Meta-analysis of safety and immunogenicity of DTaP-IPV-Hib-HepB hexavaccine / 中国生物制品学杂志

@#Objective To compare the differences of safety and immunogenicity of DTaP-IPV-Hib-HepB hexavaccine,DTaPIPV-Hib pentavaccine plus HepB single vaccine or DTaP-IPV-HepB pentavaccine plus Hib single vaccine,so as to provide a reference for the marketing and use of hexavaccine in China.Methods Randomized controlled trials(RCTs)of DTaP-IPVHib-HepB hexavaccine,DTaP triple vaccine,Hib,IPV and HepB vaccines published at home and abroad were searched.The safety and immunogenicity of the hexavaccine were evaluated by Meta-analysis using Revman 5.4.1 software.Results A total of 7 articles,8 RCTs and 3 429 subjects were included. Meta-analysis of safety showed that there was no significant difference in the incidence of injection site and systemic adverse reactions after vaccination with hexavaccine and pentavaccine plus single vaccine(P > 0. 05)except for induration at the inoculation site and crying. Meta-analysis of immunogenicity showed no significant difference in antibody indexes after vaccination with hexavaccine and pentavaccine plus single vaccine(P > 0. 05).Conclusion The safety and immunogenicity of DTaP-IPV-Hib-HepB hexavaccine in basic immunity was comparable to that of the control vaccine,and might be applied to infants and young children to prevent related diseases. However,due to the limitations of the quantity and quality of included studies,the above conclusions still depend on the further development of larger sample,multicenter and high-quality

Research progress on combined vaccines based on diphtheria-tetanus and acellular pertussis vaccine / 中国生物制品学杂志

@#Combined vaccine is a single vaccine preparation made by mixing two or more different organism or purified antigens by physical methods.The use of combined vaccine can reduce the number of immunization shots and improve the compliance of children and acceptance of parents;reduce the costs of transportation,storage and management;avoid missing vaccination and improve vaccination rate.At present,a variety of combined vaccines have been licensed abroad,which have good safety and immunogenicity;some combined vaccines have been put on the market in China,and many combined vaccines are in clinical trials.In recent years,with the successful development of component pertussis vaccine and inactivated poliovirus vaccines of Sabin strain Ⅰ,Ⅱ and Ⅲ in China,the combined vaccines based on diphtheria-tetanus-acellular pertussis vaccine(DTaP) have been greatly developed.In this paper,the research progress on combined vaccines based on DTaP,which have been licensed and in clinical trials at home and abroad,was reviewed,in order to provide ideas for the development of related combined vaccines in China.

Monitoring of adverse reaction of Haemophilus influenzae type b vaccine in Songjiang District， Shanghai / 上海预防医学

ObjectiveTo determine the reporting rate of adverse reaction of Haemophilus influenzae type b （Hib） containing vaccine in Songjiang District from 2016 to 2020， so as to provide evidence for the inclusion of Hib vaccine in children's immunization planning and safety monitoring. MethodsThe adverse reaction data of Hib vaccination were collected through the Chinese Disease Prevention and Control Information System and presented by descriptive methods. ResultsFrom 2016 to 2020， the reporting rate of adverse reaction of various Hib-containing vaccines in Songjiang District was determined to be 747.76/105 doses， among which the rates of general reaction and abnormal reaction were 734.31/105 doses and 13.45/105 doses， respectively. The reporting rate of general reaction was significantly higher than that of abnormal reaction （χ2=1 400.18，P<0.001）. Moreover， the reporting rate of adverse reaction did not differ significantly by sex or registered residence， whereas it differed significantly by age groups （χ2=366.07，P<0.001）. Children ≥12 months old had the highest reporting rate， which was caused by higher rate of general reaction （χ2=360.48，P<0.001） compared with other age groups； in contrast， there was no difference in the reporting rate of abnormal reactions across age groups. The reporting rate of adverse reaction differed significantly across four Hib-containing vaccines （χ2=508.51，P<0.001）， among which the reporting rate of pentavalent vaccine was the highest， followed by tetravalent vaccine， and Hib vaccine and meningococcal HI vaccine. This difference was mainly caused by general reaction （χ2=499.19，P<0.001）. The reporting rate of booster Hib-containing vaccines was significantly higher than that of basic immunization （χ2=462.85，P<0.001）. Furthermore， the reporting rate differed between DTaP-Hib vaccine and DTaP-IPV-Hib vaccine by injection sites（χ2=13.63，P=0.001；χ2=78.48， P<0.001）； the reporting rate on the thigh was lower than that on the hip or upper arm. Among the 1 501 reported adverse reactions， 97.21% of the general reactions and 85.19% of the abnormal reactions occurred within 72 hours following immunization. Principal clinical diagnosis was fever， redness and nodules （n=1 454）， accounting for 96.87% of the total reported adverse event following immunization（AEFI）， followed by allergic rash. ConclusionThe four types of Hib-containing vaccines have high safety. Health care practitioners at points of vaccination should improve the pre-examination， standardized operation and full notification in strict accordance with the requirements. It also warrants strengthening the AEFI monitoring， investigation and response， so as to effectively reduce the incidence and severity of adverse reactions.

Adult Diphteria: Possible Transmission of Corynebacterium diphtheriae from Unvaccinated Child?

@#A case of a toxigenic strain of Corynebacterium diphtheriae in an immunocompetent adult is presented, with the possibility of the adult acquiring the infection from her unvaccinated child. The abovementioned adult is a 29-year-old housewife who was previously immunised with diphtheria, tetanus, and pertussis (DTaP) vaccination in childhood, who presented fever, cough, sore throat, hoarseness of voice, odynophagia, and bilaterally enlarged tonsils. A throat swab confirmed the presence of toxigenic Corynebacterium diphtheriae. The patient was given 80,000 international units (IU) dose of diphtheria antitoxin (DAT) and treated with 2.4 million units (MU) QID intravenous penicillin and oral erythromycin 800 mg twice daily for two weeks. The patient responded well to the treatment and recovered with no cardiovascular or neurotoxicity.

Effects of different concentrations of aluminum hydroxide adjuvant and adsorption methods on the immunogenicity of diphtheria-tetanus-acellular pertussis and inactivated poliovirus combined vaccine / 中华微生物学和免疫学杂志

Objective To investigate the effects of different concentrations and adsorption methods of aluminum hydroxide adjuvant produced by different manufacturers on the immunogenicity of the diphtheria-tetanus-acellular pertussis and inactivated poliovirus combined vaccine ( DTaP-sIPV) . Methods Five anti-gens of DTaP were adsorbed onto different concentrations (0. 42 mg/ml, 0. 47 mg/ml and 0. 52 mg/ml) of aluminum hydroxide from different manufacturers through sequential and separate adsorption. Adsorbability, anti-pertussis toxin ( PT)/filamentous hemagglutinin ( FHA)/pertactin ( PRN)/diphtheria toxoid ( DT)/tet-anus toxoid ( TT) antibodies and the potency of vaccines were detected. Results The adsorbability of alu-minum hydroxide adjuvant slightly decreased with the reduction of concentration. No significant difference in potency and antibody level was observed between sequential and separate adsorption. Moreover, no signifi-cant difference in antibody level was observed between vaccines prepared with aluminum hydroxide adjuvant produced by General Chemical Corp and our institute. Conclusion Aluminum hydroxide adjuvant produced by our institute at the concentration of 0. 52 mg/ml and separate adsorption method are suitable for prepara-tion of DTaP-sIPV.

The Immunogenicity and Safety of a Combined DTaP-IPV//Hib Vaccine Compared with Individual DTaP-IPV and Hib (PRP~T) Vaccines: a Randomized Clinical Trial in South Korean Infants

Recommended infant vaccination in Korea includes DTaP-IPV and Hib vaccines administered as separate injections. In this randomized, open, controlled study we assessed the non-inferiority of immunogenicity of DTaP-IPV//Hib pentavalent combination vaccine (Pentaxim™) compared with licensed DTaP-IPV and Hib (PRP~T) vaccines. We enrolled 418 healthy Korean infants to receive either separate DTaP-IPV and Hib vaccines (n = 206) or the pentavalent DTaP-IPV//Hib (n = 208) vaccine at 2, 4, 6 months of age. Antibodies to all components were measured before the first vaccination and one month after the third, and safety was assessed after each vaccination including recording of reactions by parents. We confirmed the non-inferiority of DTaP-IPV//Hib compared with DTaP-IPV and Hib vaccines; 100% of both groups achieved seroprotection against D, T, IPV and PRP~T, and 97.5%-99.0% demonstrated seroresponses to pertussis antigens. Antibody levels were similar in both groups, except for those to the Hib component, PRP~T. In separate and combined groups geometric mean concentrations of anti-PRP~T antibodies were 23.9 and 11.0 µg/mL, respectively, but 98.3% and 97.4% had titers ≥ 1 µg/mL, indicative of long-term protection. All vaccines were well tolerated, with no vaccine-related serious adverse event. Both groups had similar safety profiles, but the combined vaccine group had fewer injection site reactions. The immunological non-inferiority and similar safety profile of DTaP-IPV//Hib vaccine to separate DTaP-IPV and Hib vaccines, with the advantage of fewer injections and injection site reactions, supports the licensure and incorporation of DTaP-IPV//Hib into the Korean national vaccination schedule (Clinical trial registry, NCT01214889).

Milk aspiration as a Result of Hypotonic-hyporesponsive Episodes after DTaP and Polio Co-immunization / 대한법의학회지

We analyzed autopsy findings of 5 neonates and infants who suddenly died after DTaP and Polio Coimmunization. Microscopically, there were multifocal small amounts of pinkish amorphous materials within the alveolar spaces with marked proliferation of alveolar macrophages. Immunohistochemical stain using anti-human alpha-lactalbumin shows intense staining to these foreign materials. We concluded that milk aspiration and asphyxia may play an important role in course of death after DTaP and Polio Co-immunization and assumed that hypotonic-hyporesponsive episodes as an adverse events of immunization could be a preceding cause of milk aspiration. Education of parents about the risk of milk aspiration after immunization should be included in guideline.

Age Related Serosurvey of Immunity to Tetanus in Korean Populations / 감염

BACKGROUND: The incidence of tetanus in adults and neonatal tetanus have been markedly reduced by world-wide use of DTP vaccines. But, tetanus is still one kind of major health problems in many developing countries, and several serosurvey stduies in developed countries revealed that substantial proportions of adult population may lack immunity against tetanus and immunity level against tetanus is continuously decreasing by age. In Korea, tetanus outbreaks have been disappeared since the 1980s by high acceptant DTaP vaccination rates. Annually, few tetanus patient has been reported since 1990s. But, there have been no seroepidemiological studies to tetanus, no trials to assess tetanus immunizations. And we do not use Td vaccine in adults for maintaning tetanus immunity. In this aspect, we conducted age related survey of immunity to tetanus and indirectly assessed the immunogenecity of tetanus vaccines, used in Korea. METHODS: For the evaluation of age related serosurvey of tetanus immunity in Korean population, study subjects were classified into 16 groups (A~J group; below 10 years with one year interval, K~O group; 11~60 yrs with 10 years interval, P group; over 60 yrs). The numbers of each group were 100, and sex distributions of each group were almostly equal. And for the indirect assessment of tetanus immunization in Korean children, children under 15 years old age were classified into 6 groups (I~VI) according to the status of DTaP vaccination. The numbers of this each group were 50, and sex ratio was almostly equal. Specific IgG antibody to tetanus toxin were detected by ELISA. And the ANOVA repeated t-test was used to compare antibody levels in study groups. RESULTS: In age related groups, the antibody levels to tetanus toxin were well maintained until 20 years old age group (L group), but thereafter the titers abruptly decreased below 0.1 IU/mL and over 75% populations among the groups over 30 years old age needed maintenance of protective immunity to tetanus. The antibody level of male was statistically higher than that of female in P group. In the groups related DTaP vaccination status, the antibody titer was very low in prevaccination group (I), but the titers after primary vaccinations were sharply increased and highly maintained until 15 years. CONCLUSOIN: The results of our study revealed that the immunity to tetanus was dramatically decreased in age groups over 30 years old. This result indicates that Td vaccination program in adults should be considered for maintenance of immunity to tetanus. And our study indicate that DTaP vaccination programs and vaccines, used in Korea, are effective for acquisition and maintenance of tetanus immunity in Korean children.

Age Related Seroepidemiological Study of Diphtheria among Koreans / 감염

BACKGROUND: The incidence of diphtheria has been markedly reduced and almostly eradicated by widespread use of DTP vaccines in developed countries. However, outbreaks of this disease may be occurred under some circumstances of ineffective immunization. In recent time, some studies reported persistent outbreaks of diphtheria in developed countries and indicated the existence of a large pool of susceptible individuals with potential for epidemic infection. In Korea, diphtheria vaccination has been well maintained since 1956 with high acceptant vaccination rates. So, there has been no reported diphtheria patient since 1987. But, there has been few study to diphtheria serosuvey, and no assessment of diphtheria immunization. Also, we do not use Td vaccine in adults for maintenance of diphtheria immunity. In this aspect, we conducted age related seroepidemiology of diphtheria and indirectly assessed the immunity of diphtheria vaccines, used in Korea. METHODS: For the evaluation of age related serosurvey of diphtheria immunity in Korean populations, study subjects below 10 years old aged children were classified into 10 groups (A~J) with one year interval, and beyond this age to 60 years old aged adults were classified into 5 group (K~O) with 10 years interval. And the adults over 60 years old age was classified into the last group (P). The numbers of each group were 100, and sex distributions of each group were almostly equal. And for the indirect assessment of diphtheria immunization in Korean children, children under 15 years old were classified into 6 groups (I~ VI) according to the status of DTaP vaccination. The numbers of this each group were 30, and sex ratio was almostly equal. Detection of specific IgG antibody to diphtheria toxin were determined by ELISA (contained fragment A & B toxin; IBL, Germany). RESULTS: In age related groups, the antibody titers to diphtheria toxin were well maintained until 10 years old age group, thereafter the titers abruptly decreased below 0.1 IU/mL and then slightly elevated after 30 years old age group and then maintained with low levels. In the groups related DTaP vaccine status, the antibody titers were very low (below 0.07 IU/mL) in prevaccination status, but the titers after primary vaccinations were markedly increased and maintained (above 0.6 IU/mL) until 15 years. And diphtheria antitoxin levels in the groups (L, M, N) showed no significant differences between males and females. CONCLUSION: The results of our study showed that the antibody titers to diphtheria toxin in the 20~50 years old aged groups dramatically decreased. This result indicated that vaccine induced diphtheria immunity did not last throughout life, and Td vaccination program in adults should be considered for maintenance of diphtheria immunity. And the immunity to diphtheria in Korean children indicated that 3 timesprimary and 2 times booster diphtheria immunizations were optimal.