Postbooster Antibodies from Humans as Source of Diphtheria Antitoxin

Diphtheria antitoxin for therapeutic use is in limited supply. A potential source might be affinity-purified antibodies originally derived from plasma of adults who received a booster dose of a vaccine containing diphtheria toxoid. These antibodies might be useful for treating even severe cases of diphtheria.     

Diphtheria in the postepidemic period, Europe, 2000-2009

Diphtheria incidence has decreased in Europe since its resurgence in the 1990s, but circulation continues in some countries in eastern Europe, and sporadic cases have been reported elsewhere. Surveillance data from Diphtheria Surveillance Network countries and the World Health Organization European Region for 2000-2009 were analyzed. Latvia reported the highest annual incidence in Europe each year, but the Russian Federation and Ukraine accounted for 83% of all cases. Over the past 10 years, diphtheria incidence has decreased by >95% across the region. Although most deaths occurred in disease-endemic countries, case-fatality rates were highest in countries to which diphtheria is not endemic, where unfamiliarity can lead to delays in diagnosis and treatment. In western Europe, toxigenic Corynebacterium ulcerans has increasingly been identified as the etiologic agent. Reduction in diphtheria incidence over the past 10 years is encouraging, but maintaining high vaccination coverage is essential to prevent indigenous C. ulcerans and reemergence of C. diphtheriae.     

DTP immunization status and tetanus antitoxin titers of Mexican American children ages six months through eleven years.

Data from the Mexican American portion of the Hispanic Health and Nutrition Examination Survey (HHANES), conducted in 1982-83, were analyzed for the number of diphtheria, tetanus, and pertussis (DTP) immunizations reported for Mexican American children 6 months-11 years of age and for levels of tetanus antitoxin titers in Mexican American children 4-11 years of age. In Mexican American children 6 months-11 years, 98.2 per cent had one or more DTP immunizations reported (95 per cent CI: 97.5, 98.9%); 85.1 per cent had three or more DTP immunizations reported (95 per cent CI: 83.2, 87.0%). The reported immunization coverage in Mexican American children was corroborated by the tetanus antitoxin titers which were above the minimum protective level (greater than or equal to 0.01 IU/ml) in 99.6 per cent of the 4-11 year olds. Using the American Academy of Pediatrics' (AAP) recommendations for the number of DTP immunizations, 61.1 per cent of the children 6 months-11 years of age had the age-appropriate number of immunizations (95 per cent CI: 58.5, 63.7%). AAP immunization completion rates were higher for children who: had a source of care reported (62.1 vs 44.3%; 95% CI of the difference: 7.1, 28.5); had insurance coverage (63.5 vs 56.1%; 95% CI of the difference: 2, 12.8); lived in a standard metropolitan statistical area (SMSA)-not central city as compared to SMSA-central city or not SMSA (66.6 vs 57.1%; 95% CI of the difference: 4.3, 14.7); and had 12 or more completed years of education for the head of the household (65.4 vs 58.3%; 95% CI of the difference: 1.8, 12.4).(ABSTRACT TRUNCATED AT 250 WORDS)     

鞍山地区一起白喉爆发流行的调查报告

本文报告了自1984年12月至1987年12月鞍山地区发生的一起白喉爆发流行的情况和采取相应预防措施后的效果。这起白喉爆发流行主要发生在劳教所和疗养院,是在人群抗体水平较高的条件下发生的,且主要是由无毒菌株引起发病。经采取注射白喉类毒素和环境消毒等综合措施后,疫情得到控制。     

滨州地区巩固消除白喉成果调查分析

山东省滨州地区1988－1992年实施《山东省消除白喉方案》,落实以预防接种为主的综合性防治措施,以市地为单位适龄儿童白喉类毒素免疫接种率达90％以上,人群免疫水平保持在90％左右,连续5年未检出带菌者,连续15年无病例发生,在经济欠发达的农业地区实现了消除白喉的目标。1992年以后,各项工作指标仍然保持在消除白喉阶段的水平,22年无病例发生,消除白喉的成果得到巩固和提高,进一步证实,人群白喉免疫水平达到90％,可基本保持不发病的结论,提示了在全球范围内消灭白喉的可能性。     

Antibody titres in women six to eight years after the administration of RA2713 and Cendehill rubella vaccines

Titres of haemagglutination-inhibiting antibody have been measured repeatedly in young women during a period of 6-8 years after the administration of RA27/3 and Cendehill attenuated rubella vaccines. Mean antibody titres were initially 217 after RA27/3 and 159 after Cendehill, but the difference diminished after the first year. Antibody titres were subsequently well maintained in both groups and did not reveal any need for regular revaccination. Mean titres in the Cendehill group were partly maintained by symptomless reinfection which was commoner after Cendehill than after RA27/3. Significant falls in titre were equally common after both vaccines, but low titres of 30 or less were more frequent in subjects who had received Cendehill. Mean neutralizing antibody titres were initially 15.4 after RA27/3 vaccine and 9 after Cendehill. Titres remained higher after RA27/3 for 3 years, but the difference then diminished and became insignificant during the fifth year. Revaccination of women with low antibody titres produced significant increases in 69% of subjects when standard RA27/3 vaccine was used; a special preparation of RA27/3 of higher potency produced a similar number of rises (70%) but elicited higher titres and might occasionally be useful for revaccinating women who are likely to come into contact with rubella. Challenge with RA27/3 vaccine produced weaker responses in women who had experienced natural infection than in those whose antibody was vaccine-induced. Rises in antibody titre after revaccination consisted mainly of IgG, but traces of IgM antibody were detected in one vaccinee who had recently experienced natural reinfection and in 1 woman with naturally acquired antibody who had been challenged with high titre RA27/3 vaccine.     

2010—2018年河北省含麻疹成分疫苗常规免疫和补充免疫疑似预防接种异常反应对比分析

目的了解河北省2010—2018年含麻疹成分疫苗(measles-containing vaccine,MCV)常规免疫和补充免疫中疑似预防接种异常反应(adverse event following immunization,AEFI)监测数据的差异,为优化MCV补充免疫策略提供科学依据。方法通过中国免疫规划信息管理系统收集的AEFI个案数据、常规免疫疫苗接种数据和各市专项上报的MCV补充免疫接种数据,采用描述流行病学方法对河北省2010—2018年MCV常规免疫和补充免疫中AEFI监测特征进行统计分析。结果河北省2010—2018年MCV常规免疫和补充免疫分别共报告AEFI个案9352例和2590例。常规免疫中AEFI总报告发生率、一般反应报告发生率、异常反应报告发生率分别为47.81/10万剂、45.31/10万剂和2.32/10万剂;补充免疫的分别是64.40/10万剂、54.03/10万剂和9.08/10万剂。严重异常反应中,常规免疫的热性惊厥、血小板计数减少、急性严重过敏反应报告发生率分别为0.07/10万剂、0.16/10万剂和0.02/10万剂;补充免疫的分别是0.35/10万剂、0.07/10万剂和0.15/10万剂。结论2010—2018年河北省MCV常规免疫和补充免疫不良反应均以一般反应为主,严重异常反应罕见。河北省MCV安全性较好。     

Antibody titres in women six to eight years after the administration of RA2713 and Cendehill rubella vaccines.

Titres of haemagglutination-inhibiting antibody have been measured repeatedly in young women during a period of 6-8 years after the administration of RA27/3 and Cendehill attenuated rubella vaccines. Mean antibody titres were initially 217 after RA27/3 and 159 after Cendehill, but the difference diminished after the first year. Antibody titres were subsequently well maintained in both groups and did not reveal any need for regular revaccination. Mean titres in the Cendehill group were partly maintained by symptomless reinfection which was commoner after Cendehill than after RA27/3. Significant falls in titre were equally common after both vaccines, but low titres of 30 or less were more frequent in subjects who had received Cendehill. Mean neutralizing antibody titres were initially 15.4 after RA27/3 vaccine and 9 after Cendehill. Titres remained higher after RA27/3 for 3 years, but the difference then diminished and became insignificant during the fifth year. Revaccination of women with low antibody titres produced significant increases in 69% of subjects when standard RA27/3 vaccine was used; a special preparation of RA27/3 of higher potency produced a similar number of rises (70%) but elicited higher titres and might occasionally be useful for revaccinating women who are likely to come into contact with rubella. Challenge with RA27/3 vaccine produced weaker responses in women who had experienced natural infection than in those whose antibody was vaccine-induced. Rises in antibody titre after revaccination consisted mainly of IgG, but traces of IgM antibody were detected in one vaccinee who had recently experienced natural reinfection and in 1 woman with naturally acquired antibody who had been challenged with high titre RA27/3 vaccine.     

两种百白破联合疫苗免疫后百日咳的血清学效果

为了解无细胞百白破联合疫苗(DPTa)和全细胞百白破联合疫苗(DPTw)的血清学免疫效果,在上海市卢湾区随机选取3月龄健康婴儿,分两组分别用DPTa和DPTw做基础免疫;又选取18月龄健康儿童也分两组,分别用两种联合疫苗做加强免疫,免疫前和免疫后1、6个月采血,用微量凝集试验检测百日咳凝集抗体,用酶联免疫吸附试验检测抗百日咳毒素抗体(抗-PT)和抗丝状血凝素抗体(抗-FHA)的水平.结果表明经DPTw基础免疫和加强免疫后,凝集抗体阳性、保护率和几何平均滴度(GMT)均明显高于DPTa;免疫后6个月,凝集抗体GMT仍维持在保护水平以上,证明DPTw是有效的.采用DPTa做基础免疫和为以DPTw做基础免疫者的加强免疫,免疫后抗-PT和抗-FHA抗体均明显高于DPTw;免疫后6个月抗-PT、抗-FHA抗体还显著高于保护水平,说明DPTa既可用于基础免疫,也可用于对以DPTw做基础免疫的婴儿的加强免疫.     

上海市浦东新区18岁及以上人群接种新型冠状病毒灭活疫苗疑似预防接种异常反应监测结果分析

目的 评价上海市浦东新区18岁及以上人群接种新型冠状病毒灭活疫苗(简称新冠灭活疫苗)的安全性,为人群接种提供科学依据。方法 收集中国疾病预防控制信息系统中2020年12月—2021年6月浦东新区新冠灭活疫苗疑似预防接种异常反应(Adverse Events Following Immunization, AEFI)监测数据进行统计分析。结果 浦东新区共报告新冠灭活疫苗AEFI病例2 430例,其中一般反应1 240例(51.03%)、异常反应260例(10.70%)、心因性反应699例(28.76%)、偶合症231例(9.51%),不良反应报告发生率为20.63/10万剂次,其中一般反应和异常反应报告发生率分别为17.06/10万剂次和3.58/10万剂次。女性不良反应报告发生率(27.71/10万剂次)高于男性(14.72/10万剂次),第1剂次(28.08/10万剂次)高于第2剂次(12.12/10万剂次)。结论 浦东新区接种的新冠灭活疫苗在安全性范围内。     

2010年石家庄市麻疹疫苗强化免疫疑似预防接种异常反应监测分析

目的分析石家庄市麻疹疫苗强化免疫活动后,疑似预防接种异常反应(adverse events following immunization,AEFI)的发生状况,探讨麻疹疫苗强化免疫活动的安全性。方法采用描述分析方法对监测数据进行分析。结果石家庄市2010年麻疹强化免疫期间共报告AEFI 181例,发生率12.02/10万剂次。其中一般反应161例,异常反应16例,偶合症4例;绝大多数病例转归良好。结论 AEFI监测敏感性高,麻疹疫苗安全性好,未发现严重疑似预防接种异常反应。     

2012年扬州市麻风疫苗效价与基础免疫成功率监测分析

目的了解扬州市麻疹风疹联合减毒活疫苗(简称麻风疫苗)的效价和免疫成功率,考核疫苗管理和冷链运转状况。方法采集60名8月龄儿童麻风疫苗免疫前、后1个月双份血清标本,分别进行麻疹、风疹IgG抗体测定。选择市、县疾病预防控制中心和乡接种点各2支麻风疫苗,采用微量细胞板培养法检测,进行麻风疫苗效价测定。结果免后麻疹抗体阳性59人,阳性率98.33%,免疫成功58人,免疫成功率96.67%,GMT 1∶1 285.13;风疹抗体阳性35人,阳性率58.33%,免疫成功35人,免疫成功率58.33%,GMT 1∶19.67;市、县、乡三个点的麻风疫苗效价均在102.5 TCID50/0.1mL以上,均为合格疫苗。结论扬州市疫苗管理和冷链系统运转状况良好,能保证疫苗的质量。麻风疫苗所包含的麻疹成分免疫原性好,风疹成分免疫原性较差。须进行后续的加强免疫是必要的,还应适时开展大中学生麻风类疫苗追加免疫。     

不同免疫策略的疑似预防接种异常反应影响分析

目的 分析辖区内相关疫苗的疑似预防接种异常反应的发生率及其他要素,给免疫规划工作人员和受种者提供客观真实的接种建议。 方法 分析2012年—2018年6月的687例疑似预防接种异常反应(AEFI)个案,AEFI以一般反应为主。 结果 单剂次疫苗的AEFI总发生率和一般反应发生率较高,各疫苗的安全性良好。 结论 为预防疫苗相关传染病,在联合疫苗及灭活疫苗供货不足的情况下,建议家长和预防接种单位工作人员尽早接种有相同预防效果的替代疫苗,提高疫苗接种的及时性。     

2789例10岁以上儿童重组乙型肝炎疫苗加强免疫效果评价

目的 比较不同重组乙型肝炎(乙肝)疫苗加强免疫效果.方法 选择1周岁内完成血源乙肝疫苗基础免疫的10岁以上儿童2789例,分别接种4种国内常用的不同重组乙肝疫苗,分为A、B、C、D4组,采集血清,使用化学发光法检测HBsAg、抗-HBs、抗-HBc,仅抗-HBs阳性者接种1剂次、抗-HBs阴性者接种3剂次相应疫苗,免疫1个月后采血检测抗-HBs.结果 加强免疫前、免疫1剂次及3剂次后A、B、C、D 4组抗-HBs阳性率分别为36.43%、37.59%、42.91%、46.46%;89.20%、91.52%、90.96%、85.45%;99.12%、99.47%、98.87%、98.85%;加强免疫前、免疫1剂次及3剂次后两两之间抗-HBs阳性率差异均有统计学意义(P值均＜0.05).抗-HBs阴性者加强免疫1剂次、3剂次后,抗-HBs阳转率分别为83.01%、86.41%、84.16%、72.82%;98.62%、99.16%、98.03%、97.84%;与抗-HBs阳性者加强免疫1剂次相比,4组抗-HBs阳转率差异均有统计学意义(P＜0.05).抗-HBs阳性者加强免疫1剂次后几何平均滴度(GMT)分别为2853.21、6254.23、3581.40、3021.32 mIU/ml.抗-HBs阴性者加强免疫1剂次、3剂次后4组GMT分别为273.08、648.52、387.87、245.36 mIU/ml;632.30、2341.14、563.97、394.08 mIU/ml.结论 采用上述4种重组乙肝疫苗对抗-HBs阳性的10岁以上儿童加强免疫1剂次、对抗-HBs阴性的10岁以上儿童加强免疫3剂次,免疫效果良好.

Abstract：

Objective To study the efficiency of booster immunization with different recombinant hepatitis B vaccines.Methods 2789 children aged over 10 years who had completed the basic immunization of hepatitis B vaccine under 1 year old were selected.All the sampled children were classified into four groups (A,B,C and D) and immunized with different hepatitis B vaccines produced by different campanies respectively.Before booster immunization,their blood plasma specimens were detected for hepatitis B virus (HBV) surface antigen (HBsAg),antibodies to HBV surface antigen (anti-HBs) and antibodies to HBV core antigen (anti-HBc) by chemiluminescence.In each group,the anti-HBs positive children were immunized with one dosage and anti-HBs negative children were immunized three dosages of the same vaccine.Their blood specimens were collected again after 1 month,and detected for anti-HBs.Results The anti-HBs positive rates of A,B,C and D group were 36.43%,37.59%,42.91% and 46.46% respectively before immunization while 89.20%,91.52%,90.96% and 85.45% respectively after immunization with one dosage,99.12%,99.47%,98.87% and 98.85% respectively after immunization with three dosages.The differences of anti-HBs positive rates in the four respective groups showed statistical significances between any two rates of pre-immunization,post-immunization with one dosage and post- immunization with three dosages (all P＜0.05).The anti-HBs positive conversion rates of four groups were 83.01%,86.41%,84.16% and 72.82% respectively after immunization with one dosage.The anti-HBs positive conversion rate of four groups were 98.62%,99.16%,98.03% and 97.84% respectively after immunization with three dosages and the difference of positive conversion rates in each group showed statistical significances between booster immunization with one dosage and booster immunization with three dosages.The average GMTs in anti-HBs positive children in the four groups were 2853.21,6254.23,3581.40 and 3021.32 mIU/ml respectively after immunization with one dosage.The average GMTs of anti-HBs negative children in the four groups were 273.08,648.52,387.87 and 245.36 mIU/ml respectively after immunization with one dosage,and were 632.30,2341.14,563.97 and 394.08 mIU/ml respectively after immunization with three dosages.Conclusion Our data showed that it would be suitable to anyone to use the four vaccines for anti-HBs positive children aged over 10 years with one dosage and for anti-HBs negative children aged over 10 years with three dosage booster immunization.     

Epidemiology of Diphtheria in Yemen, 2017-2018: Surveillance Data Analysis

BackgroundAs a consequence of war and the collapse of the health system in Yemen, which prevented many people from accessing health facilities to obtain primary health care, vaccination coverage was affected, leading to a deadly diphtheria epidemic at the end of 2017.ObjectiveThis study aimed to describe the epidemiology of diphtheria in Yemen and determine its incidence and case fatality rate.MethodsData were obtained from the diphtheria surveillance program 2017-2018, using case definitions of the World Health Organization. A probable case was defined as a case involving a person having laryngitis, pharyngitis, or tonsillitis and an adherent membrane of the tonsils, pharynx, and/or nose. A confirmed case was defined as a probable case that was laboratory confirmed or linked epidemiologically to a laboratory-confirmed case. Data from the Central Statistical Organization was used to calculate the incidence per 100,000 population. A P value <.05 was considered significant.ResultsA total of 2243 cases were reported during the period between July 2017 and August 2018. About 49% (1090/2243, 48.6%) of the cases were males. About 44% (978/2243, 43.6%) of the cases involved children aged 5 to 15 years. Respiratory tract infection was the predominant symptom (2044/2243, 91.1%), followed by pseudomembrane (1822/2243, 81.2%). Based on the vaccination status, the percentages of partially vaccinated, vaccinated, unvaccinated, and unknown status patients were 6.6% (148/2243), 30.8% (690/2243), 48.6% (10902243), and 14.0% (315/2243), respectively. The overall incidence of diphtheria was 8 per 100,000 population. The highest incidence was among the age group <15 years (11 per 100,000 population), and the lowest incidence was among the age group ≥15 years (5 per 100,000 population). The overall case fatality rate among all age groups was 5%, and it was higher (10%) in the age group <5 years. Five governorates that were difficult to access (Raymah, Abyan, Sa''ada, Lahj, and Al Jawf) had a very high case fatality rate (22%).ConclusionsDiphtheria affected a large number of people in Yemen in 2017-2018. The majority of patients were partially or not vaccinated. Children aged ≤15 years were more affected, with higher fatality among children aged <5 years. Five governorates that were difficult to access had a case fatality rate twice that of the World Health Organization estimate (5%-10%). To control the diphtheria epidemic in Yemen, it is recommended to increase routine vaccination coverage and booster immunizations, increase public health awareness toward diphtheria, and strengthen the surveillance system for early detection and immediate response.     

Immune responses to pertussis antigens eight years after booster immunization with acellular vaccines in adults

Pertussis-specific antibody and cell-mediated immune (CMI) responses were studied in adults 8 years after booster immunization with either a bicomponent (pertussis toxin and filamentous hemagglutinin) or a monocomponent (pertactin) acellular vaccine and in age-matched healthy controls. The levels of vaccine-induced antibodies were also compared between the serum samples collected before, 1 month, 4 years, and 8 years after immunization. Over the follow-up period, geometric mean values (GMV) of antibodies to the vaccine antigens decreased in both groups of vaccinees. However, the 8-year postimmunization GMV were 3-20 times higher than preimmunization GMV (all P values <0.01). Moreover, both antibody and CMI responses to the vaccine antigens were significantly higher in the vaccinees than in the controls (all P<0.01 for antibody; all P<0.001 for CMI responses). The results show that antibody and CMI responses induced by acellular pertussis vaccines can persist for up to 8 years after booster immunization of adults primed with whole-cell vaccine.     

Antibody persistence in mothers one year after pneumococcal immunization in pregnancy

Background

Pneumococcal infections are a significant cause of morbidity and mortality, and young infants are particularly vulnerable to infection. Maternal immunization can protect infants, but there are limited data on the duration of pneumococcal vaccine antibody in pregnant women. We report on maternal antibody concentrations one year after immunization with 23-valent pneumococcal polysaccharide (23vPPS) vaccine.

Method

The Mother's Gift study randomly assigned 340 pregnant Bangladeshi mothers between ages 18 and 36 to receive either inactivated influenza vaccine (Fluarix^®) or the 23vPPS vaccine (Pneumovax^®) during the third trimester. Sera were collected before immunization, at delivery, and at one year post-delivery. We determined anti-capsular IgG antibody to 9 pneumococcal serotypes by a multiplex Luminex ELISA. We report antibody geometric mean concentrations (GMCs) for 9 serotypes, 12 month/delivery geometric mean ratios (GMRs) and proportions seroprotected (>0.35 mcg/mL) in 23vPPS vaccine recipients and controls at delivery and at 12 months.

Results

Among pneumococcal vaccinees, GMCs remained stable, with an overall 12 month/delivery GMR of 0.83 (95% CI, 0.75–0.92). In the control group, GMCs increased with a mean ratio of 1.98 (95% CI, 1.81–2.17; P < 0.0001). GMCs in these vaccinees did not decline significantly in the 12 months after antenatal immunization.

Conclusion

GMCs in these adult vaccinees and controls did not decline significantly in the 12 months after antenatal immunization. Interestingly, mothers who did not receive 23vPPS in pregnancy show a substantial increase of GMC for most serotypes in the first year after immunization. Further studies are needed to determine the need for repeat doses of 23vPPS vaccine in subsequent pregnancies more than a year later.     

成人乙肝疫苗免疫失败危险因素配对病例对照研究

目的：探讨成人乙肝疫苗免疫失败的危险因素,为采取干预措施提供依据。方法：采用配对病例对照研究方法,对330对病例和对照进行问卷调查,应用SPSS13．0软件进行统计分析。结果：共全程接种4273人,免疫失败率为8．3％,单因素分析显示：体重指数（BMI）、吸烟、饮酒、乙肝家族史与免疫失败有统计学关联（P〈0．01）,多因素分析显示：吸烟、肥胖、有乙肝家族史是乙肝疫苗免疫失败发生的危险因素,OR值分别是1．029-2．722、3．198-25．760和3．999～35．820。结论：控制体重、禁烟、预防家庭内交叉感染可促进免疫成功。     

Zoonotic Transmission of Diphtheria from Domestic Animal Reservoir,Spain

Toxigenic Corynebacterium ulcerans is as an emerging zoonotic agent of diphtheria. We describe the zoonotic transmission of diphtheria caused by toxigenic C. ulcerans from domestic animals in Spain, confirmed by core-genome multilocus sequence typing. Alongside an increasing number of recent publications, our findings highlight the public health threat posed by diphtheria reemergence.