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전공의강의 예방접종바로알기 충북대학교의과대학 가정의학교실강희택

Contents 예방접종의일반지침 Vaccine Influenza Virus Hepatitis B Virus Hepatitis A Virus S. Pneumoniae Diphtheria/Tetanus/Pertussis Varicella Zoster Virus Neisseria Meningitidis (Meningococcus) (Pneumococcus) Human Papilloma Virus

예방접종의일반지침 추천되는접종간격이내, 또는추천되는최소연령이전에백신을접종해서는안된다. 여러번의접종이필요한백신의경우접종간격이미루어진다하여예방효과가감소하지는않는다. 하지만최소접종간격이내에접종하게되면항체생성이저하되어예방효과가감소할수있다. 불활성화백신은항체함유제제투여에의해영향을받지않지만, 약독화생백신은항체함유제제에의해영향을받을수있다. 모든백신은다른백신과동시접종이가능하다.

예방접종의일반지침 표준접종시기월 ( 月 ) 단위일경우 해당개월의마지막날까지로정의예 ) 생후 2 개월 : 3 개월이되는날하루전까지 표준접종시기년 ( 年 ) 단위일경우 해당년의마지막날까지로정의예 ) 만 6 세 : 만 7 세가되는날하루전까지 최소접종간격 1 주를 7 일, 1 개월은다음달같은날짜의하루전까지

예방접종의일반지침 최소연령 충분한면역반응을위해최소연령을지켜야함 만약최소연령을지키지않고 MMR 백신등을접종한경우접종하지않은것으로간주 최소간격 접종간격이표준접종간격보다길어져도면역효과에는영향을미치지않음 최소접종간격보다앞당겨접종하면면역형성이잘되지않기때문에최소접종간격을지켜야함 최소접종간격을지키지못한경우, 잘못된접종 으로부터최소접종간격계산하여다시접종 대한소아과학회예방접종지침서 2008 p15

예방접종의일반지침 Q: 접종간격이길어진경우다시접종해야하나? A: 다시접종을시작하거나추가로접종할필요없음 Q: 이전접종력을모를경우는? A: 감염의가능성이있는것으로간주하여접종 ( 항체가있어도특별 히이상반응이증가하지않음 )

생백신 vs 사백신 Live attenuated vaccines 면역반응 실험실에서반복배양하여인위적으로약화시킨백신 체내에서증식, but 질병유발못함 실제질병에걸렸을때얻는능동면역과유사한면역반응 소량으로면역유도가능부작용 드물게백신주가돌연변이를일으켜독성을회복할수있음 면역저하자에게질병유발가능 면역성유지위해냉장보관필요 Inactivated vaccines 병원체를배양시킨후열이나화학약품으로불활성화시킨백신 면역을얻기위해생백신에비해서많은양의항원필요, 여러번접종필요 독성회복, 질병유발을하지않음 인체내항체의영향을받지않음 면역증강제등에의해발열, 쇼크및뇌병증등이발생할수있음

생백신 vs 사백신 약독화생백신 BCG MMR 일본뇌염생백신수두인플루엔자생백신로타바이러스경구용장티푸스경구용폴리오 불활성화백신 A, B형간염 DTaP DTaP-IPV Td/Tdap Hib 폐렴구균인플루엔자사백신일본뇌염사백신신증후군출혈열주사용폴리오주사용장티푸스인유두종바이러스

동시접종과접종간격예방접종의일반지침 1) 서로다른백신의동시접종 - 일반적으로동시에접종하지못하는백신은없음 - 단, 콜레라백신과황열백신은동시에접종해서는안됨 - 서로다른백신을동시접종하여도항체생성률이떨어지거나이상반응이증가하지않음 - 단, 콜레라백신과황열백신을동시에접종하면두백신에대한항체생성이모두감소 (3주이상의간격을두고접종 ) - 두가지이상의백신을동시에접종할때에한주사기에혼합해서는안됨 - 서로다른주사기를이용해서다른부위에주사

동시접종과접종간격예방접종의일반지침 2) 동시에접종하지않는서로다른백신의접종간격 - 생백신과생백신은 4주간격을두고접종 - 단, OPV와 MMR, OPV와경구용장티푸스백신간에는해당되지않음 * 서로다른백신을동시에접종하지않을때지켜야할원칙 (1) 비활성화백신과비활성화백신, 비활성화백신과생백신은최소접종간격은없음예외 ) 콜레라백신과황열백신은동시에접종해서는안됨 (2) 생백신과생백신은동시에접종하지않을경우, 4주이상의간격을두고접종

예방접종의일반지침 서로다른백신의동시접종 같은날 2 가지이상의백신을서로다른부위에접종 백신 불활성화백신 & 약독화생백신 동시접종가능여부 가능 2가지이상불활성화백신가능 2가지이상약독화생백신가능 ( 단같은날접종을못한경우 4주이상의간격으로접종 ) 생백신을접종할때 2 번째생백신이첫번째생백신접종후 4 주미만의간격으로접종 2 번째생백신접종시점에서최소 4 주이상의간격으로 2 번째생백신을재접종해야함 같은부위에접종시국소반응구별을위해적어도 2.5cm 이상의간격유지

동시접종과접종간격예방접종의일반지침 3) 동일백신의접종간격 - 여러번접종하여야하는동일백신의경우, 접종간격이표준접종간격보다멀어져도면역효과에는큰영향을미치지않음 - 표준접종간격보다좁혀서접종하면면역형성이잘되지않음 ( 최소접종간격유지 ) 4) 면역글로불린투여와백신의접종간격 - 비활성화백신은혈액내항체에영향을받지않으므로, 비활성화백신과면역글로불린을동시에투여 ( 예 :B형간염백신과 HBIG) 하여도상관없음 - 생백신은혈액내항체와간섭을일으켜동시에접종하여서는안됨 ( 면역글로불린과생백신은일정한간격을두어야함 ) - 생백신 ( 홍역또는 MMR) 을먼저접종한경우 : 면역글로불린은최소 2주뒤에투여, 면역글로불린을먼저투여한경우 : 홍역또는 MMR 백신의접종은 3~11개월후투여

예방접종의일반지침 항체와백신의상호작용 혈중에특정백신항원에대한항체가존재할경우 백신접종시면역반응이저하되거나전혀없을수있음 간섭 (Interference) 백신형태 혈중항체양

예방접종의일반지침 항체와백신의상호작용 항체함유제제투여시기와상관없이접종가능 항체함유제제 간섭 불활성화백신 약독화생백신 생백신을먼저접종한경우최소 2 주가경과한후항체함유제제투여 생백신접종 2 주이내항체함유제제를투여한경우백신에대한항체 생성여부검사또는재접종필요

예방접종의일반지침 항체와백신의상호작용 항체함유제제가 MMR 또는수두백신보다먼저투여되었을경우 항체에대한간섭의가능성을줄이기위해 항체가소실될때까지백신투여를미룰필요가있음 항체함유제제와생백신과의접종간격은제제에포함된항체의농도에따라다르나 최소 3 개월, 최대 11 개월까지길어질수있음

예방접종의일반지침 항체함유제제투여후 MMR/ 수두백신접종 종류및적응증 투여량 간격 ( 개월 ) 파상풍예방 (TIG) 250 units(10 mg IgG/kg)/IM 3 A형간염 (IG) 접촉자발병예방해외여행 0.02 ml/kg(3.3 mg IgG/kg)/IM 0.06 ml/kg(10 mg IgG/kg)/IM 3 3 B형간염예방 (HBIG) 0.06 ml(10 mg IgG/kg)/IM 3 공수병예방 (HRIG) 20 IU(22 mg IgG/kg/IM) 4 수두예방 (VZIG) 125 units/10 kg(60~200 mg IgG/kg)/IM 5 (maximum 625 units) 홍역예방 (IG) 정상인면역결핍자 0.25 ml/kg(40 mg IgG/kg)/IM 0.50 ml/kg(80 mg IgG/kg)/IM 5 6 수혈 세척적혈구 (washed RBCs) 10 ml/kg(negligible IgG/kg)/IV adenine-saline이추가된적혈구 10 ml/kg(10 mg IgG/kg)/IV 농축적혈구 10 ml/kg(60 mg IgG/kg)/IV 전혈 10 ml/kg(80~100 mg IgG/kg)/IV 혈장, 혈소판제제 10 ml/kg(160 mg IgG/kg)/IV 대상포진 / 황열백신 / 경구용또는비강투여약독화생백신 항체함유제제와접종간격에제한을받지않음 0 3 6 6 7

예방접종의일반지침 예방접종의일반지침 교차접종 교차접종가능 일반적으로대부분의백신은백신제조사와관계없이교차접종가능 교차접종불가 교차접종후방어면역획득과이상반응에문제가없는것으로확인되어교차접종이가능한백신 Hib, HBV, HAV 효율성, 독성및안전성에대한표준화가이루어지지않았으며교차접종에대한연구결과가없어교차접종이권장되지않는백신 DTaP, DTaP-IPV 로타바이러스 1가 ( 로타릭스 )/5가( 로타렉 ) HPV 2가 ( 서바릭스 )/4가/9가( 가다실 ) 폐렴구균 10가 ( 신플로릭스 )/13가( 프리베나 13주 ) 일본뇌염약독화생백신 / 불활성화백신 이전제조사의백신이없거나모를경우에는접종을연기하는것보다 교차접종하는것이권장된다.

예방접종의일반지침 금기사항 백신을접종받는사람에게심각한백신작용이발생할가능성 을증가시키는경우 일반적으로금기사항이있는경우백신접종을하면안됨 영구적인금기사항 생백신의일시적인금기사항 백신성분또는이전백신접종후에심각한알레르기반응 ( 아나필락시스 ) 이발생한경우 백일해백신투여 7일이내에원인을알수없는뇌증이발생한경우 임신 면역저하

예방접종의일반지침 백신접종이심각한백신반응의발생가능성을높이거나효과를 주의사항 저하시킬수있는상태 일반적으로주의사항에해당하는상황에서는접종을하지않지만, 백신접종으로질병을예방하여얻어지는편익이이상반응의위험을능가하는경우백신접종을고려할수있음 접종 48 시간이내에 40 C 이상발열 접종 48 시간이내에발생한탈진또는쇼크와 같은상태 접종 48 시간이내에발생한 3 시간이상달래 지지않고지속되는울음 발열여부와관계없이접종 3 일이내에발생 한경련 소아기백일해함유백신접종의영구적인주의사항 일시적인주의사항 중등도또는중증의급성기질환 ( 모든백신에해당 ) 최근에항체함유제제를투여받은경우생백신접종시주의 ( 대상포진, 경구용또는비강투여약독화생백신예외 )

예방접종의일반지침 예방접종주의및금기사항 피접종자의상태에따른금기및주의사항 피접종자상태약독화생백신불활성화백신 백신성분에대한심한알레르기반응 접종금기 접종금기 심한질병 주의해서접종 주의해서접종 임신 접종금기 적응증이되면접종 면역결핍 접종금기 적응증이되면접종 최근혈액제제투여 주의해서접종 적응증이되면접종 뇌증 - 접종금기

대한민국성인예방접종

해외여행자에게권장하는예방접종 http://wwwnc.cdc.gov/travel/destinations/list/

Influenza virus

Influenza virus A highly contagious respiratory disease in humans Considerable morbidity and mortality Seasonal influenza Global (WHO fact sheet, 2014) Estimated to affect 5 10% in adults and 20-30% in children, annually [Mortality] > 250,000~500,000/yr (elderly: > 90% of total) Occasional global pandemics Can infect 20 40% of the population in a single year. (Philos Trans R Soc Lond B Biol Sci. 2001) 2009 H1N1 pandemic: highest attack rates among children and young adults. Vaccine (2016) 34:1617-22

Influenza virus Antigenic drift As population immunity builds up against circulating influenza viruses, these viruses evolve to escape the immune response rendering individuals susceptible to re-infection. Antigenic shift Abrupt and major change in the influenza A viruses, resulting in new hemagglutinin and/or neuraminidase proteins as a new influenza A subtype. Occurred in 2009 when an H1N1 virus with a new combination of genes emerged to infect people and quickly spread, causing a pandemic. Vaccine (2016) 34:1617-22

Type A Influenza virus The greatest genetic diversity (18 HA subtypes, 11 NA subtypes) Infects the widest range of host species (human/avian/swine) Causes severe disease in human, including the great pandemics Subtypes found in people: H1N1, H3N2 1994-2005: H3N2 (90.6%), H1N1 (8%), H1N2 (1.1%) 2009-2010 (2009 H1N1 pandemic): H1N1 ( 98% in US) Type B Associated with seasonal epidemics but not with pandemics No subtypes, but 2 lineages (B/Yamagata, B/Victoria) Divergence in the HA1 domain of HA protein Nat Rev Genet (2007) 8:196

Influenza vaccines Influenza virus Frequent mismatch for influenza B virus strains Six mismatch for ten seasons between 2000 and 2010 Low cross-reactivity against mismatched lineages Influenza strain circulation among cases (US,2000-2013) Influenza Other Respir Viruses (2015) 9:39-46

Influenza virus Vaccine efficacy 불활성화백신 건강한성인 : 백신주와유행주의항원성이맞을때 70-90% 노인 : 건강한성인에비해예방효과가낮지만, 입원예방 50-60%, 사망예방 80% 정도효과있음 항체지속효과는 1년미만 약독화생백신 생후 60-84개월건강한소아 : 인플루엔자예방 87%, 열성중이염 27% 감소 18-49세건강한성인 : 열성질환 20%, 열성상기도감염 24%, 열성질환으로인한의료기관방문일 18-37% 감소

Influenza virus 구분 일반권장 우선권장 대상 모든성인연령별 50세이상성인질환별만성폐질환자, 만성심장질환자, 만성간질환자, 만성신질환자, 신경 / 근육질환, 혈액 / 종양질환, 당뇨병환자, 면역저하자직업및상황별의료인, 사스 / 조류인플루엔자대응기관종사자닭 / 오리 / 돼지농장및관련업계종사자만성질환으로사회복지시설등집단시설에서치료, 요양, 수용중인사람임신부또는인플루엔자유행시기에임신예정인가임기여성만성질환자, 임신부또는 65세이상의노인과함께거주하는자 6개월미만의영아를돌보는자

Hepatitis B virus

Hepatitis B virus Genome Circular DNA Transmission Percutaneous by blood Mucosal by sexual contact HBV infection Increased risk for cirrhosis and hepatocellular carcinoma Suggested that HBV may increase the risk of pancreatic cancer

Hepatitis B virus Prevalence of HBV infection in Korea Overall prevalence of HBsAg has decreased from 4.6% (1998) to 2.9% (2008), and has been maintained at 2.9% since 2013 Prevalence of HBsAg by age and sex group from the 2014 KNHANES A nationwide seroprevalence of HBsAg in 2009 From 18 th annual meeting of the Korean Association for the study of the Liver Cho EJ et al., Current status and strategies for hepatitis B control in Korea Clin Mol Hepatol. 2017;23:205-11

Hepatitis B virus Persons recommended to receive HBV vaccination All infants Unvaccinated children aged < 19 years Persons at risk for infection by sexual exposure Persons at risk for infection by percutaneous or mucosal exposure to blood https://www.cdc.gov/vaccines

Hepatitis B virus Persons recommended to receive HBV vaccination Persons at risk for infection by sexual exposure Sex partners of HBsAg-positive persons Sexually active persons with more than one sex partner during the previous 6 months Men who have sex with men https://www.cdc.gov/vaccines

Hepatitis B virus Persons recommended to receive HBV vaccination Persons at risk for infection by percutaneous or mucosal exposure to blood Current or recent injection-drug users Household contacts of HBsAg-positive persons Residents and staff of facilities for developmentally disabled persons Hemodialysis patients and predialysis, peritoneal dialysis, and home dialysis patients Persons with diabetes aged 19-59 years; persons with diabetes aged 60 years at the discretion of the treating clinician https://www.cdc.gov/vaccines

Hepatitis B virus Persons recommended to receive HBV vaccination Others International travelers to countries with high or intermediate levels of endemic HBV infection (HBsAg prevalence 2%) Persons with HCV infection Persons with chronic liver disease (L/C, fatty liver disease, alcoholic liver disease, autoimmune heaptitis, ALT/AST levels 2 upper limit of normal) Persons with HIV infection All other persons seeking protection from HBV infection https://www.cdc.gov/vaccines

Hepatitis B virus Persons recommended to receive serologic testing prior to vaccination Household, sexual, or needle contacts of HBsAg-positive persons HIV-positive persons Persons with elevated ALT/AST of unknown etiology Hemodialysis patients Men who have sex with men Past or current persons who inject drugs Persons born in countries of high and intermediate HBV endemicity Persons needing immunosuppressive therapy, including chemotherapy, immunosuppression related to organ transplantation, and immunosuppression for rheumatologic or gastroenterologic disorders Donors of blood, plasma, organ, tissues, or semen https://www.cdc.gov/vaccines

Hepatitis B virus Vaccine efficacy A positive immune response to develop anti-hbsab 10 miu/ml Overall seroconversion rate: about 95% in healthy adults Unnecessary to check anti-hbsab after completing vaccination https://www.cdc.gov/vaccines

Hepatitis B virus Duration of protection Protection has been estimated to persist for up to 30 years Protection from clinical disease is felt to occur even in the setting of declining or undetectable anti-hbs levels, due to the priming of memory cells Uptodate

Hepatitis B virus Management of nonresponders Patients with underlying medical conditions such as chronic kidney disease and immunosuppressed states Response rate 50-60%, 70% by doubling the dose of vaccine Individuals in whom the lack of response appears to be genetically determined HLA haplotype-b8, SC01, DR3 etc Individuals who failed to respond as a result of technical errors including intra-gluteal injection or inappropriate storage conditions Uptodate

Hepatitis B virus Management of nonresponders Administer one or more additional doses An adequate antibody response is seen in 15-25 % after one additional dose and in 50 % after three additional doses Individuals who fails to respond after three additional doses of vaccine are unlikely to benefit from further vaccination Further evaluation of management of nonresponders Vaccination with a double dose of the combined HAV/HBV Uptodate

Hepatitis B virus Revaccination Revaccination is not generally recommended for person with a normal immune status who were vaccinated as infants, children, adolescents, or adults Revaccination when anti-hbsab is < 10 miu/ml is recommended for the following persons Infants born to HBsAg-(+) mother: single dose revaccination 1-2 months F/U Health care providers Hemodialysis patients Other immunocompromised persons https://www.cdc.gov/vaccines

Hepatitis B virus 구분 일반권장 연령별 대상 과거감염력또는예방접종력이없는모든성인 없음 질환별만성간질환자, 혈액투석환자, HIV 감염인, 혈액제제를자주투여받는환자 우선권장 직업및상황별 HBsAg과 anti-hbs 검사결과가모두음성인성인중 B형간염바이러스에노출될위험이높은환경에있는사람 ( 의료기관종사자, 수용시설의수용자및근무자, 단체생활을하는지체장애인과이들을보호하는직원, B형간염바이러스보유자의가족, 주사용약물중독자, 성매개질환의노출위험이큰집단 ) * 감염위험이높은의료기관종사자, 혈액투석환자, HIV 감염인, B형간염바이러스보유자의가족등은예방접종후항체검사를시행하여음성이면재접종

Hepatitis A virus

Hepatitis A virus 원인과역학 HAV 감염에의하여발생하는급성간염 전파경로 : 분변-경구경로, 간혹성접촉, 수혈을통해전파 역학 : 위생및생활환경개선으로소아, 젊은성인층에서 A형간염항체의보유율감소및성인연령층에서현성 A형간염발생위험증가 임상적특징 잠복기 : 평균 28일의잠복기후에임상증상발현 발현양상 : 6세미만의소아에서는약 70% 에서무증상이나 6세이상의소아나성인에서는간염의증상이대부분동반 임상증상 : 고열, 권태감, 식욕부진, 오심, 복통, 진한소변, 황달이급격히발생

A 형간염 Hepatitis A virus A 형간염발생빈도가높은지역 ( 저개발국가 ) 1) 어린이때에대부분감염 2) 증상이없이항체를획득하는경우가대부분, 대부분인구가항체를보유 A 형간염발생빈도가중간정도인지역 1) 생활환경이개선되어비교적저개발국에비해높은연령대에서감염 2) 청소년, 성인연령에서항체를보유하지않은감염위험군이많음 3) 따라서현성 A형간염발생률이높고, 음식 / 식수에의해대규모 A형간염발생이많음 A 형간염발생빈도가낮은지역 ( 선진국 ) 선진국에서는 A 형간염발생빈도가매우낮아전체인구에서낮은항체보유율을보임

A 형간염 Hepatitis A virus Seroepidemiology of hepatitis A in Korea: changes over the Past 30 years Lee H et al. JKMS 2011;26:791-796

A형간염 Hepatitis A virus 백신의효과 - A형간염백신은 2회접종 - 정상성인에서 1회접종시 94~100% 의항체양성률, 2회접종후 100% 에가까운항체양성률과 95% 이상의간염예방효과 - 항체형성에 4주정도의시간이걸림 A형간염에이미노출된경우, 백신보다는면역글로블린이효과적 - 40-50대이후부터는항체검사를하고음성일때접종하는것이비용-효과적

Hepatitis A virus 구분 일반권장 우선권장 연령별 질환별 직업및상황별 대상 없음면역력이없는 20-39세성인만성간질환자혈액제제를자주투여받는혈우병환자등군인, 외식업종사자, 보육시설종사자, A형간염바이러스에노출될위험이있는의료인및실험실종사자 A형간염유행지역여행자또는근무예정자, 남성동성애자, 약물중독자, 최근 2주이내에 A형간염환자와의접촉자

S. Pneumoniae (Pneumococcus)

S. Pneumoniae (Pneumococcus) Microbiology gram-positive Surface polysaccharide capsule > 90 different serotypes: 6, 14, 18, 19, and 23 are most prevalent Pathogenesis A major cause of infection in children and adults Asymptomatic nasopharyngeal carriage, otitis media, pneumonia, sepsis, meningitis etc The most common cause of community-acquired pneumonia

S. Pneumoniae (Pneumococcus) Pneumococcal pneumonia The most cause of community-acquired pneumonia > 75% of pneumonia in the pre-antibiotic era 5-15% of pneumonia in US but higher proportion in other countries The decline in S. pneumoniae as a cause of CAP in US may be partly contributed by pneumococcal vaccines Invasive pneumococcal infections Associated diseases: bacteremia, sepsis, meningitis, endocarditis, septic arthritis, osteomyelitis, etc Overall mortality rates for patients with pneumococcal bacteremia: 15-20% in the antibiotic era Highest incidence: < 2years of age, immunocompromized conditions, >65 years of age

S. Pneumoniae (Pneumococcus)

S. Pneumoniae (Pneumococcus) Pneumococcal polysaccharide vaccine (PPSV) Capsular polysaccharides from the 23 most commonly infecting serotypes Lower efficacy in immunocompromised hosts against invasive and noninvasive pneumococcal disease OR for invasive pneumococcal disease (IPD) 0.26 (0.14-0.45) & non-ipd 0.46 (0.25-0.84) OR for all-cause pneumonia 0.54 (0.43-0.67) PPSV did not reduce all-cause mortality Pneumococcal conjugate vaccine (PCV) PCV stimulates mucosal antibody suppress nasal carriage of S. pneumoniae In 2013, PCV 13 stimulates antibody to serotypes that caused 28-42% of invasive pneumococcal disease in US PCV has reduced the usual reservoir of pneumococcal carriage, thus can induce herd immunity Vaccine efficacy (VE) for pneumonia 46% and for IPD 75% against vaccinetype infection

S. Pneumoniae (Pneumococcus) Changes in invasive pneumococcal disease (IPD) Children aged <5 years Adults aged 65 years Pilishvili T et al., Sustained reductions in invasive pneumococcal disease in the era of conjugate vaccine. J Infect Dis 2010;201:32

S. Pneumoniae (Pneumococcus)

S. Pneumoniae (Pneumococcus) Summary plot of meta-analyses of clinical trials of PPSV RR for presumptive pneumonia 1.20 (0.75-1.92) RR for all-cause pneumonia 1.19 (0.95-1.49) Brown circles show summary estimates from trials of higher methodologic quality Huss A et al., Efficacy of pneumococcal vaccination in adults: a meta-analysis CMAJ 2009;180:48-58

S. Pneumoniae (Pneumococcus) Community-Acquired Pneumonia Immunization Trial in Adults (CAPITA) for PCV13 Participants: 65 years, no previous pneumococcal vaccination, immunocompetent Mean duration: 3.94 years End point and analysis Infection with vaccine-type strain Confirmed community-acquired pneumonia (CAP) PCV13 (N=42,240) Placebo (N=42,256) Vaccine efficacy Per protocol analysis 49 90 45.6 (21.8-62.5) Modified ITT analysis 66 106 37.7 (14.3-55.1) Invasive pneumococcal disease (IPD) Per protocol analysis 7 28 75.0 (41.4-90.8) Modified ITT analysis 8 33 75.8 (46.5-90.3) Bonten MJ et al., Polysaccharide conjugate vaccine against pneumococcal pneumonia in adults. N Engl J Med 2015; 372:1114-25

S. Pneumoniae (Pneumococcus) End point and analysis Infection with any pneumococcal strain Confirmed community-acquired pneumonia (CAP) PCV13 (N=42,240) Placebo (N=42,256) Vaccine efficacy Per protocol analysis 100 144 30.6 (9.8-46.7) Modified ITT analysis 135 174 22.4 (2.3-38.5) Invasive pneumococcal disease (IPD) Per protocol analysis 27 56 51.8 (22.4-70.7) Modified ITT analysis 34 66 48.5 (20.9-67.0) Community-acquired pneumonia Death Modified ITT analysis 747 787 5.1 (-5.1-14.2) From confirmed vaccine-type CAP or IPD 2 2 0 (-1279-92.8) From confirmed pneumococcal CAP or IPD 6 7 14.3 (-197.9-76.2) Bonten MJ et al., Polysaccharide conjugate vaccine against pneumococcal pneumonia in adults. N Engl J Med 2015; 372:1114-25

S. Pneumoniae (Pneumococcus) Recommendations for pneumococcal vaccination in immunocompromised adults Immunocompromising conditions Congenital or acquired immunodeficiency HIV infection Chronic renal failure, nephrotic syndrome Malignancy including leukemia, lymphoma, Hodgkin disease, multiple myeloma Solid organ transplantation Iatrogenic immunosuppression including long-term systemic glucocorticoids and radiation therapy Uptodate s recommendations differ from those of ACIP

S. Pneumoniae (Pneumococcus) 구분 일반권장 우선권장 대상 없음연령별 65세이상성인질환별만성심혈관질환자 ( 만성심부전, 심근병증포함, 고혈압은제외 ) 만성폐질환자 ( 만성폐쇄성폐질환, 폐기종, 천식포함 ) 만성간질환자 ( 간경변증포함 ), 당뇨환자뇌척수액누출환자, 기능적 / 해부학적무비증환자면역저하자 ( 선천성면역저하, HIV 감염, 만성신부전, 신증후군, 백혈병, 림프종, 호치킨병, 종양, 장기간코르티코스테로이드를포함한면역억제제투여, 치료방사선요법, 고형장기이식, 조혈모세포이식, 다발성골수종환자 ) 직업및상황별인공와우이식상태, 알코올중독자, 흡연자

Human Papilloma Virus (HPV)

1) 전세계적으로 HPV 감염의유병률은 9~13% 2) 우리나라 HPV 감염의유병률은 15~17% 로추정 3) HPV 감염이안된젊은여자에서추적관찰시, 24개월째 32%, 36개월에 43% 가감염 4) 감염시 60~75% 가 30개월내음전 (self-limiting) 이되고감염기간은 8개월정도 5) 일생동안성적으로활발한여성들이 HPV에감염될확률은 70% 이상

한국여성 (18-79 year) 10 명중 3 명이 HPV 에감염 49.9% HPV prevalence by age 36.0% 30.7% 32.2% 33.1% 36.6% 34.2% 18-79 세의한국여성약 6 만명 평균 3 명중한명이 HPV 에감염 18-29 30-39 40-49 50-59 60-69 70-79 Total 연령에따른 HPV 유병률 젊은여성층 (18~29 세 ): 49.9% N 4,297 16,907 20,661 13,552 3,612 1,746 60,775 Adapted from Lee EH et al. Lee EH et al., J Korean Med Sci 2012; 27:1091-1097.

>120 types identified 1 About 40 types infect the anogenital area 1 Low Risk HPV Types *1,2 HPV 6, 11 High Risk HPV Types 1,3 Oncogenic HPV 16, 18, 31, 33, 45, 52, 58 Though most infections clear on their own, persistence of certain HPV types can lead to cancer or other diseases. 1 1 CDC. Human papillomavirus. In: Hamborsky J et al, eds. Epidemiology and Prevention of Vaccine-Preventable Diseases. 13th ed. Washington, DC: Public Health Foundation; 2015:175-186. 2 CDC. Quadrivalent human papillomavirus vaccine. Recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR 2007;56(RR-2):1 2 3. Hopenhayn C et al. Prevalence of human papillomavirus types in invasive cervical cancers from seven US cancer registries prior to vaccine introduction. J Low Genit Tract Dis. 2014;18(2):182 189.

- Other Cancers; Attribution to HPV Cervical Cancer ~100% 70-75% Vaginal Cancer Vulvar Cancer 30% 90% Genital Warts Anal Cancer 85-90% Percentages represent cases attributable to all HPV types

Vaccine efficacy of HPV The FUTURE II Study group, NEJM 2007;356:1915-27

Immunogenicity of 2 doses of HPV vaccination in younger adolescents Dobson et al., JAMA 2013;309:1793-802

구분 일반권장 우선권장 연령별 질환별 직업및상황별 대상 11-12세에예방접종을완료하지못한 25-26세이하여성 -4가백신 : 26세이하여성 -2가백신 : 25세이하여성없음없음없음

Diphtheria/Tetanus/Pertussis

Diphtheria/Tetanus/Pertussis 후궁반장 파상풍 Clostridium tetani 에의한급성독소매개신경계질환 골격근의경련성연축과전신강직초래 피부와점막의상처를통해세균침입 디프테리아 Corynebacterium diphtheriae 에의한급성독소매개질환 호흡기계전파 인체의모든점막을침범, 침범부위의막형성이특징 혈관에흡수된독소는심근염, 신경염등을합병시킴 백일해 Bordetella pertussis 에의한 2 주이상의발작적기침이특징인급성감염성호흡기질환 호흡기비말을통해전파 발작적기침은주로 2-3 주간유지 (~10 주 ) 이차세균폐렴합병, 저산소증 ( 경련, 뇌증 ) 신생아파상풍

파상풍, 디프테리아, 백일해 Diphtheria/Tetanus/Pertussis 접종용량및방법 상박이나넓적다리앞옆쪽에 0.5ml 를근육주사 이상반응 가. 접종부위에동통, 홍반, 경화등국소반응이나타날수있음 나. 간혹아르투스양반응 (Arthus reaction) 이나타날수있음 다. 심한전신반응으로전신두드러기, 아나필락시스, 신경계합병증이나타날수있음 라. 매우드물게길랑 - 바레증후군이나말초신경병증이보고된바있다. 주의 - 금기사항 가. 백신의구성성분에중증알레르기가있는사람에게는투여불가 나. 중등도이상의급성질환을앓고있는사람이라면접종을늦추어야함 다. 국내제조사에서는임신부를금기로명기하고있으나근거가없음

Diphtheria/Tetanus/Pertussis 구분 일반권장 우선권장 연령별 질환별 직업및상황별 대상 모든성인없음없음생후 12개월미만신생아및영야등의백일해고위험군을진료하는의료인보육시설종사자신생아가있는가족내성인 ( 육아로신생아와접촉이잦은성인 ) 가임기여성상처를통한감염예방이필요한성인 (Td접종력과상처의청결도에따라결정 )

Varicella Zoster Virus (VZV)

Varicella Zoster Virus (VZV) Double-stranded DNA virus 적어도 5가지종류 Herpesviridae HSV-1 HSV-2 Varicella zoster virus Epstein-Barr virus Cytomegalovirus. 2-4 1. Steiner I, et al.. "The neurotropic herpes viruses: herpes simplex and varicella-zoster". Lancet Neurol 2007;6 (11): 1015 1028. 2. Chayavichitsilp P, et al., "Herpes simplex". Pediatr Rev 2009;30 (4): 119 29 3. Staras SA et al., Seroprevalence of cytomegalovirus infection in the United States, 1988 1994 Clin. Infect. Dis. 2006;43 (9): 1143 51.

Varicella Zoster Virus (VZV) Varicella Zoster Virus 는최초감염후재활성화 Dorsal root ganglion VZV moves along the sensory nerve to the dorsal root ganglion Spinal cord Varicella rash Skin VZV establishes latency in the dorsal root ganglion

Varicella Zoster Virus (VZV) Competent cell-mediated immunity VZV Memory T Cells 외인성수두노출 잠복바이러스의무증상재활성화 대상포진예방백신접종 Varicella infection Herpes zoster Protective CMI for herpes zoster Zoster threshold Age VZV-CMI : varicella zoster virus specific cell mediated immunity Arvin A. N Engl J Med. 2005;352:2266 2267.

Varicella Zoster Virus (VZV) Efficacy: 60 대이상노인에서예방효과 51.3% Efficacy (95% CI) 51.3% (44.2% 57.6%) 63.9% (55.5% 70.9%) 37.6% (25.0% 48.1%) 700 600 642 Placebo ZOSTAVAX TM 500 400 300 315 334 308 200 122 193 100 0 (n=19,247) (n=19,254) (n=10,356) (n=10,370) (n=8,891) (n=8,884) All Subjects Aged 60-69 Years Aged 70 Years SPS, Shingles Prevention Study; HZ, herpes zoster; PHN, postherpetic neuralgia; CI, confidence interval 1. Oxman MN et al. A Vaccine to Prevent Herpes Zoster and Postherpetic Neuralgia in Older Adults. N Engl J Med. 2005;352:2271 2284. Adapted from Oxman et al. 87

Varicella Zoster Virus (VZV) 대상포진백신의장기예방효과 접종후기간 Zoster PHN 1년 62.0 83.4 5년 43.1 73.8 7년 46.0 26.3 10년 14.1 44.2 4.7-11.6년 21.1 35.4 STPS: Short-Term Persistence Substudy, LTPS=Long-term Persistence Study PHN: Post-Herpetic Neuralgia Morrison V.A et al. Long-Term Persistence of Zoster Vaccine Efficacy Clin Infect Dis 2014; 60: 900-9

Varicella Zoster Virus (VZV) Possible Infection or transmission of herpes zoster caused by live attenuated vaccine-strain VZV Tseng HT et al., Clin Infect Dis 2014;58:1125-8

Varicella Zoster Virus (VZV) 구분 일반권장 우선권장 대상 없음 연령별 60세이상성인 질환별 없음 ( 특히, 대상포진과거력유무상관없음 ) 직업및상황별 없음

Neisseria Meningitidis (Meningococcus)

N. Meningitidis (Meningococcus) Etiology: Neisseria meningitidis One of the most devastating infections Mortality Approximately 10-15 % despite antibiotic treatment

N. Meningitidis (Meningococcus) Etiology: Neisseria meningitidis One of the most devastating infections Annual incidence of meningococcal disease 0.8-1.0 per 100,000 persons during 1993-1996 in USA 1.1 per 100,000 persons during 1993-1996 in Europe 2.2 per 100,000 persons in Korean soldiers Mortality Approximately 10-15 % despite antibiotic treatment Lee SO et al., Meningococcal disease in the republic of Korea Army: incidence and serogroups determined by PCR. JKMS 2003;18:163-6

N. Meningitidis (Meningococcus) Recommendations All individuals between 11 and 18 years of age Individual 10 years of age and individuals 19 years of age at increased risk for invasive meningococcal disease Travelers to regions in which meningococcal disease is hyperendemic or epidemic Military recruits Microbiologist exposed to Neisseria meningitidis Individuals with immunosuppression (functional or anatomical asplenia, complement deficiency, treated with eculizumab etc) Men who have sex with men with epidemiologic exposure to other MSM (NY, LA etc)

구분대상 일반권장 없음 우선권장 연령별 없음 질환별 보체결핍환자해부학적또는기능적무비증 직업및상황별 신입훈련병대학기숙사거주신입생아프리카수막염벨트여행자, 사우디아라비아메카순례자기타수막구균이유행하는지역여행자나체류자직업적으로수막구균에노출되는실험실요원소속집단또는거주지역에서유행시

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