| Objective:The study was conducted by following children in Yunnan Province after the implementation of hepatitis B mother-to-child blockade in 2011 and 11 years later in 2022.The analysis explores the HBV infection of these children under longterm exposure(at least one HBsAg-positive mother in the family)and assesses the changes in HBsAb levels,so as to assess the long-term immune protective effect of hepatitis B mother-to-child blockade and to explore the factors influencing the immune effect,and to provide a scientific basis for the follow-up preventive and control measures for successful hepatitis B mother-to-child blockade and the prevention and control of hepatitis B in children living in high-risk environments.Methods:1.Newborns born to HBsAg-positive mothers hospitalized from January to June 2011,venous blood was collected from newborns at 7-12 months of age for serological screening of the five HBV items after successful implementation of mother-to-child blockade,and the remaining serum of the samples after testing was stored at-40℃ in the laboratory of the Yunnan Provincial Centre for Disease Control and Prevention.The serum specimens were divided into two groups:no immune response/low immune response and normal immune response/high immune response,and the sample size was calculated to be 202 based on the rate of mother-to-child interruption of HBV breakthrough infection.Due to the long follow-up period and the problem of missed visits,based on a 15%missed visit rate(which was actually kept within 10%where possible),233 cases actually needed to be included as respondents,and children who met the inclusion and exclusion criteria were selected by simple random sampling method.2.On-site survey was conducted on the sampled respondents and serum samples were collected.The survey includes the name of the subject,date of birth,time of sample collection and test results,etc.Descriptive epidemiological methods are used to provide a descriptive analysis of the basic conditions of the subject.3.HBsAb is measured quantitatively and HBsAg and HBcAb are measured qualitatively using laboratory testing techniques including enzyme-linked immunosorbent assay,chemiluminescent microparticle immunoassay,HBV DNA testing,nucleic acid extraction,nested PCR amplification of HBV DNA S region,electrophoresis and gene sequencing.HBsAg positive samples are further tested for serological indicators and genotyping.4.Single factor analysis and multi-factor logistic regression analysis of factors influencing HBV breakthrough infection.Results:1 Basic informationA total of 215 cases were investigated,68 children in the non-immune/low immune response group and 147 children in the normal/high immune response group,with a loss of follow-up rate of 7.73%.2 Detection of five serological markers of HBV infection and HBV breakthrough infectionA total of 8 serological combinations were detected in children in 2022,with a single positive HBsAb detection rate of 54.42%and a full negative indicator detection rate of 32.09%.7 infection patterns were detected in children in 2011,with a single positive HBsAb detection rate of 51.63%and a full negative indicator detection rate of 20.00%.13.49%of children had a breakthrough HBV infection after 11 years and 1.86%had a breakthrough chronic HBV infection.The rates of HBsAb,HBeAb and HBcAb detection in children were all higher in 2011 than in 2022,and the differences were statistically significant.3 Comparative analysis of immune protection levels in 2011 and 2022 in different immune response groupsThe percentages of no immune response,low immune response,normal immune response and high immune response in 2011 were 23.72%,7.91%,35.35%and 33.02%respectively;the percentages of no immune response,low immune response,normal immune response and high immune response in 2022 were 40.93%,27.91%,22.33%and 8.84%respectively,with statistically significant differences(χ~2=70.229,P<0.001).4 Detection rates of the two antibody markers in 2022 for children in the nonimmune/low immune response and normal/hyperimmune response groupsThe positive HBsAb detection rate of children in the non-immune/low immune response group was significantly lower than that of children in the normal/hyperimmune response group by 68.03%,with a statistically significant difference(χ~2=0.033,P=0.033,<0.05),indicating that although HBsAb levels in children in the normal/hyperimmune response group decreased over time,the antibody levels in children in the normal/hyperimmune response group decreased after 11 years.The level of antibody protection was still higher than that of the nonimmune/low immune response group after 11 years,although the level of HBsAb decreased over time.5 Different immune response levels and HBsAb quantification results in the no/low immune response and normal/high immune response groupsHBsAb quantification GMC in children in 2011 declined by 82.75%after 11 years.The HBsAb quantification GMC of children in the non-immune/low immune response group was enhanced after 11 years,but all were at non-immune response level.The HBsAb quantification GMC of children in the normal/hyperimmune response group declined by 96.26%after 11 years;although some children in the nonimmune response/low immune response group developed antibodies in 2022,most children were still at the non-immune response and low immune response levels and did not reach the effective protection level.6 Analysis of maternal HBeAg infection status and the rate of HBV breakthrough infection in childrenThe prevalence of HBV breakthrough chronic infection in children born to HBeAg-positive mothers was higher than that in children born to HBeAg-negative mothers,but the difference was not statistically significant.(χ~2=0.717,P=0.356).The rate of HBV breakthrough infection was significantly higher in children of HBeAgpositive mothers in the non-immune/low immune response group than in children in the normal/hyperimmune response group,with a non-statistically significant difference(χ~2=0.217,P=0.641).7 Results of various tests and genetic traceability of HBV breakthrough chronic infection paired samplesA total of four children with breakthrough chronic HBV infection were paired with their mothers and found that two children were genotypically identical to their mothers,both with the C2 genotype;two children were genotypically different from their mothers,with the child’s C2 genotype and mother’s B2 genotype and the child’s B2 genotype and mother’s C2 genotype,respectively.8 Analysis of factors influencing the occurrence of breakthrough HBV infectionThe results of the univariate analysis showed that the factors associated with the occurrence of HBV breakthrough infection were ethnicity,the infection status of the HBeAg mother,and whether or not to revaccinate.Multi-factor logistic regression analysis revealed that breakthrough infection occurred 4.008 times more frequently in Hani children than in Han children(OR=4.008,95%CI:1.174-13.682 and P=0.027.<0.05);children with HBeAg-positive mothers were 3.547 times more likely to have HBeAg-negative mothers compared to children with HBeAg-negative mothers times(OR=3.547,95%CI:1.206-10.433,and P=0.021,<0.05).9 A case of a child with acute self-limited hepatitis B infectionOne case of acute self-limited hepatitis B was identified during the follow-up of the survey.The results suggest that spontaneous recovery can occur not only in adults with acute hepatitis B infection,but also in children over 10 years of age with acute hepatitis B infection.Conclusions:1.11 years after mother-to-child interruption in Yunnan Province,the incidence of HBV breakthrough infection in children was 13.49%and the incidence of HBV breakthrough chronic infection was 1.86%.Breakthrough infections occurred in both the non-immune/low immune response group and the normal immune response/high immune response group in children with long-term(11 years)exposure(at least one mother in the family was HBsAg positive).2.After 11 years there was attenuation of HBsAb levels in children in the longterm exposure setting.Children in the non-immune/low immune response group did not reach protective levels after 11 years,although they were enhanced.HBsAb levels in the normal/hyperimmune group were still protective after 11 years,although they had declined.3.Genotyping led to the conclusion that the source of breakthrough infection in some children was not necessarily the mother.By univariate analysis,the factors influencing HBV breakthrough infection were ethnicity,maternal HBeAg infection status,and whether to revaccinate;revaccination with hepatitis B vaccine was effective in preventing the occurrence of breakthrough infection.Multi-factor regression analysis found that Hani ethnicity was a risk factor for HBV breakthrough infection in children,and HBeAg-positive mothers were a risk factor for HBV breakthrough infection in children.4.The study identified one child as an acute self-limited case of hepatitis B.This suggests that children over 10 years of age can also recover spontaneously from acute hepatitis B infection. |
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