The Safety, Immunogenicity, and Immunopersistence of Hepatitis A Vaccine in HBs-Ag-Positive Participants: A Retrospective Study.

Objectives: To compare the safety, immunogenicity, and immune persistence of hepatitis A (HA) vaccines between HBs-Ag-positive and -negative participants. Method: 9000 participants were enrolled in the phase IV study of live attenuated HA (HA-L) or inactivated HA (HA-I) vaccines. The HBs-Ag-positive subjects were detected and became an independent observation group. Adverse reactions (ARs), geometric mean concentrations (GMCs) and seroconversion rates (SRs) of the vaccines were analyzed at five time points until three years after vaccination. Results: 120 HBs-Ag-positive subjects were screened out, only 1 participant had grade 1 experienced ARs after HA-L injection. Except the time point of two years, the SRs of HBs-Ag-positive group were 100% for both vaccines. The GMCs were not statistically different between HBs-Ag-positive and -negative groups after the HA-L vaccination. The logarithmically transformed GMCs for HBs-Ag-positive and -negative groups were 3.21 mIU/mL (95% CI, 2.03-4.39 mIU/mL) and 2.95 mIU/mL (95% CI, 2.88-3.02 mIU/mL) 28 days after the HA-L vaccination, respectively. Conclusions: Both HA-L and HA-I vaccines were safe for HBs-Ag-positive participants and may provide an excellent long-term protection against HAV in this study. The results indicated that people positive or negative for HBs-Ag can receive both HA-L and HA-I vaccines (ClinicalTrials.gov number, NCT02601040).

Vaccines and the risk of Guillain-Barré syndrome.

The role of vaccination in the development of Guillain-Barré syndrome (GBS) is controversial, although cases of GBS have been reported following a wide range of vaccines. A nested case-control study was conducted between January 2011 and December 2015 in three Chinese cities. Four controls were matched to a case by gender, age, address and index date. An independent expert committee validated the diagnoses of cases and controls according to the Brighton Collaboration GBS case definition. Data on vaccinations were obtained from computerized vaccination records. Causal relations were assessed by conditional logistic regression. 1056 cases of GBS and 4312 controls were included in the analyses. Among paediatric and adult population, adjusted ORs for GBS occurrence within 180 days following vaccination were 0.94 (95% CI 0.54-1.62) and 1.09 (95% CI 0.88-1.32), respectively. No increased risk of GBS was detected for vaccination against hepatitis B, influenza, hepatitis A, varicella, rabies, polio(live), diphtheria, pertuss(acellular), tetanusis, measles, mumps, rubella, Japanese Encephalitis, and meningitis vaccines. Adjusted ORs for the recurrence of GBS after vaccination among paediatric and adult population were 0.85 (95% CI 0.07-9.50) and 1.18 (95% CI 0.49-2.65), respectively. In this large retrospective study, we did not find evidence of an increased risk of GBS and its recurrence among either paediatric (≤ 18 years) or adult (> 18 years) individuals within the 180 days following vaccinations of any kind, including influenza vaccination.

Vaccines and the risk of acute disseminated encephalomyelitis.

BACKGROUND: It is important to examine the risk of Acute disseminated encephalomyelitis (ADEM) after vaccination. METHODS: We conducted a nested case-control study between January 2011 and December 2015. Four controls per case were matched for age, gender, address. An independent expert committee validated the diagnoses of cases and controls. Data on vaccinations were obtained from computerized vaccination records. The analyses were conducted with the use of conditional logistic regression. RESULTS: The analyses include 272 cases of ADEM and 1096 controls. No increase in the risk of ADEM was observed for vaccination against hepatitis B, influenza, polio(live), diphtheria, pertuss(acellular), tetanusis, measles, mumps, rubella, Japanese Encephalitis, meningitis, hepatitis A, varicella and rabies vaccines. Vaccine was associated with a statistically significant increase in risk in the 31-60-day exposure interval (OR, 4.04 [95% CI, 1.07-12.69]), but not the 0-30 and 61-180-day interval. There was no association between vaccine received and the recurrence of ADEM. CONCLUSIONS: Findings from the present study do not demonstrate an association of vaccines with an increased risk of ADEM and its recurrence among either paediatric (≤18 years) or adult (>18 years) individuals within the 180 days after vaccinations. The finding in children in the 31-60 day risk interval is likely coincidental and was not confirmed in separate self-control analyses.

Demographic transition and the dynamics of measles in six provinces in China: A modeling study.

BACKGROUND: Industrialization and demographic transition generate nonstationary dynamics in human populations that can affect the transmission and persistence of infectious diseases. Decades of increasing vaccination and development have led to dramatic declines in the global burden of measles, but the virus remains persistent in much of the world. Here we show that a combination of demographic transition, as a result of declining birth rates, and reduced measles prevalence, due to improved vaccination, has shifted the age distribution of susceptibility to measles throughout China. METHODS AND FINDINGS: We fit a novel time-varying catalytic model to three decades of age-specific measles case reporting in six provinces in China to quantify the change in the age-specific force of infection for measles virus over time. We further quantified the impact of supplemental vaccination campaigns on the reduction of susceptible individuals. The force of infection of measles has declined dramatically (90%-97% reduction in transmission rate) in three industrialized eastern provinces during the last decade, driving a concomitant increase in both the relative proportion and absolute number of adult cases, while three central and western provinces exhibited dynamics consistent with endemic persistence (24%-73% reduction in transmission rate). The reduction in susceptible individuals due to supplemental vaccination campaigns is frequently below the nominal campaign coverage, likely because campaigns necessarily vaccinate those who may already be immune. The impact of these campaigns has significantly improved over time: campaigns prior to 2005 were estimated to have achieved less than 50% reductions in the proportion susceptible in the target age classes, but campaigns from 2005 onwards reduced the susceptible proportion by 32%-87%. A limitation of this study is that it relies on case surveillance, and thus inference may be biased by age-specific variation in measles reporting. CONCLUSIONS: The age distribution of measles cases changes in response to both demographic and vaccination processes. Combining both processes in a novel catalytic model, we illustrate that age-specific incidence patterns reveal regional differences in the progress to measles elimination and the impact of vaccination controls in China. The shift in the age distribution of measles susceptibility in response to demographic and vaccination processes emphasizes the importance of progressive control strategies and measures to evaluate program success that anticipate and react to this transition in observed incidence.

Comparison of the effect of increased hepatitis B vaccine dosage on immunogenicity in healthy children and adults.

Hepatitis B (HepB) infection remains a global public health problem, particularly in China. Vaccination for children and adult who are unvaccinated is an effective method for preventing the disease. In this study, we aimed to compare the effects of increased dosage of HepB vaccine on immunogenicity in healthy children and adults. A phase III, controlled, double-blinded clinical trial was performed. The subjects were assigned into groups I (age 5-14 y), II (age 15-24 y), and III (age ≥ 25 y). Subjects were randomly administered either 10 or 5 µg recombinant HepB vaccine; blood samples were collected before and after vaccination to estimate immunogenicity. The results showed that the seroconversion rate and geometric mean concentration of antibody to hepB surface antigen (anti-HBs) did not differ significantly between the dosages in each age group. Anti-HBs levels were reduced with age, and this effect was more obvious in adults administered 5 µg HepB vaccine. In conclusion, both vaccine dosages could be used to immunize children, and the 10 µg vaccine could be used for adults ages 15-24 y, whereas a higher dosage of the HepB vaccine may be required for adults ages 25 y and older.

Risk factors for measles infection in 0-7 month old children in China after the 2010 nationwide measles campaign: A multi-site case-control study, 2012-2013.

INTRODUCTION: Endemic measles persists in China, despite >95% reported coverage of two measles-containing vaccine doses and nationwide campaign that vaccinated more than 100 million children in 2010. We performed a case-control study in six Chinese provinces during January 2012 through June 2013 to identify risk factors for measles infection among children aged 0-7 months. METHODS: Children with laboratory-confirmed measles were neighborhood matched with three controls. We interviewed parents of case and control infants on potential risk factors for measles. Adjusted matched odds ratios (mOR) and 95% confidence intervals (CIs) were calculated by multivariable conditional logistic modeling. We calculated attributable fractions for risk factors that could be interpreted as causal. RESULTS: Eight hundred thirty cases and 2303 controls were enrolled. In multivariable analysis, male sex (mOR 1.6 [1.3, 2.0]), age 5-7 months (mOR 3.9 [3.0, 5.1]), migration between counties (mOR 2.3 [1.6, 3.4]), outpatient hospital visits (mOR 9.4 [6.6, 13.3]) and inpatient hospitalization (mOR 107.1 [48.8, 235.1]) were significant risk factors. The calculated attributable fractions for hospital visits was 43.1% (95% CI: 40.1, 47.5%) adjusted for age, sex and migration. CONCLUSIONS: Hospital visitation was the largest risk factor for measles infection in infants. Improved hospital infection control practices would accelerate measles elimination in China.

Seroepidemiology of mumps in the general population of Jiangsu province, China after introduction of a one-dose measles-mumps-rubella vaccine.

The mumps surveillance data from 2004 to 2011 showed that the incidence of mumps remained high after the one-dose measles-mumps-rubella (MMR) vaccine was introduced in China in 2008. A cross-sectional survey of mumps IgG in the general population of Jiangsu province was conducted in 2012 to gain comprehensive information on the immunity profile of the general population. The mean incidence was 15.2 per 100 000 individuals in Jiangsu province from 2004-2013. Two mumps incidence peaks were observed each year after introduction of the one-dose MMR vaccine. The seroprevalence did not significantly differ by region or sex, while the GMC significantly differed by region and sex. The overall GMC in Jiangsu province was 99.1 IU/ml (95% CI: 90.1-108.2), while the seroprevalence was only 59.1% (95% CI: 56.5-61.6). The seroprevalences for the 2 age groups that received the one-dose MMR vaccine, with reported coverage exceeding 95%, were 42.6% and 70.0%, respectively. The data on the incidence, MMR coverage, and seroprevalence in children younger than 6 years of age indicate that a two-dose MMR strategy should be considered. Mumps surveillance should be strengthened in children aged 6-11 and in those aged 12-17 because of their high contact rates and relatively low seroprevalences.

[Evaluation of safety of haemophilus influenza type b(Hib) conjugate vaccine in postmarketing based on the immunization information management system].

OBJECTIVE: To analyze the occurrence feature of adverse events following immunization (AEFI) of Hib conjugate vaccine (HibCV) and to evaluate the safety of HibCV in postmarketing. METHODS: 2008-2013 HibCV AEFI data were collected through national AEFI information management system, which were downloaded in March 18, 2014.The demographic information and inoculation quantity of HibCV were from Immunization information management system in Jiangsu province. The incidence rate and 95% CI value of AEFI, common vaccine reaction and rare vaccine reaction following immunization of HibCV were calculated. The differences in the incidence rate of common vaccine reaction and rare vaccine reaction among sex, months of age, and number of injections were compared by means of (χ² tests. RESULTS: A total of 6.16 million doses of vaccine were administered in Jiangsu province during 2008-2013, and 4 718 vaccinees reported having adverse event, for a rate of 76.60/100 000 (95% CI: 74.42/100 000-78.79/100 000). The incidence rate of common vaccine reaction and rare vaccine reaction was 71.10/100 000 (95% CI: 68.99/100 000-73.20/100 000) and 5.16/100 000 (95% CI: 4.60/100 000-5.73/100 000), respectively. The main symptoms of common vaccine reactions were fever, swelling, indurations and gastrointestinal reactions. The incidence rates of them were 40.54/100 000, 35.09/100 000, 12.94/100 000 and 0.36/100 000 in turn. The main symptoms of rare vaccine reactions were anaphylactic rashes and angioedema, the incidence rates of which were 4.77/100 000 and 0.15/100 000 respectively. 91.39% (4 002/4 379) of common vaccine reactions and 88.36% (281/318) of rare vaccine reactions happened within 1 d after vaccination. Anaphylactic shock (3 cases) and laryngeal edema (1 case) all happened within 1 d after vaccination. The incidence rate of common vaccine reactions among boys (79.72/100 000, 2 641/3 313 071) was higher than that of girls (61.07/100 000, 1 738/2 846 001) (χ² = 74.92, P < 0.001). The incidence rate of common vaccine reactions among children aged ≥ 12 month-old (86.82/100 000, 2 200/2 533 949) was higher than that among children aged 2-11 month-old (60.11/100 000, 2 179/3 625 123) (χ² = 149.79, P < 0.001). The incidence rate of common vaccine reactions in children vaccinated the first dose (78.93/100 000, 2 666/3 377 614) was higher than that in children vaccinated the second or third or fourth dose (61.59/100 000, 1 713/2 781 458) (χ² = 64.59, P < 0.001). The incidence rate of rare vaccine reactions in children vaccinated the first dose (6.69/100 000, 226/3 377 614) was higher than that in children vaccinated the second or third or fourth dose (3.31/100 000, 92/2 781 458) (χ² = 33.82, P < 0.001). CONCLUSION: The safety of HibCV among children was relative good. However, the surveillance should still focus on the anaphylactoid reactions of anaphylactic shock and laryngeal edema after HibCV immunization.

Efficacy of antigen dosage on the hepatitis B vaccine response in infants born to hepatitis B-uninfected and hepatitis B-infected mothers.

OBJECTIVE: To compare the safety and immunogenicity of two dosages of recombinant hepatitis B (HB) vaccine administered to infants born to HB-uninfected and HB-infected mothers. METHODS: A phase III, controlled, single-blinded clinical trial was conducted with 506 healthy newborns. The newborns were assigned to three groups based on maternal levels of HB surface antigen (HBsAg) and HB e antigen (HBeAg): Group A, HBsAg negative; Group B, HBsAg positive and HBeAg negative; and Group C, HBsAg positive and HBeAg positive. Three doses of 10 or 5 µg recombinant HB vaccine were randomly administered by 1:1 within 24 h after birth, at 1 month and at 6 months. Safety data and pre- and postvaccination blood samples were collected. RESULTS: A total of 326, 93, and 87 subjects were included in Groups A, B, and C, respectively. Both dosages of HB vaccine were well tolerated by all subjects. The most common injection-site adverse reactions (ARs) and systemic ARs were pain and fever. After 1 month of the third dose, the Group A infants who received the 10 µg HB vaccine achieved a higher geometric mean concentration (GMC) of HB surface antibody (anti-HBs) than those who received the 5 µg dosage. Maternal anti-HBs serostatus did not influence HB vaccine immunogenicity at either dosage. In contrast, there was no significant difference in the anti-HBs seroconversion rate, GMCs, or estimated vaccine efficacy (EVE) against perinatal transmission between Groups B and C, regardless of dosage. However, the seroconversion rate and EVE of the 5 µg HB vaccine was lower in Group C than in Group B. CONCLUSIONS: Both dosages of the HB vaccine were well tolerated and elicited a good immune response in infants of Group A, regardless of the maternal anti-HBs serostatus. EVE did not significantly differ between Groups B and C. Clinicaltrials.gov identifier: NCT02152709.

Incidence of acute disseminated encephalomyelitis in the Jiangsu province of China, 2008-2011.

BACKGROUND: It is important to have an estimate of the incidence of acute disseminated encephalomyelitis (ADEM) because the incidence of ADEM is unknown and the outcomes undefined in China. OBJECTIVES: This study attempts to describe ADEM incidence in large Chinese populations located in four geographically different and moderately distant areas of the same province. METHODS: A retrospective investigation was conducted with ADEM patients in Nanjing, Nantong, Yancheng and Xuzhou. The survey was carried out in regions that might have received patients meeting the case definition of ADEM provided by the International Pediatric MS Study Group from 2008 to 2011. A total of 125 hospitals were included and 412 patients were identified through the hospital information systems (HIS). RESULTS: The incidence of ADEM was 0.32/100,000/year. There are two peaks on the age-specific ADEM rates curve. One is 0.77/100,000/year among 0- to 9-year-olds, the other is 0.45/100,000/year in those aged 50-59 years. The incidence rate found for ADEM in males was 0.34/100,000/year, and in females was 0.29/100,000/year. The highest incidence rate was in Nanjing (0.40/100,000/year). CONCLUSIONS: The average annual incidence of ADEM was 0.32/100,000/year. The peak age of onset was 50-59 years old and 0-9 years old. The incidence among males was insignificantly higher than that among females. There was no significant difference in incidence by seasonal variation.

Prospective cohort study of the safety of an influenza A(H1N1) vaccine in pregnant Chinese women.

To monitor and evaluate the safety of the influenza A(H1N1) vaccine in pregnant women and its influence on the fetus and neonate, we performed a prospective study in which 122 pregnant Chinese women who received the influenza A(H1N1) vaccine and 104 pregnant women who did not receive any vaccine (serving as controls) were observed. The results indicated that the seroconversion rate in the vaccinated group was 90.4% (95% confidence interval [CI], 82.6% to 95.5%). The rate of adverse events following immunization in the pregnant women who received the influenza A(H1N1) vaccine was 3.3%. The spontaneous abortion rates in the vaccinated group and the unvaccinated group were 0.8% and 1.9%, respectively (exact probability test, P = 0.470), the prolonged-pregnancy rates were 8.2% and 4.8%, respectively (χ(2) = 1.041, P = 0.308), the low-birth-weight rates were 1.6% and 0.95%, respectively (exact probability test, P = 1.000), and the spontaneous-labor rates were 70.5% and 75%, respectively (χ(2) = 0.573, P = 0.449). All newborns who have an Apgar score of ≥7 are considered healthy; Apgar scores of ≥9 were observed in 38.5% and 57.7% of newborns in the vaccinated group and the unvaccinated group, respectively (χ(2) = 8.274, P = 0.004). From these results, we conclude that the influenza A(H1N1) vaccine is safe for pregnant women and has no observed adverse effects on fetal growth. (This study has been registered at ClinicalTrials.gov under registration no. NCT01842997.).

Cross-sectional surveys of measles antibodies in the Jiangsu Province of China from 2008 to 2010: the effect of high coverage with two doses of measles vaccine among children.

BACKGROUND: Changes in the epidemiological characteristics of measles since 2007 appeared in the Jiangsu province. Although the reported coverage with two doses of measles vaccine was greater than 95% in most regions of the province, measles incidence remained high across the whole province. Cross-sectional serological surveys of measles antibodies in the Jiangsu province of China were conducted from 2008 to 2010 to assess and track population immunity. METHODS: Measles-specific IgG levels were measured in serum samples using ELISA. GMTs and seroprevalence with 95% CIs were calculated by region, gender, and age. ANOVA and χ(2) tests were used to test for statistically significant differences between groups for GMT levels and seroprevalence, respectively. RESULTS: Seroprevalence showed a significantly increasing trend annually (CMH χ(2) = 40.32, p<0.0001). Although the seroprevalence among children aged 2-15 years was consistently over 95%, vaccine-induced measles antibodies may wane over time. Measles seropositivity in the Jiangsu province was 91.7% (95% CI: 90.1-93.2%) in 2010. Among adults aged 15 to 29-year-olds, the seropositivity rate was 88.4% (95% CI: 82.7-92.8%). CONCLUSIONS: Vaccination strategies may need to be adjusted depending on the individual age and regions, particularly individuals between the ages of 8 months-14 years old and 20-29 years old. Additional SIAs are likely required to eliminate measles in China.

Review of hepatitis B surveillance in China: improving information to frame future directions in prevention and control.

BACKGROUND: As the WHO verified that China reached the target of 1% prevalence of chronic hepatitis B infection among children targeted by universal hepatitis B immunization of newborns, the country considered new options for hepatitis B prevention and control. We reviewed hepatitis B surveillance in the broader context of viral hepatitis surveillance to propose recommendations to improve the system. METHODS: We described surveillance for viral hepatitis in China with a specific focus on hepatitis B. We assessed critical attributes of the system, including data quality, predictive positive value and usefulness. RESULTS: While remarkable progress in hepatitis B immunization of infants and children has likely almost eliminated transmission in younger age groups, reported rates of hepatitis B increased steadily in China between 1990 and 2008, probably because of a failure to distinguish acute from chronic infections. Elements that prevented a clearer separation between acute and chronic cases included (1) missed opportunity to report cases accurately among clinicians, (2) low availability and use of tests to detect IgM against the hepatitis B core antigen (IgM anti-HBc) and (3) lack of systems to sort, manage and analyze surveillance data. CONCLUSIONS: To improve hepatitis B surveillance, China may consider (1) training clinicians to diagnose acute cases and to use IgM anti-HBc to confirm them, (2) improving access and use of validated IgM anti-HBc tests and (3) developing data management and analysis techniques that sort out acute from chronic cases.

Sero-epidemiology of measles in general population in Jiangsu province of China: application of mixture models to interpret the results from a cross-sectional study.

A cross-sectional survey of measles seroprevalence in general population was conducted in Jiangsu province of China. Data were analyzed by employing commercial ELISA cut-offs and mixture models. The results suggest that the overall measles seroprevalence rate in Jiangsu province (88.7%, 95% confidence interval 87.7-89.6%) was lower than the level believed to be necessary for the elimination of measles. Mixture model could provide a more comprehensive understanding of these results by investigating the different levels of antibody response to vaccination or natural infection in the population, and suggest that the vaccine-induced antibody levels may wane with time. Additional actions should be conducted in the young adult cohorts aged 15-19 years in center region. SIAs for susceptible birth cohorts over the whole province are urgent.

[Study on epidemiological effect of the freeze-dried attenuated live varicella vaccine].

OBJECTIVE: To evaluate the safety and epidemiological effect of the Freeze-dried Live attenuated varicella vaccine. METHODS: A random, double-blind control clinical trial was adopted. RESULTS: In the observation period, the incidence of varicella was 0.8 per thousand in the experimental group and 8.7 per thousand in control group. There was a significant difference (B.P=0.000017). Vaccine effectiveness (VE(%)) was 90.8%, the lower limit of 95%CI was 88.7%. CONCLUSION: The varicella vaccine produced by Changchun keygen biological products co., Ltd. was safe and effective.

[Study on immunogenicity of group A and group C meningococcal conjugate vaccine with coupling group B meningococcal outer membrane protein].

OBJECTIVE: To evaluate the Immunogenicity of Group A and Group C Meningococcal conjugate Vaccine with coupling Group B Meningococcal Outer Membrane Protein (Men B-OMP). METHODS: 458 healthy children aged 3-5 months, 6-23 months, 2-6 years and 7-24 years were given the Groups A and C conjugate Vaccine with MenB-OMP or other vaccine as control group to measure the pre-and post-vaccination Men A and C and B by Serum Bactericidal Assay (SBA) in the double-blind randomized controlled trial. RESULTS: 97.65%-100% were 4 times or greater increase in SBA titer for the healthy children given the Groups A and C conjugate Vaccine with MenB-OMP, The geometric mean titer of SBA were 1:194-1:420, which significantly higber than controls. CONCLUSION: The Group A and C conjugate Vaccine with MenB-OMP was safe and well immunogenic.

[Study on the strategy of Japanese encephalitis immunization using live attenuated vaccine combined with inactivated vaccine].

OBJECTIVE: Using the advantages of Japanese encephalitis live attenuated and inactivated vaccine, to reduce the rate of immunization reaction and to increase the effect, we conducted a study on the strategy of immunization in Japanese encephalitis using live attenuated vaccine combined with inactivated vaccine. METHODS: Observing the safety and immune effects of different groups. RESULTS: Data on side effect showed that the rate of moderate and severe systematic reactions of the group who were inoculated with combined vaccine was 0.73%, with local reaction 1.46% while the combined rate of moderate and severe systematic reaction of the group who were inoculated with inactivated vaccine was 2.8%. Under the detection of serum neutralizing antibody, the GMT rose from 1:1.05 - 1:3.35 before vaccination to 1:47.34 - 1:101.30 after vaccination in the different groups. Neutralizing antibody was detected in 97.67% of the combined group. There was a significant difference by comparing neutralizing antibody seroconversion rate of the combined group with the inactivated group (chi(2) = 3.89, P < 0.05), but no significant difference with attenuated group (chi(2) = 0.74, P > 0.05). CONCLUSION: Results showed that in children who previously had been immunized with two doses of inactivated vaccine, the booster administration of live attenuated vaccine was both effective and safe.