|Year : 2015 | Volume
| Issue : 5 | Page : 140-143
Mother to child transmission of hepatitis B virus: A cause for concern
AM Ismail1, A Raghavendran1, J Sivakumar1, M Radhakrishnan1, W Rose2, P Abraham1
1 Department of Clinical Virology, Christian Medical College, Vellore - 632004, Tamil Nadu, India
2 Department of Child Health, Christian Medical College, Vellore - 632004, Tamil Nadu, India
|Date of Submission||21-Mar-2014|
|Date of Acceptance||03-Jul-2014|
|Date of Web Publication||6-Feb-2015|
Department of Clinical Virology, Christian Medical College, Vellore - 632004, Tamil Nadu
Source of Support: The study was supported by Intramural Research
fund of the Department of Clinical Virology, Christian Medical College,
Vellore, India, Conflict of Interest: None
Mother to child transmission of hepatitis B virus (HBV) is an important public health issue. India introduced HBV vaccine in 10 states as part of its Universal Immunization Program (UIP). Here we show evidence of mother-to-child transmission of HBV in three families from Jharkhand and Bihar states where HBV vaccination is not yet included in the UIP. This report illustrates the need for active screening of HBV in pregnant women and implementation of HBV vaccine across all states in India to reduce the burden of disease.
Keywords: Hepatitis B virus transmission, Hepatitis B virus, vaccine
|How to cite this article:|
Ismail A M, Raghavendran A, Sivakumar J, Radhakrishnan M, Rose W, Abraham P. Mother to child transmission of hepatitis B virus: A cause for concern. Indian J Med Microbiol 2015;33, Suppl S1:140-3
|How to cite this URL:|
Ismail A M, Raghavendran A, Sivakumar J, Radhakrishnan M, Rose W, Abraham P. Mother to child transmission of hepatitis B virus: A cause for concern. Indian J Med Microbiol [serial online] 2015 [cited 2020 Apr 9];33, Suppl S1:140-3. Available from: http://www.ijmm.org/text.asp?2015/33/5/140/150931
| ~ Introduction|| |
Hepatitis B virus (HBV) infection in pregnant women is a serious threat to infants. The risk of developing chronic HBV infection in infants born to HBeAg-positive mother is 70-90% and the risk is 10-31% for infants born to HBeAg-negative mother. ,
Mother-to-child transmission of HBV can be prevented by providing infants with hepatitis B immunoglobulin (HBIG) and HBV vaccine within 12 hours of birth.  India introduced the HBV vaccine in 10 states including Andhra Pradesh, Himachal Pradesh, Jammu and Kashmir, Karnataka, Kerala, Madhya Pradesh, Maharashtra, Punjab, Tamil Nadu, and West Bengal as part of its Universal Immunization Program (UIP) in 2007-08.  Here, we demonstrate mother-to-child transmission of HBV in three families from Jharkhand and Bihar states where HBV vaccination is not included in the UIP.
| ~ Case Reports|| |
On 11 th January 2013, four children between 4-10 years of age from a family in Jharkhand state were referred to the department of Clinical Virology for quantitative HBV DNA estimation. All children tested positive for hepatitis B surface antigen (HBsAg). They were screened for HBV as the mother was detected positive for HBsAg on routine preoperative screening. On testing of additional HBV markers, all were positive for HBeAg and HBV DNA levels ranged between 8.7 and 9.6 log 10 IU/mL [Figure 1]. Liver function tests and ultrasound of the abdomen were normal. Samples were collected from the parents for additional investigation. The mother was also detected to be HBeAg positive with HBV DNA levels of 6 log 10 IU/mL. She gave information of continuing adefovir monotherapy for 2 months which was started prior to the visit to this hospital. The father was positive for HBV core antibody (anti-HBc) and negative for other HBV serology markers and HBV DNA. HBV PCR and sequencing was performed for mother and children sample who were positive for HBV DNA. All study samples clustered together and were determined as HBV genotype D and HBsAg subtype ayw2 [Figure 2].
|Figure 1: Flow chart of the study *Died of HBV-associated hepatocellular carcinoma $Known HBsAg positive case (not tested in this lab)|
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|Figure 2: Phylogenetic analysis of HBV reverse transcriptase nucleotide sequences (1046 positions) was conducted in MEGA6 using the neighbour joining method and maximum composite likelihood model. GenBank reference sequences are shown by HBV genotype and accession number. Woolly monkey HBV (WM HBV) was used as an out-group. Nucleotide similarity for sequences in each family is calculated with respective to the mother (M) HBV sequence or with the available first generation family sequences as shown|
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Another family from Jharkhand visited the liver clinic of this hospital on 25 th April 2013. A total of nine members from the family were screened for HBsAg and seven children of generation 1 and generation 2 were identified to be positive [Figure 1]. The family gave a history of their maternal grandmother who died of HBV-associated hepatocellular carcinoma. Therefore, we report a case of mother-to-child transmission of HBV for two successive generations. On phylogenetic analysis, the study samples clustered together and were determined as HBV genotype D [Figure 2]. Further, the predicted HBsAg subtype in the samples is ayw2.
A family of seven members whose ancestor mother was a known case of HBV infection were screened for HBV on 1 st October 2013. The family comprised of two children and a husband in generation 1, three children in generation 2 and one child in generation 3. Both children in generation 1 and one daughter in generation 2 were positive for HBsAg. The remaining two children in generation 2 and one child in generation 3 were negative for HBsAg. All three HBsAg-negative children were vaccinated for HBV. However, child 2 in generation 2 had been administered with only two dosage of vaccine and showed evidence of exposure to HBV infection (anti-HBs negative and anti-HBc positive). Among the samples tested, two samples in generation 1 and 2 with HBV DNA levels of 9.3 and 2.82 log 10 IU/mL respectively were sequenced [Figure 1]. Both the samples were determined as HBV genotype D and subtype ayw2 [Figure 2]. The remaining one HBV DNA positive sample could not be sequenced as the HBV DNA levels was low (1.76 log 10 IU/mL) and therefore failed sequence analysis.
| ~ Discussion|| |
In regions of high HBV endemicity, World Health Organization (WHO) recommends HBV vaccination at birth to prevent mother-to-child transmission, independent of the HBV maternal status. In intermediate and low HBV-endemic region, selective immunization of infants born to HBsAg-positive mothers is recommended. HBV vaccine has reduced the rate of hepatitis B prevalence and its associated sequelae. Therefore, WHO Expanded Program of Immunization (EPI) recommend HBV vaccination in the national immunization program for all countries (Reviewed by Denis and Ranger-Rogez, 2004  ).
In our study, it is very evident that the children were infected with HBV through vertical transmission, particularly evident in cases 2 and 3 where HBV seems to have been transmitted across two generations. This clearly illustrates the need for active screening of HBV in all pregnant women and immunization of infants born to HBV infected mothers. Due to transmission so early in life, chronic infection was established with high HBV DNA levels, also increasing risk in long term sequelae. HBV DNA levels in the HBeAg-positive mother (case 1) were relatively low (6 log 10 IU/mL) as she was continuing antiviral therapy. Interestingly, the male members (adults) in the described cases have been exposed to HBV and show evidence of natural clearance.
In case 3, HBV DNA levels tested in both mothers (generation 1 and generation 2) were lower and were HBeAg-negative. Child 2 in generation 2 received only two doses of HBV vaccine, and hence showed markers of HBV infection. This further reiterates the need for administration of the recommended 3 dose of vaccine to ensure protection against HBV infection.
Among the children born to the HBeAg-positive mother in cases 1 and 2, 9 (90%) had high HBV DNA levels of >7.48 log 10 IU/mL. The remaining one child described in case 2 had low HBV DNA levels (2.42 log 10 IU/mL) with anti-HBe seroconversion. The study results thus correspond to the earlier reported proportion of HBV-infected infants at increased risk for developing chronic HBV infection. , As observed in this study, India has a predominant HBV genotype D circulation. A previous study from the Indian subcontinent showed the association of genotype D with severe liver disease and HCC as compared to genotype A in young adults.  Since mother-to-child transmission increases the risk of developing chronic HBV infection, active screening of HBsAg in all pregnant women is recommended. Additionally, implementation of HBV vaccine across all states in countries like India with intermediate HBV endemicity would reduce the burden of disease as demonstrated in Taiwan and Italy. ,
On phylogenetic analysis all sequences from the respective family members clustered closely together. The nucleotide similarity between the sequences ranged between 99.6 and 100%, indicating the sequences are very close to identical. This cannot exclusively prove mother-to-child transmission as there is a likely chance of horizontal transmission in early childhood. However, in a meta-analysis survey, it was shown that unlike vertical or sexual transmission of HBV, horizontal route is a less efficient mode of transmission. 
We show evidence of three or more children in each generation to be infected with HBV and with large age differences in some cases. Therefore, the probability that every child in the family acquired HBV through saliva or open wound is less likely. These points strongly suggest that mother-to-child transmission would be the major mode of HBV transmission in all three families. The demonstration of the same strain in siblings across generations in these families, reiterates the importance of neonatal HBV vaccination as it prevents against both forms of familial transmission.
In summary, we show evidence of mother-to-child transmission of HBV across three generations. This report illustrates the need for active screening of HBV in pregnant women and implementation of HBV vaccine across all states in India to reduce the burden of disease.
| ~ Acknowledgements|| |
The authors acknowledge all the study participants.
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[Figure 1], [Figure 2]