infected by just five source cases. MMWR 52(18);405-411

Life Cycle of a Virus in the Host and the Environment Aerosols Oral-fecal Direct Contact Modified from Keroack, Science; 1986;232:1635

Immunopathology for SARS Harm to the lung might be caused by immunopathological damage as a result of an aberrant host response, a direct viral infection or both. The hypothesis of so called “cytokine storm” may explain the immunopathogenesis of lung damage in SARS patients. The intensive inflammation developed in the lung will generate cytokines that stimulate lung epithelial cells to undergo pathological changes.

Treatment Protocol by HK 1) Antibacterial treatment Levofloxacin or clarithromycin plus amoxicillin and clavulanic acid. 2) Ribavirin and methylprednisolone Add combination treatment when exacerbation. 3) Pulsed methylprednisolone When clinical condition, chest radiograph, or oxygen saturation worsens (at least two of these), and lymphopenia persists. 4) Ventilation Consider non-invasive ventilation or mechanical ventilation if oxygen saturation <96% while on >6 L per min oxygen or if patient complains of increasing shortness of breath. So L. Development of a standard treatment protocol for severe acute respiratory syndrome. Lancet 2003; 361:1615-6.

台大醫院內科部SARS藥物治療指引 抗病毒藥物治療(Antiviral therapy: Ribavirin) 一、口服給藥：起始劑量一次給予 2000mg。 二、靜脈給藥：嚴重感染及對口服藥耐受性不佳。 免疫調節製劑(Immunomodulating agents) 一、類固醇 1.不要在開始使用Ribavirin的48小時內使用，通常在發病7天後開始。 2.在使用Ribavirin後，若病程仍持續惡化則考慮使用。 二、靜脈免疫球蛋白療法：臨床上顯示有噬血症候群的病患可能有效。 http://www.cdc.gov.tw/sars/4國內SARS相關資訊/「嚴重急性呼吸道症候群」治療建議.htm

Ribavirin Against a variety of RNA viruses. Treat HCV with interferon. In vitro data show that even at very high concentrations, there is no inhibition of replication of the SARS virus. In some patients the viral load peaked after 14 days of systemic ribavirin therapy. Toxicity in Canadian series. 71 patients (49%) experienced a decrease in hemoglobin level of at least 2 g/dL. 76% evidence of hemolysis. Canada health officials no longer provided routine access after May 1. Avendano M. Clinical course and management of SARS in health care workers in Toronto: a case series. CMAJ 2003; 168. Health Canada. Management of SARS in Adults: Interim Guidance for Health Care Providers. May 1, 2003

Lopinavir (Kaletra®) A B C Case /n K as initial Rx / 34 K as early rescue / 33 K as late rescue Control/n Ribavirin / 690 Riba + pulse MP / 431 Riba +pulse MP + E-T/ 77 Death rate by D 30 Case Control P-value A 0% 10.4% 0.04 B 3.0% 8.8% 0.34 NS C 21.2% 42.9% 0.03 http://www.who.int/csr/sars/conference/june_2003/materials/presentations/en/clinical_diagnosis.pdf

Immunomodulating Agents Steroids Changes in lung tissue suggest that part of the lung damage is due to cytokines induced by the microbial agent. Concern: might have contributed to increased viral replication and a protracted clinical course. Intravenous immunoglobin (IVIG) Hemophagocytic syndrome

Plasma Therapy 年齡 38.7 47.9 0.087 入院 LDH 258.1 247.7 0.7 21日內出院比率 康復者血清(CS)與大劑量激素(MP)之比較 (香港中文大學) MP + CS (n= 19) MP (n = 21) P值 年齡 38.7 47.9 0.087 入院 LDH 258.1 247.7 0.7 21日內出院比率 73.7% 19% 0.001 死亡個案 5 0.049 Wong VWS. Treatment of SARS with convalescent plasma. Hong Kong Med J 2003;9:199-201 http://www.cuhk.edu.hk/sars_care/c2_018_01_chi.ppt

Experience of using convalescent plasma for SARS among healthcare workers in a Taiwan hospital. Kuo-Ming Yeh, et al. JAC 2005;56:919-922

P’t 1 Fluorescent intensity Copies/mL

P’t 2 Fluorescent intensity Copies/mL

Risk Factors Associated with Clinical Deterioration Authors N Risk factors Lee et al. 138 Older age, high neutrophil count, high LDH peak Peiris et al. 50 Older age, severe lymphopenia, impaired alanine aminotransferase, delayed starting of ribavirin and steroids 75 Older age, chronic hepatitis B infection Booth et al. 144 Diabetes mellitus and other co-morbid conditions, (trend for older age) Wong et al. 157 Older age, high LDH 31 Low CD4 and CD8 counts at presentation Lee N. A Major Outbreak of SARS in Hong Kong. N Engl J Med 2003; 348:1986-94. Peiris JS. Coronavirus as a possible cause of SARS. Lancet 2003, 361:1319-25. Published online Apr 8, 2003. Peiris JS. Clinical progression and viral load in a community outbreak of coronavirus-associated SARS pneumonia. Lancet 2003; 361:1767-72. Booth CM. Clinical features and short-term outcomes of 144 patients with SARS in the greater Toronto area. JAMA 2003; 289:2801-9. Wong KT. SARS: Radiographic Appearances and Pattern of Progression in 138 Patients. Published online before print May 20, 2003b. Wong R. Haematological manifestations in patients with SARS: retrospective analysis. BMJ 2003; 326: 1358-62.

Staged approach to surveillance: Alert, Verification and Public Health Management of SARS in the Post-outbreak Period (14 August 2003) Staged approach to surveillance: Low risk areas: Surveillance for clusters of "alert" cases. Nodal areas: SARS Alert AND enhanced surveillance. Potential zone of re-emergence: special studies for SARS-CoV. SARS Alert Two or more health care workers in the same health care unit fulfilling the clinical case definition of SARS and with onset of illness in the same 10-day period. Enhanced surveillance Atypical pneumonia in nursing homes, rehabilitation units, community health care centres and in private practice. Persons discharged from hospital with a diagnosis of unspecified atypical pneumonia. Absenteeism among health care workers. Serological surveillance of high risk populations.

公共衛生「三段五級」預防架構及措施

防治政策架構 公共衛生「三段五級」預防架構 初段預防 次段預防 末段預防 衛生教育 早期監視早期防治 群聚及大流行之疫情處理 早期診斷與早期治療 末段預防 避免併發症與死亡

初段預防 維持良好衛生習慣，勤洗手。 均衡的飲食、適量的休息及運動。 注意呼吸道衛生與咳嗽禮節。 保持居家環境衛生及空氣流通。 打噴嚏或咳嗽時請掩住口鼻。 妥善處理分泌物。 保持居家環境衛生及空氣流通。

流行期衛教重點項目 發燒病人處理原則 配合發燒監測作業 口罩政策 三不政策 不發燒-不傳染-不隔離

次段預防~ 策略及作為 早期監視早期防治 群聚事件或大流行之因應處置 早期診斷早期治療 傳染病監視通報系統 檢體採檢與送驗 疫情調查 事件定義 中央流行疫情指揮中心 防制措施 早期診斷早期治療 傳染病防治醫療網 治療方法

傳染病監視與通報系統 法定傳染病個案通報系統 人口密集機構傳染病監視作業系統 醫院不明原因發燒監視通報作業系統 確實填寫附加資訊欄位 可上網通報：https://ida2.cdc.gov.tw/ida2/ 人口密集機構傳染病監視作業系統 監視監獄、安養護等人口密集機構 可上網通報：http://issap.cdc.gov.tw/ 醫院不明原因發燒監視通報作業系統 監視醫院不明原因發燒及群聚感染事件 可上網通報：http://feverap.cdc.gov.tw/

邊境管制作業：決戰境外 「傳染病防制調查表」 體溫測量 自疫區入境者自主健康管理10天 居家隔離 入境旅客體溫超過38℃，經診斷未排除為SARS病例者；來自疫區旅客，自主健康管理期間出現發燒等症狀者。

檢體採集與送驗 SARS採檢送驗作業流程 檢體種類

疫情調查作業 「傳染病疫情調查系統」下載疫調單 調查時機：疑似病例通報後 疫情調查重點： 過去病史、發病時間、症狀、就醫情形及過程 國內/外旅遊史、動物接觸史及活動史 密切接觸者名單 環境是否進行噴藥消毒 個案治療及預後狀況

密切接觸者疫情調查 同屋居住的家人及曾照顧個案者（含家屬、看護及陪病人員）。 醫院及診所曾照顧個案之醫護人員。 在醫院或診所有病例聚集或院內感染的可能傳染期間進入危險動線範圍之內者。 同一辦公室、百貨公司及賣場之同事（病患固定工作位置之半徑3公尺區域內之同事）。 學校中固定同一教室上課之同班同學。 同一班機病例前後各3排乘客及該班機服務此區域之空服員。 長途客運（車程1小時以上）之病例前後3排乘客及駕駛；長程火車之病例同車廂前後3排旅客。 衛生機關公布管制的對象。

密切接觸者調查重點 接觸者是否出現疑似症狀？ 就醫情形 流行病學接觸史、接觸情形 國內/外旅遊史 危險因子暴露情形 連絡方式 尤其是發燒、咳嗽 症狀出現起迄時間 就醫情形 流行病學接觸史、接觸情形 國內/外旅遊史 危險因子暴露情形 連絡方式

聚集事件定義 在相同的地點或場所有兩個或更多的人員符合SARS病例定義 且在相同的10日內發病

成立「中央流行疫情指揮中心」 法源依據 傳染病防治法第十七條 組織架構 指揮官1名 副指揮官1至3名 依任務需要設立若干處

SARS疫情動員分級 準備期/Ｏ級/A級/B級/C級 啟動時機 疫情狀況 指揮層級 降級基準 國內發生第一例次級傳染確定病例(C),國內發生第一例確定病例(B),國外報告第一例確定病例(A) 疫情狀況 國內發生次級傳染案例時(C),國內發生初級傳染案例時(B) 指揮層級 行政院指揮(B,C),衛生福利部指揮(A),疾病管制署指揮(O,準備期) 降級基準 國內最後一例個案之隔離日後三週公告降級

密切接觸者管理 依據疫情調查追蹤密切接觸者 名冊上網登錄造冊 自主健康與居家隔離管理資訊系統 網址：https://ida2.cdc.gov.tw/ida2/ 依據「SARS病例之密切接觸者自主健康管理及SARS居家隔離實施對象及天數」進行管理

自主健康管理實施對象與措施 早晚量體溫一次。 共計10天。 電話訪視。 如有發燒等症狀，衛生機關人員協助就醫。

居家隔離實施對象與措施 流行地區入境旅客於自主健康管理期間出現發燒症狀，經醫師診斷未能排除SARS者，應居家隔離觀察3天（如能確定發燒原因，可排除為SARS者，則不需居家隔離）。 SARS病例密切接觸者於自主健康管理期間出現發燒症狀時，應居家隔離觀察（含住院隔離治療期間）3天。 SARS病例於退燒之日起未滿10日即出院者，出院後仍應接受居家隔離至退燒之日起期滿10日為止。 居家隔離期間不得外出，並且監控體溫變化情形。

衛生福利部疾病管制署庫存防疫物資管理 直轄市及各縣市衛生局。 600家醫療院所。 防疫物資庫存申請移撥系統。 疾病管制署、直轄市及各縣市衛生局。 申請品項、數量，列出效期最近之品項、數量，確認及核准需求量，移撥需求量。

醫院感染管制措施(1/3) 病患的安置 單獨具有負壓控制的隔離病房。 負壓隔離病房每小時換氣次數應達6~12次為宜。 排氣口前需加設高效能的空氣過濾設備(HEPA filter)。 病患在室內時，應保持房門的關閉。 除非負壓隔離病房不足時，才考慮將感染相同微生物的病患安置在同一個房間裡；但前提必須是兩名病患都沒有其他急性或活動性感染。

醫院感染管制措施(2/3) 個人防護裝備（呼吸道防護） 進入病室前應佩帶呼吸道防護裝備（N95 口罩）。 防護面罩、手套及防護衣。

醫院感染管制措施(3/3) 病患床位的調動或在醫院內的轉送 如非必要應避免病患的調動或轉送。 如因特殊需要進行床位的調動或病患的轉送，應在限制的範圍內和管制的路線下進行轉送，盡可能減少在運送過程中經由飛沫或空氣散播病原。

SARS病例居家消毒作業原則 消毒時機 消毒範圍 消毒對象 「SARS病例居家消毒作業流程」 接獲通報病例後 病例之住家 發病期間經常活動之場所 消毒對象 通報病例（含密切接觸者） 「SARS病例居家消毒作業流程」

居家隔離者排泄物處理流程 廢棄物種類包括： 先以塑膠袋密封，再置感染性事業廢棄物專用紅色塑膠袋。 口鼻分泌物或體液等之衛生紙及口罩等。 先以塑膠袋密封，再置感染性事業廢棄物專用紅色塑膠袋。 用稀釋(1%)家用漂白水擦抹廁座邊、廁板和廁蓋，再用清水擦抹。 抽水馬桶注入約20 ㏄家用漂白水。

消毒種類與方法(1/2) 消毒地點、消毒種類、消毒方式、停留時間。 室內外地面/0.05%漂白水/噴灑或擦拭。 濺落之排泄物或分泌物/0.05%漂白水。 大量時於清潔前用0.5%漂白水/用拋棄式紙巾或抹布吸收主要濺落物/再消毒30分鐘以上。 嘔吐物、排泄物/0.5%漂白水/溶液充分混合後靜置30分鐘以上。

消毒種類與方法(2/2) 餐具 加熱法：煮沸100℃5分鐘 0.02%漂白水溶液浸泡30分鐘以上 衣服被褥

傳染病防治醫療網 法源依據 傳染病防治法第14條、第17至19條、第32條、第53條、第57條 依據全民防衛動員準備法第13條、第22條 依據災害防救法第20條 依據「指定徵用設立檢疫隔離場所及徵調相關人員作業程序與補償辦法」

傳染病防治醫療網運作與收治醫院 6區「傳染病防治醫療網指揮中心」及「疾病管制署諮詢委員會傳染病防治醫療網小組」 6家傳染病防治醫院 直轄市及各縣市衛生局、全國醫療院所

SARS病患轉運送作業 業務執掌 醫院感染症病例轉送至跨縣市傳染病防治醫院流程。 離島地區傳染病病例後送本島就醫作業流程。 醫療院所：通報、準備病床、救護車、隨車醫護人員。 衛生局：依據指揮官指定收治醫院，聯繫、協調各醫療院所；安排其他醫院接收感染症防治醫院清空之一般病患；聯繫救護車。 醫院感染症病例轉送至跨縣市傳染病防治醫院流程。 離島地區傳染病病例後送本島就醫作業流程。

治療方法 發病初期，醫師依據病患臨床表現投予抗病毒藥物。 如有出現肺部發炎等症狀時，依醫師處方使用類固醇。 配合呼吸治療及其他支持性療法。 應注意藥物副作用、免疫抑制反應。

避免併發症與死亡 避免併發症 避免死亡 危險因子 致病機轉 治療成效評估 適當治療以防止疾病的惡化並避免發生進一步的併發症。 提供適當醫療處置。 持續進行SARS致病機轉與治療之相關研究。 危險因子 致病機轉 治療成效評估

Non-specific clinical and laboratory characteristics of severe acute respiratory syndrome (SARS): an emphasis on the importance of standard precaution and development of early specific diagnostic methods during the outbreak

課程結束