流感重症分析的目的 : 準備好因應大流 行

王振泰醫師台大醫院內科部感染科

流感重症分析的目的 : 準備好因應大流 行 1918, Spanish influenza H1N1 1957, Asian influenza H2N2 1968, Hong Kong influenza H3N2 1997 & 2003, Hong Kong & mainland China H5N1 (remain candidate only till now) 2009, swine influenza H1N1

Complicated Influenza Presence of 1 of the following complications within 4 weeks after onset of ILI 1. Need of hospitalization due to pulmonary complications 2. Neurological complications 3. Myocarditis or pericarditis 4. Invasive bacterial infection 5. Others: ICU admission or death CDC, Taiwan

Outline of this Presenatation 季節性流感成人重症之臨床分析 成人之表現鮮少被提及 整理發表 Retrospective study & prospective study Swine-origin H1N1 重症前 100 例之分析

Retrospective Study: CDC Data Complicated influenza pneumonia reported to CDC, Taiwan Age > 15 years Jan. 2001 Jun. 2007 Outcome analysis: In-hospital mortality rate Ho YC, et al. J Infect 2009;58:439 45.

Results: 38 patients were enrolled, 44.7% died Annual distribution as following:

Results: Demographic Data & Presenting Symptoms

Results: Diseases Severity It s reasonable that patients who died of complicated influenza pneumonia presented with a more severe disease

Results: Signs and Laboratory Tests

Results: Treatment and Vaccination (only 4 patients received anti viral treatment within 48 hours)

Results: Risk factors for Mortality

Discussion and Key Message Disease severity at presentation dominated the clinical course The effect of anti-viral treatment can t be well evaluated in the present study Among the enrolled patients, vaccination rate is low (4/38) The mortality rate is high Biased results: critically ill patients more easily enrolled

胡婉妍醫師, 王振泰醫師, 盤松青醫師, 張上淳醫師

Prospective Study on Seasonal Flu Duration: 95.8 to 98. 3 Target population: adults matching ILI criteria presenting to NTUH Overall: 360 patients were enrolled 206 patients were documented influenza Flu A: 174 patients Flu B: 31 patients Flu A+B: 1 patient

Performance of Various Diagnostic Tools 100 80 % 60 40 20 0 Rapid test Virus isolation PCR Serology All Uncomplicated Complicated

100% 80% 60% 40% 20% Distribution of Types of Influenza Virus 0% 2006/12-2007/4 2007/12-2007/3 2008/12-2009/3 H3 H1 B unsubtypable

Results: 重症患者 :30 人 Pneumonia: 28 patients Encephalitis: 2 patients All did not receiving vaccination within past one year 2 patients dead of influenza, both within 3 days after diagnosis

Clinical characterisitics

Laboratory findings 0.003

Mortality rate : 1%

Viral load from pharyngeal specimens

Predictors of development of complicated influenza

Key Message form This Study Underlying diseases and severity of disease at presentation were the major effectors for mortality Among the patients with complicated diseases: H3 in early study period H1 in late study period (not novel H1N1) Mortality rate: 1% Biased, overestimated

Emergence of S-OIV April, 2009: An outbreak of respiratory illness detected and reported by Mexican Secretariat of Health WHO classified the global spread June 11, 2009: Phase 6 pandemic alert Over 70 countries affected till now

Clinical Manifestations Similar to seasonal flu Range from severe non-febrile mild URI to severe or fatal pneumonia Most being uncomplicated, spontaneous recovery Most commonly reported symptoms Cough, fever, sore throat, malaise, headache GI symptoms were high in U.S.A.

Percentage of Who Becoming Severely Ill Hospitalized: 2 5% of confirmed cases in USA 6% in Mexico Hospitalized with pneumonia 60% Hospitalized with multilobar infiltrates 40% Hospitalized with the need of ventilator support 1/6 1/3

台灣 H1N1 新型流感前 100 例住院住院重症調查報告 Duration: Jun. 21, 2009 起, 前 100 例住院病患, 並追蹤至 9 月 18 日 Laboratory confirmed novel H1N1 infection Both pediatric and adult population Analyzing the clinical outcome 簡郁珊等 疫請報導,2009; 網路預報

結果 :Histogram

結果 : 人口學特徵 Median age: 16.5 years 46% in 18-65 years Adult: 39 years (18 83 years) Children: 8 years (8 mo 15 years) Male to female ratio: 64/36

結果 :Underlying Conditions Underlying diseases: 38 Cognitive or Neurological Disorders: 12(31.6%) Asthma or COPD : 12(31.6%) Cardiovascular diseases (except hypertension) : 9(23.7%) Diabetes mellitus : 9(23.7%) Chronic anemia : 9(23.7%) Liver Disease : 6(15.8%) Malignancy: 5(13.2%) Chronic renal disease: 5(13.2%) Compromised Immunity : 4(10.5%) Bedridden: 4(10.5%) Morbid obesity: 6(14%) Pregnancy: 2

Results: Presenting Symptoms Fever: 99% Cough: 93% Fatigue/ Malaise : 61% Sore throat : 49% Rhinorrhea/Nasal congestion: 49% Myalgia : 42% Headache: 19% Nausea/Vomiting: 24% Diarrhea: 17% Dyspnea: 42% Chest pain: 13% Consciousness change: 10% Seizures: 5% Cyanosis:1%

Results: Laboratory Examinations Rapid test: 84% positive Days from illness onset to test: 3 (0-14) WBC: 6630 (1260-19290) Leukopenia: 22% Lymphocyte: 986 ( 54-5626) Lymphopenia: 47% PLT: 178 K (7-381 K) Thrombocytopenia: 8% CK: 150 U/L (37 1029) (29/31) LDH: 595.5 U/L (135 1249) (7/7) CRP: 52/60 abnormal

Results: CXR findings No obvious finding: 8 (8.2%) 1 lung quadrants: 35 (35.7%) 2 lung quadrants: 38 (38.8%) 3 lung quadrants: 9 (9.2%) 4 lung quadrants: 8 (8.2%)

Results: Treatment Antiviral agents: Oseltamivir Days from illness onset to Tx: median 4 days(0-21) <48 hrs: 40 Only 3 had double dose Steroid: 22 Hydrocortisone, 300 mg/day : 8 Methyl-prednisolone, 2mg/kg/day: 7 Methyl-prednisolone, > 2mg/kg/day: 7 ECMO: 9 Mean: 17.7 days 5 complications 2 successfully remove IVIG: 3 Hospital stay: median 6 days(1-34 days) Death: 9

Results: Complications ICU admission: 42 Viral pneumonia: 89 Liver impairment : 19 Encephalitis: 8 Oxygenation: 52 4 had image diagnosis Mechanical ventilation: 23 ARDS: 17 Renal impairment : 15 4 had renal replacement Myocardial dysfunction: 3 DIC: 4 Secondary infection: 12 Mechanical ventilation : 23 Vasopressor: 13

Results: Analysis for Mortality Duration from admission to death: 6 (2 27) days BMI > 35: 1 adult Obese child: 1 HCC with liver cirrhosis and CKD: 1 CP: 1 DM + COPD + CKD: 1 No underlying condition: 3

Results for Mortality: Risk Factors Duration from onset to rapid test: 6 v.s. 2 days, P < 0.01 Duration from onset to tamiflu 6 v.s. 3 days, P = 0.01

Discussions: Clinical presentation and laboratory findings: Similar to other reports Risk for severe disease Underlying conditions, obesity, pregnancy, aged 2 5 years Best treatment modality: Issue left to resolve