吸附全细胞和吸附无细胞百白破联合疫苗接种不良反应观察

目的评价吸附全细胞百白破联合疫苗(DwPT)和吸附无细胞百白破联合疫苗(DaPT)临床不良反应发生情况,探讨防治和处置经验。方法按照国家规定的免疫程序和方法将百白破联合疫苗接种于健康适龄儿童,观察其临床反应发生情况。结果 DaPT接种不良反应发生率3.81%(57/1497)明显低于DwPT的23.46%(672/2865),两者有明显统计学意义。百白破联合疫苗随着接种次数的增多,发生不良反应情况也同样增多。结论 DaPT比DwPT接种安全性高,不良反应发生率低。接种前充分摇匀,深部肌肉注射,再次接种时更换接种位置,可以减少不良反应发生。     

百白破联合疫苗接种反应1420名婴儿观察

吸附无细胞百白破联合疫苗（diphtheria，tetanua and acellular aertussis combined vaccine，adsorbed，DTaP）是预防儿童百日咳、白喉和破伤风的替代传统全细胞百白破联合疫苗的新型疫苗。传统疫苗由于使用百日咳全菌体配制，接种后会伴有严重的副反应。为此作者从2004年改用吸附无细胞百白破联合疫苗。为了解该疫苗注射后的反应，接种门诊对接种的儿童采用注射后随访及电话咨询方式调查反应发生情况，现报告如下。     

吸附无细胞百白破联合疫苗安全性观察

目的探讨吸附无细胞百白破联合疫苗的安全性。方法对600名3个月~6周岁足月出生的健康儿童,以2∶1的比例按照计划免疫程序随机分别接种试验疫苗和对照疫苗,进行安全性观察。结果发热反应总发生率为15.38%(178/1159),其中2 3级反应率为3.28%(38/1159)。局部反应发生率疼痛为0.60%(7/1159),其中2和3级反应率为0.26%(3/1159),红为l.12%(13/1159),肿为0.78%(9/1159),其中2和3级反应率为0.09%(1/1159),所有受试者在观察期内均未观察到4级(潜在的生命危胁)不良反应。结论试验用吸附无细胞百白破联合疫苗对3月龄及其以上人群具有较好的安全性。     

无细胞百白破疫苗不良反应的研究

目的了解全细胞百白破三联疫苗（WPDT）和无细胞百白破联合疫苗（APDT）接种后的不良反应情况。方法 2006—2009年在电白县疾病预防控制中心预防接种门诊采用单盲法将1000名3月龄～2岁儿童分成2组,其中247名接种WPDT,753名接种APDT,观察局部与全身反应。结果接种WPDT和APDT者,总体不良反应发生率分别为6.50%、1.3%;两者差异有统计学意义（χ2=19.48,P〈0.01）。结论 APDT的接种反应较WPDT低、安全性好。     

吸附无细胞百白破联合疫苗的安全性和免疫原性研究

目的评价某公司研制的吸附无细胞百白破联合疫苗(DTaP)的安全性和免疫原性。方法选择1 200名3~5月龄知情同意、无百白破疫苗接种史、无百日咳白喉破伤风病史、无百白破疫苗接种禁忌症的健康婴幼儿,按1∶1比例随机接种3针次试验疫苗和对照疫苗,每针次间隔1个月。在观察期内对受试者进行安全性观察,采集免前和全程免疫后第28d血清样本,进行免疫原性观察。结果免疫后试验组抗百日咳毒素(PT)、丝状血凝素(FHA)、白喉类毒素(DT)、破伤风类毒素(TT)抗体阳转率均99%,与对照组相比,差异均无统计学意义(P值均0.05),试验组非劣效于对照组。4种抗体几何平均浓度(GMC)试验组均高于对照组(P值均0.01);抗体几何平均增长倍数(GMFI)除PT抗体外,其他3种抗体水平试验组均高于对照组(P值均0.05)。两组全身和局部不良反应均以1级和2级为主,3级不良反应发生率均2%,仅疲倦乏力、肿、疼痛等发生率试验组(2.17%~6.17%)高于对照组(0.67%~3.50%)(P值均0.05)。结论该公司研制的吸附无细胞百白破联合疫苗与同类上市疫苗相比,免疫原性较好,不良反应轻微,安全性可以耐受,可进一步进行多联疫苗探索和研究。     

两种吸附无细胞百白破疫苗免疫接种后不良反应分析

目的:了解两种无细胞百白破疫苗在婴儿群体中免疫接种后的不良反应情况。方法:将3~5月龄的健康婴儿600例分成2组,每组300例,第1组婴儿接种国产吸附无细胞百白破疫苗;第2组婴儿接种进口吸附无细胞百白破疫苗,观察两组婴儿进行免疫接种后1周的不良反应情况。结果:进口吸附无细胞百白破疫苗的免疫接种不良反应率1.0%,局部红肿硬结反应发生率0.7%;国产吸附无细胞百白破疫苗的免疫接种不良反应率4.0%,局部红肿硬结反应发生率5.7%。结论:进口吸附无细胞百白破疫苗的免疫接种不良反应率和局部红肿硬结反应发生率比国产吸附无细胞百白破疫苗低。     

接种吸附无细胞百白破联合疫苗偶合败血症1例

吸附无细胞百白破联合疫苗 (diphtheria,tetanus and acellular pertussis combined vaccine,adsorbed,DTaP) 是预防儿童百日咳、白喉和破伤风的疫苗。按照国家计划免疫程序,出生3 个月~6周岁儿童必须接种百白破联合疫苗。接种DTaP疫苗后一般无反应,有的出现局部反应：如局部红肿、硬结、疼痛等,全身反应：发热、皮疹、惊厥、小儿烦躁不安、吵闹等,偶有过敏性皮疹、血管神经性水肿、无菌性化脓等,发生败血症的报道罕见。现将2013年8月,湖南省儿童医院在儿童免疫接种中遇到1例接种吸附无细胞百白破联合疫苗后,偶合败血症的病例报道如下。     

吸附无细胞和全细胞百白破联合疫苗上市后预防接种安全性的比较分析

目的 评价中国(未包括香港、澳门特别行政区和台湾地区,下同)吸附无细胞百白破联合疫苗(Diphtheria Teta-nus and Acellular Pertusis Combined Vaccine,Absorbed;DTaP)和吸附全细胞百白破联合疫苗(Diphtheria,Tetanus andwhole-cell Pertusis Combined Vaccine,Absorbed;DTwP)上市后预防接种的安全性.方法 通过全国疑似预防接种异常反应(Adverse Events Following Immunization,AEFI)监测系统,收集10个试点省2005～2006年DTaP和DTwP严重不良反应监测数据,采用描述性方法对两种疫苗不良反应的发生特征进行比较分析.结果 中国DTaP和DTwP上市后,严重不良反应总发生率分别为3.5/10万剂和3.3/10万剂;DTaP以过敏反应为主,且第4剂反应危险性高;DTwP以无菌脓肿为主,高危险性反应剂次因反应的临床损害不同而异;部分疫苗品种和批号的反应存在聚集性,DTwP聚集性反应危险高于DTaP.结论 DTaP和DTwP上市后均具有较好的预防接种安全性;聚集性分析显示,DTaP安全性优于DTwP;需进一步加强对每批DTaP或DTwP上市前的质量控制.     

接种吸附无细胞百白破疫苗致1例过敏反应

2004年11月15日，天津市宁河县妇幼接种门诊接种山联泰吸附无细胞百日咳、白喉、破伤风联合疫苗（以下简称无细胞百白破疫苗）后，发生1例过敏反应，现将调查处理过程报告如下。     

无细胞和全细胞百白破疫苗接种不良反应观察

目的比较接种吸附无细胞百白破疫苗（DTaP）与全细胞百白破疫苗（DTwP）后发生疑似预防接种异常反应的差异。方法对2009年1月-2010年12月在辖区内预防接种门诊接种百白破疫苗出现疑似预防接种异常反应进行回顾性分析。结果 62 214名接种DTaP者发生疫苗疑似预防接种异常反应8例,反应率12.86/10万;62 182名接种DTwP者发生疫苗疑似预防接种异常反应54例,反应率86.84/10万;DTwP反应发生率高于DTaP,差异有统计学意义（P〈0.01）。结论 DTaP的接种副反应较DTwP低、安全性好,接种百白破联合疫苗时最好使用吸附无细胞百白破疫苗（DTaP）。     

百白破应急接种效果观察

观察了百白破混合疫苗和安慰剂应急接种控制百日咳爆发点疫情的血清学和现场流行病学效果。观察对象为有百日咳免疫史及接触史的4~6岁幼儿园儿童,随机分成两组,百白破接种76人,安慰剂接种72人。结果:接种后未见强反应及异常反应;百白破应急接种二周及三个月百日咳的GMT比接种前分别上升18.14、4.73倍;接种后21天(百日咳最长潜伏期)内,两组百日咳罹患率、发病距接种平均天数、平均痉咳天数均无差别(P>0.2);三个月内疫苗保护率为62.11%,表明百白破应急接种控制百日咳爆发点疫情安全有效。     

Diphtheria antitoxin response to DTP vaccines used in Swedish pertussis vaccine trials, persistence and projection for timing of booster

Data from two Swedish pertussis vaccine trials with various combination vaccines were used to compare anti-diphtheria antitoxin concentrations over time between different vaccines, vaccine lots and vaccine schedules. The immune responses were measured with a validated ELISA method.Results are given for 1326 children, born 1992, that were recruited to the placebo (DT)-controlled Trial I which used a 2, 4, 6 month schedule. Two DTP acellular and one DTP whole cell vaccine were used. No DT boosters were given until 5 years of age.Trial II recruited children born 1993-94 and compared three DTP acellular vaccines with one DTP whole cell vaccine. Results are given for 306 children in a 2, 4, 6 month schedule and for 531 children in a 3, 5, 12 month schedule. The latter schedule gave significantly higher diphtheria antitoxin concentrations post third dose.The various DTP acellular vaccines and an inefficacious DTP whole cell vaccine gave lower antitoxin concentrations than both an efficacious DTP whole cell vaccine and the DT vaccine. The larger differences in antigen response between vaccines was reduced in the course of time. Generally, an initial rapid decline of antitoxin concentration was followed by a slower decline; the change typically occurring when the antitoxin concentration reached 0.13-0.16 EU/ml. The time needed to reach this level was between 6 and 10 months based on the initial vaccine response.A "best-fit" combined exponential regression model was used to predict the optimal timing for booster vaccinations against diphtheria.Our data support a 3, 5, 12 month schedule followed by a fourth dose 4-5 years after the third dose, depending upon the vaccine used.     

Safety and immunogenicity of hydrogen peroxide-inactivated pertussis toxoid in 18-month-old children.

The immunogenicity and adverse effects of an acellular pertussis vaccine consisting of a purified pertussis toxin inactivated with hydrogen peroxide (PTxd) was evaluated. Children aged 15 to 30 months were injected with 10 (n = 33) or 50 micrograms (n = 34) of PTxd or with diphtheria and tetanus toxoids and whole cell pertussis vaccine (DTP) (n = 34). All children had previously received three doses of DTP during infancy. Both dosages of PTxd induced higher IgG antibody (p less than 0.05 for 10 micrograms dose and p less than 0.01 for 50 micrograms dose) and pertussis antitoxin responses (p less than 0.01 for 50 micrograms dose) than DTP. The 50 micrograms dose gave slightly higher (though not significantly) antibody responses than the 10 micrograms dose of PTxd. None of the vaccines induced detectable IgM or IgA antibody responses to pertussis toxin. At 24 h, local reactions occurred in none of the children injected with 10 micrograms PTxd, 12% with 50 micrograms PTxd and 78% with DTP. Fever at 24 h occurred in 13% after 10 micrograms PTxd, in none after 50 micrograms PTxd and in 53% after DTP. Recipients of DTP, but not of PTxd, had significant increases in neutrophils and decreases in lymphocytes and haematocrit at 24 h (all p less than 0.05). None of the groups showed changes in blood glucose at 24 h. PTxd induced pertussis toxin antibody levels similar to those observed in patients convalescing from natural pertussis. This acellular pertussis vaccine deserves further evaluation for safety and immunogenicity in infants and for efficacy in preventing pertussis.     

吸附全细胞百白破乙肝四联疫苗效果观察

目的 考察武汉生物制品研究所研制的全细胞百日咳、白喉、破伤风、乙肝联合疫苗的安全性和免疫原性，探讨联合疫苗的免疫程序。方法 进行2期临床观察。将研究对象随机分为3组，第1组按照2、4、6月龄接种吸附百白破乙肝(CHO)联合疫苗；第2组按照3、4、5月龄接种吸附百白破乙肝(CHO)联合疫苗；第3组按照3、4、5月龄接种吸附百白破联合疫苗。2期研究也随机分为3组，第1组按照2、4、6月龄接种“百白破乙肝联合疫苗”；第2组按照2、4、6月龄左侧上臂接种乙肝对照疫苗，右侧上臂接种百白破三联对照疫苗。结果 一期安全性试验观察对象91名，其中接种四联疫苗的两组各有1名体温有较弱升高，分别占接种例数的3．3％。二期共接种365例，完成全程免疫共319例。其中四联疫苗2，4，6月龄接种组有4例出现副反应，发生率为3．1％；按2，4，6月龄左臂接种乙肝疫苗、右臂接种白百破三联疫苗组有5例发生副反应，发生率4．2％；第3组0、1、6月龄接种乙肝对照疫苗，3、4、5月龄接种百白破三联对照疫苗。共有14例发生副反应。发生率为12．2％。1、2期临床观察均未发现严重副反应。接种四联疫苗后，接种对象血清白喉、破伤风、乙肝抗体阳转率均达100％，百日咳抗体阳转率大于85％，免疫前后抗体水平具有显性差异。结论 吸附全细胞百白破乙肝四联疫苗具有较好的安全性和有效性，可用于免疫接种；采用2、4、6月龄接种程序可有效诱导产生百日咳、白喉、破伤风、乙肝的保护性抗体反应．     

Characteristics of children with diagnosed pertussis

In 1997 a significant increase in the incidence of pertussis in the ?ód? voivodship was noticed--the incidence increased from 3.32 in 1996 to 26.34. The aim of this work was the analysis of the course of pertussis in the ?ód? voivodeship. Epidemiological history was analysed of 331 children with diagnosed pertussis from the end of 1996 to February 1998. The diagnosis was made on the basis of clinical picture and passive haemagglutination reaction (PHR). The highest incidence occurred between September and November 1997 (196/331--59.2%). Children aged 7-15 years and toddlers constituted the most numerous groups (respectively: 60.7% and 24.5%). The majority of children with pertussis (83%) received four doses of DTP vaccine, according to the current vaccination schedule. Only 8.2% of children did not receive DTP vaccination or received only 1 or 2 doses. In the majority of properly vaccinated children (73.5%--202/275) the disease appeared mainly after 6-15 years from the last 4th dose of DTP vaccine. From the group of children with pertussis, 18.7% required hospitalisation--these were mainly neonates and children aged 2 and 3 years. The number of children who developed pertussis was highest in school age children after 6-15 years from the last dose of vaccine. The severity of the disease, evaluated on the basis of the percentage of hospitalisations, was highest in the youngest age groups. The laboratory methods used (PHR) are not sufficient for proper diagnosis of pertussis, and cannot provide epidemiological data to assess the incidence of the disease. Increasing number of pertussis cases requires a revision in the schedule of prophylactic vaccination.     

Pertussis vaccines: The first hundred years

Vaccines against pertussis have been used for more than a hundred years. This review describes the development of whole-cell (wP) and acellular pertussis (aP) vaccines, which, as DTP combination vaccines, have significantly reduced morbidity and mortality from pertussis, and which currently serve as the building blocks for a variety of vaccines used to immunize all infants worldwide. Two series of efficacy trials done in the 1950s for wP vaccines and in the 1990s for aP-vaccines have established standards for studying vaccine effectiveness. However, irrespective of their longtime use, critical aspects of pertussis vaccines remain unknown, including the exact mechanisms of protective immunity and a correlate of protection. Research to improve on the effectiveness and the duration of protection is ongoing, but although the vaccines are not perfect, only their continued use with a high coverage will ensure that infants and children are being protected from pertussis.     

Interchangeability of Quinvaxem during primary vaccination schedules: Results from a phase IV,single-blind,randomized, controlled,single-center,non-inferiority study

Combination vaccines against diphtheria, tetanus and pertussis (DTP) represent the core of childhood vaccination programs. Quinvaxem, a fully-liquid, pentavalent combination vaccine containing inactivated hepatitis B (HepB), Haemophilus influenzae type b (Hib) and whole-cell pertussis (wP) antigens, and tetanus and diphtheria toxoids, has been shown to be suitable for boosting children primed in infancy with another DTwP–HepB–Hib vaccine. This single-blind, randomized, controlled study was designed to demonstrate non-inferiority of a primary vaccination course (6–10–14 week schedule) of Tritanrix HB + Hib (first dose) and Quinvaxem (second/third doses) versus three doses of Quinvaxem with respect to the seroprotection/seroconversion rates for all antigens one month after vaccination course completion. Four hundred healthy subjects eligible for the local Expanded Program on Immunization were enrolled and equally randomized to the two treatment regimens. All subjects achieved seroprotection for tetanus and Hib, all except one for diphtheria, and all except two achieved seroconversion against Bordetella pertussis. Seroprotection against hepatitis B was achieved by 97.4% of Tritanrix HB + Hib followed by Quinvaxem and 94.9% of Quinvaxem subjects. Therefore, one month after vaccination course completion, seroprotection rates (seroconversion rate for B. pertussis) of Tritanrix HB + Hib followed by Quinvaxem were non-inferior to those elicited by Quinvaxem only, thus meeting the primary objective. Adverse events were comparable between the groups and were in line with the safety profile of the vaccines. The switch of vaccine had no apparent effect on safety endpoints. Our results support the use of Quinvaxem interchangeably with Tritanrix HB + Hib in a primary vaccination course and provides further evidence for the interchangeability of pentavalent vaccines (Clinical Trials.gov registry: NCT01357720).     

The safety and reactogenicity of a reduced-antigen-content diphtheria-tetanus-acellular pertussis (dTpa) booster vaccine in healthy Vietnamese children

Despite effective infant immunization against pertussis, the disease continues to circulate due to waning immunity. Booster vaccinations against pertussis beyond infancy are widely recommended. In Vietnam, however, no recommendations for pertussis boosters beyond the second year of life exist. This open-label, single-centre study was designed to assess the safety of a single booster dose of reduced-antigen-content-diphtheria-tetanus-acellular-pertussis vaccine (dTpa) in 300 healthy Vietnamese children (mean age 7.9 years), who had completed primary vaccination against diphtheria, tetanus and pertussis. Solicited symptoms were recorded for 4 days and unsolicited and serious adverse events (SAEs) for 31 days post-vaccination. Pain and fatigue were the most common solicited local and general symptoms in 35.0% and 14.0% of children, respectively. Grade 3 swelling occurred in 3 children; no large injection site reactions or SAEs were reported. The dTpa booster vaccine was well tolerated and this study supports its administration in school age Vietnamese children.     

Persistence of antibodies at 5-6 years of age for children who had received a primary series vaccination with a pentavalent whole-cell pertussis vaccine and a first booster with a pentavalent acellular pertussis vaccine: immunogenicity and tolerance of second booster with a tetravalent acellular vaccine at 5-6 years of age

The main objective of this study was to assess in 5-6-year-old French children (n=162) the persistence of antibodies induced by a primary series vaccination (at 2-4 months of age) with a pentavalent whole-cell pertussis combined vaccine (DTwcP-IPV-Hib; Pentacoq) and a first booster (at 12-16 months of age) with a pentavalent two-component acellular pertussis combined vaccine (DTacP-IPV-Hib; Pentavac). The second objective was to evaluate in these 5-6-year-old French children the safety and the immunogenicity of a tetravalent pertussis combined vaccine (DTacP-IPV, Tetravac) given as a second booster. RESULTS: before the 2nd booster, more than 90% of children had antibody titers above the defined threshold for polyribosyl ribitol phosphate (PRP), tetanus, diphtheria and poliomyelitis; antibody titers were very low for pertussis. One month after the second booster, all children had sero-protective post-booster titers for tetanus, diphtheria and poliomyelitis types 1-3; over 90% of children had a four-fold rise in titers against DTacP-IPV antigens. Adverse events were mostly solicited reactions, with no serious adverse event. A strong anamnestic response was also observed after the second booster injection with Tetravac, with a satisfactory safety profile. CONCLUSION: Pentavac and Tetravac (acellular pertussis containing vaccines) may thus be administered as first and second boosters respectively, in children primed with Pentacoq (whole-cell pertussis containing vaccine).     

Associated or combined vaccination of Brazilian infants with a conjugate Haemophilus influenzae type b (Hib) vaccine, a diphtheria-tetanus-whole-cell pertussis vaccine and IPV or OPV elicits protective levels of antibodies against Hib

This study investigated the immunogenicity and safety of including a Haemophilus influenzae type b vaccine (polyribosylribitol phosphate conjugated to tetanus toxoid, PRP-T) in three different vaccination schemes: (1) PRP-T reconstituted with a combined diphtheria-tetanus-pertussis-inactivated poliovirus vaccine (DTP-IPV//PRP-T); (2) PRP-T reconstituted with DTP and administered concomitantly with an oral poliovirus vaccine (DTP//PRP-T+OPV); and (3) PRP-T administered concomitantly with DTP at a different injection site and OPV (DTP+PRP-T+OPV). Vaccines were given at 2, 4, and 6 months of age. A total of 252 infants were enrolled, and randomly assigned to one of the three vaccination groups (84 infants in each group); 241 infants were followed until the end of the study. Antibody production against PRP, diphtheria, tetanus and pertussis antigens was satisfactory for each vaccination scheme used. A good response to Hib vaccine was elicited in each group, and 3 months after the third vaccine dose, at least 97% of children in each group had levels of PRP antibody considered to be seroprotective (>0.15 microg/ml), and over 90% of children in each group had levels over 1. 0 microg/ml. The solicited local and systemic adverse events following vaccination were mild in all groups and resolved within 4 days without medical intervention. With the exception of fever, which was more common after the second dose in children who received DTP-IPV//PRP-T, local and systemic reactions did not differ between the vaccination groups. Due to the practical advantages of combined vaccines, their use in routine immunization programs in developing countries is highly desirable. Our results show that Hib conjugate vaccine can be included in routine immunization programs that include either OPV or IPV with satisfactory immunogenicity and safety profiles. This flexible approach should facilitate the inclusion of the Hib conjugate vaccine in routine immunization programs on a world-wide scale.