Persistence follow-up of immune memory to hepatitis B vaccine among infants with non- and low-response to primary vaccination after revaccination with three doses / 中华预防医学杂志

This study followed up the immune memory after 3-dose revaccination among infants with non-and low-response following primary hepatitis B (HepB) vaccination. About 120 children without self-booster doses were finally included who had anti-HBs<10 mIU/ml (anti-HBs negative) at the time of follow-up, of whom 86 children completed blood sampling and anti-HBs testing. Before the challenge dose, all 86 children were negative for anti-HBs, and the GMC of anti-HBs was<10 mIU/ml. The seropositive conversion rate of anti-HBs was 100% and the GMC of anti-HBs was 886.11 (95%CI: 678.15-1 157.84) mIU/ml after the challenge dose. Compared with those with GMC<7 mIU/ml before the challenge dose, infants with GMC>7 mIU/ml had a higher anti-HBs level after the challenge dose. The β value (95%CI) was 0.82 (0.18-1.46) (P=0.012). Compared with those with GMC<1 000 mIU/ml at primary vaccination, infants with GMC≥1 000 mIU/ml had a higher anti-HBs level after the challenge dose. The β value (95%CI) was 0.78 (0.18-1.38)(P=0.012). The results showed a stronger immune memory was found at 9 years after revaccination among infants with non-and low-response to HepB.

Economic burden and related factors on inpatients with HBV-related diseases in Shandong province / 中华流行病学杂志

<p><b>OBJECTIVE</b>To investigate the economic burden of patients with acute and chronic hepatitis B, cirrhosis and liver cancer caused by hepatitis B virus (HBV).</p><p><b>METHODS</b>Cluster sampling was used on cases consecutively collected during the study period. Questionnaire survey was conducted and information on the expenses during hospitalization was collected from the hospital records and through interviewing those patients.</p><p><b>RESULTS</b>Yearly costs related to patients with acute hepatitis B, severe hepatitis B, chronic hepatitis B, cirrhosis, hepatocellular carcinoma were 66.7, 138.1, 127.4, 151.7 and 377.2 thousand Yuan, respectively.</p><p><b>RESULTS</b>from multiple linear regression model showed that the type of medical insurance scheme, annual days of hospitalization, classifications of HBV-related diseases and personal income were major influencing factors on the cost.</p><p><b>CONCLUSION</b>HBV infection caused considerable burden to families and the society, indicating that HBV infection control programs would bring huge potential benefits. The reform of insurance scheme should be administrated to promote social fairness.</p>

Preliminary analysis on the prevalence and causes of breakthrough hepatitis B virus infection among children in Shandong province, China / 中华预防医学杂志

<p><b>OBJECTIVE</b>To know the prevalence and probable causes of breakthrough hepatitis B virus (HBV) infection among children born after the introduction of universal infant hepatitis B vaccination in Shandong province, China.</p><p><b>METHODS</b>The subjects of this study were selected from the provincial hepatitis B serosurvey conducted in 2006, who were born between 1992 and 2005 (aged 1-15 years) and were confirmed to have completed three or more doses of hepatitis B vaccine. Finally 3527 subjects were involved in this study and were investigated using a unified question are. Blood samples were collected from them to detect hepatitis B surface antigen (HBsAg), antibody against HBsAg (Anti-HBs) and antibody against hepatitis B core antigen (Anti-HBc). The parents of children positive for HBsAg were followed up. Blood samples were collected from their parents to detect for HBsAg. The rate and correlative factors of breakthrough HBV infection were gotten by single-factor and multiple-factor analysis.</p><p><b>RESULTS</b>For the 3527 subjects, the overall prevalence rates of breakthrough HBV infection were 3.15% (111/3527), which decreased while birth year grew (χ(2)(Trend) = 44.83, P < 0.01) , the rate of subjects born in 1992 was the highest (9.9%, 16/161) , subjects born in 2000 was the least (0.8%, 2/258) , the rate of the self-report positive HBsAg status of mother, father and the other family members (15.22%, 7/46;34.09%, 15/44;17.65%, 6/34) were higher than the negative (2.99%, 104/3481, 2.76%, 96/3483, 3.01%, 105/3493) (χ(2) values were 22.28, 13.97, 23.68, respectively, all P values were < 0.01) , timely first dose of hepatitis B vaccine (5.37%, 41/763) was higher than the subjects that not in time (2.53%, 70/2764) (χ(2) = 15.596, P < 0.01) . The overall prevalence rates of breakthrough chronic HBV infection was 1.08% (38/3527), which decreased while birth year grew (χ(2)(Trend) = 9.96, P < 0.05) , the rate of subjects born in 1992 was the most (3.1%, 5/161) , subjects born in 1997 was the least (0.4%, 1/261) , the rate of the self-report positive HBsAg status of mother, father and the other family members (13.04%, 6/46;29.55%, 13/44;17.65%, 6/34) were higher than the negative (0.92%, 32/3481;0.72%, 25/3483;0.92%, 32/3493) (χ(2) values were 62.62, 338.80, 88.44, respectively, all P values were < 0.05) , timely first dose of hepatitis B vaccine (1.83%, 14/763) was lower than the subjects that not in time (0.87%, 24/2764) (χ(2) = 5.16, P = 0.02) . Multiple factors analysis showed that compared to the negative, the self-report positive HBsAg status of father, mother increased the risk of breakthrough HBV infection,OR (95%CI) values were 3.73 (1.09-12.75) and 26.76 (11.86-60.37) , respectively (all P values were < 0.05) , compared with eastern cities, the risk of western cities were the highest (OR (95%CI) = 6.00 (2.50-14.40) , P < 0.05) the risk of children born in 1992-2001 was higher than those born in 2002 ( (OR (95%CI) = 1.91 (1.10-3.32) , P < 0.05) . Compared to the negative, the self-report positive HBsAg status of father, mother and the other family members increased the risk of breakthrough chronic HBV infection,OR (95%CI) values were 7.51 (1.44-39.17) , 99.99 (34.29-291.62) , 8.94 (1.81-44.10) , respectively (all P values were < 0.05) , compared with eastern cities, the risk of western rural areas were the highest (OR (95%CI) = 12.51 (2.78-56.25) , P < 0.05) , sharing tooth brush with the others increased the risk (OR (95%CI) = 8.67 (1.14-66.14) , P < 0.05) . Among HBsAg-positive children, those with HBsAg positive mother and father accounted for 12/23 and 6/19, respectively.</p><p><b>CONCLUSION</b>The prevalence of breakthrough HBV infection and breakthrough chronic HBV infection among children was low in Shandong province. Mother to infant transmission might be the main reason for the infection while the role of the horizontal transmission within the family shouldn't be ignored.</p>

Study on antibody response to revaccination of hepatitis B vaccine among firstly low-response adults / 中华预防医学杂志

<p><b>OBJECTIVE</b>To evaluate and compare the antibody to hepatitis B virus (HBV) surface antigen (anti-HBs) response and the influent factors of revaccination of 4 kinds of hepatitis B vaccine (HepB) among firstly low-response adults.</p><p><b>METHODS</b>A total of 11 590 adults who were 18 - 49 years old, never received HepB vaccination, without HBV infection history, HBs-Ag negative, and had been living at 3 towns of Zhangqiu county in Shandong province Ji'nan city for more than half a year, were selected in the study in July, 2009. Self-designed questionnaire was used to select the basic information of the subjects. The subjects were divided into 4 groups by cluster sampling, and were vaccinated according to the "0-1-6" immune procedure with 10 µg HepB made by recombinant deoxyribonucleic acid techniques in Saccharomyces Cerevisiae (HepB-SC), 10 µg HepB made by recombinant deoxyribonucleic acid techniques in Hansenula Polymorpha (HepB-HP), 20 µg HepB-SC and 20 µg HepB made by recombinant deoxyribonucleic acid techniques in Chinese hamster ovary cell (HepB-CHO), 3 doses respectively. The adults who were low-response to the primary hepatitis B vaccination (10 mU/ml ≤ anti-HBs < 100 mU/ml) were divided into four groups by cluster sampling. These groups were revaccinated with one-dose of above-mentioned four kinds of HepB respectively. Blood samples were drawn from each person one month after the revaccination. Anti-HBs was detected by chemiluminescence microparticle immunoassay and compared by the vaccine type. The influence factors about antibody response were also analyzed.</p><p><b>RESULTS</b>Out of the 11 590 subjects, 8592 adults had accepted the primary vaccination of hepatitis B and been collected the blood samples; among whom, 1306 subjects showed low-response, at the rate of 15.20%. A total of 1034 low-response subjects accepted secondary strengthened vaccination and were collected blood samples; 55.13% of them showed anti-HBs seroconversion (anti-HBs ≥ 100 mU/ml); while the seroconversion rate in each group was 44.54% (106/238) in 10 µg HepB-SC group, 57.14% (156/273) in 10 µg HepB-HP group, 56.08% (143/255) in 20 µg HepB-SC group and 61.57% (165/268) in 20 µg HepB-CHO group, respectively. There was significant difference among the groups (χ² = 17.14, P < 0.01). The rates of anti-HBs seroconversion were significantly higher in 10 µg HepB-HP and 20 µg HepB-CHO groups than it in 10 µg HepB-SC group (χ² were 8.09 and 14.70 respectively, P < 0.01). The geometric mean concentration (GMC) of anti-HBs was 178.24 mU/ml among the low-responders after one dose of revaccination. The GMC was 109.77, 243.50, 144.98 and 242.83 mU/ml in 10 µg HepB-SC group, 10 µg HepB-HP group, 20 µg HepB-SC group and 20 µg HepB-CHO group, respectively. There was significant difference among groups (F = 9.52, P < 0.01).</p><p><b>CONCLUSION</b>Anti-HBs response could be strengthened effectively after one-dose of HepB revaccination among the low-response adults. Many factors like the vaccine types could effect the immune effects to HepB. A better response could be achieved if the 20 µg HepB-CHO or 10 µg HepB-HP was used for revaccination.</p>

Multi-center matching study on antibody response between preterm and full-term infants after primary immunization of hepatitis B vaccine / 中华流行病学杂志

Objective To compare the antibody response between preterm and full-term infants after primary immunization of hepatitis B vaccine (HepB).Methods Infants who were aged 7-12 months and had completed primary immunization with 5 μg HepB made by recombinant dexyribonucleic acid techniques in saccharomyces cerevisiae (HepB-SC) or 10 μg HepB made by recombinant dexyribonucleic acid techniques in Hansenula polymorpha (HepB-HP) on 0-1-6 schedule were investigated in four provinces (municipality) including Beijing,Shandong,Jiangsu and Guangxi of China.Among them,all preterm infants were selected to form the preterm group and the 1:1 matching full-term infants with the same month-age,gender and residence were randomly selected to form the full-term group.Their HepB history was determined by immunization certificate and all of their parents were interviewed with standard questionnaire to get their birth information.Blood samples were obtained from all anticipants and were tested for Anti-HBs by chemiluminescence microparticle immuno-assay (CMIA).Results Total anticipants were 648 pairs of infants.The rates of non-response,low-response,normal-response and high-response after the primary immunization were 1.39％,8.64％,45.83％ and 44.14％ in the preterm group,respectively.The corresponding rates were 1.08％,9.26％,44.91％ and 44.75％ in the full-term group.The above four rates did not show significant differences between the two groups (P＞0.05).The geometric mean concentrations (GMC) of anti-HBs in the pre-term and full-term group were 755.14 and 799.47 mIU/ml respectively.There was no significantly difference in the GMCs between the two groups (P＞0.05).Results from multivariable conditional logistic analysis showed that preterm was not an influencing factor to the antibody response after HepB primary immunization among newborns even after debugging the other influencing factors.Conclusion The autibody response after HepB primary immunization were similar among the preterm and full-term infants.The preterm newborns could be immunized under the same HepB immunization strategy.

Comparison on the antibody response after primary immunization of 5 μg and 10 μg hepatitis B vaccine made bv recombinant DNA techniques among newborns / 中华流行病学杂志

Objective To compare the antibody response induced by primary immunization with 5 μ g and 10 μ g hepatitis B vaccine made by recombinant DNA techniques among the newborns.Methods Healthy infants who had completed primary immunization with 5 μg hepatitis B vaccine made by recombinant dexyribonucleic acid techniques in Saccharomyces (Hep-SC) or 10 μg hepatitis B vaccine made by recombinant dexyribonucleic acid techniques in Hansenula polymorpha (HepB-HP) were included in the study.Kids under study were 7-12 months of age and had been on 0-1-6 schedule.Standardized questionnaire was used and blood samples were collected.The titer of antibody to hepatitis B surface antigen (anti-HBs) was detected by Chemiluminescence Microparticle Imunoassay (CMIA).If anti-HBs happened to be under 10 mIU/ml,HBV DNA was further detected by nested-PCR to distinguish occult hepatitis B virus infection.Sero-conversion rate and titer of anti-HBs were compared between the two kinds of hepatitis B vaccines.Multivariate analysis was used to find the relationship between the kind of hepatitis B vaccine as well as the antibody response after debugging the other influencing factors including month-age,gender,birth-weight,premature birth and mother' s HBsAg status.Results 8947 infants vaccinated with 5 μg HepB-SC and 4576 infants vaccinated with 10 μg HepB-HP were investigated.In the 5 μg group,the rates of non-,low-,normal- and high-response were 1.88％,15.18％,61.42％ and 21.52％ respectively.In the 10 μg group,the corresponding rates were 0.15％,2.16％,29.42％ and 68.26％ respectively.The non-,low-,normal-response rates were all higher in 5 μg group than in 10 μg group (P＜0.01),while the high-response rate was much higher in 10 μg group than in 5 μ g group (P＜0.01).The geometric mean concentration (GMC) of anti-HBs were 354.81 mIU/ml (95％ CI:338.84-363.08 mIU/ml) and 1778.28 mIU/ml (95％CI:1698.24-1819.70 mIU/ml) in the 5 μg group and 10 μg group respectively.The GMC was statistically higher in the 10 μg group than in the 5 μg group (P＜0.001).The seroconversion rate and GMC were significantly different between the two groups even after debugging the other influencing factors.Conclusion Better anti-HBs response could be achieved by primary immunization with 10 μg HepB-HP than with 5 μg HepB-SC among newborns.

Identification and phylogenic analysis of Coxsackie-virus B5 during an outbreak of aseptic meningitis in Shandong / 中华流行病学杂志

Objective To identify the pathogen that caused an outbreak of aseptic meningitis in Shandong province in 2005. Phylogenic analysis was carried out on Coxsackie-virus B5 (CVB5) which was isolated during this outbreak. Methods 78 stool and 58 cerebrospinal fluids (CSF) specimens were collected from some inpatients during this outbreak. Virus isolation and reverse transcription-polymerase chain reaction (RT-PCR) was then performed. Phylo-genetic trees based on entire and partial VP1 sequences were constructed among CVB5 isolates and others published in GenBank. Results The isolation rates of stool and CSF specimens were 38.5% (30/78) and 48.3% (28/58) respectively. Among the results of serotype identification and molecular typing of 58 positive isolates, 54 were identified as CVB5, 2 as ECHO24, 1 as CVB3 and 1 as CVA9. Results from viral investigation showed that CVB5 was the main pathogen causing this outbreak. Data from homological comparisons indicated that Shandong strains had the highest nucleotide acid identity with the Zhejiang/ 12/02 strain (97.5%-97.8%), and lower identity (78.3%-78.6%) with the prototype strain (Faulkner strain). Phylogenic tree in VP1 region showed that CVB5 could be separated into four genotypes. Isolates of this outbreak belonged to genotype D. Conclusion CVB5 was the major etiological agent correlated with this outbreak. The shift of predominant genotype might serve as one of the causes that associated with the outbreaks of aseptic meningitis.

The analysis of "a" dominant mutation of hepatitis B virus in community-based population of Shandong Province, China / 中华实验和临床病毒学杂志

<p><b>OBJECTIVE</b>To determine the rate and type of "a" dominant mutation of hepatitis B virus (HBV) in community-based population of Shandong province and the possible effect of hepatitis B vaccination upon "a" dominant mutation.</p><p><b>METHODS</b>The anticipants aged 1-59 years were selected by multi-stage random sampling from the general population of Shandong province. Hepatitis B vaccination status was obtained by inquisition (for those over 15 years old) or immunization record (for those under 14 years old). The blood samples were collected and detected for HBsAg by ELISA. HBV DNA was extracted from the sera with positive HBsAg and S gene was amplified by nested-PCR. The PCR produce was sequenced and compared with the standard sequence.</p><p><b>RESULTS</b>Overall, 7601 anticipants were investigated. HBV DNA was successfully amplified and sequenced in 102 of 239 samples with positive HBsAg. 14.70% sera samples mutated in HBV "a" determinant region and 13 mutation types were detected. There were no statistically differences in the mutation rate by age groups (born before or after national universal infant hepatitis B vaccination) and hepatitis B vaccination status.</p><p><b>CONCLUSION</b>The "a" determinant mutation seemed to be uncommon in community-based population of Shandong province and the mutation sites were relatively scattered. Hepatitis B vaccination has no effect on "a" dominant mutation of hepatitis B virus.</p>