嬰幼兒疫苗預防接種
最新趨勢
藥師:林育成
INTRODUCTION
age
24hr 內
24hr 後
3~5day
1 month
2 month
4 month
6 month
新型三合一(第三劑)
9 month
1 year
1y3m
1y6m
2y3m
國小一年級
出生
法定疫苗
B型肝炎免疫球蛋白 (一劑 )
卡介苗(一劑 )
B型肝炎疫苗(第一劑 ) B型嗜血桿菌 (第一劑 )
新型三合一(第一劑)
B型肝炎疫苗(第二劑 )
白喉百日咳破傷風(第一劑 ) +小兒麻痺疫苗 (第一劑 )
白喉百日咳破傷風(第二劑 ) +小兒麻痺疫苗 (第二劑 )
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 ) B型嗜血桿菌 (第二劑 )
新型三合一(第二劑)
麻疹(一劑 )
B型嗜血桿菌 (第三劑) + 水痘 (一劑)
麻疹腮腺炎德國麻疹 (一劑 ) + 日本腦炎(第一劑 / 第二劑)
白喉百日咳破傷風(隔兩週追加 ) +小兒麻痺疫苗(追加 )
日本腦炎(第三劑)
新型三合一(追加)
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)
預防接種部位、途徑及疫苗保存方法
疫苗名稱
接種部位
途徑
保存方法及注意事項
免疫球蛋白
大腿前外側
肌肉
2-8℃ 勿冷凍
卡介苗
左上臂三角肌中
央
皮內
2-8℃ 避光
B型肝炎疫苗
大腿前外側
肌肉
2-8℃ 勿冷凍
白喉百日咳破傷風
大腿前外側
肌肉
2-8℃ 勿冷凍
口服
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
小兒麻痺
麻疹
上臂外側
皮下
2-8℃ 避光
麻疹腮腺炎德國麻
疹MMR
上臂外側
皮下
2-8℃ 避光 溶劑勿冷凍 開封後
8hr內用完
日本腦炎
上臂外側
皮下
2-8℃避光勿冷凍
水痘
大腿或上臂外側
皮下
2-8℃ 避光
大腿或上臂外側
肌肉
2-8℃ 避光
大腿或上臂外側
肌肉
2-8℃避光勿冷凍
B型嗜血桿菌
流行性感冒
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vaccineassociated 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)
OPV(sabin)
IPV( salk)
優點
1)便宜2)服用方便3)
Has not been
誘導的長期免疫與自 associated with VAPP
然感染相似4)可提供 or other reactions.
高度的腸道免疫力,防
止帶原者.
缺點
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.
注射給予,
IPV is the only poliovirus
vaccine that should be
used in patients with an
immunodeficiency
disorder,those receiving
immunosupressive
chemotherapy.
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, hypotonichyporesponsiveness,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.
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
30﹪
25﹪
5﹪
10﹪
20﹪
8﹪
全身不適
厭 食
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
• 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.
(2)
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
Vaccination Regimens for ACT-HIB
By Age Groups ( IM administration )
Age (Months)
at First Dose
Primary
Age (Months)
at Booster Dose
(two-dose regimen
before 12 months of age) (not earlier than 2
months after the
second dose.)
6
6-12
3 doses, 1-2 mo. part
2 doses, 2 mo. apart
12-60
1 dose
18
18
--
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 :
嬰護寧五合一疫苗
– Others :
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 2phenoxyethanol.
– 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
Effect of Combinations Based on Acellular Pertussis
Vaccines on the Immunogenicity of Individual Antigens
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.
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)
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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