干扰素γ和肿瘤坏死因子α基因单核苷酸多态性与宫内乙肝病毒感染易感性研究

目的探讨IFN_γ基因和TNF_α基因单核苷酸多态性(SNP)与HBV宫内感染的遗传易感因素。方法选择在确定时期内乙肝疫苗随访门诊定期随访儿童中凡属宫内HBV感染免疫失败者为Ⅰ组、未感染且免疫有效者为Ⅱ组,另选非HBV高危的健康儿童作对照组Ⅲ组,应用实时荧光定量PCR技术检测IFN_γ基因 874A/TSNP及CA重复序列,TNF_α基因-238G/A、-308G/ASNP。结果IFN_γ 874A等位基因频率Ⅰ组显著高于Ⅱ组和Ⅲ组(χ2=7.238、5.199,P均<0.05);CA重复序列12次频率(CA12) 明显低于Ⅱ组(χ2=7.548,P<0.01);TNF_α-238A等位基因频率Ⅰ组显著高于Ⅱ组和Ⅲ组(χ2=6.797、9.513,P均<0.01),-308位点等位基因频率Ⅰ组与Ⅱ组和Ⅰ组与Ⅲ组间差异无显著性(χ2=1.361、0.051,P均>0.05)。结论干扰素γ 874位点A等位基因占优势、IFN_γCA重复序列基因多态性和肿瘤坏死因子α-238A等位基因占优势对决定个体宫内HBV感染遗传易感性有一定意义,而TNF_α-308位点G/A等位基因单核苷酸多态性对个体乙肝病毒宫内感染易感性并无作用。     

白细胞介素-8-251A/T和781C/T基因多态性与呼吸道合胞病毒毛细支气管炎的相关性

目的 探讨白细胞介素-8(IL-8)-251A/T和781C/T基因多态性与呼吸道合胞病毒(RSV)毛细支气管炎易感性的关系.方法 应用聚合酶链反应-限制性酶切片段长度多态性技术检测150例RSV毛细支气管炎患儿和120例健康对照儿童血IL-8-251A/T和781C/T的单核苷酸多态性(SNP),分析其基因型、等位基因型的分布,并对2个SNP位点进行连锁和单体型分析.结果 1.病例组和健康对照组均发现IL-8-251A/T位点基因多态性,均可见AA、AT和TT 3种基因型;其中病例组AA、AT、TT基因型频率分别为12.0%、56.7%、31.3%,A、T等位基因频率分别为40.3%、59.7%;健康对照组AA、AT、TT基因型频率分别为7.5%、54.2%、38.3%,A、T等位基因频率分别为34.6%、65.4%;病例组IL-8-251A/T基因型及等位基因频率与健康对照组比较,差异均无统计学意义(x2=2.373,1.875 P0.05).2.病例组和健康对照组均发现IL-8 781C/T位点基因多态性,均可见CC、CT、TT3种基因型;其中病例组CC、CT、TT基因型频率分别为38.7%、40.7%、20.6%,C、T等位基因频率分别为59.0%、41.0%;健康对照组CC、CT、TT基因型频率分别为40.8%、41.7%、17.5%,C、T等位基因频率分别为61.7%、38.3%,二组基因型及等位基因频率比较,差异均无统计学意义(x2=0.442,0.396 P0.05).3.IL-8-251A和781C是连锁的(D'=0.348±0.019,r2=0.114 P<0.05).4.病例组AC单体型频率显著增加(x2=9.047 P<0.05).结论 IL-8-251A和781C形成的AC单体型与RSV毛细支气管炎易感性相关,即部分RSV毛细支气管炎的易感基因可能存在于含有AC单体型的基因片段或与该段基因紧密连锁.     

IL-19基因多态性与儿童乙型肝炎病毒易感性研究

目的 探讨白介素19（IL-19）基因的单核苷酸多态性（SNP）与儿童乙型肝炎病毒（HBV）易感性的关系。方法 采用病例对照研究,收集HBsAg阳性儿童136例（病例组）,HBsAg阴性的健康儿童297例（对照组）,应用PCR 聚合酶链反应和DNA测序法进行基因分型。结果 IL-19基因的rs1798位点的基因型在病例组和对照组人群中频率分布差异有统计学意义,病例组的CG 基因型的比例显著高于对照组（P < 0.05）;IL-19基因的rs2243191位点的基因型和等位基因在HBV感染高危儿童感染组和未感染组人群中频率分布差异有统计学意义,感染组TC、CC基因型以及C等位基因的比例显著高于未感染组（P < 0.05）。结论 IL-19 基因SNP 位点rs1798的基因多态性可能与儿童乙型肝炎易感性相关;rs2243191的基因多态性可能与HBV感染高危儿童突破感染易感性相关。     

白介素28B基因多态性与乙型肝炎病毒母婴传播免疫阻断效果的初步研究

目的 探讨IL28B基因多态性与乙型肝炎病毒（HBV）母婴传播免疫阻断结局的相关性。方法 以2011年6月至2012年9月复旦大学附属儿科医院就诊的、母亲慢性HBV感染史的、出生后按计划免疫接种乙肝疫苗的患儿为病例组;根据HBV血清学检测结果,分为母婴传播免疫阻断成功亚组和免疫阻断失败亚组。以母亲无慢性HBV感染史、出生后按计划免疫接种乙肝疫苗的健康儿童作为正常对照组;分别检测病例组2个亚组和正常对照组儿童IL28B基因rs12979860、 rs12980275及rs8099917位点的基因型。 结果 病例组109例（免疫阻断成功亚组65例,免疫阻断失败亚组44例）,正常对照组221例。IL28B基因rs12979860位点及rs12980275位点基因型的分布频率在免疫阻断成功亚组、免疫阻断失败亚组和正常对照组间差异均无统计学意义（P分别0.266和0.051）;rs8099917位点的基因型分布频率在上述3组中均以TT基因型占优势,且差异总体上有统计学意义(P=0.009),免疫阻断成功亚组TT基因型频率高于免疫阻断失败亚组 (P=0.008)。在校正年龄、性别因素后,发现免疫阻断成功率TT基因型是非TT（TG/GG）基因型的6.48倍（ OR=6.48,95%CI：1.27~32.0,P=0.025）。结论 IL28B基因rs8099917位点的TT基因型频率HBV母婴传播免疫阻断成功患儿高于免疫阻断失败患儿。     

INF-γ/A+874T位点基因多态性与呼吸道合胞病毒毛细支气管炎的相关性

目的：干扰素-γ(IFN-γ)分泌不足可能在严重呼吸道合胞病毒(RSV)感染的发病中发挥重要作用。IFN-γ/A+874T基因位点存在多态性,可能与RSV感染的病情存在关联。该研究分析INF-γ/A+874T基因位点在温州地区汉族儿童的分布特征;进一步探讨INF-γ/A+874T位点基因多态性与RSV毛细支气管炎易感性、病情的相关性及对鼻咽分泌物 INF-γ和血清总IgE水平的影响。方法：采用DNA测序法检测114例住院的汉族RSV毛细支气管炎患儿和90例汉族健康体检儿童INF-γ/A+874T位点基因多态性;采用酶联免疫吸附法测定鼻咽分泌物INF-γ水平,化学发光法测定血清总IgE水平。结果：两组均存在INF-γ/A+874T位点基因多态性,以AA纯合子基因型为主,其中RSV毛细支气管炎组AA、AT基因型频率分别为82.5%,17.5%,对照组分别为AA 77.8%,AT 21.1%,两组差异无显著性意义;病例组等位基因频率分别为A 90.4%,T 9.6%,对照组分别为A 88.3%,T 11.7%,两组差异均无显著性意义。轻度和中重度患儿INF-γ/+874位点2种基因型的差异亦无显著性意义。病例组2种基因型鼻咽分泌物INF-γ及血清总IgE水平差异均无显著性意义。结论：温州地区汉族儿童存在INF-γ/A+874T位点基因多态性,但未发现该位点变异与RSV毛细支气管炎易感性、病情、鼻咽分泌物INF-γ及血清总IgE水平存在关联。［中国当代儿科杂志,2009,11（1）：21-24］     

肿瘤坏死因子-α和干扰素-γ多态性与婴儿巨细胞病毒肝炎的关系

目的探讨肿瘤坏死因子-α(TNF-α)基因 238位点和 308位点G/A及干扰素-γ(TFN-γ) 874位点A/T单核苷酸多态性与婴儿巨细胞病毒(CMV)肝炎的关系。方法对CMV肝炎患儿87例和同期入院非CMV肝炎患儿89例,应用ABIPrism7700高通量荧光PCR系统进行测定TNF-α基因 238和 308及TFN-γ 874位点单核苷酸多态性。结果婴儿CMV肝炎患儿TNF-α基因 238和 308位点与对照组比较无显著性差异。IFN-γ 874位点在婴儿CMV肝炎患儿中AA型64例,AT型20例,TT型3例;对照组AA型45例,AT型26例,TT型18例,两组基因型和A/T等位基因频率分布存在显著差异(P=0.001,P<0.001)。结论IFN-γ单核苷酸多态性与婴儿CMV肝炎的易感性有一定的相关性;TNF-α 238和 308单核苷酸多态性与CMV肝炎易感性可能无关。     

乙肝免疫球蛋白联合乙肝疫苗阻断乙型肝炎病毒母婴传播长期随访研究

目的研究乙肝免疫球蛋白(HBIG)联合乙肝疫苗阻断乙型肝炎病毒(HBV)母婴传播的长期效果。方法624例乙型肝炎病毒表面抗原(HBsAg)携带者母亲的婴儿随机分组,按0、1、6月龄单用乙肝疫苗20μg或出生时注射HBIG100IU,然后于1、2、7月龄接种乙肝疫苗20μg。静脉采血随访HBsAg,平均(6.34±1.71)年。结果同单用疫苗比较,HBIG联合免疫使1岁时慢性HBV感染率由17.6%降为5.0%;总慢性HBV感染率双阳性组由24.5%降至10.6%(P<0.005),单阳性组由10.7%降至3.8%(P<0.025)。双阳性组初现HBsAg阳性婴儿慢性化率也降低,在出生时HBsAg阴性而1～6个月时出现HBsAg阳性婴儿,慢性化率由40.9%降至0(P＜0.05),出生时HBsAg阳性婴儿1月龄HBsAg阴转率由26.4%提高至58.8%(P<0.05)。结论HBIG联合乙肝疫苗明显提高母婴传播阻断效果,减少慢性HBV感染率。其机理之一是减少初现HBsAg阳性婴儿的慢性化。     

mTOR基因多态性与小儿癫癎易感性的相关性

目的 探讨哺乳动物雷帕霉素靶蛋白(mTOR)基因两个SNP 位点rs2295080 和rs2536 的多态性与小儿癫癎易感性的关系。方法 采用病例对照研究, 选取480 例癫癎患儿(包括116 例难治性癫癎)以及503 例健康儿童作为研究对象。利用PCR-RFLP 方法进行两个SNP 位点的多态性检测, 比较两组儿童基因型及等位基因的分布频率。结果 癫癎组SNP 位点rs2295080 的基因型(TT、TG、GG)频率和等位基因频率与健康对照组比较差异均无统计学意义(P>0.05);SNP 位点rs2536 的基因型(AA、AG、GG)频率两组比较差异亦无统计学意义(P>0.05), 但癫癎组的等位基因G 频率显著高于健康对照组(OR=1.344, P=0.042, 95%CI：1.010~1.789)。结论 mTOR 基因SNP 位点rs2536 与癫癎的易感性可能相关。     

胰岛因子1基因2个SNP位点与儿童先天性心脏病的相关性研究

目的：探讨天津地区汉族儿童胰岛因子1（Islet1,ISL1）基因2个单核苷酸多态性（SNP）位点rs41268421、rs1017与先天性心脏病（CHD）的相关性。方法：应用聚合酶链反应（PCR）和基因测序技术对35例CHD患儿和30名除外CHD儿童的rs41268421、rs1017位点进行检测,分别比较两个SNP位点基因型频率和等位基因频率在两组的分布情况,并进行单体型分析。结果：SNP位点rs41268421存在GG、GT、TT 3种基因型,CHD组T等位基因频率及携带T等位基因的基因型（包括GT和TT）频率高于对照组（P<0.05）,携带T等位基因的儿童患CHD的危险是G等位基因的4.833倍;rs1017 位点存在AA、AT、TT 3种基因型,CHD组T等位基因频率及携带T等位基因的基因型（包括AT和TT）频率高于对照组（P<0.05）,携带T等位基因的儿童患CHD的危险是A等位基因的4.491倍;2个SNPs位点得出4种单体型,以TT型儿童发生CHD的危险性最高（OR=7.813）。结论：天津地区汉族儿童中ISL1基因单体型TT的出现很可能会增加CHD的患病风险。     

阻断乙型肝炎病毒宫内传播的随机对照研究

目的 最近10多年的研究表明，用乙肝疫苗主被动联合免疫能阻断母婴间乙肝病毒（HBV）传播，保护效果达到70％－90％，而宫内已感染HBV是生后免疫接种失败的主要原因，我们研究用乙肝免疫球蛋白（HBIG）多次产前注射，观察阻断HBV宫内传播的效果。方法 980例携带HBsAg孕妇随机分成两组，一组孕妇产前3个月（妊娠28周起）每4周肌注HBIG 200IU－400IU，直至临产，称HBIG组；另一组不注射为对照，称对照组。所有对象和其所生孩子出生时即采外周血，检测HBsAg、HBeAg，部分测HBV DNA，所有新生儿随访1年。结果 496例新生儿为对照组母亲所生，生后仅接种乙肝疫苗和HBIG；491例新生儿为HBIG组母亲所生，生后同样给予主被动联合免疫。结果显示对照组婴儿的宫内感染率为难4．3％；而HBIG组婴儿的宫内感染率为5．7％（x^2＝20．11，P＜0．001），宫内感染HBV的高危因素是母亲呈HBsAg、HBeAg双阳性或HBV DNA阳性。结论 研究提出产前多次肌注HBIG可有效减少HBV的宫内传播，未发现任何副作用。     

Interferon-gamma Low producer genotype +874 overrepresented in Bacillus Calmette-Guerin nonresponding children

BACKGROUND: There are limited reports on the influence of the immune regulatory genotypes on the efficacy of Bacillus Calmette-Guerin (BCG) in man. This study was designed to evaluate the influence of the cytokine genotype interferon (IFN)-gamma +874T/A on T cell in vitro assays in BCG nonresponders (negative to either in vivo or in vitro test with purified protein derivative or both). METHODS: Ninety healthy children who were without any clinical evidence of the disease, 45 with a BCG-scar and the remaining 45 without scar were assessed for in vitro T cell responses. CD4+ and CD8+ cell counts were measured by flow cytometry. r32kDaBCG (Ag85A-BCG) protein was used to stimulate T cells and IFN-gamma cytokine concentration in the cultures were measured by enzyme-linked immunosorbent assay. Polymorphism in IFN-gamma (+874T/A) region was detected by amplification refractory mutation system-polymerase chain reaction. RESULTS: T cell subsets were within the normal range in all subjects. Children with TT genotype showed significantly higher antigen-induced IFN-gamma (P < 0.001) as compared with those with AT/AA genotype. The highest values were observed in children with TT genotype combined with positive antigen-specific peripheral blood mononuclear cells proliferation. Seventy-five percent of the vaccinated children with TT genotype showed high amounts of stimulated IFN-gamma compared with 66% of scar negative and 16% of scar positive but with AA genotype. CONCLUSIONS: IFN-gamma (+874T/A) polymorphism seemed to be a strong and independent predictor for clinical outcome of both scar-positive and scar-negative children. These results may help in planning future vaccination strategies. The ability to mount in vitro lymphoproliferation did not distinguish the success or failure of BCG vaccination nor predict susceptibility to the disease.     

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.     

Persistence of antibody to hepatitis B and protection from disease among Alaska natives immunized at birth

BACKGROUND: Alaska Native (AN) children were at high risk of acquiring hepatitis B virus (HBV) infection before vaccination began in 1983. We evaluated the long-term protection from hepatitis B (HB) vaccination among AN children immunized when infants. METHODS: During 1984-1995, we recruited a convenience sample of AN children who had received a three dose series of HB vaccine starting at birth and had serum antibody to hepatitis B (anti-HBs) concentrations of >/= 10 mIU/mL at 7-26 months of age. We evaluated anti-HBs concentrations and the presence of anti-HBc in participants' sera every other year up to age 16 years. Anti-HB core antigen (anti-HBc)-positive specimens were tested for hepatitis B surface antigen and for HBV DNA. RESULTS: We followed 334 children for 3151 person-years (median, 10 years per child) with 1610 specimens collected. Anti-HBs concentrations dropped rapidly among all participants. Among children 2, 5 and 10 years of age, 37 of 79 (47%), 33 of 176 (19%) and 8 of 95 (8%), respectively, had anti-HBs concentrations of >/= 10 mIU/mL. Receipt of recombinant vaccine was significantly associated with a more rapid antibody decline (P < 0.001). Six (1.8%) children acquired anti-HBc, 3 of whom had definite breakthrough infections (at least 2 consecutive anti-HBc-positive specimens or at least 1 anti-HBc-positive specimen and HBV DNA detection by PCR). None of these children had detectable hepatitis B surface antigen, and none had symptoms of hepatitis. CONCLUSIONS: Anti-HBs concentrations declined over time among AN infants successfully immunized with HB vaccine starting at birth. Transient anti-HBc appeared in a small percentage of children; however, none developed clinical signs of hepatitis or chronic HBV infection.     

Cytokine release of peripheral blood mononuclear cells in children with chronic hepatitis B virus infection.

BACKGROUND: Immune response to hepatitis B virus (HBV) antigens or mitogens in Asian children with chronic HBV infection who are mainly perinatally infected has not been studied in connection with the production of various cytokines, although these patients are considered to be less responsive to antiviral therapy. METHODS: The production of the cytokines interferon (IFN)-gamma, lymphotoxin, interleukin (IL)-4, tumor necrosis factor (TNF)-alpha, and interleukin (IL)-1beta by peripheral blood mononuclear cells (PBMCs) was studied in 17 hepatitis B surface antigen (HBsAg) carrier children with raised alanine transferase levels (group 1), 17 HBsAg carrier children with normal alanine transferase levels (group 2), and 20 healthy noncarrier control subjects (group 3). RESULTS: Hepatitis B core antigen (HBcAg)-stimulated IFN-gamma production was significantly higher in group 1 than in groups 2 and 3, serum HBeAg cleared within 1 year in five of eight children in group 1 with stimulation indexes higher than 3, and HBcAg-induced IL-4 secretion was minimal in all groups. Interferon-gamma produced by PBMCs stimulated by purified HBsAg did not differ among the three groups. Higher lymphotoxin production by PBMCs stimulated by HBcAg was also noted in groups 1 and 2 than in group 3. Lipopolysaccharide (LPS)-stimulated TNF-alpha production by PBMCs was significantly higher in group 1 than in group 2. There was no association between HBeAg-anti-HBe status and production of various cytokines. No differences were seen in the profile of cytokines induced by HBV antigens or LPS in children of carrier mothers compared with children of HBsAg-negative mothers. CONCLUSION: Increased IFN-gamma production resulting from HBcAg-specific T-helper lymphocyte type 1 response, and increased TNF-alpha production may contribute to cell-mediated antiviral immune response in children with chronic hepatitis B. In HBV carrier children, the ability to produce the studied cytokines is related to whether an endogenous immune attempt to eliminate HBV infection emerges in the patients but is not related to the different modes of acquisition of HBV infection.     

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。     

Seroepidemiology of hepatitis B virus infection among children in Mongolia: Results of a nationwide survey

BACKGROUND: Because Mongolia is one of the highly endemic countries for hepatitis B virus (HBV) infection in the world, hepatitis B (HB) vaccine was introduced into the National Expanded Program on Immunization in 1991. However, relatively few data are available concerning HBV infection among children born after the start of the program, so far. The aim of the present paper was to describe the seroepidemiology of HBV infection among primary school children using representative national data. METHODS: In 2004, a nationwide school-based cross-sectional serosurvey was carried out throughout Mongolia, covering both urban and rural areas. Serum samples were tested for hepatitis B surface antigen (HBsAg), antibody to hepatitis B core antigen (anti-HBc) and hepatitis B e antigen (HBeAg) as well as for liver enzymes. RESULTS: A total of 1145 children aged 7-12 years were studied, which represents nearly 2% of the second grade population of elementary schools in Mongolia. The overall prevalence of HBsAg and anti-HBc was 5.2% (95% confidence interval [CI]: 3.9-6.5%) and 15.6% (95%CI: 13.5-17.7%), respectively. Among HBsAg-positive children 67.8% (95%CI: 55.9-79.7%) were also positive for HBeAg. The prevalence of chronic HBV infection increased by age and was significantly higher among children from rural areas compared to those from urban areas (7.7% vs 3.0%; P < 0.001). In the multivariate logistic regression analysis, rural residence (odds ratio [OR]: 2.57; 95%CI: 1.45-4.58), male sex (OR: 1.9; 95%CI: 1.08-3.26) and age (OR: 1.5; 95%CI: 1.10-2.05) were independent demographic predictors for chronic HBV infection. CONCLUSIONS: The prevalence of chronic HBV infection has been decreasing in the Mongolian young generation, most likely due to infant HB vaccination. However, significant rural-urban differences in the prevalence of HBV infection were found that demand further investigation to estimate the potential causes.     

Hepatitis B precore mutant in children with chronic hepatitis B virus infection

BACKGROUND: In adults, hepatitis B virus (HBV) with a G to A point mutation at nucleotide 83 in the precore region (mutant HBV 83), is commonly found in HB e antibody positive HBV carriers. It has been reported that this mutant is not able to produce HB e antigen. The exact prevalence of mutant HBV 83 in patients with chronic HBV infection is not fully understood, especially in children. METHODS: To investigate the role of mutant HBV 83 in children with chronic HBV infection, sera were tested for the presence of mutant HBV 83 using a mutation site-specific assay. RESULTS: Mutant HBV 83 was detected in 15 of 22 children (68%). Seven children were followed longitudinally, of which three were asymptomatic carriers and the other four had chronic hepatitis B on entry. There was no clear relationship between the disease activity and the presence of mutant HBV 83. CONCLUSIONS: It was concluded that mutant HBV 83 is commonly present in children with chronic HBV infection and this mutant is not necessarily associated with activation of hepatitis.     

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.     

Immune response of immunocompromised children with malignancies to a recombinant hepatitis B vaccine

The aim of this study was to interpret the antibody response to hepatitis B vaccination following an intensified four-dose schedule in 140 cancer patients who presented at our clinic between January 1, 1993 and December 31, 1994. According to therapy status, the patients were divided into two groups: group A consisted of 76 patients undergoing chemotherapy and group B of 64 patients in complete remission and off treatment. The eligibility requirements were negative hepatitis B virus (HBV), HCV, and human immunodeficiency virus serologic markers. A total of four doses (20 μg per dose) of recombinant HB vaccine was administered intramuscularly in the deltoid region at 0, 1, 2, and 6 months. Blood from the vaccinated subjects was obtained at months 1,2,3, and 7 in order to measure anti-HBs titer levels. Protective anti-HBs titers were considered to be those 10 mlU/mL. The overall seroconversion rate 1 month after the fourth dose was 57% (80/140 patients), and the seroconversion rates for groups A and B were 31.5% (24/76 patients) and 87.5% (56/64 patients), respectively. Our results indicated that immunocompromised children undergoing chemotherapy (although less responsive than children in complete remission and off treatment) still preserved their potential to produce protective titers of anti-HBs. On this basis we recommend (1) HB vaccination after diagnosis of malignancy in pediatric patients whenever a high prevalence of HB infection exists and (2) vaccination of patients off therapy and in complete remission.