The efficacy of two different dosages of hepatitis B immunoglobulin combined with hepatitis B vaccine in preventing mother-to-child transmission of hepatitis B virus: A prospective cohort study.

BACKGROUND/AIMS: A birth dose of hepatitis B immunoglobulin (HBIG), in combination with hepatitis B vaccine (HepB), is recommended for infants born to hepatitis B surface antigen (HBsAg)-positive mothers. However, the optimal dosage of HBIG remains to be resolved. This prospective cohort study aimed to compare the efficacy of two dosages of HBIG combined with HepB to prevent mother-to-child transmission (MTCT) of HBV. METHODS: From 2009 to 2011, we prospectively enrolled mother-infant pairs with positive maternal HBsAg in China. Infants were assigned to receive one dose of 100 IU or 200 IU HBIG within 12 h of birth according to maternal numbering, followed by completion of the 3-dose 10 µg HepB series. At 7 months, post-vaccination serologic testing (PVST) was performed in 545 and 632 infants in 100 IU and 200 IU HBIG groups, respectively, among whom, 451 and 529 were followed up to 12 months. RESULTS: Maternal and birth characteristics were comparable between infants in 100 IU and 200 IU HBIG groups. At 7 months, the rates of perinatal infection were 1.5% (8/545) and 1.9% (12/632) in 100 IU and 200 IU HBIG groups, respectively (p = .568). One non-responder infant in 200 IU HBIG group became newly infected at 12 months. The antibody to hepatitis B surface antigen (anti-HBs) positive rates were 98.5% (529/537) and 98.2% (609/620) in 100 IU and 200 IU HBIG groups at 7 months, respectively (p = .704), and the corresponding figures were 98.2% (431/439) and 97.1% (496/511) at 12 months (p = .266). The anti-HBs geometric mean concentrations were comparable between two groups at 7 months (707.95 mIU/mL vs. 602.56 mIU/mL, p = .062) and 12 months (245.47 mIU/mL vs. 229.09 mIU/mL, p = .407). CONCLUSIONS: One birth dose of 100 IU HBIG, combined with the HepB series, might be enough for preventing MTCT of HBV in infants born to HBsAg-positive mothers.

The maternal viral threshold for antiviral prophylaxis of perinatal hepatitis B virus transmission in settings with limited resources: A large prospective cohort study in China.

BACKGROUND: Antiviral therapy has been documented to reduce perinatal transmission of hepatitis B virus (HBV) in highly viremic mothers. This large prospective cohort study conducted in China aims to delineate the maternal viral threshold for consideration of antiviral prophylaxis in settings with limited resources. METHODS: A total of 1177 mother-infant pairs with positive maternal hepatitis B surface antigen (HBsAg) under current passive-active prophylaxis regimen were enrolled from community health centers in Jiangsu and Henan provinces, China. Maternal hepatitis B e antigen (HBeAg) status and viral load were tested at 36-40 weeks of gestation. Post-vaccination serologic testing was performed at 7 and 12 months of age. RESULTS: HBeAg-positive mothers (419/1177; 35.6%) had significantly higher viral loads, compared with HBeAg-negative mothers (758/1177; 64.4%) (8.12 vs. 2.69 log IU/mL, p < .0001). Twenty infants, born to HBeAg-positive mothers with high viral loads (median, 8.38; range: 7.82-9.22 log IU/mL), were infected at 7 months of age. In contrast, none of the HBeAg-negative mothers transmitted HBV to their offspring. After adjustment for the other risk factor, a higher maternal viral load was significantly associated with a higher risk of transmission (adjusted odds ratio, 3.78; 95% confidence interval: 1.46-9.81; p = .006). The rates of passive-active immunoprophylaxis failure were 0.0% (0/789), 0.0% (0/27), 0.0% (0/32) and 6.1% (20/329) at maternal viral loads of <5, 5-6, 6-7 and ≥7 log IU/mL, respectively. The antibody to hepatitis B surface antigen (anti-HBs) response rate was 98.4% (1138/1157) at 7 months of age. CONCLUSIONS: Results from this study indicate that the maternal viral threshold associated with perinatal transmission of HBV is 7 log IU/mL, which may be appropriate for consideration of antiviral prophylaxis in settings with limited resources.

Occult HBV Infection in Immunized Neonates Born to HBsAg-Positive Mothers: A Prospective and Follow-Up Study.

OBJECTIVE: Occult HBV infection (OBI) has been reported in infants born to HBsAg-positive mothers despite immunization. This study aims to determine the maintenance of this status in a prospective birth cohort. METHODS: A total of 158 neonates born to HBsAg-positive mothers were enrolled. All received passive-active immunization against HBV according to a 0-1-6 schedule. Sera were collected at 7 months of age. Those diagnosed with OBI were serially followed up at 12, 24 and 36 months of age. HBV serological markers were determined by Abbott i2000 system. HBV DNA was quantitated by Abbott m2000 system. Standard PCR followed by direct sequencing were applied for mother-child HBV pairs. Homology and phylogenetic comparisons were done by BLAST and Mega 5. RESULTS: All the 158 neonates were HBsAg-negative and anti-HBs-positive at 7 months of age, and 32 (20.3%) of them were diagnosed with OBI, with a median HBV DNA level of 1.97 (1.20-3.71) log IU/mL. Of them, HBV DNA was positive in 25.0%, 21.9% and 7.7% at 12, 24 and 36 months of age, respectively. HBV DNA disappeared at one of the follow-up points in 31 neonates, however, rebounded to low levels in 6 of them thereafter. HBV DNA persisted at low levels during follow-ups in the other one neonate apart from the above 31. All remained negative for HBsAg. Only two (6.3%) neonates were positive for anti-HBc after 24 months of age. HBV showed close homology and phylogenetic relationships for mother-child pairs. S-escape mutant, G145R, was not discovered. The first vaccine dose within 6 hours of birth significantly reduced the occurrence of OBI (59.4% vs. 83.3%, p = 0.003). CONCLUSIONS: HBV may be controlled in immunized neonates of HBsAg-positive mothers, after being diagnosed with OBI. Timely vaccination against HBV may provide the utmost protection. Long-term and close monitorings are needed.

[Evaluating the current protocol of influenza A (H1N1) based on the epidemic situations of Zhengzhou,a middle-sized city in China].

OBJECTIVE: From May 2009-January 2010, a total of 3768 biosamples were tested for influenza A (H1N1) infection at Zhengzhou center for disease control and prevention, China. 1452 cases were laboratory confirmed H1N1 infection and 2316 were considered suspected victims. To evaluate the current protocol of influenza A (H1N1) based on the epidemic situations of Zhengzhou, relationships among features were explored and whether additional clinical characteristics should be part of H1N1 diagnosis protocols were determined. METHODS: Both clinical and epidemiologic findings as well as statistical analyses were described in this article. Test for independence between features related to the disease diagnosis has been proposed. Furthermore, logistic regression was carried out to measure the association among features and latent class analysis was performed to identify additional crucial features in laboratory confirmed H1N1 by building various latent models with different combinatorial features. RESULTS: The mean generation time for H1N1 was estimated as 3.59 +/- 1.41 days (range = 2.01-7.26). The estimated infection rate was 0.258 +/- 0.088 3, and reproduction number was 1.94 (95% CI = 1.12-3.18). Our results revealed that the six features, including molecular detections using three separate primer/probe sets, gender, age and temperature, are all associated with clinical diagnosis of H1N1, and that three separate primer/probe sets for laboratory confirmed H1N1, age and temperature are associated with each other. CONCLUSION: Additional clinical features applied into the H1N1 diagnosis with current three primers/probe sets can increase the diagnostic efficiency.

A predictive value of quantitative HBsAg for serum HBV DNA level among HBeAg-positive pregnant women.

BACKGROUND: The high maternal HBV DNA level is the most important factor contributing to HBV perinatal transmission. This study is to explore whether HBsAg can be used as a surrogate marker of serum HBV DNA for HBsAg-positive pregnant women. METHODS: A total of 975 HBsAg-positive pregnant women and their infants were enrolled in this study. All infants received three doses of a yeast-derived recombinant Hepatitis B vaccine at 0, 1 and 6 months. They were also given Hepatitis B immunoglobulin (HBIG) at birth. HBsAg and HBeAg were determined using Abbott Architect assays while serum HBV DNA level was detected by the Abbott Real Time HBV DNA assay. RESULTS: Of the 975 subjects, 367 (37.6%) were HBeAg-positive and 608 (62.4%) were HBeAg-negative. Among the HBeAg-positive group, the samples with HBV DNA levels of ≥7.0 logIU/mL were 76.6% (281/367), and it was only 0.7% (4/608) for the HBeAg-negative group. HBV DNA level was positively correlated with HBsAg in HBeAg-positive group (r=0.786, p<0.001) but not in HBeAg-negative group (r=0.022, p=0.593). Among HBeAg-positive group, the area under the receiver-operator curve (ROC) of HBsAg titer for high HBV DNA level (≥7.0 logIU/mL) was 0.961 (95% CI, 0.940-0.983, p<0.001). The optimum cut-off point HBsAg titer above 4.1 logIU/mL had a sensitivity of 85.1%, specificity of 96.5%, and accuracy of 87.5% to predict HBV DNA levels of ≥7.0 logIU/mL. Of 367 infants born to mothers with HBeAg-positive, perinatal transmission was detected in 24 infants (6.5%, 24/367). Their mothers all had serum HBV DNA levels of ≥7.0 logIU/mL, 23 (95.8%) had HBsAg titers of ≥4.1 logIU/mL and the other mother had HBsAg titer of 3.9 logIU/mL. Of 608 infants born to mothers with HBeAg-negative, only one (0.2%, 1/608) became HBsAg-positive at the age of 7 months, and the mother of the infant had serum HBV DNA level of 3.4 logIU/mL and HBsAg titer of 1.8 logIU/mL, respectively. CONCLUSION: Serum HBsAg titer may be used as a surrogate marker of serum HBV DNA for HBeAg-positive pregnant women.