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1 개원의와함께하는임상강좌 2011 흔한상기도바이러스질환들 경희대학교의과대학감염내과학교실 이미숙 General 상기도감염 감기, 인두염, 후두염, 후두기관지염등을포함 급성질환의 1/2 이상을차지 - 의료인이가장흔히접하는질환 이환율 : 3.5~6 cases/person/year in USA ( app. 1 billion) 주원인 : 8 종, 200 여혈청형에달하는 virus, seasonal variation - Spring, Summer, early Fall : Rhinovirus (symptoms above the neck) - Winter : Adenovirus, parainfluenza virus, coronavirus, and influenza viruses, more likely to get into the bronchi, trachea, and cause more fever and bronchitis) 임상적고려 : the proximity to the brain, mediastinum the potential for airway obstruction prompt recognition and treatment of head & neck infections Viruses causing respiratory infection by frequency Upper respiratory Rhinovirus Coronavirus Adenovirus Parainfluenza virus Echovirus Respiratory syncytial virus Coxsackie A virus Influenza A and B virus Lower respiratory Respiratory syncytial virus Influenza A and B virus Parainfluenza virus Measles virus Adenovirus Rhinovirus Coronavirus 개원의와함께하는임상강좌

길라잡이 Factors associated with increased incidence of respiratory infections Day-care or kindergarten attendance Siblings : school-age > preschool ; number of siblings Urban > rural Maternal smoking

2 길라잡이 Factors associated with increased incidence of respiratory infections Day-care or kindergarten attendance Siblings : school-age > preschool ; number of siblings Urban > rural Maternal smoking Age : maximum 6 months to 4 years Bottle > breast-feeding Psychological stress 상기도감염 - 기관별 Common colds 원인 주원인 - Rhinovirus (15-40%), Coronavirus (10-20%) 기타원인 - RSV, Parainfluenza virus, S. pyogenes 등 역학 1인당매년1-6회, 성인평균 2-4회, 소아 6-8회발생 long lasting immunity 결여 전파 large droplet, small droplet (aerosol) 에의한호흡기전파 secretions on hand - 신체오염시 4시간이상생존가능 16 개원의와함께하는임상강좌 2011

이미숙 : 흔한상기도바이러스질환들 Common colds 임상증상 잠복기 : 48-72 시간 콧물, 코막힘, 재치기, 인후통, 기침, 목쉼, 후각과미각의이상등 전신증상이거의없음 - influenza 와대조적 증상은 2-4 일째최고에달하며, virus 분비가가장높음

25% phenylephrine, 1% ephedrine, pseudoephedrine - 해열 : acetaminophen, aspirin - 기침 : dextromethophan, codeine - 기타 : vitamin C, zinc, Echinacea,

3 이미숙 : 흔한상기도바이러스질환들 Common colds 임상증상 잠복기 : 시간 콧물, 코막힘, 재치기, 인후통, 기침, 목쉼, 후각과미각의이상등 전신증상이거의없음 - influenza 와대조적 증상은 2-4 일째최고에달하며, virus 분비가가장높음 합병가능질환 - sinusitis, acute otitis media, tracheobronchitis 진단 임상적진찰로균구별불가능, 치료에도움 (-) Common colds 치료 : 대부분자연치유 Symptomatic - 비충혈 : 0.25% phenylephrine, 1% ephedrine, pseudoephedrine - 해열 : acetaminophen, aspirin - 기침 : dextromethophan, codeine - 기타 : vitamin C, zinc, Echinacea, etc 이차세균감염치료 - H. influenzae, S. pneumoniae : amoxicillin, TMP/SXT Common colds 예방 hand washing 코와결막보호 환자와접촉회피 비타민 C의대량투여? vaccine not effective 개원의와함께하는임상강좌

길라잡이 Acute pharyngitis Tonsilitis, pharyngotonsilitis 포함 원인 : infection, agranulocytosis, trauma, or injury by chemicals or

Viral - EBV, HSV, adenovirus, RSV, parainfluenza virus, influenza virus - 서서히진행되는발열, 병감, 식욕부진, 인두통 (2-3일) 애성, 기침, 비염, 결막염 -

gonorrheae - 두통, 복통, 구토, 고열 (1-4 일 ), 인두통 - 편도종창, 삼출액, 인두발적 ; 1/3 에서관찰 - 경부임파선종대, 압통 ; 심하면 2 주지속 합병증 : 세균성 - 편도주위농양, 부비동염,

주증상 : 지속적, 불분명한변성 (hoarseness, weakness) 종류 : Acute laryngotracheobronchitis (Croup) Acute epiglottitis (supraglottitis) Croup

4 길라잡이 Acute pharyngitis Tonsilitis, pharyngotonsilitis 포함 원인 : infection, agranulocytosis, trauma, or injury by chemicals or radiation 임상증상 : sore throat, dysphagia 1. Viral - EBV, HSV, adenovirus, RSV, parainfluenza virus, influenza virus - 서서히진행되는발열, 병감, 식욕부진, 인두통 (2-3일) 애성, 기침, 비염, 결막염 - 인두의작은궤양, 삼출액 ; 5일내호전 Acute pharyngitis 2. Bacterial - Group A beta-hemolytic streptococci, N. gonorrheae - 두통, 복통, 구토, 고열 (1-4 일 ), 인두통 - 편도종창, 삼출액, 인두발적 ; 1/3 에서관찰 - 경부임파선종대, 압통 ; 심하면 2 주지속 합병증 : 세균성 - 편도주위농양, 부비동염, 중이염, 급성사구체신염, 류마티스열 치료 : 세균성 - Penicillin, 1 st generation cephalosporins Amx/Clav, Erythromycin, Clarithromycin Laryngitis 주증상 : 지속적, 불분명한변성 (hoarseness, weakness) 종류 : Acute laryngotracheobronchitis (Croup) Acute epiglottitis (supraglottitis) Croup Acute infection of the lower air passages < age 3 원인 : parainfluenza virus, diphtheria, M. tuberculosis, fungi 특징 : 개짖는기침, 흡기성천명 Lateral neck X-ray : epiglottic edema *Steeple sign 치료 : 심하면 hospitalization, humidification, oxygenation 18 개원의와함께하는임상강좌 2011

. 31 ~ 2011. 1. 8) Rhinovirus infections 원인 single stranded RNA genome, 100 serotypes, 1 subtype 인체의 nasal passage temp.

5 이미숙 : 흔한상기도바이러스질환들 상기도감염에흔한바이러스 Upper Respiratory Viral Infections in Korea 최근 10 주간급성호흡기감염증원인바이러스별발생현황 ( ~ ) Rhinovirus infections 원인 single stranded RNA genome, 100 serotypes, 1 subtype 인체의 nasal passage temp C에적응 역학 감기증상의성인가운데 15-40% 전파 : respiratory droplets inhalation infected secretion - direct or hand to hand contact, self-inoculation (conjunctiva, nasal mucosa) cold temperature, fatigue, sleep deprivation 과는무관 receptors : ICAM (intercellular adhesion molecule)-1 개원의와함께하는임상강좌

길라잡이 Rhinovirus infections 치료및예방 mild, self-limited disease, 치료는거의필요하지않음 analgesics, nasal decongestants, 육체활동제한, 휴식 anti-viral therapy : not recommended, not available interferon sprays prevention

6 길라잡이 Rhinovirus infections 치료및예방 mild, self-limited disease, 치료는거의필요하지않음 analgesics, nasal decongestants, 육체활동제한, 휴식 anti-viral therapy : not recommended, not available interferon sprays prevention by antibodies, vaccines :? barrier precaution : effective - hand washing - 손또는결막등을보호대로보호하여 inoculation 방지 Influenza RNA, enveloped virus Viral family: Orthomyxoviridae Size: nm ( 직경 μm) Major 3 types Type A : 가장심한임상유형모든연령감염, 다양한숙주, 항원대변이및대유행 Type B : 사람만숙주, 주로소아감염, 치명률낮음 Type C : 무증상, 사람에서는문제안됨 Influenza 역학 매년평균 10-20% 가감염미국 : 매년 110,000명입원, 20,000명이사망 범세계적인유행 (pandemic): A형 (> 90%) 대유행은온대에서 2-4년마다겨울철에출현, 1개월이내지속 감염자는 1-2주동안바이러스분비 가장높은유병률 : 어린이, 가장높은치명률 : 노인 면역저하환자, 심질환, 만성폐질환자, 당뇨병, 만성신질환 예방 Vaccine (formalin 불활성화백신 ) : 2 A virus + 1 B virus 매년 10-11월접종, 70% 에서예방가능 20 개원의와함께하는임상강좌 2011

이미숙 : 흔한상기도바이러스질환들 Influenza Air borne transmission Incubation 1 to 3 days Abrupt onset of symptoms Symptoms fever, feverishness, chills body aches and pains malaise, tiredness respiratory symptoms ;

7 이미숙 : 흔한상기도바이러스질환들 Influenza Air borne transmission Incubation 1 to 3 days Abrupt onset of symptoms Symptoms fever, feverishness, chills body aches and pains malaise, tiredness respiratory symptoms ; dry cough, sore throat Influenza vs. the Common cold Presentation Influenza Common cold Clinical spectrum Systemic Local Nose & Throat Speed of onset Abrupt Gradual Fever Usually high Usually mild Presentation Chills, myalgia, malaise Cough, sore throat Degree of exhaustion Marked Mild Sneezing, sore throat Nasal congestion Course of illness Unwell for 1-2 weeks, chest problems common. Malaise Rapid recovery can last for longer Complication Severe, e.g. pneumonia Mild Occurrence Seasonal, six weeks autumn/winter All year round Influenza 임상적진단 : Influenza like illness (ILI) 체온 37.7 C 호흡기증상 ( 기침, 인두통, 부비동증상 ) 전신증상 ( 두통, 피로, 전신쇠약, 근육통, 발한, 오한등 ) Symptom Students with Colds (%) Students with Flu (%) Fever Chills Muscle aches Cough Headache Sore throat Runny nose 개원의와함께하는임상강좌

길라잡이 Types of influenza testing Influenza virus 신속항원검사 (POCT, RAT) * 국내제품민감도 91.8% 특이도 98.

specificity : 90~95% * false positive : occur when influenza is uncommon in community RAT : Negative for

result does not exclude influenza - based on a patient s clinical presentation, empiric antiviral treatment

8 길라잡이 Types of influenza testing Influenza virus 신속항원검사 (POCT, RAT) * 국내제품민감도 91.8% 특이도 98.9% 신속항원검사해석 RAT : Positive for Influenza type A - can not distinguish influenza A virus subtypes - specificity : 90~95% * false positive : occur when influenza is uncommon in community RAT : Negative for Influenza A and B - Sensitivity : novel influenza A (10-70%), seasonal influenza A (20-100%) - negative result does not exclude influenza - based on a patient s clinical presentation, empiric antiviral treatment should be considered, if indicated If more conclusive testing is desired, follow-up confirmatory testing with RT-PCR is warranted 22 개원의와함께하는임상강좌 2011

9 이미숙 : 흔한상기도바이러스질환들 인플루엔자의치료 항바이러스제 종류 : 타미플루 (tamiflu), 리렌자 (relenza) 페라미플루 (peramivir) 효과 : 계절인플루엔자 -30% (1.5 일 ) 의증상기간단축 증상중증도 40% 감소 폐렴, 급성호흡곤란등의중증합병증예방 증상후 12 시간내투여가최적, 48 시간내치료권장 증상치료 해열제 ( 아세트아미노펜등 ) : 아스피린금기 항히스타민제 진해제, 거담제등 휴식, 충분한수분및영양섭취 Antiviral agents 개원의와함께하는임상강좌

길라잡이 Coronavirus infections 원인 : single stranded RNA virus B814, 229E, OC43 역학 : limited studies common colds 의 10-20% rhinovirus 가주춤하는늦가을, 겨울, 이른봄매 2 년에 OC43, 2-4 년마다 229E 발생 임상증상 : 연구필요 Respiratory

(fusion) protein ; 침범과관련 역학 소아 : 늦가을, 겨울, 봄 ( 여름에는거의없음 ) 성인 : coryza-like syndrome 노인 : severe pneumonitis 가족간전파가잘됨유행시소아과직원 25-50% 감염 *nosocomial pathogen 가능 재감염시경한임상경과 immunity : 불완전하고단기간지속 nasal

10 길라잡이 Coronavirus infections 원인 : single stranded RNA virus B814, 229E, OC43 역학 : limited studies common colds 의 10-20% rhinovirus 가주춤하는늦가을, 겨울, 이른봄매 2 년에 OC43, 2-4 년마다 229E 발생 임상증상 : 연구필요 Respiratory tract, GI tract, CNS, kidney, liver 침범잠복기는 3 일이며질환은 6-7 일지속신병의폐렴, 만성기관지염의악화가능 치료 : common colds 과대동소이 Respiratory syncytial virus infections 원인 single stranded RNA virus envelope G protein ; 부착, F (fusion) protein ; 침범과관련 역학 소아 : 늦가을, 겨울, 봄 ( 여름에는거의없음 ) 성인 : coryza-like syndrome 노인 : severe pneumonitis 가족간전파가잘됨유행시소아과직원 25-50% 감염 *nosocomial pathogen 가능 재감염시경한임상경과 immunity : 불완전하고단기간지속 nasal IgA neutralizing Ab가 serum Ab보다감염예방 RSV infections 임상증상및진단 성인 : 잠복기 (4-6 일 ), 콧물, 인두통, 기침 소아 : 증상심함. 미열, 전신증상, 기침, 천명 pneumonia, bronchiolitis, tracheobronchitis 1-2주지나면회복 chest X-ray : peribronchial thickening, diffuse interstitial infiltrates, consolidation congenital cardiac disease, bronchopulmonary dysplasia, immunosuppression 때증상이심해짐 진단 : 유행시의심 객담, 인두도말, 비인두도말이나세척액에서 virus culture 후 immunofluorescence, ELISA로동정 24 개원의와함께하는임상강좌 2011

이미숙 : 흔한상기도바이러스질환들 RSV infections 치료및예방 대증적치료 - hydration, suctioning of secretion, humidifier, oxygenation, antibronchospastic agents aerosolized ribavirin vaccine - inactivated whole-virus vaccines

11 이미숙 : 흔한상기도바이러스질환들 RSV infections 치료및예방 대증적치료 - hydration, suctioning of secretion, humidifier, oxygenation, antibronchospastic agents aerosolized ribavirin vaccine - inactivated whole-virus vaccines : ineffective - immunization with purified F and G surface glycoproteins - live attenuated virus vaccines barrier methods : 손, 결막보호 Parainfluenza virus infections 원인 enveloped, single-stranded RNA, 4 serotypes envelope protein : hemagglutinin, neuraminidase 활성 fusion activity 임상증상 성인 : 감기증상, hoarseness, cough 소아 : coryza, sore throat, hoarseness, cough (croup) 심하면 croup, fever, worsening coryza chest X-ray ; air trapping, interstitial infiltrates Parainfluenza virus infections 역학 빈도 : 성인호흡기질환의 5% 정도소아는 %, 소아 LRTIs에서 RSV 다음의원인 Type 1, 2 : 홀수년가을에유행 * Type 3 : 매년봄 Type 1 : croup Type 3 : 구분과역할 불분명 Type 2 : bronchiolitis, pneumonia Type 4 : mild illness 전파경로 : 감염된호흡기분비물, personal contact 잠복기 : 3-6일 Type 1, 2에대한immunity : 호흡기의 local IgA에의해발현 수동적 serum neutralizing antibody : Type 1, 2에대해효과 (+), 차이있지만 Type 3 역시예방가능 개원의와함께하는임상강좌

길라잡이 Parainfluenza virus infections 진단 hemagglutination, cytopathic effect, IF of viral antigens 혈청학적진단 : HI, CF, or neutralization tests 감별진단 : acute epiglottitis by H.

12 길라잡이 Parainfluenza virus infections 진단 hemagglutination, cytopathic effect, IF of viral antigens 혈청학적진단 : HI, CF, or neutralization tests 감별진단 : acute epiglottitis by H. influenzae type b (bacterial croup), Influenza A virus 치료및예방 대증적요법 : bed rest, moist air no specific antiviral therapy : ribavirin in vitro? no effective vaccines Adenovirus infections 원인 complex DNA virus : replication cycle - lytic infection, latent infection (lymphoid cells) some : oncogenic transformation, but not in humans 역학 성인호흡기질환의 2%, 소아 3-5% adenovirus serotypes 4, 7 (3, 14, 21) - 겨울, 봄철신병들의 acute respiratory diseases 전파 : aerosolized virus inhalation, conjunctival sacs, fecal-oral route type-specific antibody : 동일혈청형에대한예방능력 Respiratory infections caused by Adenoviruses Illness Comments Most common types Tonsillitis or pharyngitis Common; epidemics 1, 2, 3, 5, 7 Pharyngoconjunctival fever Common; epidemics 2, 3, 4, 5, 7,14 Common cold Rare; sporadic 1, 2, 3, 5, 7 Pneumonia Common; epidemics 3, 7, 21 Acute respiratory diseases Epidemics in military recruits 4, 7 Laryngotracheitis (croup) Rare; sporadic 1, 2, 3, 5, 6, 7 Bronchiolitis Rare complication 3, 7, 21 Bronchiolitis obliterans Very rare; late complication 7, 개원의와함께하는임상강좌 2011

13 이미숙 : 흔한상기도바이러스질환들 Adenovirus infections 임상증상 성인 : acute respiratory diseases (type 4, 7) sore throat, fever, cough, coryza, regional lymph node pharyngeal edema, injection, tonsilar enlargement 소아 : URI, pharyngoconjunctival fever, febrile pharyngitis, acute diarrheal illness - adenovirus type 40, 41 Hemorrhagic cystitis : adenovirus type 11, 21 Epidemic keratoconjunctivitis : type 8, 19, 37 Pneumonia in immunosuppressed patients : AIDS Adenovirus infections 진단 epidemiologic setting : ARD 감별진단 확진 : culture, virus 분리동정, PCR adenovirus type 40, 41 ( 소아의설사질환 ) tissue culture cell 필요, direct ELISA of stool serum Ab 상승 : CF, neutralization test, ELISA, radioimmunoassays, HI tests 치료와예방 대증요법 live vaccines (adenovirus serotypes 4, 7) : for military recruits Summary of features of respiratory virus infection Rinoviruses Incubation period 1-3 days Modes of transmission Secretion on hands > 100 serotypes Large droplets Main diseases Colds, URTIs, Sinusitis, otitis media, wheeze, pneumonia *infect nasal mucosa or conjunctiva Coronaviruses 2-4 days Large droplets Colds, URTIs, wheeze, 2 main serotypes Aerosols (small droplets) pneumonia Adenoviruses 3-7 days Small droplets See previous slide > 40 serotypes Large droplets *asymptomatic nose, pharynx, or conjunctival shedding can persist for months 개원의와함께하는임상강좌

14 길라잡이 Summary of features of respiratory virus infection Incubation period Parainfluenza 1-4 days Large droplets Modes of Main diseases transmission Type 1 : croup-like illness autumn, every 2 nd year Secretion on hands Type 2 : bronchiolitis, pneumonia autumn, every 1-2 yrs Type 3 :? spring, every year Type 4 : mild illness, cold, URTIs sporadic, reinfection common Influenza 1-6 days Small droplets Influenza, croup, pneumonia Type A, B, C Large droplets Type A can cause pandemics Secretion on hands 28 개원의와함께하는임상강좌 2011

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°Ç°�°úÁúº´6-2È£ K O R E A C E N T E R S F O R D I S E A S E C O N T R O L & P R E V E N T I O N PHWR Vol. 6 No. 2 www.cdc.go.kr 2013 1 11 6 2 ISSN:2005-811X Flavivirus surveillance in mosquitoes collected from the quarantine