Diphtheria is a fulminant bacterial disease caused by toxigenic strains of Corynebacterium diphtheriae whose local and systemic manifestations are due to the action of the diphtheria toxin (DT). The vaccine which is u...Diphtheria is a fulminant bacterial disease caused by toxigenic strains of Corynebacterium diphtheriae whose local and systemic manifestations are due to the action of the diphtheria toxin (DT). The vaccine which is used to prevent diphtheria worldwide is a toxoid obtained by detoxifying DT. Although associated with high efficacy in the prevention of disease, the current anti-diphtheria vaccine, one of the components of DTP (diphtheria, tetanus and pertussis triple vaccine), may present post vaccination effects such as toxicity and reactogenicity resulting from the presence of contaminants in the vaccine that originated during the process of production and/or detoxification. Therefore, strategies to develop a less toxic and at the same time economically viable vaccine alternatives are needed to improve existing vaccines in use worldwide. In this study, the Moreau substrain of BCG which is used in Brazil as a live vaccine against human tuberculosis was genetically modified to carry and express the gene encoding for the diphtheria toxin fragment B (DTB). As such, the DNA sequence encoding the dtb gene was cloned into the pUS977 shuttle vector for cytoplasmic expression and successfully introduced into BCG cells by electroporation. Mice immunized with recombinant BCG expressing DTB showed seroconversion with the detection of specific antibodies against DTB. Also, rBCGs stably expressing DTB persisted up to 60 days in the absence of selective pressure in mice and cell viability did not change significantly during the period tested. Finally, immune sera from BALB/c mice vaccinated with rBCGpUS977dtbPW8 were preliminarily tested for their capacity of neutralizing the diphtheria toxin in the Vero Cells assay.展开更多
The genetic modification of the live attenuated Mycobacterium bovis BCG to deliver a protective Corynebacterium diphtheriae antigen in vivo could be a safer and less costly alternative to the new and more expensive DT...The genetic modification of the live attenuated Mycobacterium bovis BCG to deliver a protective Corynebacterium diphtheriae antigen in vivo could be a safer and less costly alternative to the new and more expensive DTP vaccines available today, in particular to third world-countries. The stability of expression of heterologous antigens in BCG, however, is a major challenge to the use of live recombinant bacteria in vaccine development and appears to be dependent to a certain extent, on a genetic compatibility between the expression cassette within the plasmid construct and the mycobacterium host. In the quest for the best recombinant BCG transformant to express the dtb gene of C. diphtheriae we generated two new rBCG strains by transforming the Moreau substrain of BCG with the mycobacterial expression vectors pUS973 and pUS977, each one carrying a different promoter to drive the expression of the target antigen. After transformation recombinant BCG clones were selected on Middlebrook 7H10 kanamycin Agar plates, expanded in Middlebrook 7H9 kanamycin Broth and analyzed by agarose gel electrophoresis and immunoblotting. rBCGs transformed with the construct carrying the weak PAN promoter from M. paratuberculosis stably expressed the dtb gene. Conversely, rBCGs transformed with the construct carrying the strong mycobacterium hsp60 promoter were unstable and consequently unfit for the expression of the C. diphtheriae gene.展开更多
AIM To establish an inducible liver injury mouse model and transplant human hepatocytes to obtain liverhumanized mice.METHODS We crossed three mouse strains,including albumin(Alb)-cre transgenic mice,inducible diphthe...AIM To establish an inducible liver injury mouse model and transplant human hepatocytes to obtain liverhumanized mice.METHODS We crossed three mouse strains,including albumin(Alb)-cre transgenic mice,inducible diphtheria toxin receptor(DTR) transgenic mice and severe combined immune deficient(SCID)-beige mice,to create Alb-cre/DTR/SCID-beige(ADSB) mice,which coincidentally harbor Alb-cre and DTR transgenes and are immunodeficient. As the Cre expression is driven by the liver-specific promoter Alb(encoding ALB),the DTR stop signal flanked by two lox P sites can be deleted in the ADSB mice,resulting in DTR expression in the liver. ADSB mice aged 8-10 wk were injected intraperitoneally(i.p.) with diphtheria toxin(DT) and liver damage was assessed by serum alanine aminotransferase(ALT) level. Two days later,mouse livers were sampled for histological analysis,and human hepatocytes were transplanted into the livers on the same day. A human ALB enzyme-linked immunosorbent assay was performed 7,14,21 and 28 d after transplantation. Human CD68 immunohistochemistry was performed 30 and 90 d after transplantation.RESULTS We crossed Alb-cre with DTR and SCID-beige mice to obtain ADSB mice. These mice were found to have liver damage 4 d after i.p. injection of 2.5 ng/g bodyweight DT. Bodyweight began to decrease on day 2,increased on day 7,and was lowest on day 4(range,10.5%-13.4%). Serum ALT activity began to increase on day 2 and reached a peak value of 289.7 ± 16.2 IU/m L on day 4,then returned to background values on day 7. After transplantation of human liver cells,peripheral blood human ALB level was 1580 ± 454.8 ng/m L(range,750.2-3064.9 ng/m L) after 28 d and Kupffer cells were present in the liver at 30 d in ADSB mice.CONCLUSION Human hepatocytes were successfully repopulated in the livers of ADSB mice. The inducible mouse model of humanized liver in ADSB mice may have functional applications,such as hepatocyte transplantation,hepatic regeneration and drug metabolism.展开更多
Three diphtheria toxin (DT) mutants CRM-197, DT-del (148) and DT-El48S-K516A-F530A were cloned in B- Subtilis plasmid PSM604 under the subtilisin signal sequence. The expression was effective in both SMS300 and SMS118...Three diphtheria toxin (DT) mutants CRM-197, DT-del (148) and DT-El48S-K516A-F530A were cloned in B- Subtilis plasmid PSM604 under the subtilisin signal sequence. The expression was effective in both SMS300 and SMS118, but higher yield of 7. 1 mg/L was observed in SMS300 compared with 2. 1 mg/L in SMS118. Western blot showed that the recombinant protein could be effectively secreted into the culture medium as a 58 ku peptide, and could be de-graded into two peptides of 37ku and 21ku.展开更多
Objective： This study aimed to express a fusion protein of diphtheria toxin and human B cell-activating factor （DT388sBAFF） in Escherichia coli （E. coli） and investigate its activity in human B-lineage acute lymp...Objective： This study aimed to express a fusion protein of diphtheria toxin and human B cell-activating factor （DT388sBAFF） in Escherichia coli （E. coli） and investigate its activity in human B-lineage acute lymphoblastic leukemia 1 cells （BALL-1）. Methods： A fragment of DT388sBAFF fusion gene was separated from plasmid pUC57-DT388sBAFF digested with Nde I and Xho I, and inserted into the expression vector pcold II digested with the same enzymes. Recombinants were screened by the colony polymerase chain reaction （PCR） and restriction map. The recombinant expression vector was transformed into BL21 and its expression was induced by isopropyl β-D-1-thiogalactopyranoside （IPTG）. The recombinant protein was identified by sodium dodecyl sulfate-polyacrylamide gel electrophoresis （SDS-PAGE） and Western blot, and then purified by Ni2＋-NTA affinity chromatography. The expression level of B cell-activating factor receptor （BAFF-R） on BALL-1 cells was assessed by real-time PCR. The receptor binding capacity of recombinant protein was determined by cell fluorescent assay. The specific cytotoxicity of recombinant protein on BALL-1 cells was detected by 3-（4,5-dimethylthiazolyl-2）-2,5-diphenyltetrazolium bromide （MTT） assay. Results： The expression level of recombinant protein was 50% of total bacterial proteins in E. coli, and the recombinant protein could bind to BAFF-R-positive BALL-1 cells and thereby produce a cytotoxic effect on the cells. Conclusion： The fusion protein expression vector DT388sBAFF was successfully constructed and the recombinant protein with selective cytotoxicity against BALL-1 cells was obtained, providing foundation for further study of the therapy of human B-lineage acute lymphoblastic leukemia.展开更多
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-sc...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.展开更多
Objective: To study the effects of recombinant expression vector containing human breast cancer DF3 promotor and diphtheria toxin A fragment on human breast cancer cells. Methods: Constructing recombinant expression v...Objective: To study the effects of recombinant expression vector containing human breast cancer DF3 promotor and diphtheria toxin A fragment on human breast cancer cells. Methods: Constructing recombinant expression vector PGL3-DF3-DTA and transfecting it into human breast cancer cells of DF3 positive and negative. By means of RT-PCR to measure the expression of DTA in human breast cancer cells. MTT color-imetry was used to examine the effect of PGL3-DF3-DTA on growth of human breast cancer cells. By experiment on nude mice to observe the killing effect of PGL3-DF3-DTA on human breast cancer cells. Results: Recombinant expression vector PGL3-DF3-DTA was highly expressed in human breast cancer cell line of DF3 positive, and it could kill the human breast cancer cells not only in vitro but also in vivo. Conclusion: Recombinant expression vector PGL3-DF3-DTA could produce specific killing effect on human breast cancer cell line of DF3 positive.展开更多
Background: Diphtheria is still endemic in India due to inadequate immunization. The incidence of myocarditis is higher in these patients. Objectives: The objective of this study was to study clinical profile, clinica...Background: Diphtheria is still endemic in India due to inadequate immunization. The incidence of myocarditis is higher in these patients. Objectives: The objective of this study was to study clinical profile, clinical outcomes as well as immunization status of the patients diagnosed with diphtheria myocarditis in Indian scenario. Methodology: This prospective observational study was carried out in one of the tertiary care hospital of south India from August 2011 to December 2012. A total of 33 cases with clinically confirmed diagnosis of diphtheria myocarditis were enrolled depending upon the inclusion and exclusion criteria of the study. Electrocardiography and 2-dimensional echocardiography was done at the time of admission and repeated when required. Results: The most common age group affected is 5 - 10 years, with no sex difference in occurrence. Only 1 patient, out of 33 patients, was adequately immunized. Asymptomatic myocardial involvement (with only changes in electrocardiogram) was seen in 21 patients whereas 12 patients were symptomatic. The average duration of resolution of electrocardiographic changes was 4 - 6 weeks. It should be noted that out of 28 patients who developed conduction abnormalities, 24 patients died. Temporary pacemaker support was given for 8 patients, of whom only one patient recovered. The patient was followed till hospital discharge. Conclusion: The mortality associated with diphtheria myocarditis is higher in Indian population. As diphtheria can be prevented by adequate vaccination, efforts should be maximized for 90% coverage with three doses of diphtheria toxoid in children below one year of age and immunity towards it should be maintained by booster doses.展开更多
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 adu...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.展开更多
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 whet...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.展开更多
<strong>Background:</strong> In Nigeria Pentavalent vaccine had replaced Diphtheria-Pertussis- Tetanus [DPT] vaccine in the prevention of pertussis since 2012. <strong>Aims and Objectives:</strong...<strong>Background:</strong> In Nigeria Pentavalent vaccine had replaced Diphtheria-Pertussis- Tetanus [DPT] vaccine in the prevention of pertussis since 2012. <strong>Aims and Objectives:</strong> 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. <strong>Subjects and Methods:</strong> 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. <strong>Results:</strong> 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 [<em>p</em> = 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 [<em>p</em> = 0.18]. No single factor investigated predicted the development of protective levels of antibody in the multivariate analysis. <strong>Conclusion/Recommendation:</strong> 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.展开更多
Background Diphtheria,caused by Corynebacterium diphtheriae,remains a serious public health threat in areas with low vaccination coverage,despite global declines due to widespread immunization and improved clinical ma...Background Diphtheria,caused by Corynebacterium diphtheriae,remains a serious public health threat in areas with low vaccination coverage,despite global declines due to widespread immunization and improved clinical management.A major outbreak in Nigeria from 2022 to 2023 underscored the persistent risk in regions with inadequate vaccination.This study aims to assess the transmission dynamics of diphtheria in Kano State,the epicenter of the outbreak,by estimating key epidemiological parameters,including the generation time(GT),approximated in our study by serial interval,and effective reproduction number(R).Methods We analyzed diphtheria case-based data from Kano State,Nigeria,collected between August 18,2022,and November 29,2023.Generation time was approximated using serial intervals in confirmed cases within the same geographical areas.The effective reproduction number(R)was calculated using four methods:Maximum Likelihood Estimation(MLE),Exponential Growth(EG),Sequential Bayesian(SB),and Time-Dependent(TD),focusing on the period of maximum exponential growth.A sensitivity analysis was conducted to quantify the impact of uncertainties in the GT derived from our data on the estimation of R.Results Over the 469-day outbreak period,13,899 diphtheria cases were reported,with complete data available for 9406 cases.The estimated mean generation time was 2.8 days(SD=3.48 days),with 97%of cases having a GT of less than 21 days.The Restimates varied across methods,with the TD method producing the highest reproduction number of 2.21 during the peak growth period.Sensitivity analysis showed that Restimates increased with longer generation times.The models,except for the SB method,demonstrated a generally strong fit with the outbreak exponential growth period.Conclusion The ongoing diphtheria outbreak in Nigeria highlights the critical threat posed by declining vaccination coverage.This study provides valuable insights into the transmission dynamics of diphtheria during a prolonged and widespread outbreak,enhancing our understanding of disease spread in this context.While certain limitations may influence the interpretation of our estimates,the findings offer valuable information for future diphtheria outbreak preparedness and response in the African context.展开更多
OBJECTIVE: To test whether the diphtheria toxin A (DT-A) chain coding sequence linked to murine immunoglobulin Kappa light chain (IgKappa) promoter and enhancer have selective cytocidal effects on IgKappa producing ce...OBJECTIVE: To test whether the diphtheria toxin A (DT-A) chain coding sequence linked to murine immunoglobulin Kappa light chain (IgKappa) promoter and enhancer have selective cytocidal effects on IgKappa producing cells. METHODS: The diphtheria toxin A gene or beta galactosidase (beta-gal) gene were linked to a murine IgKappa promoter and enhancer to construct pcDNA3IgKappaDTA or pcDNA3IgKappaLacZ plasmids. These plasmids were transfected into IgKappa producing or non-producing cells by the liposome coated DNA method. Expression of beta-gal activity and effects on cell growth of transfected cells were assessed. RESULTS: The beta-gal gene, under the control of cytomegalovirus (CMV) promoter, can express in all cell lines. Expression of beta-gal under the control of the IgKappa promoter was detected only in the IgKappa producing cell line, CA46. Expression of beta-gal was greatly suppressed when cotransfected with pcDNA3IgKappaDTA in CA46 cells.Cell growth of CA46 cells transfected with pcDNA3IgKappaDTA plasmid was significantly inhibited compared with CA46 cells transfected with pcDNA3IgKappaLacZ. CONCLUSION: Selective killing of IgKappa producing cells can be attained by introducing the diphtheria toxin A gene under the control of IgKappa promoter and enhancer.展开更多
Background Certain infectious diseases are caused by specific bacterial pathogens,including syphilis,gonorrhea,typhoid and paratyphoid fever,diphtheria,pertussis,tetanus,leprosy,and tuberculosis.These diseases signifi...Background Certain infectious diseases are caused by specific bacterial pathogens,including syphilis,gonorrhea,typhoid and paratyphoid fever,diphtheria,pertussis,tetanus,leprosy,and tuberculosis.These diseases significantly impact global health,contributing heavily to the disease burden.The study aims to thoroughly evaluate the global burden of syphilis,gonorrhea,typhoid and paratyphoid fever,diphtheria,pertussis,tetanus,and leprosy.Methods Leveraging the Global Burden of Disease(GBD)study 2021,age-specific and Socio-demographic Index(SDI)-specific incidence,disability-adjusted life-years(DALYs),and death for eight specific bacterial infections across 204 countries and territories from 1990 to 2021 were analyzed.Percentage changes in age-standardized incidence rate(ASIR),DALY rate,and mortality rate(ASMR)were also examined,with a focus on disease distribution across different regions,age groups,genders,and SDI.Results By 2021,among the eight diseases,gonococcal infection had the highest global ASIR[1096.58 per 100,000 population,95%uncertainty interval(UI):838.70,1385.47 per 100,000 population],and syphilis had the highest global age-standardized DALY rate(107.13 per 100,000 population,95%UI:41.77,212.12 per 100,000 population).Except for syphilis and gonococcal infection,the age-standardized DALY rate of the remaining diseases decreased by at least 55%compared to 1990,with tetanus showing the largest decrease by at least 90%.Globally,significant declines in the ASIR,age-standardized DALY rate,and ASMR for these eight bacterial infections have been observed in association with increases in the SDI.Regions with lower SDI,such as sub-Saharan Africa,experienced a relatively higher burden of these eight bacterial infections.Conclusions Although there has been an overall decline in these eight diseases,they continue to pose significant public health challenges,particularly in low SDI regions.To further reduce this burden in these areas,targeted intervention strategies are essential,including multi-sectoral collaboration,policy support,improved WASH management,and enhanced research efforts.展开更多
The COVID-19 pandemic caused significant disruptions in the healthcare system,affecting vaccinations and the management of diphtheria cases.As a consequence of these disruptions,numerous countries have experienced a r...The COVID-19 pandemic caused significant disruptions in the healthcare system,affecting vaccinations and the management of diphtheria cases.As a consequence of these disruptions,numerous countries have experienced a resurgence or an increase in diphtheria cases.West Java province in Indonesia is identified as one of the high-risk areas for diphtheria,experiencing an upward trend in cases from 2021 to 2023.To analyze the situation,we developed an SIR model,which integrated DPT and booster vaccinations to determine the basic reproduction number,an essential parameter for infectious diseases.Through spatial analysis of geo-referenced data,we identified hotspots and explained diffusion in diphtheria case clusters.The calculation of R0 resulted in an R0=1.17,indicating the potential for a diphtheria outbreak in West Java.To control the increasing cases,one possible approach is to raise the booster vaccination coverage from the current 64.84%to 75.15%,as suggested by simulation results.Furthermore,the spatial analysis revealed that hot spot clusters were present in the western,central,and southern regions,posing a high risk not only in densely populated areas but also in rural regions.The diffusion pattern of diphtheria clusters displayed an expansion-contagious pattern.Understanding the rising trend of diphtheria cases and their geographic distribution can offer crucial insights for government and health authorities to manage the number of diphtheria cases and make informed decisions regarding the best prevention and intervention strategies.展开更多
Due to the use of vaccines,infections caused by Corynebacterium diphtheriae are now rare.Here we describe a case of bacteremia complicated with pneumonia caused by C.diphtheriae in a 69-year-old male patient.The patie...Due to the use of vaccines,infections caused by Corynebacterium diphtheriae are now rare.Here we describe a case of bacteremia complicated with pneumonia caused by C.diphtheriae in a 69-year-old male patient.The patient presented at the emergency department with a 2 days history of fever of unknown origin.Subsequent examinations revealed pneumonia and bacteremia.Non-toxigenic C.diphtheriae strains were isolated from blood and sputum.The patient had antimicrobial therapy with good improvement.We highlight the important role of C.diphtheriae in causing bacteremia and pneumonia,and its accurate and timely diagnosis is needed to avoid poor visual outcomes.展开更多
The localized outbreaks of diphtheria still happened in some areas in recent years. The case—fatality rate Of diphtheria is rising and so is the case—fatality rate of toxic myocarditis. About 16 years ago, reviewing...The localized outbreaks of diphtheria still happened in some areas in recent years. The case—fatality rate Of diphtheria is rising and so is the case—fatality rate of toxic myocarditis. About 16 years ago, reviewing the clinical data concerning patients who had died of diphtheria in our hospital, we learned a lesson from our faults in the treatment of diphtheria for the pur-展开更多
目的 评价2020—2022年吉林省适龄儿童接种含无细胞百白破成分疫苗的安全性,以期为后续预防接种工作中疫苗的安全使用提供参考。方法 通过吉林省免疫规划信息管理系统和国家免疫规划信息管理系统疑似预防接种异常反应(adverse event fol...目的 评价2020—2022年吉林省适龄儿童接种含无细胞百白破成分疫苗的安全性,以期为后续预防接种工作中疫苗的安全使用提供参考。方法 通过吉林省免疫规划信息管理系统和国家免疫规划信息管理系统疑似预防接种异常反应(adverse event following immunization,AEFI)功能管理模块,收集2020年1月1日—2022年12月31日吉林省适龄儿童接种吸附无细胞百白破联合疫苗(diphtheria,tetanus and acellular pertussis combined vaccine,DTaP)、无细胞百白破-b型流感嗜血杆菌联合疫苗(diphtheria,tetanus,acellular pertussis and Haemophilus influenzae type b combined vaccine,DTaP-Hib)和无细胞百白破-灭活脊髓灰质炎-b型流感嗜血杆菌联合疫苗[diphtheria,tetanus,pertussis(acellular,component),poliomyelitis(inactivated)vaccine and Haemophilus type b conjugate vaccine,adsorbed,DTaP-IPV/Hib]后发生AEFI的个案报告信息,采用描述性流行病学方法进行分析,并应用统计学方法比较组间差异。结果 2020—2022年吉林省适龄儿童接种DTaP、DTaP-Hib和DTaP-IPV/Hib共1 301 812剂次,共计报告AEFI个案3 132例(240.59/10万剂次),其中一般反应3 122例(99.68%,239.82/10万剂次),异常反应7例(0.22%,0.54/10万剂次),偶合症3例(0.1%,0.23/10万剂次)。3种含DTaP成分疫苗的AEFI报告发生率分别为257.00/10万剂次(3 025例)、175.61/10万剂次(34例)、69.26/10万剂次(73例),差异有统计学意义(χ^(2)=145.53,P<0.001);3种含DTaP成分疫苗加强免疫AEFI报告发生率高于基础免疫,差异有统计学意义(χ^(2)分别为254.98、18.03、20.39,P均<0.05);报告的AEFI病例以一般反应为主,包括发热、局部红肿、局部硬结等,主要发生于接种疫苗后0~1 d内。结论 2020—2022年吉林省适龄儿童接种DTaP、DTaP-Hib和DTaP-IPV/Hib的AEFI以一般反应为主,总体安全性良好。建议持续加强接种后AEFI监测,并优化被动监测系统以减少漏报偏倚。展开更多
基金The authors gratefully acknowledge supported by Bio-Manguinhos/FIOCRUZ,PAPESII/FIOCRUZ,FAPERJ,CNPq,CAPES,Programa de Nucleo de Excelencia(PRONEX/MCT/CNPq)We thank Fundacao Ataulfo de Paiva for the strain of BCG.
文摘Diphtheria is a fulminant bacterial disease caused by toxigenic strains of Corynebacterium diphtheriae whose local and systemic manifestations are due to the action of the diphtheria toxin (DT). The vaccine which is used to prevent diphtheria worldwide is a toxoid obtained by detoxifying DT. Although associated with high efficacy in the prevention of disease, the current anti-diphtheria vaccine, one of the components of DTP (diphtheria, tetanus and pertussis triple vaccine), may present post vaccination effects such as toxicity and reactogenicity resulting from the presence of contaminants in the vaccine that originated during the process of production and/or detoxification. Therefore, strategies to develop a less toxic and at the same time economically viable vaccine alternatives are needed to improve existing vaccines in use worldwide. In this study, the Moreau substrain of BCG which is used in Brazil as a live vaccine against human tuberculosis was genetically modified to carry and express the gene encoding for the diphtheria toxin fragment B (DTB). As such, the DNA sequence encoding the dtb gene was cloned into the pUS977 shuttle vector for cytoplasmic expression and successfully introduced into BCG cells by electroporation. Mice immunized with recombinant BCG expressing DTB showed seroconversion with the detection of specific antibodies against DTB. Also, rBCGs stably expressing DTB persisted up to 60 days in the absence of selective pressure in mice and cell viability did not change significantly during the period tested. Finally, immune sera from BALB/c mice vaccinated with rBCGpUS977dtbPW8 were preliminarily tested for their capacity of neutralizing the diphtheria toxin in the Vero Cells assay.
基金Research supported by Bio-Manguinhos/FIOCRUZ,PAPES II/FIOCRUZ,FAPERJ,CNPq,CAPES,Programa de Núcleo de Excelencia(PRONEX/MCT/CNPq).
文摘The genetic modification of the live attenuated Mycobacterium bovis BCG to deliver a protective Corynebacterium diphtheriae antigen in vivo could be a safer and less costly alternative to the new and more expensive DTP vaccines available today, in particular to third world-countries. The stability of expression of heterologous antigens in BCG, however, is a major challenge to the use of live recombinant bacteria in vaccine development and appears to be dependent to a certain extent, on a genetic compatibility between the expression cassette within the plasmid construct and the mycobacterium host. In the quest for the best recombinant BCG transformant to express the dtb gene of C. diphtheriae we generated two new rBCG strains by transforming the Moreau substrain of BCG with the mycobacterial expression vectors pUS973 and pUS977, each one carrying a different promoter to drive the expression of the target antigen. After transformation recombinant BCG clones were selected on Middlebrook 7H10 kanamycin Agar plates, expanded in Middlebrook 7H9 kanamycin Broth and analyzed by agarose gel electrophoresis and immunoblotting. rBCGs transformed with the construct carrying the weak PAN promoter from M. paratuberculosis stably expressed the dtb gene. Conversely, rBCGs transformed with the construct carrying the strong mycobacterium hsp60 promoter were unstable and consequently unfit for the expression of the C. diphtheriae gene.
基金Supported by Shanghai Science and Technology Development Foundation Project,No.12140900300Shanghai Municipal Commission of Health and Family Planning Project,No.20144Y0073+1 种基金Shanghai Public Health Clinical Center Project,No.2014M08National Science and Technology Major Project,No.2017ZX10304402-001-012
文摘AIM To establish an inducible liver injury mouse model and transplant human hepatocytes to obtain liverhumanized mice.METHODS We crossed three mouse strains,including albumin(Alb)-cre transgenic mice,inducible diphtheria toxin receptor(DTR) transgenic mice and severe combined immune deficient(SCID)-beige mice,to create Alb-cre/DTR/SCID-beige(ADSB) mice,which coincidentally harbor Alb-cre and DTR transgenes and are immunodeficient. As the Cre expression is driven by the liver-specific promoter Alb(encoding ALB),the DTR stop signal flanked by two lox P sites can be deleted in the ADSB mice,resulting in DTR expression in the liver. ADSB mice aged 8-10 wk were injected intraperitoneally(i.p.) with diphtheria toxin(DT) and liver damage was assessed by serum alanine aminotransferase(ALT) level. Two days later,mouse livers were sampled for histological analysis,and human hepatocytes were transplanted into the livers on the same day. A human ALB enzyme-linked immunosorbent assay was performed 7,14,21 and 28 d after transplantation. Human CD68 immunohistochemistry was performed 30 and 90 d after transplantation.RESULTS We crossed Alb-cre with DTR and SCID-beige mice to obtain ADSB mice. These mice were found to have liver damage 4 d after i.p. injection of 2.5 ng/g bodyweight DT. Bodyweight began to decrease on day 2,increased on day 7,and was lowest on day 4(range,10.5%-13.4%). Serum ALT activity began to increase on day 2 and reached a peak value of 289.7 ± 16.2 IU/m L on day 4,then returned to background values on day 7. After transplantation of human liver cells,peripheral blood human ALB level was 1580 ± 454.8 ng/m L(range,750.2-3064.9 ng/m L) after 28 d and Kupffer cells were present in the liver at 30 d in ADSB mice.CONCLUSION Human hepatocytes were successfully repopulated in the livers of ADSB mice. The inducible mouse model of humanized liver in ADSB mice may have functional applications,such as hepatocyte transplantation,hepatic regeneration and drug metabolism.
文摘Three diphtheria toxin (DT) mutants CRM-197, DT-del (148) and DT-El48S-K516A-F530A were cloned in B- Subtilis plasmid PSM604 under the subtilisin signal sequence. The expression was effective in both SMS300 and SMS118, but higher yield of 7. 1 mg/L was observed in SMS300 compared with 2. 1 mg/L in SMS118. Western blot showed that the recombinant protein could be effectively secreted into the culture medium as a 58 ku peptide, and could be de-graded into two peptides of 37ku and 21ku.
基金supported by grants from the National "973" Basic Research Program of China (No.2012CB944703)the National Key Technology Research and Development Program of China (No.2011BAI17B00)the Shandong Provincial Science and Technology Development Projects (No.2009GG10002008 and No.2011GSF12103)
文摘Objective： This study aimed to express a fusion protein of diphtheria toxin and human B cell-activating factor （DT388sBAFF） in Escherichia coli （E. coli） and investigate its activity in human B-lineage acute lymphoblastic leukemia 1 cells （BALL-1）. Methods： A fragment of DT388sBAFF fusion gene was separated from plasmid pUC57-DT388sBAFF digested with Nde I and Xho I, and inserted into the expression vector pcold II digested with the same enzymes. Recombinants were screened by the colony polymerase chain reaction （PCR） and restriction map. The recombinant expression vector was transformed into BL21 and its expression was induced by isopropyl β-D-1-thiogalactopyranoside （IPTG）. The recombinant protein was identified by sodium dodecyl sulfate-polyacrylamide gel electrophoresis （SDS-PAGE） and Western blot, and then purified by Ni2＋-NTA affinity chromatography. The expression level of B cell-activating factor receptor （BAFF-R） on BALL-1 cells was assessed by real-time PCR. The receptor binding capacity of recombinant protein was determined by cell fluorescent assay. The specific cytotoxicity of recombinant protein on BALL-1 cells was detected by 3-（4,5-dimethylthiazolyl-2）-2,5-diphenyltetrazolium bromide （MTT） assay. Results： The expression level of recombinant protein was 50% of total bacterial proteins in E. coli, and the recombinant protein could bind to BAFF-R-positive BALL-1 cells and thereby produce a cytotoxic effect on the cells. Conclusion： The fusion protein expression vector DT388sBAFF was successfully constructed and the recombinant protein with selective cytotoxicity against BALL-1 cells was obtained, providing foundation for further study of the therapy of human B-lineage acute lymphoblastic leukemia.
文摘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.
基金Health Department Scientific Research Foundation of Hubei province (No. NX200501)
文摘Objective: To study the effects of recombinant expression vector containing human breast cancer DF3 promotor and diphtheria toxin A fragment on human breast cancer cells. Methods: Constructing recombinant expression vector PGL3-DF3-DTA and transfecting it into human breast cancer cells of DF3 positive and negative. By means of RT-PCR to measure the expression of DTA in human breast cancer cells. MTT color-imetry was used to examine the effect of PGL3-DF3-DTA on growth of human breast cancer cells. By experiment on nude mice to observe the killing effect of PGL3-DF3-DTA on human breast cancer cells. Results: Recombinant expression vector PGL3-DF3-DTA was highly expressed in human breast cancer cell line of DF3 positive, and it could kill the human breast cancer cells not only in vitro but also in vivo. Conclusion: Recombinant expression vector PGL3-DF3-DTA could produce specific killing effect on human breast cancer cell line of DF3 positive.
文摘Background: Diphtheria is still endemic in India due to inadequate immunization. The incidence of myocarditis is higher in these patients. Objectives: The objective of this study was to study clinical profile, clinical outcomes as well as immunization status of the patients diagnosed with diphtheria myocarditis in Indian scenario. Methodology: This prospective observational study was carried out in one of the tertiary care hospital of south India from August 2011 to December 2012. A total of 33 cases with clinically confirmed diagnosis of diphtheria myocarditis were enrolled depending upon the inclusion and exclusion criteria of the study. Electrocardiography and 2-dimensional echocardiography was done at the time of admission and repeated when required. Results: The most common age group affected is 5 - 10 years, with no sex difference in occurrence. Only 1 patient, out of 33 patients, was adequately immunized. Asymptomatic myocardial involvement (with only changes in electrocardiogram) was seen in 21 patients whereas 12 patients were symptomatic. The average duration of resolution of electrocardiographic changes was 4 - 6 weeks. It should be noted that out of 28 patients who developed conduction abnormalities, 24 patients died. Temporary pacemaker support was given for 8 patients, of whom only one patient recovered. The patient was followed till hospital discharge. Conclusion: The mortality associated with diphtheria myocarditis is higher in Indian population. As diphtheria can be prevented by adequate vaccination, efforts should be maximized for 90% coverage with three doses of diphtheria toxoid in children below one year of age and immunity towards it should be maintained by booster doses.
文摘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.
文摘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.
文摘<strong>Background:</strong> In Nigeria Pentavalent vaccine had replaced Diphtheria-Pertussis- Tetanus [DPT] vaccine in the prevention of pertussis since 2012. <strong>Aims and Objectives:</strong> 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. <strong>Subjects and Methods:</strong> 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. <strong>Results:</strong> 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 [<em>p</em> = 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 [<em>p</em> = 0.18]. No single factor investigated predicted the development of protective levels of antibody in the multivariate analysis. <strong>Conclusion/Recommendation:</strong> 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.
文摘Background Diphtheria,caused by Corynebacterium diphtheriae,remains a serious public health threat in areas with low vaccination coverage,despite global declines due to widespread immunization and improved clinical management.A major outbreak in Nigeria from 2022 to 2023 underscored the persistent risk in regions with inadequate vaccination.This study aims to assess the transmission dynamics of diphtheria in Kano State,the epicenter of the outbreak,by estimating key epidemiological parameters,including the generation time(GT),approximated in our study by serial interval,and effective reproduction number(R).Methods We analyzed diphtheria case-based data from Kano State,Nigeria,collected between August 18,2022,and November 29,2023.Generation time was approximated using serial intervals in confirmed cases within the same geographical areas.The effective reproduction number(R)was calculated using four methods:Maximum Likelihood Estimation(MLE),Exponential Growth(EG),Sequential Bayesian(SB),and Time-Dependent(TD),focusing on the period of maximum exponential growth.A sensitivity analysis was conducted to quantify the impact of uncertainties in the GT derived from our data on the estimation of R.Results Over the 469-day outbreak period,13,899 diphtheria cases were reported,with complete data available for 9406 cases.The estimated mean generation time was 2.8 days(SD=3.48 days),with 97%of cases having a GT of less than 21 days.The Restimates varied across methods,with the TD method producing the highest reproduction number of 2.21 during the peak growth period.Sensitivity analysis showed that Restimates increased with longer generation times.The models,except for the SB method,demonstrated a generally strong fit with the outbreak exponential growth period.Conclusion The ongoing diphtheria outbreak in Nigeria highlights the critical threat posed by declining vaccination coverage.This study provides valuable insights into the transmission dynamics of diphtheria during a prolonged and widespread outbreak,enhancing our understanding of disease spread in this context.While certain limitations may influence the interpretation of our estimates,the findings offer valuable information for future diphtheria outbreak preparedness and response in the African context.
文摘OBJECTIVE: To test whether the diphtheria toxin A (DT-A) chain coding sequence linked to murine immunoglobulin Kappa light chain (IgKappa) promoter and enhancer have selective cytocidal effects on IgKappa producing cells. METHODS: The diphtheria toxin A gene or beta galactosidase (beta-gal) gene were linked to a murine IgKappa promoter and enhancer to construct pcDNA3IgKappaDTA or pcDNA3IgKappaLacZ plasmids. These plasmids were transfected into IgKappa producing or non-producing cells by the liposome coated DNA method. Expression of beta-gal activity and effects on cell growth of transfected cells were assessed. RESULTS: The beta-gal gene, under the control of cytomegalovirus (CMV) promoter, can express in all cell lines. Expression of beta-gal under the control of the IgKappa promoter was detected only in the IgKappa producing cell line, CA46. Expression of beta-gal was greatly suppressed when cotransfected with pcDNA3IgKappaDTA in CA46 cells.Cell growth of CA46 cells transfected with pcDNA3IgKappaDTA plasmid was significantly inhibited compared with CA46 cells transfected with pcDNA3IgKappaLacZ. CONCLUSION: Selective killing of IgKappa producing cells can be attained by introducing the diphtheria toxin A gene under the control of IgKappa promoter and enhancer.
文摘Background Certain infectious diseases are caused by specific bacterial pathogens,including syphilis,gonorrhea,typhoid and paratyphoid fever,diphtheria,pertussis,tetanus,leprosy,and tuberculosis.These diseases significantly impact global health,contributing heavily to the disease burden.The study aims to thoroughly evaluate the global burden of syphilis,gonorrhea,typhoid and paratyphoid fever,diphtheria,pertussis,tetanus,and leprosy.Methods Leveraging the Global Burden of Disease(GBD)study 2021,age-specific and Socio-demographic Index(SDI)-specific incidence,disability-adjusted life-years(DALYs),and death for eight specific bacterial infections across 204 countries and territories from 1990 to 2021 were analyzed.Percentage changes in age-standardized incidence rate(ASIR),DALY rate,and mortality rate(ASMR)were also examined,with a focus on disease distribution across different regions,age groups,genders,and SDI.Results By 2021,among the eight diseases,gonococcal infection had the highest global ASIR[1096.58 per 100,000 population,95%uncertainty interval(UI):838.70,1385.47 per 100,000 population],and syphilis had the highest global age-standardized DALY rate(107.13 per 100,000 population,95%UI:41.77,212.12 per 100,000 population).Except for syphilis and gonococcal infection,the age-standardized DALY rate of the remaining diseases decreased by at least 55%compared to 1990,with tetanus showing the largest decrease by at least 90%.Globally,significant declines in the ASIR,age-standardized DALY rate,and ASMR for these eight bacterial infections have been observed in association with increases in the SDI.Regions with lower SDI,such as sub-Saharan Africa,experienced a relatively higher burden of these eight bacterial infections.Conclusions Although there has been an overall decline in these eight diseases,they continue to pose significant public health challenges,particularly in low SDI regions.To further reduce this burden in these areas,targeted intervention strategies are essential,including multi-sectoral collaboration,policy support,improved WASH management,and enhanced research efforts.
基金funded by Institut Teknologi Bandung(Research Grant ITB 2024).
文摘The COVID-19 pandemic caused significant disruptions in the healthcare system,affecting vaccinations and the management of diphtheria cases.As a consequence of these disruptions,numerous countries have experienced a resurgence or an increase in diphtheria cases.West Java province in Indonesia is identified as one of the high-risk areas for diphtheria,experiencing an upward trend in cases from 2021 to 2023.To analyze the situation,we developed an SIR model,which integrated DPT and booster vaccinations to determine the basic reproduction number,an essential parameter for infectious diseases.Through spatial analysis of geo-referenced data,we identified hotspots and explained diffusion in diphtheria case clusters.The calculation of R0 resulted in an R0=1.17,indicating the potential for a diphtheria outbreak in West Java.To control the increasing cases,one possible approach is to raise the booster vaccination coverage from the current 64.84%to 75.15%,as suggested by simulation results.Furthermore,the spatial analysis revealed that hot spot clusters were present in the western,central,and southern regions,posing a high risk not only in densely populated areas but also in rural regions.The diffusion pattern of diphtheria clusters displayed an expansion-contagious pattern.Understanding the rising trend of diphtheria cases and their geographic distribution can offer crucial insights for government and health authorities to manage the number of diphtheria cases and make informed decisions regarding the best prevention and intervention strategies.
基金financially supported by the National Key Research and Development Program of China[grant number 2021YFC2302002]project supported by Hainan Province Clinical Medical Center.
文摘Due to the use of vaccines,infections caused by Corynebacterium diphtheriae are now rare.Here we describe a case of bacteremia complicated with pneumonia caused by C.diphtheriae in a 69-year-old male patient.The patient presented at the emergency department with a 2 days history of fever of unknown origin.Subsequent examinations revealed pneumonia and bacteremia.Non-toxigenic C.diphtheriae strains were isolated from blood and sputum.The patient had antimicrobial therapy with good improvement.We highlight the important role of C.diphtheriae in causing bacteremia and pneumonia,and its accurate and timely diagnosis is needed to avoid poor visual outcomes.
文摘The localized outbreaks of diphtheria still happened in some areas in recent years. The case—fatality rate Of diphtheria is rising and so is the case—fatality rate of toxic myocarditis. About 16 years ago, reviewing the clinical data concerning patients who had died of diphtheria in our hospital, we learned a lesson from our faults in the treatment of diphtheria for the pur-
文摘目的 评价2020—2022年吉林省适龄儿童接种含无细胞百白破成分疫苗的安全性,以期为后续预防接种工作中疫苗的安全使用提供参考。方法 通过吉林省免疫规划信息管理系统和国家免疫规划信息管理系统疑似预防接种异常反应(adverse event following immunization,AEFI)功能管理模块,收集2020年1月1日—2022年12月31日吉林省适龄儿童接种吸附无细胞百白破联合疫苗(diphtheria,tetanus and acellular pertussis combined vaccine,DTaP)、无细胞百白破-b型流感嗜血杆菌联合疫苗(diphtheria,tetanus,acellular pertussis and Haemophilus influenzae type b combined vaccine,DTaP-Hib)和无细胞百白破-灭活脊髓灰质炎-b型流感嗜血杆菌联合疫苗[diphtheria,tetanus,pertussis(acellular,component),poliomyelitis(inactivated)vaccine and Haemophilus type b conjugate vaccine,adsorbed,DTaP-IPV/Hib]后发生AEFI的个案报告信息,采用描述性流行病学方法进行分析,并应用统计学方法比较组间差异。结果 2020—2022年吉林省适龄儿童接种DTaP、DTaP-Hib和DTaP-IPV/Hib共1 301 812剂次,共计报告AEFI个案3 132例(240.59/10万剂次),其中一般反应3 122例(99.68%,239.82/10万剂次),异常反应7例(0.22%,0.54/10万剂次),偶合症3例(0.1%,0.23/10万剂次)。3种含DTaP成分疫苗的AEFI报告发生率分别为257.00/10万剂次(3 025例)、175.61/10万剂次(34例)、69.26/10万剂次(73例),差异有统计学意义(χ^(2)=145.53,P<0.001);3种含DTaP成分疫苗加强免疫AEFI报告发生率高于基础免疫,差异有统计学意义(χ^(2)分别为254.98、18.03、20.39,P均<0.05);报告的AEFI病例以一般反应为主,包括发热、局部红肿、局部硬结等,主要发生于接种疫苗后0~1 d内。结论 2020—2022年吉林省适龄儿童接种DTaP、DTaP-Hib和DTaP-IPV/Hib的AEFI以一般反应为主,总体安全性良好。建议持续加强接种后AEFI监测,并优化被动监测系统以减少漏报偏倚。
