甲肝减毒活疫苗及加服牛磺酸在接种乙肝疫苗免疫失败儿童中的 …

目的 为了估价甲肝减毒活疫苗在接种乙肝疫苗免疫失败儿童中的致免疫性和牛磺酸对该疫苗免疫性的影响。方法 应用随机对照临床试验。选择９０名健康儿童随机分为二组：４３名接种甲肝减毒活疫苗和口服牛磺酸（Ｉ组）；４７名接种疫苗加口服安慰剂（Ⅱ组）。另选择６２名由携带ＨＢＶ的无症状母亲所生接种过乙肝疫苗但是免疫失败者（Ⅲ组）和４４名同龄由ＨＢｓＡｇ阴性母亲所生接种乙肝疫苗正常免疫反应的健康儿童（Ⅳ组），均接种     

宫内感染HBV婴儿接种乙肝疫苗免疫失败的机理和预后研究

为了解宫内受乙型肝炎（简称乙肝）病毒（ＨＢＶ）感染婴儿接种乙肝疫苗导致免疫失败的机理和预后，用植物血凝素（ＰＨＡ）作淋巴细胞增殖试验，用ＨＢＶ前Ｓ２多肽特异性扩增ＨＢＶＤＮＡＳ区基因并分析其变异情况。对４９７名携带ＨＢＶ母亲所生新生儿单纯接种乙肝疫苗，并对携带ＨＢＶ母亲产前注射免疫球蛋白（ＨＢＩＧ）（妇产组）；对携带ＨＢＶ产前不注射ＨＢＩＧ母亲所生４９０名新生儿生后注射ＨＢＩＧ加乙肝疫苗（中山组）。两组均随访４～６年。结果显示，妇产组ＨＢＶ的宫内感染率为１４．３％，中山组ＨＢＶ的宫内感染率为５．７％；淋巴细胞增殖试验显示宫内感染ＨＢＶ后其细胞免疫功能不足，Ｔ淋巴细胞对ＨＢＶ的特异性刺激源处于免疫耐受状态。孕妇产前多次注射ＨＢＩＧ能有效减少ＨＢＶ的宫内感染；在受宫内ＨＢＶ感染的儿童中存在着乙肝病毒变异，感染变异病毒是接种乙肝疫苗免疫失败的重要原因，并易发展为慢性乙型肝炎     

阻断乙型肝炎病毒宫内传播的初步研究

宫内已感染乙型肝炎病毒（ＨＢＶ）是新生儿接种乙肝疫苗免疫失败的主要原因。为了减少新生儿产前在宫内受ＨＢＶ感染，提高乙肝疫苗接种后的免疫效果，研究给予阻断措施和观察其效果。从３６３２名孕妇筛查出ＨＢＶ无症状携带者２０４例，随机分为二组，即临产前３个月每月注射１次乙型肝炎免疫球蛋白（ＨＢＩＧ），每次２００ＩＵ，和不注射者作对照。在孕妇分娩后和新生儿出生时分别抽外周血作血清学检测。结果显示，ＨＢＩＧ组和对照组所生新生儿的宫内感染率分别是５．７％和１４．７％（Ｘ￣２＝４．５８，Ｐ＜０．０５）。分娩后二组孕妇的ＨＢｓＡｇ和ＨＢｅＡｇ的阳性率无差异，但ＨＢＩＧ组ＨＢｓＡｇ阳性滴度的均值显著低于对照组（ｔ＝４．８２，Ｐ＜０．０１）。提示产前多次肌注ＨＢＩＧ可减少携带ＨＢＶ母亲所生新生儿宫内受ＨＢＶ感染。这可能与产时减少母体外周血中的ＨＢＶ有关。接受ＨＢＩＧ在分娩前后的随访无不良反应。     

对乙型肝炎疫苗阻断母婴传播的长期随访和再接种研究

为了研究阻断乙型肝炎病毒（ＨＢＶ）母婴传播经初次全程接种乙型肝炎（简称乙肝）疫苗后何时需再接种及其措施和效果，对９８例母亲是ＨＢＶ无症状携带者的高危新生儿，随机分成两组：单纯疫苗组５５例和注射高效价免疫球蛋白（ＨＢＩＧ）后再接种乙肝疫苗组４３例，随访７年。结果表明，初次免疫后第１年抗ＨＢｓ阳性者，单纯疫苗组４５例，抗体阳性率为８１．８％，抗体平均滴度１１１．１；加注ＨＢＩＧ组抗体阳性者３９例，抗体阳性率为９０．７％，抗体平均滴度４１０．４（ｔ＝４０．１，Ｐ＜０．０１）。对抗体阳性者逐年随访，单纯疫苗组第４年抗体平均滴度降至＜１０，为６．１，而加注ＨＢＩＧ组第５年为８．３。对两组中抗体消失或滴度＜１０者，给再注射１次原剂量乙肝疫苗见抗体又升达初次免疫后第１年的水平，保护性抗体又可持续达３年。提示阻断母婴传播，乙肝疫苗联合ＨＢＩＧ效果好，单纯疫苗组３至４年需加强注射；ＨＢＩＧ加乙肝疫苗组４至５年也必须加强注射。     

孕妇乙型肝炎病毒感染与新生儿乙型肝炎基因疫苗免疫效果关系的前瞻性研究

目的探讨孕妇乙型肝炎病毒（ＨＢＶ）感染对新生儿乙型肝炎（简称乙肝）基因疫苗免疫接种效果的影响。方法采用酶联免疫吸附试验（ＥＬＩＳＡ）和聚合酶链反应（ＰＣＲ）法对乙肝基因疫苗免疫效果进行了前瞻性研究。结果在新生儿系列血清中均未检出乙型肝炎病毒（ＨＢＶ）ＤＮＡ和血清学感染标志;对照组和感染组新生儿免疫保护率分别为９３％（２８／３０）和８３％（３９／４７）（χ２＝１．７４,Ｐ＞０．０５）,两组汉族和少数民族间免疫保护率亦无统计学差异（概率法,Ｐ＝０．９８;χ２＝０．１１,Ｐ＞０．０５）。结论随着接种次数的增加,各组两民族抗ＨＢｓ阳转率均呈现出不同程度的升高,分娩时孕妇ＨＢＶ感染状态对新生儿抗ＨＢｓ阳转率可能产生一定程度的影响。     

聚合酶链反应检测H2株甲肝减毒活疫苗在人体的分布和增殖

聚合酶链反应检测Ｈ＿２株甲肝减毒活疫苗在人体的分布和增殖南京市上海梅山冶金公司医院（２１００３９）梁明，彭爱玉，刁端勤，防疫站，林雪芝本文报告应用聚合酶链反应（ＰＣＲ）检测６名疫苗受种者，２名野毒感染引起的急性甲型肝炎患者和１名从未受到ＨＡＶ感染者，...     

静脉注射丙种球蛋白治疗早产儿感染的研究

为了探讨静脉注射丙种球蛋白（ＩＶＩＧ）预防及治疗早产儿感染的价值，用单向免疫琼脂扩散法检测５１例出生１～３天（胎龄２８～３６周）的早产儿血清ＩｇＧ、ＩｇＡ、ＩｇＭ。结果显示ＩｇＧ均值随胎龄增加而升高（ｒ＝０．９９，Ｐ＜０．０１），２８～３６周者＜８．０ｇ／Ｌ（２８周仅４．５ｇ／Ｌ），＞３６周者＞８．０ｇ／Ｌ；而ＩｇＡ、ＩｇＭ差异无显著意义（２８～３６周者ＩｇＡ均值为６１５ｍｇ／Ｌ，＞３６周者为６２１ｍｇ／Ｌ；２８～３６周者ＩｇＭ均值为４２３ｍｇ／Ｌ，＞３６周者为４１８ｍｇ／Ｌ），，故胎龄越小越有应用静脉丙种球蛋白（ＩＶＩＧ）的指征。３０例重症感染的早产儿参考相似的孕周、体重及日龄，随机分为ＩＶＩＧ组及对照组各１５例，均选用同类抗生素，且不用其它免疫制剂及血浆治疗，ＩＶＩＧ组按每天０．５～１ｇ／ｋｇ稀释成５０ｍｌ在２～３小时内静脉滴注，连用２天，ＩＶＩＧ组治疗１周后均值从８．２ｇ／Ｌ升到１３．５ｇ／Ｌ（Ｐ＜０．０１）；而对照组治疗后ＩｇＧ均值仅６．７ｇ／Ｌ。提示早产儿感染用ＩＶＩＧ疗效十分满意。     

静脉注射免疫球蛋白对急性川崎病患儿淋巴细胞凋亡的影响

通过观察静脉注射免疫球蛋白（ＩＶＩＧ）对川崎病（ＫＤ）患儿淋巴细胞凋亡（ＡＰＯ）的影响，进一步探讨ＩＶＩＧ对免疫性疾病的作用机理。对２６例川崎病患儿和２０名健康儿童外周血单个核细胞（ＰＢＭＣ）经抗－ＣＤ３单克隆抗体刺激培养不同时间（０，１２，２４，４８，７２小时）ＡＰＯ百分率和ＤＮＡ片断化分析，２６例患儿随机分为两组，阿司匹林＋ＩＶＩＧ治疗组（ｎ＝１６）和阿司匹林治疗组（ｎ＝１０），并对ＰＢＭＣ经植物血凝素（ＰＨＡ）刺激淋巴细胞增殖反应进行了观察。结果：ＫＤ患儿ＡＰＯ百分率和ＤＮＡ片断化较正常儿童明显降低（Ｐ＜０．００１）和延迟；ＩＶＩＧ治疗后，降低的ＡＰＯ百分率和延迟的ＤＮＡ片断化被逆转，同时与单用阿司匹林组比较，临床症状明显改善。淋巴细胞增殖反应下调（Ｐ＜０．００１）。外周血淋巴细胞ＡＰＯ下调可能参与了ＫＤ的发病。ＩＶＩＧ治疗ＫＤ的机理可能部分归于对被抑制的淋巴细胞ＡＰＯ的逆转。ＩＶＩＧ对其它淋巴细胞凋亡不足的自身免疫性疾病治疗可能存在同样机理。     

阿根廷儿童使用灭活甲肝疫苗的安全性和免疫原性

目的是评价一种含有成人疫苗半倍量抗原的新型灭活甲型肝炎（简称甲肝）疫苗的安全性和免疫原性． 方法 选５３７名不同性别的健康儿童作为研究对象,分为三个年龄组：１２～４７月龄、４～８岁和９～１５岁．曾接受过生长激素或人免疫球蛋白治疗,对任何疫苗有变态反应或近３０天内接种过疫苗者除外．灭活甲肝疫苗来自甲肝病毒（ＨＡＶ）的ＧＢＭ株,经培养、纯化和甲醛灭活后制成,每剂０．５ｍｌ含８０抗原单位．在检测儿童ＨＡＶ血清学状态时采集血样,并在其后的第２周、２４周（第２剂加强疫苗之前）和２７周从１２～４７月龄的１２０…     

反复呼吸道感染患儿血清β－胡萝卜素、维生素A、E含量测定及分析

用高效液相色谱测定３４例反复呼吸道感染患儿血清β－胡萝卜素、维生素Ａ（ＶｉｔＡ）与维生素Ｅ（ＶｉｔＥ）的含量。同时测定了血清免疫球蛋白水平。结果显示：①患儿组β－胡萝卜素及ＶｉｔＡ含量明显低于对照组（Ｐ＜０．０５及Ｐ＜０．０１），两组ＶｉｔＥ则无显著性差异。②亚临床型ＶｉｔＡ缺乏在患儿组为２４例（２４／３４例，７０．５％），对照组中为１３例（１３／４０例，３２．５％），有显著性差异（Ｘ２＝１０．６６，Ｐ＜０．００５）。临床型ＶｉｔＡ缺乏则在两组均未见到。③患儿组ＩｇＡ水平与β－胡萝卜素、ＶｉｔＡ的相关系数ｒ分别为０．３５４（ｔ＝２．２５，Ｐ＜０．０５）及０．３２２（ｔ＝１．９２４，Ｐ＜０．０５），均显著相关。ＩｇＧ及ＩｇＭ则与两种维生素之间均无显著相关。提示，β－胡萝卜素和ＶｉｔＡ缺乏时ＩｇＡ水平降低，与呼吸道易受感染可能有关。防治反复呼吸道感染时宜服用β－胡萝卜素及／或ＶｉｔＡ，以前者防治效果为优。     

The prevalence of atopy in children with antibodies against hepatitis A virus and hepatitis B virus

To investigate the relationship between atopy and hepatitis A virus (HAV) and hepatitis B virus (HBV) infections, we studied 42 children who had had HAV infection (Group I), 28 children who had had HBV infection (Group II), and 31 children who were seronegative for both HAV and HBV infection (Control group). Serological tests for HAV and HBV infections (anti-HAV IgG, HBsAg, anti-HBc IgG) and allergic skin tests and specific IgE investigations for the detection of atopy were carried out. In this study, there was no significant divergence in the socio-demographic characteristics among the three groups. The rates of specific IgE positivity in children in the HAV seropositive group (11.9%) and in children in the HBV seropositive group (17.8%) were lower than in the control group (35.4%) (p = 0.03 and p = 0.22, respectively). Also, the number of children with respiratory allergic diseases (allergic rhinitis and/or asthma) both in the HAV seropositive group and in the HBV seropositive group were significantly lower than in the control group (p < 0.05). When atopy in all of the groups was evaluated, the prevalence of atopy was found to be more widespread in HAV seronegative children (Adjusted OR, 9.2; 95% CI, 1.7-48.2) and HBV seronegative children (Adjusted OR, 5.9; 95% CI, 1.1-31.8) than in HAV and HBV seropositive children, after adjustment for age, number of older siblings and education of the father. In conclusion, in this study, the prevalence of atopy in children who had had HAV or HBV infection was found to be low, and this situation was considered to be related to the relationship of HAV and HBV infections to poor hygiene and to the fact that these infections occur at early ages in Turkey.     

Evaluation of immunogenicity and tolerability of a live attenuated hepatitis a vaccine in Indian children

An open non comparative study of a live attenuated H2 strain Hepatitis A vaccine of Chinese origin was carried out in 143 healthy Indian children aged 1 to 12 years (mean age 4.87 2.76 years; 88 boys, 55 girls). At baseline, all were negative for IgG HAV antibodies and had normal hematological and biochemical indices. Two months after a single dose of the vaccine (given subcutaneously), 137 children (i.e. 95.8 %) developed protective antibodies of IgG > 20 mIU / mL. The hematological and biochemical parameters remained within normal limits. There were no adverse events in any except mild fever in one child. In conclusion, live attenuated H2 strain Hepatitis A vaccine in a single dose was found to be immunogenic and safe in Indian children.     

宫内感染乙型肝炎病毒免疫失败儿童1型和2型细胞因子研究

目的 从外周血单个核细胞（PBMC）在特异性和非特异性刺激下1型和2型细胞因子的反应探讨宫内感染乙型肝炎病毒（HBV）导致免疫失败的机制。方法 采用体外细胞培养和ELISA技术对29例宫内感染免疫失败儿童、9例宫内感染有效儿童及25名正常儿童PBMC在丝裂原（植物血凝素和细菌脂多糖）、酵母重组乙型肝炎表面抗原（HBsAg）及无刺激物时干扰素（IFN）－γ、白细胞介素（IL）－4和IL－12P70的分泌进行检测。结果 丝裂原刺激时IFN－γ分泌和IFN－γ自发分泌在免疫失败组有增高趋势。和自发分泌比较，在HBsAg刺激时，对照组、有效组和免疫失败组均表现为分泌增加，但免疫失败组增加值显著性低于对照组。在各种刺激时IL－4和IL－2分泌低于可检测水平。丝裂原刺激时IFN－γ分泌和血清丙氨酸转氨酶水平正相关。结论 特异性刺激时1型细胞因子分泌不足可能是宫内感染HBV导致乙肝疫苗免疫失败的原因之一，1型细胞因子非特异性反应增强可能与肝细胞损伤有关。     

乙型肝炎高危儿免疫预防效果及乙肝病毒母婴传播影响因素分析

目的 分析乙型肝炎病毒(HBV)母婴传播影响因素及乙肝高危儿免疫预防的效果,为儿童乙肝防治提供科学依据。方法 回顾性调查539例HBsAg阳性产妇及其6个月至5岁的乙肝高危儿551例,并检测乙肝高危儿的乙肝标志物,分析乙肝病毒母婴传播的影响因素。结果 乙肝疫苗接种率为100%,96.6%联合注射了乙肝疫苗和乙肝免疫球蛋白(HBIG)。各年龄段乙肝高危儿的HBsAg阳性率差异无统计学意义;HBsAb阳性率随年龄增长逐步下降 (P<0.01)。高危儿母亲为HBsAg、HBeAg双阳性者较单纯HBsAg阳性的乙肝感染率高 (15.1% vs 0.2%,P<0.01)。单纯接种乙肝疫苗的高危儿乙肝感染率 (28.6%)高于联合免疫注射者 (2.8%),P<0.01。结论 乙肝高危儿HBsAb阳性率随年龄增高逐渐下降。母亲HBsAg、HBeAg双阳性和出生未联合免疫注射是乙肝病毒母婴传播的危险因素。     

Prevention of perinatal acquisition of hepatitis B virus carriage using vaccine: preliminary report of a randomized, double-blind placebo-controlled and comparative trial

Hepatitis B is a serious disease of global significance. In developing countries, hepatitis B virus (HBV) infection and its sequelae rank among the public health problems of highest priority. Infants born to mothers who are chronic carriers of HBV are at particularly high risk of acquiring infection and becoming chronic HBV carriers. The efficacy of hepatitis B vaccine alone in preventing the transmission of HBV to infants born to HBV carrier mothers was determined in a double-blind placebo-controlled trial. Infants received plasma-derived vaccine at birth, 1 month, and 6 months of age. Of 180 infants born to hepatitis B surface antigen (HBsAg)-positive mothers, equal numbers received National Institute of Allergy and Infectious Disease (NIAID) vaccine, Beijing Institute of Vaccine and Serum (BIVS) vaccine, and placebo. The cumulative seroconversion to the vaccines at 1 year of age was 95% and 75%, respectively. Vaccine efficacy as measured by the prevention of HBsAg-positive events was 88% for the NIAID vaccine and 51% for the BIVS vaccine. Vaccine efficacy was similar among infants born to hepatitis Be antigen-positive mothers. Because of the low efficacy of the BIVS vaccine, an additional group of 28 infants was given vaccine and hepatitis B immune globulin at birth. The resulting efficacy was 83%. The results of this trial indicate that hepatitis B vaccine alone can substantially reduce perinatally acquired HBV infection and the resulting chronic carrier state.     

Inadequate humoral immunogenicity to recombinant hepatitis B virus vaccine in biliary atresia children

This study aimed to investigate the primary immunogenicity and the long-term efficacy of recombinant hepatitis B virus (HBV) vaccine in biliary atresia (BA) children. Fifty BA infants (age, 11 +/- 3.9 mo), and 23 BA patients at childhood (age, 8.5 +/- 0.22 y) were included for the evaluation of HBV surface antibody (anti-HBs) levels after three doses of recombinant HBV vaccine immunization. Age- and gender-matched healthy infants (n = 50) and children (n = 23) were enrolled as the control group. Serum samples of the study populations were collected for HBV seromarkers determination. In the absence of hepatitis B virus core antibody and HBV surface antigen, serum anti-HBs level above 10 IU/L was considered adequate immunogenicity to HBV vaccine. The prevalence of adequate anti-HBs levels after recombinant HBV vaccine in BA infants was significantly lower than those of the controls (p = 0.006). There was no difference in the prevalence between childhood BA patients and their matched controls (p = 0.538). In conclusion, adequate primary humoral immunity after the standard doses of recombinant HBV vaccine in BA infants is hard to establish. However, once immunity is acquired, BA children have adequate anti-HBs titer in the long run.     

Factors associated with immunoprophylaxis failure against vertical transmission of hepatitis B virus

In spite of adequate immunoprophylaxis, perinatal transmission of hepatitis B virus (HBV) has not been completely eliminated. This study evaluated the factors associated with the failure of HBV immunoprophylaxis. The study participants were 144 children who were born to HBsAg-seropositive mothers of known HBeAg status and they had received HB immune globulin and HB vaccine within 24 hours after birth followed by two further administrations of HB vaccine as recommended. Seventeen of the children (11.8%) suffered immunoprophylaxis failure, defined by HBsAg-seropositivity. The rate of HBV immunoprophylaxis failure was 12%, 0%, 21%, 0%, and 27% among the children born to HBsAg-seropositive, HBeAg-seronegative, HBeAg-seropositive, undetectable HBV DNA, and detectable HBV DNA mothers, respectively. The failure of HBV immunoprophylaxis was significantly associated with maternal HBeAg-seropositivity and HBV DNA seropositivity. To identify those children at high risk of HBV immunoprophylaxis failure, maternal HBeAg and HBV DNA need to be assessed prior to childbirth.     

Decline of maternal hepatitis A virus antibody levels in infants

Hepatitis A is a common viral infection causing substantial morbidity and mortality. The anti-hepatitis A virus (HAV) vaccination in infants would guarantee control of the infection. However, the immunogenicity of the HAV vaccine in infants could be impaired by the presence of passively acquired maternal HAV antibodies. This study evaluated the prevalence of HAV antibodies in 103 women at delivery and in their babies in the first year of life. Eighteen mothers (17.5%) had anti-HAV serum level >10 mIU ml(-1). In their infants the anti-HAV level was still positive in 11 out of 18 (61.1%) at 12 mo. Two out of 85 infants born to anti-HAV-negative mothers and anti-HAV negative at birth were found to be positive at 5 mo of age. Conclusion: It is proposed that all women be screened at delivery for anti-HAV antibodies. Children born to anti-HAV-negative mothers could be vaccinated early during the first year of life, whereas vaccination could be postponed in children born to anti-HAV-positive mothers, if necessary.     

Evaluation of live attenuated varicella vaccine (Oka-RIT strain) and combined varicella and MMR vaccination in 13-17-month-old children.

The Oka-RIT strain of live attenuated varicella vaccine at dose levels 5300 PFU (high titre) and 2000 PFU (low titre) was tested in 13-17-month-old children; 50% of the children received the varicella vaccine alone, and the other 50% received it together with a measles-mumps-rubella (MMR) vaccine. The high titre and low titre varicella vaccines induced 96% and 92% seroconversion rates, respectively. Following combined vaccination with MMR, the corresponding seroconversion rates for varicella were significantly lower at 85% and 72% respectively. Seroconversion rates to measles, mumps and rubella were not affected by the combination of varicella vaccine plus MMR vaccination. Single varicella vaccine at both titre levels was found safe, although 10% of the children had minor skin reactions, possibly attributable to the vaccine. Reactions typically associated with MMR vaccination did not significantly increase after the combined varicella plus MMR vaccination. This study confirmed that the Oka-RIT strain varicella vaccine is safe and immunogenic in healthy young children, but failed to find a totally satisfactory combination for a varicella-MMR vaccine.     

Efficacy of vaccination with live attenuated, cold-adapted, trivalent, intranasal influenza virus vaccine against a variant (A/Sydney) not contained in the vaccine

OBJECTIVE: To determine the safety, immunogenicity, and efficacy of revaccination of children with live attenuated influenza vaccine. STUDY DESIGN: A 2-year multicenter, double-blind, placebo-controlled, efficacy field trial of live attenuated, cold-adapted trivalent influenza vaccine administered by nasal spray to children. This report summarizes year 2 results, a year in which the epidemic strain of influenza A/Sydney was not well matched to the vaccine strains. Each year, vaccine strains were antigenically equivalent to the contemporary inactivated influenza vaccine. In year 2, a single intranasal revaccination was administered. Active surveillance for influenza was conducted during the influenza season by means of viral cultures. Influenza cases were defined as illnesses with wild-type influenza virus isolated from respiratory secretions. RESULTS: In year 2, 1358 (85%) children, 26 to 85 months of age, returned for revaccination. The intranasal vaccine was easily accepted, well tolerated, and immunogenic. Revaccination resulted in 82% to 100% of the vaccinated children in a subset studied for immunogenicity being seropositive as compared with 26% to 65% of placebo recipients, depending on the influenza strain tested. No serious adverse events were associated with the vaccine. In addition to the strains in the vaccine, antibody was induced to the variant strain A/Sydney/H3N2. In year 2, influenza A/Sydney/H3N2, a variant not contained in the vaccine, caused 66 of 70 cases of influenza A; nonetheless, intranasal vaccine was 86% efficacious in preventing A/Sydney influenza. Eight cases of lower respiratory tract disease were associated with A/Sydney influenza; all cases were in the placebo group. CONCLUSIONS: This live attenuated, cold-adapted influenza vaccine was safe, immunogenic, and efficacious against influenza A/H3N2 (including a variant, A/Sydney, not contained in the vaccine) and influenza B. The characteristics of this vaccine make it suitable for routine use in children to prevent influenza.