嬰幼兒疫苗預防接種 最新趨勢 藥師:林育成

INTRODUCTION

age 法定疫苗 出生 24hr 內 B型肝炎免疫球蛋白 (一劑 ) 24hr 後 卡介苗(一劑 ) 3~5day 新型三合一(第一劑) B型肝炎疫苗(第一劑 ) 1 month B型肝炎疫苗(第二劑 ) 2 month 白喉百日咳破傷風(第一劑 ) +小兒麻痺疫苗 (第一劑 ) 4 month 白喉百日咳破傷風(第二劑 ) +小兒麻痺疫苗 (第二劑 ) 6 month 白喉百日咳破傷風(第三劑 ) +小兒麻痺疫苗 (第三劑 ) + B型肝炎疫苗(第三劑 ) 新型三合一(第三劑) B型嗜血桿菌 (第二劑 ) 新型三合一(第二劑) 9 month 麻疹(一劑 ) 1 year B型嗜血桿菌 (第三劑) + 水痘 (一劑) 1 y 3 m 麻疹腮腺炎德國麻疹 (一劑 ) + 日本腦炎(第一劑 / 第二劑) 1. B肝 2.polio 3. A肝 4. DTaP 5. Varicella 6. Vaxigrip 7. Hib 8. COMBINATION VACCINES 1 y 6 m 白喉百日咳破傷風(隔兩週追加 ) +小兒麻痺疫苗(追加 ) 2 y 3 m 日本腦炎(第三劑) 新型三合一(追加) 國小一年級 破傷風減量白喉混和疫苗(追加) + 小兒麻痺疫苗(追加) + 日本腦炎(追加) 新型三合一(追加)

保持冷凍－15℃以下若已解凍儲存在2~8 ℃ 30天內用完 開瓶後冷藏2-8℃當天用完解凍後不可再冷凍 預防接種部位、途徑及疫苗保存方法 2-8℃避光勿冷凍 肌肉 大腿或上臂外側 流行性感冒 2-8℃ 避光 B型嗜血桿菌 皮下 水痘 上臂外側 日本腦炎 2-8℃ 避光 溶劑勿冷凍 開封後8hr內用完 麻疹腮腺炎德國麻疹MMR 麻疹 保持冷凍－15℃以下若已解凍儲存在2~8 ℃ 30天內用完 開瓶後冷藏2-8℃當天用完解凍後不可再冷凍 口服   小兒麻痺 2-8℃ 勿冷凍 大腿前外側 白喉百日咳破傷風 B型肝炎疫苗 皮內 左上臂三角肌中央 卡介苗 免疫球蛋白 保存方法及注意事項 途徑 接種部位   疫苗名稱

Hepatitis B vaccine (1) 商品名:ENGERIX-B 安在時 DESCRIPTION Engerix-B is a noninfectious recombinant DNA hepatitis B vaccine. The vaccine is derived from hepatitis B surface antigen (HBsAg) produced through recombinaaant DNA techniques from yeast cells, Saccharomyces cerevisiae. The portion of the hepatitis B gene which codes for HBsAg is cloned into yeast which is then cultured to produce hepatitis B antigen Hepatitis Immune Globulin

Hepatitis B vaccine (2) 商品名:ENGERIX-B 安在時 CLINICAL PHARMACOLOGY : Hepatitis B infection會造成嚴重的acute massive hepatic necrosis, chronic active hepatitis and cirrhosis of the liver.這些病人會變成慢性帶原者而感染其他人及增加發展 primary hepatocellular carcinoma的機會. 小孩於小於5歲前感染有特別高的危險性發展成慢性帶原. 因為D型肝炎需存在於B型肝炎感染的狀況下,所以施打此疫苗亦可防止D型肝炎的感染.

Hepatitis B vaccine (3) 商品名:ENGERIX-B 安在時 USAGE:採肌肉注射.HBsAg+母親的小孩於出生12小時內接受hepatitis immunoglobulin(HBIG)0.5ml,並於第1-2個月及第6個月接受疫苗.若母親的HBsAg狀態不確定,嬰兒應在12小時內接受疫苗,若母親發現為:HBsAg+,應盡快給予HBIG. Booster vaccinations:    For healthy vaccine recipients, protection persists for 5 years or longer in most cases. 10 mcg for children 10 years of age and under 20 mcg for adolescents 11 through 19 years of age 20 mcg for adults. 透析病人或免疫不全者若第3劑施打2個月後anti-HBs level<10mLU/ml,則需再追加第4劑. 早產兒應如同足月兒般正常時間接受預防注射

Hepatitis B vaccine (4) 商品名:ENGERIX-B 安在時 CONTRAINDICATIONS Hypersensitivity to any part of the vaccine Hypersensitivity to yeast, although no adverse effects have been published Immunosuppressive therapy:leukemia,lymphoma,congenital or acquired immunodeficiency disorders… PREGNANCY CATEGORY C

POLIO (1) DESCRIPTION:1999年Immunization Practices Advisory Committee (ACIP)建議使用all-IPV schedule,因為wild poliovirus的威脅性下降,而相對的OPV所導致的vaccine-associated paralytic polio (VAPP)危險性卻較令人無法忍受. USAGE:4 dose of IPV : 2, 4, 6-18個月, and 4-6歲 OPV只建議使用於下列狀況: 1)為控制爆發的大流行 2)小孩旅行於流行地 3)父母拒絕使用IPV(可建議此類小孩接受頭兩次的 IPV注射,接下來兩次再使用OPV.)

POLIO (2) Polio Sabin 沙賓口服疫苗

POLIO (3) 注射給予, IPV is the only poliovirus vaccine that should be used in patients with an immunodeficiency disorder,those receiving immunosupressive chemotherapy. After the first dose—VAPP.8-10/year (1 case per 750,000 children of paralytic disease )in U.S.A..特別在免疫不全患者,如B-lymphocyte disorders. 缺點 Has not been associated with VAPP or other reactions. 1)便宜2)服用方便3)誘導的長期免疫與自然感染相似4)可提供高度的腸道免疫力,防止帶原者. 優點 IPV( salk) OPV(sabin)

DIPHTHERIA, TETANUS, ACELLULAR PERTUSSIS VACCINE (DTaP ) (1) 吸附白喉破傷風無細胞性百日咳疫苗 TRIPAcel vaccine

DIPHTHERIA, TETANUS, ACELLULAR PERTUSSIS VACCINE (DTaP ) (2) DESCRIPTION 包括 Bordetella Petussis 4種antigen( pertussis toxin (PT), filamentous hemagglutinin (FHA), pertactin (Pn), fimbriae types 2 and 3 (Fim), Diphtheria toxoid, Tetanus toxoid and Al salt. Infanrix approved in 1997.ACIP建議使用副作用較少的DPaT. CLINICAL PHARMACOLOGY Acellular pertussis vaccines are used to provide active immunization against Bordetella pertussis所引起的whooping cough. Diphtheria and tetanus toxoids induce protective antitoxins against toxins produced by Cornynebacterium diphtheriae and Clostridium tetani.

DIPHTHERIA, TETANUS, ACELLULAR PERTUSSIS VACCINE (DTaP ) (3) Whole cell DPT(DTwP) Advers events :Fever,local reactions(erythema,swelling,injection site pain),and mild system reactions(drowsiness,anorexia,fretfulness).而由pertussis所誘發的反應為:Febrile,behavioral,local reactions,CNS toxicity(seizures, hypotonic-hyporesponsiveness,encephalopathy…)如:1)注射後數小時內發生的持續時間大於1小時的不可控制的哭泣 2)注射後數小時內發生的過度嗜眠 3)發燒性癲癇 4) encephalopathy 美國及日本進行的試驗指出----發燒,局部反應,其他系統事件的發生率DPaT較DTwP有意義的降低.

50﹪ 20﹪ 40﹪ 12﹪ 30﹪ 5﹪ 25﹪ 10﹪ 8﹪ 硬 結 紅 腫 發 燒 疼 痛 厭 食 舊型與新型三合一疫苗 舊型與新型三合一疫苗   副作用發生率比較表   舊型第一代 （全細胞型） 新型第一代 （非細胞型） 硬 結 50﹪ 20﹪ 紅 腫 40﹪ 12﹪ 發 燒 30﹪ 5﹪ 疼 痛 全身不適 25﹪ 10﹪ 厭 食 8﹪

DIPHTHERIA, TETANUS, ACELLULAR PERTUSSIS VACCINE (DTaP ) (4) INDICATION, DOSE, ADMINISTRATION DTaP are indicated for immunization of infants and children from 2 months to 7 years of age .Three (primary) doses at 2, 4, and 6 months of age,隔6month,the fourth dose of DTaP at age 15~18months, SC, IM.效果約為80% BOOSTER DOSE 4 to 6 y/o of age.效果增加至90%. 接下來的12年過後保護力才逐漸下降. 建議在所有的接種過程中使用同一種產品(acel-imune, tripedia,infanrix),否則沒有足夠的證據顯示是否會對免疫反應,安全性,及效力產生影響.

DIPHTHERIA, TETANUS, ACELLULAR PERTUSSIS VACCINE (DTaP ) (5) CONTRAINDICATIONS hypersensitivity to any vaccine component, History of encephalopathy within 7 days after any DTaP or DTwP dose neurologic disorder, Moderate or severe febrile illness Individuals 7 years of age and older should not receive the DTP vaccine ,改用DT( any child experiencing collapse or a hypotonic-hyporesponsive episode) Not contraindication: well-controlled seizures,a family history of seizure or other CNS disorder

Varicella virus vaccine;Chickenpox (1) 商品名:美瑞克 ( Varilrix ) DESCRIPTION : Varilrix是製備自降低活性的Varicella-zoster virus/ Oka strain,導入人類embryonic lung cell培養, 最後增殖於 human diploid cell cultures (WI-38).可提供主動免疫反應.每 0.5 mL包含至少2000 PFU (plaque forming units) of varicella virus ,當調配後可儲存於冰箱內至少2個月 (2 to 8 degrees Celsius) Varicella virus vaccine

Varicella virus vaccine;Chickenpox (2) 商品名:美瑞克 ( Varilrix ) CLINICAL PHARMACOLOGY :發生在1-9歲小孩併發嚴重合併症(e.g., bacterial superinfection, pneumonia, encephalitis, Reye‘s Syndrome)或death.血清學上,在1歲-12歲接種過水痘疫苗4-6週的孩童97%可偵測到varicella antibodies (gpELISA >0.3). DOSING INFORMATION : 12個月-12歲皮下接種一次0.5ml疫苗.大於13歲以上第一次接種0.5ml,隔4-8週後再接種第二劑,才能終身免疫. DURATION : 健康孩童身上可提供5-10年的保護力. POST EXPOSURE PROPHYLAXIS : 水痘病毒約有14天潛伏期,在潛伏期頭3天注射疫苗有90%的保護效果,超過3天疫苗可能無效.許多人接種7天後就產生抗體,大部分的人是2星期內.

Varicella virus vaccine;Chickenpox (3) 商品名:美瑞克 ( Varilrix ) ADVERSE REACTIONS : 約4-5%Fever及注射部位soreness, swelling, rash, pruritus, hematoma, induration, and stiffness were reported .小於4% varicella-like rash (一般發生於注射後7天內) 水泡量平均約只有15-32顆之內,但症狀遠比未接種疫苗而感染者輕微而短暫. Stevens-Johnson syndrome 很少見. CONTRAINDICATIONS :服用aspirin是不可以接種的,此外輸血或免疫球蛋白,高燒,未治療活動性肺結核,服用類固醇高劑量>2mg/kg/day of prednisolone,淋巴球指數<1200/mm3, HIV infection, lymphoma, and immunosuppressive therapy hypogammaglobulinemic or dysgammaglobulinemic states,以及對neomycin過敏者亦不能接種.Pregnancy Category C. PRECAUTIONS :兒童處於ALL (acute lymphoblastic leukemia )消退期;given immediately after exposure to natural varicella ;輸血後,接受免疫球蛋白或varicella zoster immune globulin 至少等待5個月後才能接種; Salicylates should not be used for 6 weeks after vaccination due to reports of Reye's syndrome following the use of salicylates during natural infection ….

Influenza Virus Vaccine (1)（Vaxigrip） DESCRIPTION : Vaxigrip是一種Types A and B [Purified Subvirion(split-virus) ] Influenza Virus. According to U.S. Public Health Service (PHS) requirements, each dose (0.5 mL) contains not less than the microgram amounts of hemagglutinin antigens (µg HA) .例如2002-2003年之病毒株為: 15 µg HA of A/New Caledonia/20/99 (H1N1), 15 µg HA of A/Panama/2007/99 (H3N2) (A/Moscow/10/99 [H3N2]-like), and 15 µg HA of B/Hong Kong/330/2001. 0.25ml syringe 0.5ml syringe VAXIGRIP (Influenza Vaccine) 巴斯德瑪里斯流感疫苗

Influenza Virus Vaccine (2)（Vaxigrip） CLINICAL PHARMACOLOGY : inactivated influenza virus 提供的保護能力通常只限於疫苗所製備的菌株或接近者.(因為抗原變異性大) Influenza virus vaccine prevents illness in approximately 70% to 90% of healthy persons younger than 65 years when the antigenic match between vaccine and circulating viruses is close. Q. 為何今年需特別注意流行性感冒的預防? DOSING INFORMATION: 6個月以上幼兒才可施打,6個月-3歲給予半劑0.25ml,3歲至成人給予一劑0.5ml.每年10月-11月中旬最佳,接種後10-15天出現免疫力,一年內有效.因接種後6個月抗體可能會下降,所以每年均須再接種一次.若孩童（小於八歲）過去未接種過或未曾感染過流行性感冒,應在間隔4週後給予第二 劑.

Influenza Virus Vaccine (3) （Vaxigrip） ADVERSE REACTIONS : 少部分的人可能發生注射部位硬化induration ,Myalgia,注射部位疼痛,紅腫redness,發燒,倦怠的輕微反應,一般約在接種後1-2天內恢復. CAUTIONS: 1.      對蛋白或硫汞thimerosal(preservation)或福馬林過敏者 2.      發燒或急性疾病,宜延後接種 3.      年齡小於6個月,不予接種,因可能無法產生有效免疫力 4.      對注射有過敏者或注射曾發生不良反應者,不予接種 5.      患有血小板減少症,血友病或其他凝血障礙者,不予接種 6.      懷孕前3個月不宜接種 7. Children and teenagers (6 months to 18 years) on long-term aspirin therapy; risk of developing Reye syndrome after influenza infection . IMPORTANT NOTE : Breast-feeding mothers can safely receive the vaccine The influenza and pneumococcal vaccine can be administered at the same time, at different sites without increasing side-effects.

HAEMOPHILUS B CONJUGATE VACCINE 商品名:ACT-HIB 巴斯得b型嗜血桿菌接合疫苗 (1) DESCRIPTION ACT-HIB is Haemophilus influenzae type b Conjugated to tetanus protein Vaccine (PRP-T)is a highly purified capsular polysaccharide (polyribosylribitol phosphate or PRP) of Haemophilus influenzae type b that is covalently bound to an tetanus protein complex of the IM2164 strain of Neisseria meningitidis serogroup B. The covalent bonding convert the T-independent antigen (PRP alone) into a T-dependent antigen resulting in both an enhanced antibody response and immunologic memory.

HAEMOPHILUS B CONJUGATE VACCINE 商品名:ACT-HIB 巴斯得b型嗜血桿菌接合疫苗 (2) CLINICAL PHARMACOLOGY Hib disease occurred primarily in children under 5 years of age . The mortality rate from Hib meningitis is about 5%. ACT-HIB is indicated for invasive disease caused by Haemophilus influenzae type b in infants and children 2 to 71 months of age. HIBERIX VACCINE 賀百克B型流行感冒嗜血桿菌疫苗

HAEMOPHILUS B CONJUGATE VACCINE 商品名:ACT-HIB 巴斯得b型嗜血桿菌接合疫苗 (3) DOSAGE AND ADMINISTRATION -- 1 dose 12-60 18 2 doses, 2 mo. apart 6-12 3 doses, 1-2 mo. part  6 Age (Months) at Booster Dose (not earlier than 2 months after the second dose.) Primary (two-dose regimen before 12 months of age) Age (Months) at First Dose Vaccination Regimens for ACT-HIB By Age Groups ( IM administration ) 1 dose = 0.5 ml

HAEMOPHILUS B CONJUGATE VACCINE 商品名:ACT-HIB 巴斯得b型嗜血桿菌接合疫苗 (4) Because of the potential for immune tolerance, Liquid ACT-HIB is not recommended for use in infants younger than 6 weeks of age 大於5歲的小孩是沒有施打Hib的需要 When sequential doses of different vaccine products are given or uncertainty exists about which products were previously administered, 3 doses of any conjugate vaccine are considered sufficient to complete the primary series, irrespective of the regimen employed. 理想的狀況下,THE PRIMARY SERIES 應該使用一樣的Hib,而我們並沒有足夠的證據證明產品相互改變所導是的免疫效果是否有變化.而在12-18個月所追加的疫苗則沒有交換使用的限制. CONTRAINDICATIONS Hypersensitivity to any component of the vaccine or the diluent. PREGNANCY CATEGORY C

COMBINATION VACCINES Advantage: reduce the number of injection before combination: 17 injections before 2 years old (Taiwan) after combination: using 5 in 1 --- 12 injections using 6 in 1 --- 9 injections

COMBINATION VACCINES THE FIRST COMBINATION DT and DTP ACELLULAR PERTUSSIS VACCINE COMBINATION DTaP-Hib : 4 different DTaPvaccines have been used to reconstitute the lyophilized PRP-T vaccine (Hib) DTaP-HB : 1997 made by SB DTaP-IPV : thiomersal –-- 2-phenoxyethanol DTaP-IPV-Hib : lower anti-PRP-T response DTaP-HB-Hib : DTaP-HB was used to reconstitute a lyophilized Hib conjugated vaccine. DTaP-IPV-HB-Hib : Others : DTaP-Hib :combination and associated的比較,D, T, P的免疫效果不會被Aluminum compounds干擾 但Hib的免疫效力會被Aluminum compounds干擾降低 (33-92%) DTaP-HB : no significant interaction of each other. DTaP-IPV : avoid the known interaction of IPV with thiomersal, DTaP antigens were preserved in 2-phenoxyethanol. 嬰護寧五合一疫苗

Clinical programs of combination vaccine 1.Safety 2.Efficacy equivalent 3.Consistency of the immune response 4.Compatibility with other vaccines given at the same time.

COMBINATION VACCINES Compatibility Component : live attenuated vaccines preservatives : avoid the known interaction of IPV with thiomersal, DTaP antigens were preserved in 2-phenoxyethanol. adjuvent : e.g, the ratio of aluminum hydroxide and aluminum phosphate, pH , buffer Toxicology Immunological interaction Reduce immune response : Antigenic overload : at what point antigenic overload will be crucial in formulating is not known. Antibody subclass response : total IgG response PHARMACEUTICAL ASPECTS OF COMBINATION VACCINES Reduce immune response : DTaP-Hib---reduce Hib immune response, DTwP-IPV---reduce P , measles vaccines + meningococcal polysaccharide type a and c results in reduced seroconversion for both vaccines. Overload : However, it is generally accepted that it will be crucial in formulating new combination vaccines to ensure that the load of distinct antigens does not exceed the capacity of the presentation system.

Effect of Combinations Based on Acellular Pertussis Vaccines on the Immunogenicity of Individual Antigens DTaP-Hib :combination and associated的比較,D, T, P的免疫效果不會被干擾 但Hib的免疫效力降低 (33-92%) DTaP-HB : no significant interaction of each other. DTaP-IPV : avoid the known interaction of IPV with thiomersal, DTaP antigens were preserved in 2-phenoxyethanol.

The effect of combination on future vaccines development Vaccine schedule Three primary immunuzation in first year of life, followed by a booster in the second year. 6 in 1 DTaP-IPV-HB-Hib : the problem is the HB vaccine only needs two primary dose, use such a combination will imply the administration of an extra dose of HB.

The effect of combination on future vaccines development HA, meningococcal conjugate, and pneumococcal conjugate vaccines : are three likely additions to future pediatric vaccine schedures. These vaccines should be given associated by separate injection.

FUTURE COMBINATION Mechanical mixing Genes from one organism to be inserted into the genome of another. Advantage : vectors are often capable of accepting multiple pieces of genetic information, each of which can be transcribed and expressed. DNA or genetic immunization By mixing plasmids containing different genes, or using plasmids that contain more than one gene, it may be possible to immunize against several antigens with a single injection. Mechanical mixing : genes encoding proteins into a suitable vector such as a naturally or artificially attenuated virus or becterium.

結論及建議 由於疫苗種類不段推陳出新,不同疫苗不同接種部位及時程,不僅常讓父母疲於奔命,也讓寶寶們挨了許多針. 目前雖有部分疫苗可同時接種但仍需在不同的部位,故今後疫苗研發的趨勢是朝向“混合更多不同疾病的抗原而調劑在一次注射”,但須注意它的有效性及安全性,疫苗引起的抗體反應與保護效果必須至少跟分開接種一樣有效,而且不會增加副作用發生率. 以前世界衛生組織曾經規劃出超理想疫苗的構想,在這構想中,一個超理想疫苗必須含有所有需要接種的疫苗種類,而且只要接種一劑就可以.以目前的科技而言,這種超理想疫苗在技術上還不可能,但是醫學界正在朝這個方向努力.

Hepatitis A Vaccine,(HAV) 商品名 :新赫寶克(Havrix) (1) DESCRIPTION : Havrix (病毒株 HM175) 增殖於人類偶極細胞MRC 5所製成的失活的無菌懸服液;單位: enzyme linked immunosorbent assay (ELISA)即(EL.U.). CLINICAL PHARMACOLOGY : A型肝炎又稱傳染性肝炎, 經糞口途徑傳染.平均潛伏期是28天 (range: 15 to 50 days).2歲以下的小孩感染通常無症狀.研究報告顯示小孩在單一劑量注射疫苗後於3星期-6個月內可產生抗體; 並可持續3年以上 HAVRIX 720 Elisa U/1ml (HAV ANTIGEN) 新赫寶克 A型肝炎病毒疫苗

Hepatitis A Vaccine,(HAV) 商品名 :新赫寶克(Havrix) (2) DESCRIPTION : Havrix (病毒株 HM175) 增殖於人類偶極細胞MRC 5所製成的失活的無菌懸服液;單位: enzyme linked immunosorbent assay (ELISA)即(EL.U.). CLINICAL PHARMACOLOGY : A型肝炎又稱傳染性肝炎, 經糞口途徑傳染.平均潛伏期是28天 (range: 15 to 50 days).2歲以下的小孩感染通常無症狀.研究報告顯示小孩在單一劑量注射疫苗後於3星期-6個月內可產生抗體; 並可持續3年以上. CLINICAL APPLICATIONS :高感染群如下:(1) 需經常旅行至高感染區,如外交官或軍人 (2) 扥兒中心工作者 (3) 藥物濫用者 (4) 男同性戀或雙性戀 (5) 犯人 (6) 食物運輸工 (7) 難民 (8) 食用海產食物 (9) 與精神障礙患者同住 (10) 其他如健康照顧者或有機會暴露於A肝患者之照護者 DOSAGE AND ADMINISTRATION : 2歲以上開始施打為0.5c.c. 720 ELISA units. 成人(18歲以上)為1c.c.含1440ELISA單位.為增加抗體效價注射第一劑之後隔6-12個月再追加一劑,共兩劑.

Hepatitis A Vaccine,(HAV) 商品名 :新赫寶克(Havrix) (3) POSTEXPOSURE PROPHYLAXIS : Havrix與Immune globulin同時給予,但置於不同針筒及不同接種位置. CONTRAINDICATIONS: Hypersensitivity PRECAUTIONS: 1. Acute infection or febrile illness 2..Immunosuppressed persons; immune response may be inadequate (HIV) ADVERSE REACTIONS : 注射部位soreness及headache 較常見. TERATOGENICITY/EFFECTS IN PREGNANC : FDA Pregnancy Category C DRUG INTERACTIONS : CORTICOSTEROIDS B. CYCLOSPORINE