Dissertation
Dissertation > Medicine, health > Internal Medicine > Infectious disease > Viral infections > Viral Hepatitis > Hepatitis B

Immunoprophylaxis Efficacy of Mother-to-Child Transmission of Hepatitis B Virus and Immunity Effects of Inoculating Hepatitis B Vaccine

Author ZhangLei
Tutor DuXiEn
School Wuhan University
Course Internal Medicine
Keywords Hepatisis B virus pregnant women HBsAg positive mother mother-to-infant transmission passive-active immunization immunoprophylaxisfailure influencing factors HBsAb placental barrier dynamic changes neonates intrauterine infection delivery infection femoral vein blood umbilical cord blood hepatitis B vaccine HBsAb seroconversion HBsAg positive father verticaltransmission
CLC R512.62
Type PhD thesis
Year 2013
Downloads 123
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Part Ⅰ Seroprevalence of hepatitis B virus, human immunodeficiency virus and syphilis among pregnant women in multi-centers in ChinaObjective To investigate the prevalence of hepatitis B virus (HBV), human immunodeficiency virus (HIV) and syphilis among women of childbearing age in China in order to help to conduct specific measures for interruption.Methods From2008to2013, pregnant women were screened for HIV, HBV and syphilis in Hubei province, Xinjiang uygur autonomous region, Shanxi and Guangdong province to survey epidemics of the three diseases.Results Among103174pregnant women, HIV, HBV and syphilis positive rate was0.24%,5.97%and0.55%respectively. The positive rate of HBV was significantly higher than HIV and syphilis, p=0.000. Among all investigation areas, HBsAg positive rate was highest (8.51%) in Guangdong, second (6.57%) in Hubei and lower in Yining city of Xinjing (4.34%) and Shanxi province (4.17%).Conclusion The multicenter, large sample study shows that infection rate of HBV is high and that of HIV and syphilis was low respectively. Among pregnant women, HBV prevalence varied in different parts of China. It is necessary to continue to strengthen the screening of maternal infection of HIV, HBV and syphilis, in order to further improve mother-to-child transmission and explore the potential reason.Part Ⅱ Efficacy of immunoprophylaxis for mother-to-infant transmission of Hepatitis B Virus:Immune interruption failure and influencing factorsObjective HBV infection is seriously prevalent in China. Mother-to-infant transmission is the major route for HBV transmission and subsequent chronicity. Hepatitis B vaccine has incorporated into national immunization programs since1992and infants born to HBsAg positive mothers are routinely given passive-active immunization in China. This study aimed to investigate the preventive outcome and influencing factors of HBV mother-to-infant transmission in order to explore the more effective interruption measures for mother-to-infant transmission.Methods From2008to2012, pregnant women were screened for HBsAg in multi-centers (Provinces of Hubei, Shanxi and Guangdong and Xinjiang). HBsAg positive mothers and their infants in Hubei and Shanxi province were performed HBV markers (HBsAg,HBsAb, HBeAg, HBeAb, HBcAb)and HBV DNA tests. The unified questionnaires were filled.Results HBsAg positive rate of pregnant women was5.97%(6156/103174). Infants’immune interruption failure rate was3.3%(40/1202) among HBsAg positive mothers and their infants of8-12months age; and it was9.4%among infants of HBeAg positive mothers. Immunoprophylaxis failure infants were all born to mothers of HBeAg positive and HBV DNA≥6log10copies/ml. Among infants of HBeAg positive mothers, immunoprophylaxis failure rate in vaccine group was significantly higher than that of vaccine plus HBIG group (16.9%vs7.9%, p=0.021). Immunoprophylaxis failure rate among pregnant women receiving HBIG in third trimester and not (10.3%vs9.0%, p=0.685), caesarean section and vaginal delivery (7.3%vs11.6%, p=0.128), and breastfeeding and formula-feeding (9.5%vs9.2%, p=0.903) showed no significant difference respectively. Multivariate logistic regression analyses revealed that mothers age lower than28and infants only receiving vaccine were the risk factors for HBV mother-to-infants transmission. Among infants with only vaccine, infants’ HBV infection rate was higher in vaginal delivery than in caesarean section group. Between vaginal delivery group and breastfeeding group, infants’ HBV infection rate was significant higher in vaccine only group than in combined immunization group.Conclusion These findings demonstrated that pregnant women are still of high HBsAg prevalence (5.97%) in China. HBV mother-to-infant transmission (3.3%) still occurred after active-passive immunization. Pregnant women of HBeAg positive and HBV DNA≥6logio copies/ml are the major population for preventing HBV mother-to-infant transmission. Active-passive immunization is necessary for neonates of HBeAg positive mothers. Breastfeeding and vaginal delivery did not put children at risk of HBV mother-to-infant transmission. Infants with only vaccine born to HBeAg negative mothers were all free from HBV infection, which indicated that it is unnecessary to give HBIG for these infants.Part Ⅲ Efficacy of immunoprophylaxis for mother-to-infant transmission of Hepatitis B Virus:Infants’ HBsAb seroconversion and its influencing factors Objective HBV infection is seriously prevalent in China. Mother-to-infant transmission is the major route for HBV transmission and subsequent chronicity. Hepatitis B vaccine has incorporated into national immunization programs since1992and infants born to HBsAg positive mothers are routinely given passive-active immunization in China. This study aimed to investigate infants’ HBsAb seroconversion and its influencing factors among those whose mothers were HBsAg positive in order to explore the more effective hepatitis B immune measures and subsequent monitoring procedure. The unified questionnaires were filled.Methods From2008to2012, HBsAg positive mothers and their infants aged8-12months in Hubei and Shanxi province were performed HBV markers (HBsAg, HBsAb, HBeAg, HBeAb, HBcAb) and HBV DNA tests.Results1202pairs of mothers-and-infants were followed and infants’ HBsAb positive rate was82.2%(988/1202). Infants’ HBsAb positive conversion rate was independent of mother with HBeAg positive or high HBV DNA level, feeding patterns and delivery modes. Multivariate logistic regression analyses revealed that mothers age older than30years, mothers receiving HBIG in third trimester, abnormal birth weight were the risk factors influencing HBsAb positive conversion.Conclusion These findings demonstrated that HBsAb positive conversion rate was82.1%among infants born to HBsAg positive mothers. Mothers age older than30years, mothers receiving HBIG in third trimester and abnormal birth weight were the risk factors for HBsAb conversion. It is necessary to have HBV markers tested when infants accomplish the whole hepatitis B schedule and to have hepatitis B revaccination for infants of non-responder, which can improve the hepatitis B vaccination efficacy among population.Part Ⅳ The effect of placental barrier on hepatitis B serological markers and occurring period of perinatal transmission in infants with passive-active immunoprophylaxisObjective Mother-to-child transmission (MTCT) of HBV still occurs after passive-active immunization. It is important to better understand the clinical serological characteristics of hepatitis B serologic markers and explore the possible occurrence period of perinatal transmission in infants.Methods From2008to2012,428pairs of mother and newborn were enrolled and infants aged8-12months were followed in Hubei and Shanxi province. Femoral vein blood (FV) samples were collected in301neonates and umbilical cord blood (UC) from127neonates. All infants received passive-active immunization on schedule. HBV markers (HBsAg, HBeAg, HBsAb, HBcAb, HBeAb) and HBV DNA were performed by quantitative detection.Results HBsAg, HBeAg, HBV DNA positive cases in neonates accounting for those of positive mothers were:35.7%,94.8%,14.0%. Neonates’ mean titers of those indexes were significantly lower than their mothers respectively. The positive rates of HBeAb and HBcAb were95.5%,99.1%and mean titers had no significant differences between neonates and mothers respectively. Most of the positive indexes turned negative during follow-up:HBsAg,88.1%, HBeAg,88.7%, HBV DNA,64.3%, HBeAb,80.9%and HBcAb,47.5%. Seventeen infants (4.4%) were HBV breakthrough, whose mothers were all HBeAg positive and HBV DNA>6log10copies/ml; Four were of high HBV DNA level from birth to follow-up considered to be intrauterine infection, six of HBV DNA turned from low level to high level considered to be infected in late stage of pregnancy or during delivery and seven of HBV DNA turned from negative to high level considered to be delivery infection. There are similar results about transplacental status and negative-converting rate of HBV markers between FV group and UC group.Conclusions Placental barrier can partly prevent maternal HBsAg, HBeAg, HBV DNA from passing through to fetus, and it can not totally prevent MTCT after passive-active immunization. There are more infants infected during delivery than in uterus and mothers with high HBV replication levels are the major cause of MTCT. Performing for HBsAg, HBeAg, HBV DNA once can neither diagnose nor exclude HBV infection in neonates. The FV or UC drawn is recommended as a routine methodPart V The effect of maternal HBsAb on the immune response of hepatitis B vaccine in infantsObjective The coverage rate for the immunization has increased each year since1992, when the Ministry of Health recommended the hepatitis B vaccine for routine immunization of infants. However, some infants do not present HBsAb even after vaccination. HBsAb seroconversion rates may be related to genetic factors or vaccine quality. Does the most widely recommended0,1and6month vaccination schedule influence hepatitis B vaccine response if neonates get HBsAb from their mothers?Methods From2011to2013, multi-center study was conducted in Hubei province. HBsAg positive mothers, their neonates and infants aged7-24months were tested for HBV markers (HBsAg, HBeAg, HBsAb, HBcAb, HBeAb).Results6,899pregnant women from Hubei province were tested for HBsAb and3,883(56.3%) were positive. HBsAb placental pass rate was94.2%with median titre of404.6IU/L vs mothers’381.2IU/L, p=0.527. HBsAb positive rate was significantly higher in infants with a low maternal HBsAb (HBsAb<500IU/L) titer (90.4%) than those with a high maternal HBsAb (HBsAb≥500IU/L) titer (80.2%), p=0.003. Infants’ HBsAb positive rate were80.2%in maternal HBsAb≥500group,90.5%in maternal HBsAb10-500group and90.3%in maternal HBsAb <10group,=0.011. The high HBsAb titer mothers (≥500IU/L)corresponded to lower HBsAb titer children while the HBsAb negative mothers (<10IU/L) corresponded to higher HBsAb titer children and the middle HBsAb titer mothers(10-500IU/L) corresponded to middle HBsAb titer children. This inverse relationship between maternal HBsAb titer and corresponding infant HBsAb titer was statistically significant (p=0.020) HBsAb non-response rate of infants among mothers of high HBsAb titer was significantly higher than mothers of low HBsAb titer. Infants of non-response of vaccine were given one dose of additional vaccine respectively and they all produced high level of antibodies after one month of administration.Conclusion HBsAb placental pass rate was94.2%and the mean titer was not less than their mothers’. Among infants born to high maternal HBsAb group, the HBsAb positive rate and the mean titer were lower than maternal HBsAb group. Non-response infants all produced high level of antibodies to hepatitis B vaccine, which indicated that maternal HBsAb have negative effects on infants’ active immunity on hepatitis B vaccines.Part Ⅵ The study of father-to-child transmission of hepatitis B virusObjective HBV infection is seriously prevalent in China. Mother-to-infant transmission is the major route for HBV transmission and subsequent chronicity. But there is no enough clinical evidence to show whether or not father can transmit HBV to child through vertical transmission.Methods From2008to2012, HBsAg positive fathers were followed in Hubei and Shanxi province. All their infants after accomplishment of hepatitis B vaccination were followed up at the age of8-24months. HBV markers (HBsAg, HBsAb, HBeAg, HBeAb, HBcAb) were tested in all and unified questionnaire were filled.Results Two hundrend and twenty-three pairs of HBsAg positive fathers and their infants aged12-24months were involved. None of the infants was found HBsAg positive.HBeAg positive rate was38.2%among all HBsAg positive fathers and59.4%were HBV DNA positive among fathers who had HBV DNA tested. The mean titer of HBV DNA in HBeAg positive fathers was significantly higher than HBeAg negative fathers.Conclusion This study shows that infants of HBsAg positive fathers and HBsAg negative mothers will not be infected HBV through vertical transmission as long as they receive hepatitis B vaccines according to0,1,6schedule.

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