Comparative Pertussis Antibody Response of Nigerian Children to Diphtheria, Pertussis, Tetanus (DPT) and Pentavalent Vaccines

Background: In Nigeria Pentavalent vaccine had replaced Diphtheria-Pertussis- Tetanus [DPT] vaccine in the prevention of pertussis since 2012. Aims and Objectives: The aim of this study was to compare the anti-pertussis immunoglobin G (IgG) response of children who received DPT with those who received the pentavalent vaccine. Subjects and Methods: This study was carried out in Akpabuyo LGA of Cross River State from April to June 2016. It was a cross-sectional survey of anti-pertussis IgG levels in children aged 6 months to 5 years who received DPT and those who received pentavalent vaccine. IgG antibody levels were determined using enzyme-linked immunosorbent assay. The protective level was set at >11 DU according to manufacturer’s cut off point. Results: Seventy eight out of 230 children [33.9%] who had received DPT had protective levels of anti-pertussis IgG compared to 74 out of 192 children [38.5%] who had received pentavalent vaccine. The difference was not statistically significant [p = 0.61]. The median IgG antibody level in those who received DPT was 8.0 DU (interquartile range (IQR) 4.0 - 13.0) compared with 9.0 DU (IQR) 4.0 - 15.0 in those who received pentavalent vaccine [p = 0.18]. No single factor investigated predicted the development of protective levels of antibody in the multivariate analysis. Conclusion/Recommendation: There was no difference in the antipertussis antibody response between DPT and pentavalent vaccines recipients. Further study is needed to elucidate factors that could be responsible for low anti-pertussis antibody response in this population.

Difference of the Pain during the DPT (Diphtheria-Pertussis-Tetanus) Vaccination

Background: The objective of this study is to determine whether analyze of the infant’s pain associated with diphtheria-pertussis-tetanus (DPT) immunization is useful for vaccination in children. It is not known whether the immunization pain can be prevented with the adequate choice of DPT vaccines among several manufacturers in Japan. Further, it is not clear whether the difference of the reaction during vaccination between gender and age. Design: Three manufacturer’s Japanese DPT vaccines were used in this study. The parents assessed their infant’s pain on a modified visual analogue scale (MVAS), the start of the crying and total crying time during the immunization. Results: The A manufacturer’s DPT vaccine was significantly lower on the proportion of crying, the duration of crying and MVAS score than the other two manufacturer’s DPT vaccines. The proportion of crying, the duration of crying and MVAS score was lower in the boy than in the girl. On the other hand, it had not found the difference of their reactions with age. Conclusions: Our studies have found that the adequate choice of DPT vaccine decreased vaccination pain. The studies also indicate that some tendencies with vaccinations were shown in children. To consider these tendencies was useful in performing less painful vaccination.

Risk factors for pertussis among children hospitalized for pertussis during 2016-2017, in Guizhou Province of China: a case-control study

Aim:Pertussis is a respiratory tract infection,the vaccine for which was introduced in the Expanded Programme on Immunization(EPI)in Guizhou Province of China(hereafter referred as Guizhou)in the 1980s.This vaccine rapidly decreased incidence rates of pertussis in the province,however,despite the wide high coverage of the diphtheria,tetanus and acellular pertussis(DTaP)combined vaccine,there has been a resurgence of pertussis since 2014.Even with this recent increase in disease transmission,risk factors for pertussis infection have not been evaluated in Guizhou.We aimed to provide information on pertussis risk factors and insight on designing targeted pertussis control policies and measures through this study.Methods:A 1:2 matched retrospective case-control study was conducted between 2016 and 2017,involving infants and children younger than 6 years old and parents of the participants.The enrolled cases included clinical and laboratory confirmed pertussis cases according to the WHO-recommended pertussis definition.Controls were selected from children in the same neighborhood who were not diagnosed with pertussis prior to our investigation and did not exhibit any clinical manifestations of pertussis.Results:The household size[Matched odds ratio(OR_(m)=1.4,95%confidence interval(Cl):1.1-1.7]and household members with antecedent cough(OR_(m)=3.6,95%CI:1.8-7.2)were significantly associated with their child’s pertussis onset.The parents’occupations were significantly associated with their child’s pertussis onset(ORm=9.4,95%CI:1.6-54.8,for mother side;ORm=4.5,95%CI:1.2-16.5,for father side),when they worked in the business and/or service industry.Having family members with a history of cough was an independent risk factor for pertussis[Adjusted odds ratio(AOR)=43.6,95%CI:2.7-694.0].Besides,the parents’demographic characteristics and DTaP doses were not found to be independent factors.Conclusion:Household exposure is an important risk factor for pertussis infection in infants and young children and should therefore be considered as a major factor during formulation of pertussis control policies and measures.

Diphtheria and Tetanus Antibody Persistence in Indian Pre-school Children and Response to a Booster Dose of DT Vaccine.

Despite effective vaccines, diphtheria (D) resurged recently in the former socialistic block, and tetanus (T) still occurs in less privileged countries. We studied the antibody persistence for D and T in Indian pre-school children who had received four doses of DTP vaccine and subsequently, the response to a booster dose. Anti-D and anti-T IgG antibodies prior to and one month after a DT vaccine were measured by ELISA in 223 healthy children of 4-6 years who had previously received four doses of the triple vaccine. Adverse reactions were monitored for one month. While 30% and 14% of subjects were susceptible to D and T, respectively, 98% and 100% of them attained seroprotection post-vaccination. Both responses were significant. Local, but not systemic reactions except fever were rather common. A high proportion of the Indian pre-school population is susceptible to D and T, despite of receiving four doses. The current policy of giving the fifth dose at this age is appropriate.

Seroimmunity to Tetanus and Diphtheria among Immunocompetent Adult Patients Admitted to a Tertiary Hospital for Any Reason

Ignoring the importance of receiving booster doses of vaccines in vast majority of adults could result in their lack of immunity against tetanus and diphtheria. In this prospective cohort study all immunocompetent adults ≥ 40 years old who were admitted for any reason during the time period of the survey were enrolled and antibody levels against tetanus and diphtheria were measured. 84 patients (48%) were 40 - 60 years old and 93 (52%) subjects aged older than 60 years. In general, anti-tetanus antibody titer was <0.1 IU/mL (non-immune range) in 83 people (46.9%). For anti-diphtheria antibody, 74 (41.8%) were considered non-immune. Of all people whose tetanus antibody level was <0.1, 19 had a complete history of childhood diphtheria and tetanus immunization and 64 had unknown vaccination history. Among people with diphtheria antibody levels < 0.1, 18 (24.3%) had complete history of childhood vaccination and 56 (75.6%) had unknown history.

吸附无细胞百白破联合疫苗疑似预防接种异常反应监测分析

目的分析吸附无细胞百白破联合疫苗(DTaP)疑似预防接种异常反应(AEFI)的发生特征,评价DTaP预防接种的安全性和AEFI监测系统的运转情况。方法通过疑似预防接种异常反应信息管理系统和中国免疫规划监测信息管理系统,收集北京市丰台区2008—2011年报告的AEFI个案数据,采用描述性方法进行流行病学分析。结果北京市丰台区2008—2011年DTaP AEFI个案61例,报告发生率为13.88/10万剂次,2008、2009、2010、2011年DTaP AEFI发生率比较,差异有统计学意义(χ2=17.312,P=0.001);其中2011年AEFI发生率高于2009年,差异有统计学意义(χ2=11.018,P=0.001)。不同剂次DTaP AEFI发生率比较,差异有统计学意义(χ2=95.586,P=0.000);其中第4剂次DTaPAEFI发生率高于第1、2、3剂次,差异有统计学意义(χ2值分别为38.604、39.805和35.105,P=0.000)。主要报告月份为5—8月。一般反应50例(11.38/10万剂次),以重度发热(≥38.6℃)和(或)局部红肿(>2.5 cm)和(或)局部硬结为主要表现;异常反应9例(2.05/10万剂次),以过敏性皮疹为主要表现;偶合症2例(0.46/10万剂次)。结论 DTaP上市后具有较好的预防接种安全性,AEFI监测系统运转正常,对评价疫苗的安全性提供科学依据。

用无细胞百日咳抗原配制的吸附精制百白破制剂的特性和人群反应及血清学效果

用50L发酵罐培养百日咳菌,经硫酸铵盐析法提取保护性抗原,戊二醛解毒后,与白喉、破伤风类毒素及Al(OH)_3配合制成的吸附精制百白破制剂(APDT),质量符合规程要求。给3～5月龄婴幼儿接种后全身和局部副反应很低,与现行吸附百白破制剂(WPDT)有非常显著性差异。免后血清中抗-PT和抗-FHA抗体均有显著增长,与WPDT制剂组相比,APDT的抗-PT和抗-FHA抗体增长更为显著。APDT免后抗白喉、抗破伤风抗体滴度均超过保护水平。本制剂的质量及免疫效果均达到了国外同类产品水平。

河南省健康人群百日咳、白喉、破伤风抗体水平分析

目的了解河南省健康人群百日咳、白喉、破伤风抗体水平,为制定DPT免疫策略提供依据。方法 2011-2012年度分4个年龄组在河南省5个县(区)抽取健康人共717名,采用间接ELISA法检测血清中百日咳、白喉、破伤风抗体水平。结果在检测的717名健康人中,百日咳IgG抗体平均阳性率为40.59%,白喉IgG抗体阳性率较高,达到82.29%,破伤风IgG抗体阳性率为75.73%。结论白喉和破伤风抗体水平较高,而百日咳抗体水平过低,提示河南省存在百日咳流行隐患,要重视百日咳疫苗接种工作,扩大接种覆盖率。

广东省部分地区人群百、白、破IgG抗体水平监测

目的了解广东省健康人群血清中百日咳、白喉和破伤风(简称百、白、破)抗体水平,为百、白、破防控提供依据。方法采取分层整群抽样法抽出潮州市、汕尾市、深圳市等三个地区部分健康人群,采用间接ELISA法(定量)检测正常人血清中百、白、破IgG抗体水平。结果三个地区健康人群百日咳IgG抗体阳性率为54.1%,白喉IgG抗体保护率为76.4%,破伤风IgG抗体保护率为77.2%。结论广东省三个地区健康人群百日咳IgG抗体阳性率较低,部分地区白喉及破伤风抗体保护率比较低,白喉及破伤风抗体保护率有随着年龄的升高而降低的趋势,提示我们要加强百、白、破的接种率和接种质量。

无细胞百白破b型流感嗜血杆菌联合疫苗的研制

目的研制无细胞百白破b型流感嗜血杆菌联合疫苗(DTaP/Hib)。方法按不同抗原配比配制3组联合疫苗,分别检测疫苗的效价及安全性,从中选择最佳配比配制3批联合疫苗,并用相应批原液,按相同配比配制3批DTaP和3批Hib疫苗作为对照,检测联合疫苗中抗原的相容性。结果3组配比的联合疫苗效价及安全性均达到《中国药典》三部(2005版)要求,联合疫苗中以每毫升含AcP18μgPN、D25Lf、T7Lf和Hib多糖抗原20μg为最佳配比。动物实验证明联合疫苗各抗原间不存在免疫干扰。结论已成功研制4种抗原配比合理的DTaP/Hib联合疫苗。

嘉兴市健康人群百日咳、白喉、破伤风抗体水平监测

目的了解嘉兴市健康人群百日咳、白喉、破伤风抗体水平状况。方法采用分层随机抽样方法,抽取4个年龄组健康人群220名,用试管凝集试验检测百日咳凝集抗体,用间接血凝试验检测白喉、破伤风抗毒素。结果百日咳抗体保护率为91.10%,GMT 1∶887.13;白喉抗毒素保护率为97.60%,GMT 0.4283 U/ml;破伤风抗毒素保护率为95.70%,GMT0.3097 U/ml。结论嘉兴市健康人群对百日咳、白喉、破伤风已形成了良好的免疫屏障。

深圳市南山区健康人群百日咳、白喉、破伤风抗体水平监测

目的了解健康人群百日咳、白喉和破伤风的免疫状况。方法随机抽查部分1～40岁健康人群进行百日咳、白喉和破伤风的抗体水平监测。结果百日咳抗体几何平均滴度1:77.63,抗体保护率21.97%;白喉、破伤风抗毒素平均滴度1.33IU/ml和0.73IU/ml,阳性率99.08%和81.92%。结论对百日咳、白喉和破伤风已经形成了较好的免疫屏障,但人群百日咳抗体水平偏低,应大力推广百白破联合疫苗。

白喉和破伤风类毒素抗原ELISA检测方法的建立

目的建立定量检测白喉和破伤风类毒素抗原的酶联免疫吸附试验(ELISA)方法。方法分别采用白喉、破伤风单抗包被酶标板,兔抗白喉、破伤风多抗作为二抗,辣根过氧化物酶标记的羊抗兔IgG抗体作为酶标抗体,以平行线法建立定量检测白喉和破伤风类毒素抗原含量的夹心ELISA法,并进行方法学验证。结果两种定量检测ELISA方法的验证结果均符合规定。检测白喉类毒素抗原ELISA方法的定量限为8.90×10-4Lf/ml,回收率为98.35%,批内变异系数(CV)≤10.59%,批间CV≤13.51%;检测破伤风类毒素抗原ELISA方法的定量限为2.13×10^(-3)Lf/ml,回收率为107.28%,批内CV≤13.96%,批间CV≤10.06%。结论建立了白喉、破伤风类毒素抗原ELISA检测方法,该法特异性强、准确度高、重复性好,可用于白喉破伤风疫苗产品的质量控制和生产过程控制。

接种百白破疫苗的护理随访效果观察

目的:探讨18～24个月龄儿童加强接种第4针百白破疫苗时给予护理随访的效果。方法:将接种百白破疫苗加强免疫幼儿714名随机分成两组进行比较,采用SPSS统计软件进行资料分析。结果:观察组不良反应发生率和中重度反应明显低于对照组,两组比较差异有统计学意义(P<0.05),家长对护理随访接种工作较满意。结论:对此年龄段幼儿的百白破疫苗加强接种,采取随访的护理方法,不仅能加强与社区之间的沟通与信任,更能减少不良反应的发生,取得良好的效果。

吸附无细胞百日咳菌苗、白喉、破伤风类毒素混合制剂Ⅲ期临床人体接种反应和血清学效果观察报告

吸附无细胞百、白、破混合制剂（ＤＴａｃＰ）于１９９５年６月至１９９７年９月在广东省４个市和陕西省大荔县进行了Ⅲ期临床人体接种反应和血清学效果观察，全程基础免疫婴幼儿６４９６１例，加强注射３８８６０例，总计为１０３８２１例，接种反应轻微，未发现有严重异常反应者。ＤＴａｃＰ在基免后１年和加强注射前抗ＰＴ和抗ＦＨＡ的抗体水平分别为１０１ＥＵ／ｍｌ和５１３ＥＵ／ｍｌ；加强注射后１个月，抗ＰＴ和抗ＦＨＡ的抗体水平显著增长，分别为２４３４ＥＵ／ｍｌ和３１１３ＥＵ／ｍｌ；加强免疫后１年，抗ＰＴ和抗ＦＨＡ的抗体水平均能维持在较高的抗感染水平，分别为２０１ＥＵ／ｍｌ和５８６ＥＵ／ｍｌ；ＤＴａｃＰ抗白喉和抗破伤风的抗体水平，不论是在基免后还是在加强注射后１个月或１年，其≥００１ＨＡＵ／ｍｌ的例数均为１００％，均显著超过儿童抗白喉和抗破伤风感染要求的保护水平（００１ＨＡＵ／ｍｌ）。

吸附精制百日咳菌苗、白喉、破伤风类毒素混合制剂稳定性的研究

将连续生产并已申报人体接种反应观察的三批吸附精制百日咳菌苗、白喉、破伤风类毒素混合制剂，分别于４～８℃、１８～２２℃、３７℃贮存半年、１年、１年半和３０天，然后以小鼠法或豚鼠法对该制剂进行安全稳定性、效力稳定性以及毒性逆转等测试。其毒力安全稳定性试验表明，三批混合制剂中的精制百日咳菌苗在４～８℃贮半年、１年、１年半后、它们的ＢＷＤＵ／ｍｌ、ＬＰＵ／ｍｌ、ＨＳＵ／ｍｌ均无显著性差异（Ｐ＞０．０５）；白喉及破伤风类毒素在４～８℃贮存半年，１年、１年半以及１８～２２℃贮存半年和３７℃贮存３０天后，三批测试组的豚鼠均健存且体重增加。在效力稳定性试验中，４～８℃贮存１年和１年半后精制百日咳菌苗的效力与贮存前（分别为２６．７３ＩＵ／ｍｌ、２１．０２ＩＵ／ｍｌ、１９．１７ＩＵ／ｍｌ）无显著性差异（ｔ＝０．１１４；Ｐ＞０．０５）；白喉及破伤风类毒素４～８℃贮存长达１年半后，效力仍在２～３．２ＩＵ／ｍｌ，动物保护率仍可达８０～１００％。三批混合制剂在３７℃贮存３０天后，通过Ｓｃｈｉｃｋ毒性试验及测定ＢＷＤＵ／ｍｌ、ＬＰＵ／ｍｌ、ＨＳＵ／ｍｌ各指标显示，精制百日咳菌苗、白喉和破伤风类毒素无毒性逆转。说明该吸附精制百、白。

百日咳、白喉、破伤风、乙型肝炎联合疫苗的实验研究

对制备无细胞百日咳菌苗、白喉、破伤风、乙型肝炎联合疫苗的实验室条件进行了初步探索，实验结果表明，联合疫苗的配方以每毫升无细胞百日咳组分１５－１８μｇ．ＰＮ、白喉类毒素３０ｌｆ、破伤风类毒素７－１０ｌｆ和基因工程乙肝表面抗原２０μｇ为宜，稀释缓冲液选用０．８５％ＮａＣｌ溶液吸附效果较好，动物实验证明联合疫苗中各组分均安全有效。

无细胞与全菌体百白破疫苗免疫接种反应对比观察

目的 比较无细胞百白破疫苗 (ADPT)和全菌体百白破疫苗 (WPDT)的接种反应差异。 方法 对满 3个月以上的儿童分别按家长意愿接种其中一种疫苗 ,接种后 6h、 2 4h、 4 8h分别观察全身反应和局部反应 ,并进行对比分析。结果 APDT接种反应 (5 93% )比WPDT(38 34% )显著降低、减轻 ;接种WPDT的发热、红肿、硬结发生率分别为 11 4 7%、 19 89%、 16 10 % ,而接种APDT的发生率分别为 3 33%、 3 4 3%、 1 0 4 % ;APDT的反应强度 (4 4 7% )明显低于WPDT(35 99% ) ,但APDT和WPDT一样仍具有接种针次增加反应率逐步增高的特性 ;2种疫苗都显示2 4h的反应率最高 ,未发现无菌性化脓。结论 APDT在全身反应和局部反应上均低于WPDT。

189例接种无细胞百白破疫苗发生疑似预防接种异常反应病例流行病学分析

目的：分析接种无细胞百白破疫苗（DTaP）发生疑似预防接种异常反应（AEFI）病例的流行病学特征，为改进疫苗质量和提高预防接种服务质量提供参考。方法：对189例报告的接种DTaP发生AEFI的病例进行调查，采用描述流行病学方法进行分析。结果：所有AEFI均为接种不良反应，其中一般反应占98.4%，病例的城乡比为1.8：1，男女比为1.3：1，年龄的中位数为1岁7个月，接种后1 d发生AEFI病例占45.5%，当天发生占42.3%，AEFI的主要临床症状局部红肿、发热和局部硬结的发生率分别为66.1%、49.7%和41.3%，局部红肿的发生率高于局部硬结，1岁~和2岁~年龄组局部红肿的发生率均高于0岁~年龄组，95.5%病例转归良好或治愈，6、7月份为高发时段，接种第4剂次后发生AEFI的比例最高。结论：DTaP安全性较好，接种单位应进一步规范接种操作，降低AEFI的发生率，同时做好接种DTaP发生AEFI的相关知识的宣传教育工作。

HPLC-RID法测定吸附无细胞百白破联合疫苗中甘油的残留量

目的:建立高效液相色谱-示差折光(HPLC-RID)法测定吸附无细胞百白破联合疫苗中甘油残留量的方法,为其检测提供参考。方法:采用NH;色谱柱(250 mm×4.6 mm,5μm),以乙腈-水(85∶15)为流动相,柱温30℃,RID检测器温度35℃,流速1.0 mL·min^(-1)。结果:甘油在43.5~2 173.0μg·mL^(-1)浓度范围内呈良好的线性关系(R^(2)=1.000),平均回收率为99.98%,RSD为0.65%(n=9)。结论:该方法简便、准确,专属性强,可用于甘油残留量的测定,使产品质量更加有效地得到控制。