1、對付新型流行性感冒的基本原則李健明 M.D.Division of Infectious DiseaseDepartment of MedicineChi Mei Medical CenterOutline1. Upper respiratory tract infection (URTI) 2. Influenza A3. Clinical presentations4. Treatment of H1N1 influenza-oseltamivir (tamiflu)5. Complications6. ConclusionsNovel (new) influenza A/H1N1 pan

2、demic-11 June 2009Upper respiratory tract infection (URTI)感冒流行性感冒上呼吸道感染鼻炎 鼻竇炎咽喉炎扁桃腺炎中耳炎Microbiological findings for 200 pts with s/s of the common coldViruses: 7 or 10Bacteria: 5Unknown: 30%Seasonality季節性:溫度和溼度0 since JuneMar. (Mexico)Influenza VirusesInfluenza A virusH(1-15)*N(1-9)Host: swine, avia

3、nInfluenza B virusInfluenza C virusVirulence factor: PB2F1Attack mitochondriaNovel influenza A/H1N1 infection of Mexico, 2009Incubation period: 1-4 daysPeriod of outbreak: 5 weeksClinical presentation of 642 novel influenza A/H1NA of USA, 2009Clinical presentation of 642 novel influenza A/H1NA, USAD

4、uration of symptoms-school of Kobe 1.Symptom-free2.One-day suffering3.One-week cough and sore throatCase presentationA 51-year-old hypertensive male consulted Dr. of Emergency Department because of fever for a week. Rapid antigen (screening) test was positive for influenza A. Therefore he has been o

5、n oseltamivir (Tamiflue; 剋流感).Address: 善化鎮胡厝里Smoker and drinkerHospitalization: 26-29 Aug. 2009 Laboratory testsWBC14,300/mm3PMNs 87%Hemoglobin 12 gm/dLBUN 28 mg/dLCreatinine2.1 mg/dLSodium 140 mEq/LPotassium2.6 mEq/LAST38 IU/LALT62 IU/L26 Aug. 200928 Aug. 2009Mycoplasma antibody 1:160New influenza

6、A/H1N1 absentTriple-reassortment swine influenza A virus without PB2F1 geneTransmission route of H1N11. Contact2. Airborne1) Droplets 5 m; 3 ft. Streptococcus pneumoniaeinfluenza virus, rhinoviruses, adenoviruses, and respiratory syncytial virus2) Droplet nuclei: 1-5 mMycobacterium tuberculosisVZV,

7、measles virus, and smallpox virusAspergillus fumigatus (spore, 1 M/h)臨床思路Q: 是上呼吸道感染嗎?Q: 有肺炎嗎?Q: 是什麼微生物感染的肺炎?一次檢驗只能檢驗一種病毒一次血液培養可培養多種細菌胸部X光絕無法判斷何種致病菌真正的肺炎必須依靠病理診斷驗痰找肺炎的致病菌很不準確Preventive consideration 白袍 聽診器 雙手 領帶 室內 診療室 房車 擁擠 季節 溼度 肥胖Diagnosis of H1N1 influenza Rapid antigen test RT-PCR Culture: level

8、 3Symptom:sensitivityspecificityFever68-86%25-73%Cough84-98%7-29%Nasal congestion6891%1941%Evidence-based treatment of novel influenza A/H1N1-Search strategy1. Cochrane Central Register of Controlled Trials (The Cochrane Library 2005, issue 1)2. MEDLINE (1966 to April 2005)3. EMBASE (January 1980 to

9、 December 2004)4. On-line GlaxoSmithKline Clinical Trials Register5. On-line Roche Clinical Trial Protocol Registry and Clinical Trial Results Database (August 2005)6. Web sites of European and US regulatory bodies and contacted manufacturers and authorsEVM of tamiflu-2005 Reduction by 7.7% (10 hour

10、s) in at risk (asthmatic) children (P = 0.54). Zanamivir: reduction by 24% (1.25 days) (P 0.001). Oseltamivir had significant reduction in the complications of influenza (particularly otitis media) Oseltamivir for the prevention of influenza transmission in households, reporting data from 222 paedia

11、tric contacts. Where index cases had laboratory-confirmed influenza, a protective efficacy of 55% was observed (P = 0.089). Brit Med J 2009;339:3172- Results None of these trials tested efficacy with the current pandemic strain Reductions in median time to resolution of symptoms or return to normal

12、activities: 0.5-1.5 daysBrit Med J 2009;339:3172- Results A 10 day course of postexposure prophylaxis with zanamivir or oseltamivir resulted in an 8% (95% CI 5% to 12%) decrease in the incidence of symptomatic influenza No reduction in overall use of antibiotics Oseltamivir: increased risk of vomiti

13、ngBrit Med J 2009;339:3172- Conclusions 1. Neuraminidase inhibitors provide a small benefit by shortening the duration of illness in children with seasonal influenza and reducing household transmission. 2. They have little effect on asthma exacerbations or the use of antibiotics. Their effects on th

14、e incidence of serious complications, and on the current A/H1N1 influenza strain remain to be determined.Virus isolation rate after the start of neuraminidase inhibitor therapy in childrenCID 2008;47:33943% was still shedding virus on day 5 under NI therapy.Complications of influenza A/ H1N1 Influen

15、za A pneumonitis On D54 of a 27-week pretermComplications of influenza A/H1N1 Upper respiratory tract Bacterial sinusitis Bacterial otitis media Lower respiratory tract Exacerbation of COPD Exacerbation of CHF Wheezing attacks in asthmatics Croup, bronchitis, bronchiolitis Pneumonia Primary viral pn

16、eumonia (PVP) Secondary bacterial pneumonia (SBP) Combined viral and bacterial pneumonia CNS: encephalitisPrimary (H1N1) viral pneumonia (PVP)lDevelops abruptly and progresses rapidlylRisky groupslRapid RR, tachycardia, cyanosis, fever, hypotensionlDiffuse pulmonary infiltratelAcute respiratory fail

17、urelHigh mortality ratelLess common than combined viral and bacterial pneumoniaAdult viral community-acquired pneumonia (CAP)Polymicrobial adult CAPSecondary bacterial pneumonia (SBP) 5-16 days after initial onset of symptoms Productive cough, pleuritic chest pain, chills Streptococcus pneumoniae, S

18、taphylococcus aureus, Hemophilus influenzae Responds to appropriate antimicrobial agents Lower case fatality rate than PVPOb/gyn complications Spontaneous abortion Stillbirths Premature births Maternal death 3rd trimesterHigh mortality rate 65 years of age and older Very young Underlying chronic cardiac, pulmonary or metabolic diseasesExcess Mortality-William Farr (1885) The number of deaths observed during an epidemic of influenza-like illness in excess of the no. expected. Base or expected no. of deaths for the win