Organ transplantation and vaccination / 器官移植

Organ transplant recipients are at a high risk of infection with high hospitalization rate, critical rate and fatality, due to low immune function caused by taking immunosuppressants for a period of long time after organ transplantation. Currently, vaccination is recognized as an effective approach to prevent infection. Organ transplant recipients may be vaccinated according to individual conditions. However, the sensitivity to vaccines may decline in organ transplant recipients. The types, methods and timing of vaccination have constantly been the hot spots of clinical trials. In this article, the general principles, specific vaccines and SARS-CoV-2 vaccines of vaccination in organ transplant recipients were briefly reviewed, aiming to provide reference for the vaccination of organ transplant recipients. Moreover, current status of SARS-CoV-2 vaccination for organ transplant recipients was illustrated under the global outbreak of novel coronavirus pneumonia pandemic.

Vacinação universal contra hepatite A no Brasil: análise da cobertura vacinal e da incidência cinco anos após a implantação do programa / Universal hepatitis A vaccination in Brazil: analysis of vaccination coverage and incidence five years after program implementation

RESUMO: Introdução: Em 2014, o Brasil introduziu programa de imunização universal contra o vírus da hepatite A (HAV) para crianças no segundo ano de vida, por meio de dose única da vacina de vírus inativado. Este estudo teve como objetivo avaliar a cobertura vacinal (CV) contra o HAV no Brasil, diante da incidência de casos notificados cinco anos após a implantação do programa. Metodologia: Dados secundários foram obtidos pesquisando-se sítios eletrônicos de acesso livre do Ministério da Saúde, Departamento de Informática do Sistema Único de Saúde (DATASUS), para análise de incidência e CV. Resultados: A CV variou entre 60,13 e 97,07%. A homogeneidade da CV contra hepatite A nos estados ficou aquém da meta estabelecida. Após 2015, houve queda da CV em todas as regiões do país. Apesar da cobertura insuficiente, houve redução concomitante da incidência da hepatite A em todo o Brasil. A taxa de incidência caiu de 3,29 para 0,80/100 mil entre 2014 e 2018. No entanto, ocorreu diminuição da velocidade de queda da incidência entre 2017 e 2018, o que pode ser consequência dos percentuais insuficientes de CV. Esse fenômeno parece acompanhar tendência geral de enfraquecimento do esforço vacinal no país, verificado também para outras vacinas, como poliomielite e tríplice viral. Conclusão: Esses números sugerem a necessidade de esforços para melhorar as taxas de CV da hepatite A no país.

ABSTRACT: Introduction: In 2014, Brazil introduced a universal immunization program against the hepatitis A virus (HAV) for children in the second year of life, using a single dose of inactivated virus vaccine. The objective of this study was to evaluate the vaccination coverage (VC) against HAV in Brazil, against the incidence of cases reported five years after the implementation of the program. Methodology: Secondary data were obtained by searching free access electronic sites of the Ministry of Health, Department of Informatics of the Unified Health System (Departamento de Informática do Sistema Único de Saúde - DATASUS), for incidence analysis and VC from 2014 to 2018. Results: VC ranged from 60.13 to 97.07%. The homogeneity of VC against hepatitis A did not reach the established goal throughout all states but for a few exceptions. After 2015, CV decreased in all regions of the country. Despite insufficient coverage, a concomitant reduction in the incidence of Hepatitis A took place throughout the country. The incidence rate fell from 3.29 to 0.80/100,000 between 2014 and 2018. However, there was an interruption in the pace of incidence fall between 2017 and 2018, which may be a consequence of insufficient VC. This phenomenon seems to be part of a widespread downward trend in vaccination effort across the country, also verified for other vaccines, such as poliomyelitis and measles, mumps and rubella vaccine. Conclusion: These figures suggest the need for implementing efforts to improve hepatitis A VC rates in the country.

Modeling the Long-term Antibody Response and Duration of Immune Protection Induced by an Inactivated, Preservative-free Hepatitis A Vaccine (Healive) in Children / 生物医学与环境科学（英文）

Objective@#Long-term seroprotection the hepatitis A vaccine is essential for the prevention of disease from the hepatitis A virus (HAV). Due to documented difficulties during decade-long follow-ups after receiving vaccines, statistical-modeling approaches have been applied to predict the duration of immune protection.@*Methods@#Based on five-year follow-up data from a randomized positive-controlled trial among Chinese children (1-8 years old) following a 0, 6 months vaccination schedule, a power-law model accounting for the kinetics of B-cell turnover, as well as a modified power-law model considering a memory-B-cell subpopulation, were fitted to predict the long-term immune responses induced by HAV vaccination (Healive or Havrix). Anti-HAV levels of each individual and seroconversion rates up to 30 years after vaccination were predicted.@*Results@#A total of 375 participants who completed the two-dose vaccination were included in the analysis. Both models predicted that, over a life-long period, participants vaccinated with Healive would have close but slightly higher antibody titers than those of participants vaccinated with Havrix. Additionally, consistent with previous studies, more than 90% of participants were predicted to maintain seroconversion for at least 30 years. Moreover, the modified power-law model predicted that the antibody titers would reach a plateau level after nearly 15 years post-vaccination.@*Conclusions@#Based on the results of our modeling, Healive may adequately induce long-term immune responses following a 0, 6 months vaccination schedule in children induction of memory B cells to provide stable and durable immune protection.

Inclusion of hepatitis A vaccine in Expanded Program on Immunization on hepatitis A incidence by interrupted time-series analysis / 预防医学

Objective @#To assess the impact of inclusion of hepatitis A vaccine in Expanded Program on Immunization（EPI）on hepatitis A incidence. @*Methods @#The data of patients with hepatitis A from 1998 to 2017 in Huzhou were collected through Huzhou Infectious Diseases Yearbook and China Disease Prevention and Control Information System. Interrupted time-series models were constructed using the year 2008 when hepatitis A vaccine was included in EPI as the intervention time point. The influence of hepatitis A vaccine into EPI on the hepatitis A incidence was evaluated by analyzing the changes in the level and slope of incidence before and after hepatitis A vaccine into EPI. @*Results @#Before the inclusion of hepatitis A vaccine in EPI,the average annual incidence rate of hepatitis A was 10.228/100 000 and the incidence of hepatitis A showed a significant descending trend with an annual decrement of 1.558/100 000. After the inclusion of hepatitis A vaccine in EPI,the average annual incidence rate of hepatitis A was 1.721/100 000 and the incidence of hepatitis A showed a significant descending trend with an annual decrement of 0.263/100 000. The average annual rate of decline in the hepatitis A incidence decreased by 1.295/100 000 after the inclusion of hepatitis A vaccine in EPI. @*Conclusion @#The incidence of hepatitis A significantly reduced after inclusion of hepatitis A vaccine in EPI,and the EPI strategy had a continuous effect on the decreasing trend of hepatitis A incidence.

Initial evaluation of universal immunization with a single dose against hepatitis A virus in Central Brazil

ABSTRACT Vaccination against the hepatitis A virus (HAV) administered in two doses has been used effectively in universal child immunization programs in several countries. A single-dose vaccination was adopted in some low-income countries in an attempt to reduce costs without losing effectiveness. In 2014, single-dose universal vaccination was introduced in Brazil for children aged two years. Since such strategy is still not universally accepted, its efficacy should be compared to the two-dose strategy. To assess the humoral response after the single-dose HAV vaccination schedule, a cross-sectional study was conducted in Primavera do Leste, in Mato Grosso state, Central Brazil, including 265 children vaccinated through the National Immunization Program. Blood was collected by using a digital puncture and further applied to filter paper cards. Anti-HAV was detected in 218 out of 265 dried blood spots (DBS). Blood venous samples were collected from 34 out of 47 children who were not anti-HAV positive in DBS samples. Eighteen of them tested positive for anti-HAV, giving a final score of 93.6% (236/252) of seropositivity. In conclusion, this study demonstrated a high rate of anti-HAV positivity in the short term after single-dose hepatitis A vaccination in the population investigated. Moreover, the DBS was shown to be a reliable tool for detecting anti-HAV antibodies.

Epidemiological analysis of viral hepatitis A in China, 2004-2015 / 中华预防医学杂志

Objective@#To analyze the epidemiological characteristics of hepatitis A cases in China from 2004 to 2015.@*Methods@#Data of hepatitis A were reported through national notifiable disease information reporting system, which covered the 31 provinces (Hong Kong, Macau and Taiwan excluded). The inclusion criteria was: date of illness onset was between January 1st 2004 and December 31st 2015, the status of reported card was confirmed, the case was classified as laboratory confirmed or clinical diagnosed, the disease was Hepatitis A. The information such as sex, date of birth, date of illness onset, place of residence was collected. The data was divided into three phases, 2004-2007, 2008-2011, 2012-2015, which represented the phase before expanded program on immunization (EPI), first 4 years after EPI, second 4 years after EPI.@*Results@#From 2004 to 2015, there were totally 574 697 hepatitis A cases in China, the mean annual incidence was 3.62/100 000. The risk ratio of hepatitis A in 2015 was 0.23 when compared with 2004. Sichuan, Xinjiang and Yunnan contributed to 27.27% of the total cases in China. In 2012-2015, the incidence of western (3.46/100 000) region was significantly higher than that in central (1.21/100 000) and eastern (1.08/100 000) regions. From 2004-2015, number of cases in each age group declined greatly, with number of cases declining from 43 711 to 5 938 in the age group of 5-9 years, from 29 722 to 3 438 in 10-14, from 23 212 to 3 646 in 15-19. The number of cases declined from 24 079 to 10 304 in the age group of 0-4 (declined by 57.21%), but in 2012-2015, the incidence of 0-4 age group was still the highest, with 77.72% cases in Xinjiang and Sichuan. Famers, students and scattered children accounted for 69.95% of total cases, with student cases declined from 24.08% (2004-2007) to 8.67% (2012-2015).@*Conclusion@#The incidence of hepatitis A in China is decreasing year by year, the risk has been decreasing to a relatively low level. However, in western regions and children under age five, the risk is still high. Precision intervention is needed for further prevention and control of hepatitis A.

Long-term Immunogenicity of Single Dose of Live Attenuated Hepatitis A Vaccine in Indian Children.

Objectives: To assess immunogenicity of a single dose of live attenuated hepatitis A vaccine in Indian children, ten years after immunization. Methods: Of 143 children vaccinated in 2004, 121 children were evaluated in 2014, clinically and for anti-HAV antibodies. Results: 13 children were early vaccine failures who received two doses of HAV vaccine subsequently. 106 (98%) of 108 remaining children had seroprotective levels with a geometric mean titer of 100.5 mIU/mL. On analysis of all 121 children, the immunogenicity was 87.6%. Conclusion: Single dose of live attenuated hepatitis A vaccine provides long-term immunity in Indian children.

Persistence of hepatitis A virus antibodies after primary immunization and response to revaccination in children and adolescents with perinatal HIV exposure / Persistência de anticorpos contra o vírus da hepatite A após imunização primária e resposta à revacinação em crianças e adolescentes com exposição perinatal ao HIV

OBJECTIVE: To assess possible factors associated with the loss of antibodies to hepatitis A 7 years after the primary immunization in children of HIV-infected mothers and the response to revaccination in patients seronegative for hepatitis A. METHODS: Quantification of HAV antibodies by electrochemiluminescence was performed in 39 adolescents followed up at the Pediatric Aids Clinic of Federal University of São Paulo (Unifesp): 29 HIV-infected (HIV group) (median age: 12.8 years) and 10 HIV-exposed but non-infected (ENI group) (median age: 13.4 years). All of them received two doses of HAV vaccine (Havrix(r)) in 2002. RESULTS: The median age at primary immunization (PI) was 5.4 years for HIV group and 6.5 years for ENI group. All children, from both groups, had antibodies to HAV >20 mIU/mL after PI. Seven years later, the ENI group showed a median concentration of antibodies = 253.5 mIU/mL, while the HIV group = 113.0 mIU/mL (Mann-Whitney test, p=0.085). All ENI group and 23/29 (79.3%) from HIV group mantained HAV antibodies 7 years after PI. The levels of hepatitis A antibodies in the primary vaccination were the only factor independently associated with maintaining these antibodies for 7 years. The group that lost HAV seropositivity was revaccinated and 83.3% (5/6) responded with antibodies >20 mUI/mL. CONCLUSIONS: The antibodies levels acquired in the primary vaccination in the HIV group were the main factor associated with antibodies loss after HAV immunization.

OBJETIVO: Avaliar possíveis fatores associados à perda de anticorpos para o vírus da hepatite A (VHA) sete anos após a imunização primária e resposta à revacinação em crianças nascidas de mães soropositivas para HIV nos pacientes soronegativos para Hepatite A. MÉTODOS: Quantificação de anticorpos para o VHA por meio da eletroquimioluminescência foi feita em 39 adolescentes acompanhados no Ambulatório de Aids Pediátrica da Universidade Federal de São Paulo (Unifesp): 29 infectados pelo HIV e 10 expostos e não infectados (ENI) pelo HIV, com mediana de idade, respectivamente, de 12,8 e 13,4 anos. Todos receberam duas doses da vacina VHA (Havrix(r)) em 2002. RESULTADOS: A mediana da idade na época da imunização primária (IP) era de 5,4 anos para o grupo HIV e 6,5 anos para o grupo ENI. As crianças dos dois grupos apresentaram anticorpos para o VHA > 20 mUI/mL após a IP. Sete anos após, o grupo ENI apresentava mediana de anticorpos = 253,5 mUI/mL e o grupo HIV = 113,0 mUI/mL (Mann-Whitney; p=0,085). Todo grupo ENI e 23/29 (79,3%) do grupo HIV mantiveram anticorpos contra o VHA sete anos após IP. Os níveis de anticorpos para hepatite A na primovacinação foram o único fator independentemente associado à manutenção desses anticorpos decorridos sete anos. O grupo que perdeu soropositividade para VHA foi revacinado e 83,3% (5/6) responderam com anticorpos >20 mUI/mL. CONCLUSÕES: Os níveis de anticorpos obtidos na primovacinação no grupo HIV foram o principal fator associado à perda de anticorpos após imunização VHA.

The Immunogenicity of a Single Dose of Hepatitis A Virus Vaccines (Havrix(R) and Epaxal(R)) in Korean Young Adults

PURPOSE: Assessing the immunogenicity of a single dose of hepatitis A virus (HAV) vaccines is important because some people receive only a single dose. However, previous studies have shown variable results and have not examined the effects of demographic characteristics other than gender. This study was performed to examine the immunogenicity of a single dose of HAV vaccine according to the vaccine type and demographic characteristics in young adults. MATERIALS AND METHODS: Seronegative medical school students were randomly allocated to receive either Havrix or Epaxal. RESULTS: After approximately 11 months, the seroconversion rate in 451 participants was 80.7%. In men, the Havrix group showed a significantly higher seroconversion rate (81.9%) than the Epaxal group (69.2%), whereas both vaccine groups showed similarly high immunogenicity in women (Havrix: 90.1%, Epaxal: 92.9%; P for interaction=0.062). According to the results of a multivariate analysis, Epaxal showed significantly lower immunogenicity than Havrix only in men. Age, obesity, drinking, smoking, and follow-up time did not significantly affect seroconversion in either gender. CONCLUSION: The seroconversion rate of single-dose HAV vaccines was low in men, particularly in those who received Epaxal. Our results suggest that gender effects should be considered when comparing the immunogenicity of different HAV vaccines.

Evaluation on the effect of immunization and safety of live attenuated and inactivated hepatitis A vaccine in China / 中华流行病学杂志

Objective To evaluate the safety of both domestic live attenuated and inactivated hepatitis A vaccines,and to provide reference for emergent vaccination after hepatitis A outbreaks.Methods 493 children aged 6-9 with negative antibody to HAV (produced by Abbott) were randomly divided into four groups as vaccinated with domestic live attenuated hepatitis A vaccine (Group A),domestic inactivated hepatitis A vaccine (Group B),imported inactivated hepatitis A vaccine (Group C) and hepatitis B vaccine (Group D) respectively.Adverse events following the immunization were observed 30 minutes,24,48 and 72 hours after the vaccination,under doubleblind method.Results The main AEFIs were:fever,local pain and scleroma but no other severe AEFIs were obvserved.The rates of AEFIs were 13.95％ in Group A,15.25％ in group B,16.80％ in group C and 25.62％ in group D,with no statistical differences between these groups (x2=6.953,P＞0.05).2 weeks after the vaccination,the positive conversion rates of domestic live attenuated hepatitis A vaccine and domestic inactivated hepatitis A vaccine were 85.00％ and 94.59％ respectively.The rate of domestic inactivated hepatitis A vaccine reached 100％ at 4 weeks after the vaccination.The antibody levels of HAV-IgG of Group A and B in 2,4 and 12 weeks of vaccination and of Group C were higher than that of Group D.After 12 weeks of vaccination,the antibody level of group B became higher than it was Group C.Conclusion There were no differences on safety among domestic live attenuated hepatitis A vaccine,domestic inactivated hepatitis A vaccine or imported inactivated hepatitis A vaccine under routine or emergency vaccination.All the vaccines showed satisfactory effects.

Long-term immunogencity and effectiveness of live attenuated hepatitis A vaccine (H2-strain )-a study on the result of 15 years' follow up / 中华流行病学杂志

Objective To evaluate the long-term immunogencity and effectiveness of live attenuated hepatitis A (HA) vaccine (H2 strain) after one dose injection, through a 15 years' follow up observation. Methods A total of 220 children with negative anti-HAV antibody (aged 1-3 y)were involved and followed up in Jiaojiang district, Taizhou city, Zhejiang province. Indicators would include seroconversion and geometric meantiter(GMT) levels after inoculation the vaccine with single dose at 2 m, 12 m, 6 years, 10 years and 15 years. Epidemiological observation was carried out within the 15 years to evaluate the relationship between vaccine coverage, the incidence of HA and the overall effectiveness. In the studied population, serum was tested by ELISA(calibrated by WHO international reference) and ABBOTT Axsym HAVAB mEIA. Results Seroconversion rates were found to be 98.6% and 81.3% after 2 months and 15 years of inoculation and slowly decreased. GMT level was 128 mIU/ml after 15 years, significantly higher than the required protective level of 20 mIU/ml,recommended by WHO experts. Effectiveness through the 15-year follow up program showed a significant correlation between vaccine coverage and incidence of HA in 1-15 years aged group (Kendall-Rank test, t =-0.931, P＜0.01). There was no HA case seen among the observed accumulated 236 413 person-year vaccines, compared to 4 HA cases discovered in the 27 206 personyear of the non-vaccinees. The overall protective rate reached 100%. Through a mass vaccination program on children, the whole population established an immune-defence to enable the incidence of HA decreased by 96.7%. Conclusion The long-term immunogencity and effectiveness of live attenuated hepatitis A vaccine (H2 strain) after one dose injection could last as long as 15 years.

Needs for Hepatitis A Virus Immunization in Healthcare Personnel / 병원감염관리

BACKGROUND: Currently, the incidence of hepatitis A is on the increase in Korea. Although there is emphasis on contact precautions, the nosocomial outbreak of hepatitis A virus (HAV) in healthcare personnel has increased within endemic areas because these workers inevitably come in close contact with patients and work under suboptimal hygiene conditions. In this study, we evaluated the necessity of immunization against HAV for healthcare personnel. METHODS: We investigated the seropositivity of serum immunoglobulin G (IgG) anti-HAV antibody (Ab) in 672 healthcare personnel on the basis of their age-group, sex, and occupation in Soon Chun Hyang University Hospital and Soon Chun Hyang University Bucheon Hospital. RESULTS: The subjects were divided into 6 groups on the basis of their ages to identify differences among the various age groups in the number of cases with HAV Ab seropositivity. Significant intergroup differences were noted in this respect: 21-25 years, 2/152 (1.3%); 26-30 years, 33/245 (13.5%); 31-35 years, 70/148 (47.3%); 36-40 years, 52/79 (65.8%); >40 years, 44/48 (91.7%). CONCLUSION: The number of seropositive cases was low among young healthy personnel: low seropositivity is an emerging risk for vulnerable population. With the increase in the incidence of hepatitis A, healthcare personnel have become a risk population for hepatitis A, as are community residents. Therefore, for healthcare personnel working in hospitals, immunization against HAV should be recommended for personnel younger than 30 years, and serological testing for older personnel.

The Meta Analysis of Protective Efficacy of Attenuated Live Hepatitis A Vaccine / 中国疫苗和免疫

Objective To evaluate protective efficacy of attenuated live hepatitis A vaccine.Methods We searched MEDLINE,EMBASE,CNKI.The randomization,concealment of allocation and blinding were included in the study. Results Meta analysis based on included studies showed that both strain of H2 and L-A-1 attenuated live hepatitis A vaccine had good protective efficacy,the protective efficacy is related to the titer of vaccine.The titer

Analysis on Coverage of Hepatitis A Vaccine among Pre-school Children in Shandong Province / 中国疫苗和免疫

Objective To reveal the hepatitis A vaccine (HepA) coverage among pre-school children in Shandong province before Hepatitis A vaccine was introduced to the EPI and to provide evidence for improving the strategy for hepatitis A control.Methods A cross-section survey was conducted among children aged between 2 and 6 years old in Shandong province in March 2008.The study population was selected by random sampling method and HepA immunization history was obtained by immunization record or recall.Results 78.90% had received one dose of HepA at least.The coverage rate decreased with age and the differences in three age groups were statistically significant (x 2 =11.54,P=0.02).The coverage rates among the boys and girls were 77.67% and 80.30% respectively,the difference was not significantly(x 2 =1.17,P=0.28).The HepA coverage rates among the children living in the eastern areas and in the richer areas were higher than the centrale and western areas and poverty areas,the difference has statistic significance (x 2 =27.25,58.17,P

Recent Epidemiological Status and Vaccination of Hepatitis A in Korea

Hepatitis A is a vaccine preventable disease. Improvement in the socio-economic status and general public health of Korea over the last 30 years has led to a shift in the seroprevalence of hepatitis A. This lowered endemicity has caused an upward shift in the average age of infection, resulting in a larger number of individuals at risk of clinically significant hepatitis A infection. Now in Korea, for those aged less than 10 years old, the anti-HAV prevalence was above 50%, which is mainly contributed to the result of vaccination. However, the prevalences of antibody in the 10s and 20s were 10 to 30%, respectively, which are significantly lower than those in other age groups. As people in this age group are at high risk for an epidemic of hepatitis A, a catch-up immunization may be considered. Also, routine immunization should be considered in the near future after cost-effectiveness studies to control the disease burden of hepatitis A.

The changing epidemiology of hepatitis A in children and the consideration of active immunization in Korea

Currently, Korea is a low endemicity country for HAV, especially in children. However, recent reports of hepatitis A outbreaks show that there has been a shift of disease incidence to adolescents and young adults, with 2 cases of acute liver failure in one reported outbreak. We need to study the immune status for HAV in order to provide information for the establishment of preventive measures and possible consequences of HAV in Korea. A total of 334 infants, children and adolescents less than 20 years of age living in rural areas of Kyonggi Province, Korea were evaluated for anti-HAV immune status in 1996. Five hundred and eighty-four primary school children living in the same area were separately evaluated for the natural seroconversion rate between 1993 and follow-up samples taken in 1996. Anti-HAV IgG antibody was measured by enzyme immunoassay (HAVAB EIA kit, Abbott Laboratories, Chicago, Illinois, USA). In comparison with previous reports of seroprevalence rates, our data confirmed a dramatic drop in seroprevalence rates among children and adolescents under 20 years of age living in rural areas, from over 63.8% two decades ago to 4.6% in 1996. Natural acquisition of HAV antibody in primary school children rarely occurs, registering only 0.5% during three years. Several outbreaks in young adults during 1996-1998 suggested that immunity against HAV in this population is so low that massive outbreaks are unavoidable. Teenagers and young adults, especially soldiers, who are likely to be exposed to contaminated food or water, would also have a greater risk of hepatitis A. Immunizing children with HAV vaccine as a routine schedule should also be considered in Korea in the future, particularly if the disease burden could be estimated and the cost-effectiveness of the vaccine could be proved.